Histology of Lymphatic system
Organs Involved:
- Red bone marrow = cells originate here.
- Encapusulated organs: lymph nodes, spleen, thymus.
- In axilla / groin = majority of nodes here, running along vasculature.
- Throughout organs / on surfaces exposed to outside world (urogenital tract, GI tract), have diffuse lymphatic tissue (not encapsulated). Include tonsils, adenoids, peyer’s patches, appendix.
Functions:
- Surface protection – non specific (keratin, mucus) MACs
- Drain excess interstitial fluid and plasma protein from tissue spaces
- Transport of dietery lipids / vitamins from GI tract.
- Facilitate immune response = specific to invading organisms. Depends on ability to recognize self / nonself. Immune system activated to neutralize / destroy antigen. B / T cells are activated by specific antigens to destroy those same antigens.
- Acute inflammation: nonspecific mediated by neutrophils, response is always the same.
Lymphatic organs / Tissues:
- Primary lymphatic organs = provide environment for stem cells to divide and mature into B and T lymphocytes. These are bone marrow and thymus. Involve changes in biochemistry / gene expression.
- B cells development completely in bone marrowà acquire B cell receptor from immunoglobulin M or D. IgM is the main one. These cells then divide into subclasses depending on which antigen they are exposed to. B memory cells seek out their specific antigenà reactà proliferate into plasma cells with antibody secretion.
- Undifferentiated noncompetent T cells go to thymus after leaving bone marrow. Here, they acquire their CD molecules that determine their development. Here, they recognize self/ non self as well.
- Secondary lymphatic organs = Sites where immune response occurs. Lymph nodes, spleen, lymphatic nodules.
Immune reactions:
- Cellular immunity = mediated by T cells, react to foreign cells or virus.
- Delayed hypersensitivity takes 1-2 days.
- No circulating factors found
- Inflammation at site
- Humoral immunity = Mediated by B cells
- immediate hypersensitivity
- Antibodies in circulation
- Antibodies inactivate or destroy foreign substances
Lymphocytes:
T cells = 65-75% of lymphocytes
- Helper cells = Regulatory. Identified by CD4. stimulate differentiation of B cells. Are destroyed by HIV.
- Suppressor (effector) cells = identified by CD8. inhibit action of Th cells and Tc cells.
- Cytotoxic cells = identified by CD8. perforin released for cell lysis.
B cells = 5-10%
Effector only – many IgM on surface, type corresponds to each antigen.
Natural killer cells = kill virus infected / malignant cells. No need activaton.
Maturation of T cells:
- Mature in thymus
- Cell mediated response: killer cells attack antigens
- T helper cells costimulate cytotoxic T / B cellsà plasma cells
- Effective against fungi, parasites, cancer, tissue transplants.
- Intercellular pathogens targeted
B cells:
- Antibody mediated response
- Plasma cells form antibodies.
- Extracellular pathogens targeted (bacteria)
Tissue Organization:
Specialized connective tissue
- Two tissue elements
-
- Reticular fibers form the stroma or famework for the tissue
- Cells in spaces between the reticular fibers = lymphocytes, MACs, plasma cells, antigen presenting cells
- Lymphatic vessels connect lymphatic system to the blood vascular system.
Thymus:
- 2 lobed organ located in mediastinum. Atrophies as an adult into fat.
- Capsule and trabeculae divide into lobules→ each lobule has cortex and medulla.
- Cortex: Tightly packed lymphocytes and MACs
- Medulla: reticular epithelial cells produce thymic hormones. Hassall’s corpuscles→ special reticular cell (type 6) unknown function. These are diagnostic for thymus.
Function:
- T cells mature = Express surface protein
- T cells become competent
- Tolerance for self / vs nonself
- T cells proliferate:
- Thymosin = T cell maturation
- Thymopoietin = T cell differentiation and platelet formation
- Thymulin = synthesis of CD molecules
- Thymic humoral factor = clonal expansion of CD8 expressing cells à one cell becomes many to await antigen.
Cortex:
- T lymphocytes, MACs, epithelial reticular cells. Essentially a basket for lymphocytes.
- Type I = isolate cortex from the body = occluding junctions (tight junctions)
- Type II = divide cortex into lymphocyte filled pockets (desmosomes)
- Type III = corticonmedullary junction that isolates the cortex from medulla (tight junctions).
- Type II and III act as antigen presenting cells
Medulla:
- Epithelial reticular cells. Fewer lymphocytes, paler in color. Cells are killed off if they recognize “self” antigens.
- Type IV = corticomedullary junction
- Type V = framework of medulla
- Type VI = hassall’s corpuscles
Thymic capsule: Within trabeculae that form lobules = find dense irregular CT with vasculature within. Arteries go to medulla → capillaries go to cortex. Don’t want cells in cortex to be exposed to body-derived antigens. Corticomedullary junction = where vessels come in and capillary bed forms.
Tolerance:
- Tolerance-recognizes self / nonself
- Do not have immune response to self antigens
- Tolerance occurs by 2 mechanisms
- Anergy = disabling of the immunocompetent cell
- Killing of immnocompetent cells that would reconigze self antigens (this occurs in the thymus)
- Thymic cortex is isolated from the body
- Type II and type III epithelial reticular cells: Antigen presenting cells, self-antigens, MHC I and MHC II → these are docking molecules required for immune response (both types).
- Cells are killed if: TCR recognizes self antigens, or if T cell CD4 / CD8 can’t recognize MHC I / II.
Groupings to associate: MHC I, CD8, Cytotoxic T cells. MHCII, CD4, T helper cells.
MACs are antigen presenting cells.
Lymph nodes:
- Bean shaped organs up to an inch long, located along lymphatic vessels. Scattered throughout body but concentrated near mammary glands / axillae and groin.
- Stroma is capsule, trabeculae (capsule dips to form pockets for cells) and reticular fibers.
- Parenchyma = 2 regions
- Cortex = lymphatic nodules with germinal centers containing dendritic cells. Here, antigen presenting cells and MACs are located. Outer part = B cell region. Inner part = paracortex = T cell region.
- Medulla = contains B cells and plasma cells in medullary cords.
Lymph flow:
- Afferent lymph vessels take fluid to node, efferent lymph nodes take cleansed lymph fluid away from node
- The purpose is to clear out antigens etc.
- Vasculature: arterties form capillary bed within cortex = high endothelial venules à specific for the post capillary bed of cortex (paracortex). Through these venules, WBCs leave blood and enter the node.
- Vessels carry blood through sinuses at all times→between cords. Sinuses are not lined by endothelial cells.
- Also in cortex: Nodules = B cells are activated and start to differentiate into plasma cells.
Pattern of flow:
- Flow is in one direction. Afferent vessels lead in, sinuses lead to efferent vessels that exit at the hilus
- Only filter lymph fluid, not blood.
- Fluid can leave at cortex / paracortex (where WBCs enter) / medulla.
- WBCs in paracortex for Ag presentation→ o up to cortex to differentiate → back to medulla to enter lymph again.
- Interior of node segments will be lighter in color if B cells are actively proliferating. Normal circumstances = Uniform color.
- Germinal centers: have active B cells = pale center of cord.
Spleen:
- 5 inch organ between stomach and diaphragm
- Hilus contains blood / lymphatic vessels
- Stroma consists of capsule with downward leading trabeculae, fibers, fibroblasts
- Parenchyma contains white / red pulp
- Each arteriole that enters the spleen acts as a center for a White pulp section of the spleen.
- White is lymphatic tissue (lymphocytes / MACs) around branches of splenic artery. Contains WBCs. Antigen presentation takes place→have germinal centers forming.
- Red is venous sinuses filled with blood / splenic tissue (splenic cords). Made up of cords of Delroth→ make up structure of the spleen.
- Sinusoids are vascular structures lined by epithelial cells and MACs. In the cords is where MACs destroy old RBCs.
- Spleen has 2 jobs: 1. filter blood in the parenchyma, RBCs are destroyed by MACs. 2. Mount an immune response whenever blood supply is involved.
Artery→ surrouned by periarteriolar lymphatic sheath made of T cells→ surrounded by surrounded by marginal zone where B cells contact antigens. Along the sinus = MACs.
Sinusoids: endothelial lined, contain MACs.
Central artery→ branches into penicillar artery with 3 regions.
- Starts as pulp arteriole
- Becomes sheathed arteriole = surrounded by sheath of MACs
- Becomes terminal capillary→ goes directly into sinus or empties into red pulp cords of Delroth (thus determines open / closed circulation).
Blood leaves the central artery to enter red pulp by: 1. open circulation and 2. closed circulation. Blood must enter splenic cordsà then enters sinusoid to exit via trabecular veins.
Mucosa associated lymphatic tissue:
Locations:
- GI tract = GALT – gut associated lymphatic tissue
- Trachea
- Tonsils (waldeyer’s ring) has nodules
- Peyer’s patch has nodules
- Appendix has nodules
Respiratory tract: BALT bronchus…
Functions: Antigen presentation / phagocytosis.
Lymphatic nodules in diffuse tissues:
- Concentrations of lymphatic tissue not surrounded by a capsule. scattered throughout CT of mucous membranes.
- Mucosa associated lymphoid tissue = MALT
Tonsils:
- Form a ring at the top of the throat
- Adenoids = pharyngeal tonsils
- Palatine tonsils = on each side wall
- Lingual tonsil = in the back of the tongue
Eyer’s Patches:
- In the ilium of the small intestine.
- 2 T cell domains on outer portion of germinal center within the follicle (B cell area). M cells are on epithelium of gut lumen à are Ag presenting cell (a phagocyte).
- If it takes up an antigen from gutà it migrates into B cell domain to present antigen.
Lymphatic circulation
Capillaries that begin as closed-ended tubes found in spaces between cells.
- Lymphatic capillary is between arterioles and venules in capillary bed.
- Fluids and protein from capillaries is collected by lymphatic capillaries and is returned to the blood
Respiratory and muscular pumps promote flow of fluidà empties into subclavian veins.
Histology of Lymphatic system
Organs Involved:
- Red bone marrow = cells originate here.
- Encapusulated organs: lymph nodes, spleen, thymus.
- In axilla / Groin = majority of nodes here, running along vasculature.
- Throughout organs / on surfaces exposed to outside world (urogenital tract, GI tract), have diffuse lymphatic tissue (not encapsulated). Include tonsils, adenoids, peyer’s patches, appendix.
Functions:
- Surface protection – non specific (keratin, mucus) MACs
- Drain excess interstitial fluid and plasma protein from tissue spaces
- Transport of dietery lipids / vitamins from GI tract.
- Facilitate immune response = specific to invading organisms. Depends on ability to recognize self / nonself. Immune system activated to neutralize / destroy antigen. B / T cells are activated by specific antigens to destroy those same antigens.
- Acute inflammation: nonspecific mediated by neutrophils, response is always the same.
Lymphatic organs / Tissues:
- Primary lymphatic organs = provide environment for stem cells to divide and mature into B and T lymphocytes. These are bone marrow and thymus. Involve changes in biochemistry / gene expression.
- B cells development completely in bone marrowà acquire B cell receptor from immunoglobulin M or D. IgM is the main one. These cells then divide into subclasses depending on which antigen they are exposed to. B memory cells seek out their specific antigenà reactà proliferate into plasma cells with antibody secretion.
- Undifferentiated noncompetent T cells go to thymus after leaving bone marrow. Here, they acquire their CD molecules that determine their development. Here, they recognize self/ non self as well.
- Secondary lymphatic organs = Sites where immune response occurs. Lymph nodes, spleen, lymphatic nodules.
Immune reactions:
- Cellular immunity = mediated by T cells, react to foreign cells or virus.
- Delayed hypersensitivity takes 1-2 days.
- No circulating factors found
- Inflammation at site
- Humoral immunity = Mediated by B cells
- immediate hypersensitivity
- Antibodies in circulation
- Antibodies inactivate or destroy foreign substances
Lymphocytes:
T cells = 65-75% of lymphocytes
- Helper cells = Regulatory. Identified by CD4. stimulate differentiation of B cells. Are destroyed by HIV.
- Suppressor (effector) cells = identified by CD8. inhibit action of Th cells and Tc cells.
- Cytotoxic cells = identified by CD8. perforin released for cell lysis.
B cells = 5-10%
Effector only – many IgM on surface, type corresponds to each antigen.
Natural killer cells = kill virus infected / malignant cells. No need activaton.
Maturation of T cells:
- Mature in thymus
- Cell mediated response: killer cells attack antigens
- T helper cells costimulate cytotoxic T / B cellsà plasma cells
- Effective against fungi, parasites, cancer, tissue transplants.
- Intercellular pathogens targeted
B cells:
- Antibody mediated response
- Plasma cells form antibodies.
- Extracellular pathogens targeted (bacteria)
Tissue Organization:
Specialized connective tissue
- Two tissue elements
-
- Reticular fibers form the stroma or famework for the tissue
- Cells in spaces between the reticular fibers = lymphocytes, MACs, plasma cells, antigen presenting cells
- Lymphatic vessels connect lymphatic system to the blood vascular system.
Thymus:
- 2 lobed organ located in mediastinum. Atrophies as an adult into fat.
- Capsule and trabeculae divide into lobules→ each lobule has cortex and medulla.
- Cortex: tightly packed lymphocytes and MACs
- Medulla: reticular epithelial cells produce thymic hormones. Hassall’s corpuscles→ special reticular cell (type 6) unknown function. These are diagnostic for thymus.
Function:
- T cells mature = Express surface protein
- T cells become competent
- Tolerance for self / vs nonself
- T cells proliferate:
- Thymosin = T cell maturation
- Thymopoietin = T cell differentiation and platelet formation
- Thymulin = synthesis of CD molecules
- Thymic humoral factor = clonal expansion of CD8 expressing cells à one cell becomes many to await antigen.
Cortex:
- T lymphocytes, MACs, epithelial reticular cells. Essentially a basket for lymphocytes.
- Type I = isolate cortex from the body = occluding junctions (tight junctions)
- Type II = divide cortex into lymphocyte filled pockets (desmosomes)
- Type III = corticonmedullary junction that isolates the cortex from medulla (tight junctions).
- Type II and III act as antigen presenting cells
Medulla:
- Epithelial reticular cells. Fewer lymphocytes, paler in color. Cells are killed off if they recognize “self” antigens.
- Type IV = corticomedullary junction
- Type V = framework of medulla
- Type VI = hassall’s corpuscles
Thymic capsule: within trabeculae that form lobules = find dense irregular CT with vasculature within. Arteries go to medullaà capillaries go to cortex. Don’t want cells in cortex to be exposed to body-derived antigens. Corticomedullary junction = where vessels come in and capillary bed forms.
Tolerance:
- Tolerance-recognizes self / nonself
- Do not have immune response to self antigens
- Tolerance occurs by 2 mechanisms
- Anergy = disabling of the immunocompetent cell
- Killing of immnocompetent cells that would reconigze self antigens (this occurs in the thymus)
- Thymic cortex is isolated from the body
- Type II and type III epithelial reticular cells: antigen presenting cells, self-antigens, MHC I and MHC II à these are docking molecules required for immune response (both types).
- Cells are killed if: TCR recognizes self antigens, or if T cell CD4 / CD8 can’t recognize MHC I / II.
Groupings to associate: MHC I, CD8, Cytotoxic T cells. MHCII, CD4, T helper cells.
MACs are antigen presenting cells.
Lymph nodes:
- Bean shaped organs up to an inch long, located along lymphatic vessels. Scattered throughout body but concentrated near mammary glands / axillae and groin.
- Stroma is capsule, trabeculae (capsule dips to form pockets for cells) and reticular fibers.
- Parenchyma = 2 regions
- Cortex = lymphatic nodules with germinal centers containing dendritic cells. Here, antigen presenting cells and MACs are located. Outer part = B cell region. Inner part = paracortex = T cell region.
- Medulla = contains B cells and plasma cells in medullary cords.
Lymph flow:
- Afferent lymph vessels take fluid to node, efferent lymph nodes take cleansed lymph fluid away from node
- The purpose is to clear out antigens etc.
- Vasculature: arterties form capillary bed within cortex = high endothelial venules à specific for the post capillary bed of cortex (paracortex). Through these venules, WBCs leave blood and enter the node.
- Vessels carry blood through sinuses at all timesà between cords. Sinuses are not lined by endothelial cells.
- Also in cortex: Nodules = B cells are activated and start to differentiate into plasma cells.
Pattern of flow:
- Flow is in one direction. Afferent vessels lead in, sinuses lead to efferent vessels that exit at the hilus
- Only filter lymph fluid, not blood.
- Fluid can leave at cortex / paracortex (where WBCs enter) / medulla.
- WBCs in paracortex for Ag presentationà go up to cortex to differentiate à back to medulla to enter lymph again.
- Interior of node segments will be lighter in color if B cells are actively proliferating. Normal circumstances = uniform color.
- Germinal centers: have active B cells = pale center of cord.
Spleen:
- 5 inch organ between stomach and diaphragm
- Hilus contains blood / lymphatic vessels
- Stroma consists of capsule with downward leading trabeculae, fibers, fibroblasts
- Parenchyma contains white / red pulp
- Each arteriole that enters the spleen acts as a center for a White pulp section of the spleen.
- White is lymphatic tissue (lymphocytes / MACs) around branches of splenic artery. Contains WBCs. Antigen presentation takes placeà have germinal centers forming.
- Red is venous sinuses filled with blood / splenic tissue (splenic cords). Made up of cords of Delrothà make up structure of the spleen.
- Sinusoids are vascular structures lined by epithelial cells and MACs. In the cords is where MACs destroy old RBCs.
- Spleen has 2 jobs: 1. filter blood in the parenchyma, RBCs are destroyed by MACs. 2. mount an immune response whenever blood supply is involved.
Artery→ surrouned by periarteriolar lymphatic sheath made of T cells→ surrounded by surrounded by marginal zone where B cells contact antigens. Along the sinus = MACs.
Sinusoids: endothelial lined, contain MACs.
Central artery→ branches into penicillar artery with 3 regions.
- Starts as pulp arteriole
- Becomes sheathed arteriole = surrounded by sheath of MACs
- Becomes terminal capillaryà goes directly into sinus or empties into red pulp cords of Delroth (thus determines open / closed circulation).
Blood leaves the central artery to enter red pulp by: 1. open circulation and 2. closed circulation. Blood must enter splenic cordsà then enters sinusoid to exit via trabecular veins.
Mucosa associated lymphatic tissue:
Locations:
- GI tract = GALT – gut associated lymphatic tissue
- Trachea
- Tonsils (waldeyer’s ring) has nodules
- Peyer’s patch has nodules
- Appendix has nodules
Respiratory tract: BALT bronchus…
Functions: Antigen presentation / phagocytosis.
Lymphatic nodules in diffuse tissues:
- Concentrations of lymphatic tissue not surrounded by a capsule. scattered throughout CT of mucous membranes.
- Mucosa associated lymphoid tissue = MALT
Tonsils:
- Form a ring at the top of the throat
- Adenoids = pharyngeal tonsils
- Palatine tonsils = on each side wall
- Lingual tonsil = in the back of the tongue
eyer’s patches:
- In the ilium of the small intestine.
- 2 T cell domains on outer portion of germinal center within the follicle (B cell area). M cells are on epithelium of gut lumen à are Ag presenting cell (a phagocyte).
- If it takes up an antigen from gutà it migrates into B cell domain to present antigen.
Lymphatic circulation
Capillaries that begin as closed-ended tubes found in spaces between cells.
- Lymphatic capillary is between arterioles and venules in capillary bed.
- Fluids and protein from capillaries is collected by lymphatic capillaries and is returned to the blood
Respiratory and muscular pumps promote flow of fluidà empties into subclavian veins.
Histology of Lymphatic system
Organs Involved:
- Red bone marrow = cells originate here.
- Encapusulated organs: lymph nodes, spleen, thymus.
- In axilla / groin = majority of nodes here, running along vasculature.
- Throughout organs / on surfaces exposed to outside world (urogenital tract, GI tract), have diffuse lymphatic tissue (not encapsulated). Include tonsils, adenoids, peyer’s patches, appendix.
Functions:
- Surface protection – non specific (keratin, mucus) MACs
- Drain excess interstitial fluid and plasma protein from tissue spaces
- Transport of dietery lipids / vitamins from GI tract.
- Facilitate immune response = specific to invading organisms. Depends on ability to recognize self / nonself. Immune system activated to neutralize / destroy antigen. B / T cells are activated by specific antigens to destroy those same antigens.
- Acute inflammation: nonspecific mediated by neutrophils, response is always the same.
Lymphatic organs / Tissues:
- Primary lymphatic organs = provide environment for stem cells to divide and mature into B and T lymphocytes. These are bone marrow and thymus. Involve changes in biochemistry / gene expression.
- B cells development completely in bone marrowà acquire B cell receptor from immunoglobulin M or D. IgM is the main one. These cells then divide into subclasses depending on which antigen they are exposed to. B memory cells seek out their specific antigenà reactà proliferate into plasma cells with antibody secretion.
- Undifferentiated noncompetent T cells go to thymus after leaving bone marrow. Here, they acquire their CD molecules that determine their development. Here, they recognize self/ non self as well.
- Secondary lymphatic organs = Sites where immune response occurs. Lymph nodes, spleen, lymphatic nodules.
Immune reactions:
- Cellular immunity = mediated by T cells, react to foreign cells or virus.
- Delayed hypersensitivity takes 1-2 days.
- No circulating factors found
- Inflammation at site
- Humoral immunity = Mediated by B cells
- immediate hypersensitivity
- Antibodies in circulation
- Antibodies inactivate or destroy foreign substances
Lymphocytes:
T cells = 65-75% of lymphocytes
- Helper cells = Regulatory. Identified by CD4. stimulate differentiation of B cells. Are destroyed by HIV.
- Suppressor (effector) cells = identified by CD8. inhibit action of Th cells and Tc cells.
- Cytotoxic cells = identified by CD8. perforin released for cell lysis.
B cells = 5-10%
Effector only – many IgM on surface, type corresponds to each antigen.
Natural killer cells = kill virus infected / malignant cells. No need activaton.
Maturation of T cells:
- Mature in thymus
- Cell mediated response: killer cells attack antigens
- T helper cells costimulate cytotoxic T / B cellsà plasma cells
- Effective against fungi, parasites, cancer, tissue transplants.
- Intercellular pathogens targeted
B cells:
- Antibody mediated response
- Plasma cells form antibodies.
- Extracellular pathogens targeted (bacteria)
Tissue Organization:
Specialized connective tissue
- Two tissue elements
-
- Reticular fibers form the stroma or famework for the tissue
- Cells in spaces between the reticular fibers = lymphocytes, MACs, plasma cells, antigen presenting cells
- Lymphatic vessels connect lymphatic system to the blood vascular system.
Thymus:
- 2 lobed organ located in mediastinum. Atrophies as an adult into fat.
- Capsule and trabeculae divide into lobules→ each lobule has cortex and medulla.
- Cortex: tightly packed lymphocytes and MACs
- Medulla: reticular epithelial cells produce thymic hormones. Hassall’s corpuscles→ special reticular cell (type 6) unknown function. These are diagnostic for thymus.
Function:
- T cells mature = Express surface protein
- T cells become competent
- Tolerance for self / vs nonself
- T cells proliferate:
- Thymosin = T cell maturation
- Thymopoietin = T cell differentiation and platelet formation
- Thymulin = synthesis of CD molecules
- Thymic humoral factor = clonal expansion of CD8 expressing cells à one cell becomes many to await antigen.
Cortex:
- T lymphocytes, MACs, epithelial reticular cells. Essentially a basket for lymphocytes.
- Type I = isolate cortex from the body = occluding junctions (tight junctions)
- Type II = divide cortex into lymphocyte filled pockets (desmosomes)
- Type III = corticonmedullary junction that isolates the cortex from medulla (tight junctions).
- Type II and III act as antigen presenting cells
Medulla:
- Epithelial reticular cells. Fewer lymphocytes, paler in color. Cells are killed off if they recognize “self” antigens.
- Type IV = corticomedullary junction
- Type V = framework of medulla
- Type VI = hassall’s corpuscles
Thymic capsule: within trabeculae that form lobules = find dense irregular CT with vasculature within. Arteries go to medullaà capillaries go to cortex. Don’t want cells in cortex to be exposed to body-derived antigens. Corticomedullary junction = where vessels come in and capillary bed forms.
Tolerance:
- Tolerance-recognizes self / nonself
- Do not have immune response to self antigens
- Tolerance occurs by 2 mechanisms
- Anergy = disabling of the immunocompetent cell
- Killing of immnocompetent cells that would reconigze self antigens (this occurs in the thymus)
- Thymic cortex is isolated from the body
- Type II and type III epithelial reticular cells: antigen presenting cells, self-antigens, MHC I and MHC II à these are docking molecules required for immune response (both types).
- Cells are killed if: TCR recognizes self antigens, or if T cell CD4 / CD8 can’t recognize MHC I / II.
Groupings to associate: MHC I, CD8, Cytotoxic T cells. MHCII, CD4, T helper cells.
MACs are antigen presenting cells.
Lymph nodes:
- Bean shaped organs up to an inch long, located along lymphatic vessels. Scattered throughout body but concentrated near mammary glands / axillae and groin.
- Stroma is capsule, trabeculae (capsule dips to form pockets for cells) and reticular fibers.
- Parenchyma = 2 regions
- Cortex = lymphatic nodules with germinal centers containing dendritic cells. Here, antigen presenting cells and MACs are located. Outer part = B cell region. Inner part = paracortex = T cell region.
- Medulla = contains B cells and plasma cells in medullary cords.
Lymph flow:
- Afferent lymph vessels take fluid to node, efferent lymph nodes take cleansed lymph fluid away from node
- The purpose is to clear out antigens etc.
- Vasculature: arterties form capillary bed within cortex = high endothelial venules à specific for the post capillary bed of cortex (paracortex). Through these venules, WBCs leave blood and enter the node.
- Vessels carry blood through sinuses at all timesà between cords. Sinuses are not lined by endothelial cells.
- Also in cortex: Nodules = B cells are activated and start to differentiate into plasma cells.
Pattern of flow:
- Flow is in one direction. Afferent vessels lead in, sinuses lead to efferent vessels that exit at the hilus
- Only filter lymph fluid, not blood.
- Fluid can leave at cortex / paracortex (where WBCs enter) / medulla.
- WBCs in paracortex for Ag presentationà go up to cortex to differentiate à back to medulla to enter lymph again.
- Interior of node segments will be lighter in color if B cells are actively proliferating. Normal circumstances = uniform color.
- Germinal centers: have active B cells = pale center of cord.
Spleen:
- 5 inch organ between stomach and diaphragm
- Hilus contains blood / lymphatic vessels
- Stroma consists of capsule with downward leading trabeculae, fibers, fibroblasts
- Parenchyma contains white / red pulp
- Each arteriole that enters the spleen acts as a center for a White pulp section of the spleen.
- White is lymphatic tissue (lymphocytes / MACs) around branches of splenic artery. Contains WBCs. Antigen presentation takes placeà have germinal centers forming.
- Red is venous sinuses filled with blood / splenic tissue (splenic cords). Made up of cords of Delrothà make up structure of the spleen.
- Sinusoids are vascular structures lined by epithelial cells and MACs. In the cords is where MACs destroy old RBCs.
- Spleen has 2 jobs: 1. filter blood in the parenchyma, RBCs are destroyed by MACs. 2. mount an immune response whenever blood supply is involved.
Artery→ surrouned by periarteriolar lymphatic sheath made of T cells→ surrounded by surrounded by marginal zone where B cells contact antigens. Along the sinus = MACs.
Sinusoids: endothelial lined, contain MACs.
Central artery→ branches into penicillar artery with 3 regions.
- Starts as pulp arteriole
- Becomes sheathed arteriole = surrounded by sheath of MACs
- Becomes terminal capillaryà goes directly into sinus or empties into red pulp cords of Delroth (thus determines open / closed circulation).
Blood leaves the central artery to enter red pulp by: 1. open circulation and 2. closed circulation. Blood must enter splenic cordsà then enters sinusoid to exit via trabecular veins.
Mucosa associated lymphatic tissue:
Locations:
- GI tract = GALT – gut associated lymphatic tissue
- Trachea
- Tonsils (waldeyer’s ring) has nodules
- Peyer’s patch has nodules
- Appendix has nodules
Respiratory tract: BALT bronchus…
Functions: Antigen presentation / phagocytosis.
Lymphatic nodules in diffuse tissues:
- Concentrations of lymphatic tissue not surrounded by a capsule. scattered throughout CT of mucous membranes.
- Mucosa associated lymphoid tissue = MALT
Tonsils:
- Form a ring at the top of the throat
- Adenoids = pharyngeal tonsils
- Palatine tonsils = on each side wall
- Lingual tonsil = in the back of the tongue
eyer’s patches:
- In the ilium of the small intestine.
- 2 T cell domains on outer portion of germinal center within the follicle (B cell area). M cells are on epithelium of gut lumen à are Ag presenting cell (a phagocyte).
- If it takes up an antigen from gutà it migrates into B cell domain to present antigen.
Lymphatic circulation
Capillaries that begin as closed-ended tubes found in spaces between cells.
- Lymphatic capillary is between arterioles and venules in capillary bed.
- Fluids and protein from capillaries is collected by lymphatic capillaries and is returned to the blood
- Respiratory and muscular pumps promote flow of fluidà empties into subclavian veins.
Histology of Lymphatic system
Organs Involved:
- Red bone marrow = cells originate here.
- Encapusulated organs: lymph nodes, spleen, thymus.
- In axilla / groin = majority of nodes here, running along vasculature.
- Throughout organs / on surfaces exposed to outside world (urogenital tract, GI tract), have diffuse lymphatic tissue (not encapsulated). Include tonsils, adenoids, peyer’s patches, appendix.
Functions:
- Surface protection – non specific (keratin, mucus) MACs
- Drain excess interstitial fluid and plasma protein from tissue spaces
- Transport of dietery lipids / vitamins from GI tract.
- Facilitate immune response = specific to invading organisms. Depends on ability to recognize self / nonself. Immune system activated to neutralize / destroy antigen. B / T cells are activated by specific antigens to destroy those same antigens.
- Acute inflammation: nonspecific mediated by neutrophils, response is always the same.
Lymphatic organs / Tissues:
- Primary lymphatic organs = provide environment for stem cells to divide and mature into B and T lymphocytes. These are bone marrow and thymus. Involve changes in biochemistry / gene expression.
- B cells development completely in bone marrowà acquire B cell receptor from immunoglobulin M or D. IgM is the main one. These cells then divide into subclasses depending on which antigen they are exposed to. B memory cells seek out their specific antigenà reactà proliferate into plasma cells with antibody secretion.
- Undifferentiated noncompetent T cells go to thymus after leaving bone marrow. Here, they acquire their CD molecules that determine their development. Here, they recognize self/ non self as well.
- Secondary lymphatic organs = Sites where immune response occurs. Lymph nodes, spleen, lymphatic nodules.
Immune reactions:
- Cellular immunity = mediated by T cells, react to foreign cells or virus.
- Delayed hypersensitivity takes 1-2 days.
- No circulating factors found
- Inflammation at site
- Humoral immunity = Mediated by B cells
- immediate hypersensitivity
- Antibodies in circulation
- Antibodies inactivate or destroy foreign substances
Lymphocytes:
T cells = 65-75% of lymphocytes
- Helper cells = Regulatory. Identified by CD4. stimulate differentiation of B cells. Are destroyed by HIV.
- Suppressor (effector) cells = identified by CD8. inhibit action of Th cells and Tc cells.
- Cytotoxic cells = identified by CD8. perforin released for cell lysis.
B cells = 5-10%
Effector only – many IgM on surface, type corresponds to each antigen.
Natural killer cells = kill virus infected / malignant cells. No need activaton.
Maturation of T cells:
- Mature in thymus
- Cell mediated response: killer cells attack antigens
- T helper cells costimulate cytotoxic T / B cellsà plasma cells
- Effective against fungi, parasites, cancer, tissue transplants.
- Intercellular pathogens targeted
B cells:
- Antibody mediated response
- Plasma cells form antibodies.
- Extracellular pathogens targeted (bacteria)
Tissue Organization:
Specialized connective tissue
- Two tissue elements
-
- Reticular fibers form the stroma or famework for the tissue
- Cells in spaces between the reticular fibers = lymphocytes, MACs, plasma cells, antigen presenting cells
- Lymphatic vessels connect lymphatic system to the blood vascular system.
Thymus:
- 2 lobed organ located in mediastinum. Atrophies as an adult into fat.
- Capsule and trabeculae divide into lobules→ each lobule has cortex and medulla.
- Cortex: tightly packed lymphocytes and MACs
- Medulla: reticular epithelial cells produce thymic hormones. Hassall’s corpuscles→ special reticular cell (type 6) unknown function. These are diagnostic for thymus.
Function:
- T cells mature = Express surface protein
- T cells become competent
- Tolerance for self / vs nonself
- T cells proliferate:
- Thymosin = T cell maturation
- Thymopoietin = T cell differentiation and platelet formation
- Thymulin = synthesis of CD molecules
- Thymic humoral factor = clonal expansion of CD8 expressing cells à one cell becomes many to await antigen.
Cortex:
- T lymphocytes, MACs, epithelial reticular cells. Essentially a basket for lymphocytes.
- Type I = isolate cortex from the body = occluding junctions (tight junctions)
- Type II = divide cortex into lymphocyte filled pockets (desmosomes)
- Type III = corticonmedullary junction that isolates the cortex from medulla (tight junctions).
- Type II and III act as antigen presenting cells
Medulla:
- Epithelial reticular cells. Fewer lymphocytes, paler in color. Cells are killed off if they recognize “self” antigens.
- Type IV = corticomedullary junction
- Type V = framework of medulla
- Type VI = hassall’s corpuscles
Thymic capsule: within trabeculae that form lobules = find dense irregular CT with vasculature within. Arteries go to medullaà capillaries go to cortex. Don’t want cells in cortex to be exposed to body-derived antigens. Corticomedullary junction = where vessels come in and capillary bed forms.
Tolerance:
- Tolerance-recognizes self / nonself
- Do not have immune response to self antigens
- Tolerance occurs by 2 mechanisms
- Anergy = disabling of the immunocompetent cell
- Killing of immnocompetent cells that would reconigze self antigens (this occurs in the thymus)
- Thymic cortex is isolated from the body
- Type II and type III epithelial reticular cells: antigen presenting cells, self-antigens, MHC I and MHC II à these are docking molecules required for immune response (both types).
- Cells are killed if: TCR recognizes self antigens, or if T cell CD4 / CD8 can’t recognize MHC I / II.
Groupings to associate: MHC I, CD8, Cytotoxic T cells. MHCII, CD4, T helper cells.
MACs are antigen presenting cells.
Lymph nodes:
- Bean shaped organs up to an inch long, located along lymphatic vessels. Scattered throughout body but concentrated near mammary glands / axillae and groin.
- Stroma is capsule, trabeculae (capsule dips to form pockets for cells) and reticular fibers.
- Parenchyma = 2 regions
- Cortex = lymphatic nodules with germinal centers containing dendritic cells. Here, antigen presenting cells and MACs are located. Outer part = B cell region. Inner part = paracortex = T cell region.
- Medulla = contains B cells and plasma cells in medullary cords.
Lymph flow:
- Afferent lymph vessels take fluid to node, efferent lymph nodes take cleansed lymph fluid away from node
- The purpose is to clear out antigens etc.
- Vasculature: arterties form capillary bed within cortex = high endothelial venules à specific for the post capillary bed of cortex (paracortex). Through these venules, WBCs leave blood and enter the node.
- Vessels carry blood through sinuses at all timesà between cords. Sinuses are not lined by endothelial cells.
- Also in cortex: Nodules = B cells are activated and start to differentiate into plasma cells.
Pattern of flow:
- Flow is in one direction. Afferent vessels lead in, sinuses lead to efferent vessels that exit at the hilus
- Only filter lymph fluid, not blood.
- Fluid can leave at cortex / paracortex (where WBCs enter) / medulla.
- WBCs in paracortex for Ag presentationà go up to cortex to differentiate à back to medulla to enter lymph again.
- Interior of node segments will be lighter in color if B cells are actively proliferating. Normal circumstances = uniform color.
- Germinal centers: have active B cells = pale center of cord.
Spleen:
- 5 inch organ between stomach and diaphragm
- Hilus contains blood / lymphatic vessels
- Stroma consists of capsule with downward leading trabeculae, fibers, fibroblasts
- Parenchyma contains white / red pulp
- Each arteriole that enters the spleen acts as a center for a White pulp section of the spleen.
- White is lymphatic tissue (lymphocytes / MACs) around branches of splenic artery. Contains WBCs. Antigen presentation takes placeà have germinal centers forming.
- Red is venous sinuses filled with blood / splenic tissue (splenic cords). Made up of cords of Delrothà make up structure of the spleen.
- Sinusoids are vascular structures lined by epithelial cells and MACs. In the cords is where MACs destroy old RBCs.
- Spleen has 2 jobs: 1. filter blood in the parenchyma, RBCs are destroyed by MACs. 2. mount an immune response whenever blood supply is involved.
Artery→ surrouned by periarteriolar lymphatic sheath made of T cells→ surrounded by surrounded by marginal zone where B cells contact antigens. Along the sinus = MACs.
Sinusoids: endothelial lined, contain MACs.
Central artery→ branches into penicillar artery with 3 regions.
- Starts as pulp arteriole
- Becomes sheathed arteriole = surrounded by sheath of MACs
- Becomes terminal capillaryà goes directly into sinus or empties into red pulp cords of Delroth (thus determines open / closed circulation).
Blood leaves the central artery to enter red pulp by: 1. open circulation and 2. closed circulation. Blood must enter splenic cordsà then enters sinusoid to exit via trabecular veins.
Mucosa associated lymphatic tissue:
Locations:
- GI tract = GALT – gut associated lymphatic tissue
- Trachea
- Tonsils (waldeyer’s ring) has nodules
- Peyer’s patch has nodules
- Appendix has nodules
Respiratory tract: BALT bronchus…
Functions: Antigen presentation / phagocytosis.
Lymphatic nodules in diffuse tissues:
- Concentrations of lymphatic tissue not surrounded by a capsule. scattered throughout CT of mucous membranes.
- Mucosa associated lymphoid tissue = MALT
Tonsils:
- Form a ring at the top of the throat
- Adenoids = pharyngeal tonsils
- Palatine tonsils = on each side wall
- Lingual tonsil = in the back of the tongue
eyer’s patches:
- In the ilium of the small intestine.
- 2 T cell domains on outer portion of germinal center within the follicle (B cell area). M cells are on epithelium of gut lumen à are Ag presenting cell (a phagocyte).
- If it takes up an antigen from gutà it migrates into B cell domain to present antigen.
Lymphatic circulation
Capillaries that begin as closed-ended tubes found in spaces between cells.
- Lymphatic capillary is between arterioles and venules in capillary bed.
- Fluids and protein from capillaries is collected by lymphatic capillaries and is returned to the blood
- Respiratory and muscular pumps promote flow of fluidà empties into subclavian veins.
Histology of Lymphatic system
Organs Involved:
- Red bone marrow = cells originate here.
- Encapusulated organs: lymph nodes, spleen, thymus.
- In axilla / groin = majority of nodes here, running along vasculature.
- Throughout organs / on surfaces exposed to outside world (urogenital tract, GI tract), have diffuse lymphatic tissue (not encapsulated). Include tonsils, adenoids, peyer’s patches, appendix.
Functions:
- Surface protection – non specific (keratin, mucus) MACs
- Drain excess interstitial fluid and plasma protein from tissue spaces
- Transport of dietery lipids / vitamins from GI tract.
- Facilitate immune response = specific to invading organisms. Depends on ability to recognize self / nonself. Immune system activated to neutralize / destroy antigen. B / T cells are activated by specific antigens to destroy those same antigens.
- Acute inflammation: nonspecific mediated by neutrophils, response is always the same.
Lymphatic organs / Tissues:
- Primary lymphatic organs = provide environment for stem cells to divide and mature into B and T lymphocytes. These are bone marrow and thymus. Involve changes in biochemistry / gene expression.
- B cells development completely in bone marrowà acquire B cell receptor from immunoglobulin M or D. IgM is the main one. These cells then divide into subclasses depending on which antigen they are exposed to. B memory cells seek out their specific antigenà reactà proliferate into plasma cells with antibody secretion.
- Undifferentiated noncompetent T cells go to thymus after leaving bone marrow. Here, they acquire their CD molecules that determine their development. Here, they recognize self/ non self as well.
- Secondary lymphatic organs = Sites where immune response occurs. Lymph nodes, spleen, lymphatic nodules.
Immune reactions:
- Cellular immunity = mediated by T cells, react to foreign cells or virus.
- Delayed hypersensitivity takes 1-2 days.
- No circulating factors found
- Inflammation at site
- Humoral immunity = Mediated by B cells
- immediate hypersensitivity
- Antibodies in circulation
- Antibodies inactivate or destroy foreign substances
Lymphocytes:
T cells = 65-75% of lymphocytes
- Helper cells = Regulatory. Identified by CD4. stimulate differentiation of B cells. Are destroyed by HIV.
- Suppressor (effector) cells = identified by CD8. inhibit action of Th cells and Tc cells.
- Cytotoxic cells = identified by CD8. perforin released for cell lysis.
B cells = 5-10%
Effector only – many IgM on surface, type corresponds to each antigen.
Natural killer cells = kill virus infected / malignant cells. No need activaton.
Maturation of T cells:
- Mature in thymus
- Cell mediated response: killer cells attack antigens
- T helper cells costimulate cytotoxic T / B cellsà plasma cells
- Effective against fungi, parasites, cancer, tissue transplants.
- Intercellular pathogens targeted
B cells:
- Antibody mediated response
- Plasma cells form antibodies.
- Extracellular pathogens targeted (bacteria)
Tissue Organization:
Specialized connective tissue
- Two tissue elements
-
- Reticular fibers form the stroma or famework for the tissue
- Cells in spaces between the reticular fibers = lymphocytes, MACs, plasma cells, antigen presenting cells
- Lymphatic vessels connect lymphatic system to the blood vascular system.
Thymus:
- 2 lobed organ located in mediastinum. Atrophies as an adult into fat.
- Capsule and trabeculae divide into lobules→ each lobule has cortex and medulla.
- Cortex: tightly packed lymphocytes and MACs
- Medulla: reticular epithelial cells produce thymic hormones. Hassall’s corpuscles→ special reticular cell (type 6) unknown function. These are diagnostic for thymus.
Function:
- T cells mature = Express surface protein
- T cells become competent
- Tolerance for self / vs nonself
- T cells proliferate:
- Thymosin = T cell maturation
- Thymopoietin = T cell differentiation and platelet formation
- Thymulin = synthesis of CD molecules
- Thymic humoral factor = clonal expansion of CD8 expressing cells à one cell becomes many to await antigen.
Cortex:
- T lymphocytes, MACs, epithelial reticular cells. Essentially a basket for lymphocytes.
- Type I = isolate cortex from the body = occluding junctions (tight junctions)
- Type II = divide cortex into lymphocyte filled pockets (desmosomes)
- Type III = corticonmedullary junction that isolates the cortex from medulla (tight junctions).
- Type II and III act as antigen presenting cells
Medulla:
- Epithelial reticular cells. Fewer lymphocytes, paler in color. Cells are killed off if they recognize “self” antigens.
- Type IV = corticomedullary junction
- Type V = framework of medulla
- Type VI = hassall’s corpuscles
Thymic capsule: within trabeculae that form lobules = find dense irregular CT with vasculature within. Arteries go to medullaà capillaries go to cortex. Don’t want cells in cortex to be exposed to body-derived antigens. Corticomedullary junction = where vessels come in and capillary bed forms.
Tolerance:
- Tolerance-recognizes self / nonself
- Do not have immune response to self antigens
- Tolerance occurs by 2 mechanisms
- Anergy = disabling of the immunocompetent cell
- Killing of immnocompetent cells that would reconigze self antigens (this occurs in the thymus)
- Thymic cortex is isolated from the body
- Type II and type III epithelial reticular cells: antigen presenting cells, self-antigens, MHC I and MHC II à these are docking molecules required for immune response (both types).
- Cells are killed if: TCR recognizes self antigens, or if T cell CD4 / CD8 can’t recognize MHC I / II.
Groupings to associate: MHC I, CD8, Cytotoxic T cells. MHCII, CD4, T helper cells.
MACs are antigen presenting cells.
Lymph nodes:
- Bean shaped organs up to an inch long, located along lymphatic vessels. Scattered throughout body but concentrated near mammary glands / axillae and groin.
- Stroma is capsule, trabeculae (capsule dips to form pockets for cells) and reticular fibers.
- Parenchyma = 2 regions
- Cortex = lymphatic nodules with germinal centers containing dendritic cells. Here, antigen presenting cells and MACs are located. Outer part = B cell region. Inner part = paracortex = T cell region.
- Medulla = contains B cells and plasma cells in medullary cords.
Lymph flow:
- Afferent lymph vessels take fluid to node, efferent lymph nodes take cleansed lymph fluid away from node
- The purpose is to clear out antigens etc.
- Vasculature: arterties form capillary bed within cortex = high endothelial venules à specific for the post capillary bed of cortex (paracortex). Through these venules, WBCs leave blood and enter the node.
- Vessels carry blood through sinuses at all timesà between cords. Sinuses are not lined by endothelial cells.
- Also in cortex: Nodules = B cells are activated and start to differentiate into plasma cells.
Pattern of flow:
- Flow is in one direction. Afferent vessels lead in, sinuses lead to efferent vessels that exit at the hilus
- Only filter lymph fluid, not blood.
- Fluid can leave at cortex / paracortex (where WBCs enter) / medulla.
- WBCs in paracortex for Ag presentationà go up to cortex to differentiate à back to medulla to enter lymph again.
- Interior of node segments will be lighter in color if B cells are actively proliferating. Normal circumstances = uniform color.
- Germinal centers: have active B cells = pale center of cord.
Spleen:
- 5 inch organ between stomach and diaphragm
- Hilus contains blood / lymphatic vessels
- Stroma consists of capsule with downward leading trabeculae, fibers, fibroblasts
- Parenchyma contains white / red pulp
- Each arteriole that enters the spleen acts as a center for a White pulp section of the spleen.
- White is lymphatic tissue (lymphocytes / MACs) around branches of splenic artery. Contains WBCs. Antigen presentation takes placeà have germinal centers forming.
- Red is venous sinuses filled with blood / splenic tissue (splenic cords). Made up of cords of Delrothà make up structure of the spleen.
- Sinusoids are vascular structures lined by epithelial cells and MACs. In the cords is where MACs destroy old RBCs.
- Spleen has 2 jobs: 1. filter blood in the parenchyma, RBCs are destroyed by MACs. 2. mount an immune response whenever blood supply is involved.
Artery→ surrouned by periarteriolar lymphatic sheath made of T cells→ surrounded by surrounded by marginal zone where B cells contact antigens. Along the sinus = MACs.
Sinusoids: endothelial lined, contain MACs.
Central artery→ branches into penicillar artery with 3 regions.
- Starts as pulp arteriole
- Becomes sheathed arteriole = surrounded by sheath of MACs
- Becomes terminal capillaryà goes directly into sinus or empties into red pulp cords of Delroth (thus determines open / closed circulation).
Blood leaves the central artery to enter red pulp by: 1. open circulation and 2. closed circulation. Blood must enter splenic cordsà then enters sinusoid to exit via trabecular veins.
Mucosa associated lymphatic tissue:
Locations:
- GI tract = GALT – gut associated lymphatic tissue
- Trachea
- Tonsils (waldeyer’s ring) has nodules
- Peyer’s patch has nodules
- Appendix has nodules
Respiratory tract: BALT bronchus…
Functions: Antigen presentation / phagocytosis.
Lymphatic nodules in diffuse tissues:
- Concentrations of lymphatic tissue not surrounded by a capsule. scattered throughout CT of mucous membranes.
- Mucosa associated lymphoid tissue = MALT
Tonsils:
- Form a ring at the top of the throat
- Adenoids = pharyngeal tonsils
- Palatine tonsils = on each side wall
- Lingual tonsil = in the back of the tongue
eyer’s patches:
- In the ilium of the small intestine.
- 2 T cell domains on outer portion of germinal center within the follicle (B cell area). M cells are on epithelium of gut lumen à are Ag presenting cell (a phagocyte).
- If it takes up an antigen from gutà it migrates into B cell domain to present antigen.
Lymphatic circulation
Capillaries that begin as closed-ended tubes found in spaces between cells.
- Lymphatic capillary is between arterioles and venules in capillary bed.
- Fluids and protein from capillaries is collected by lymphatic capillaries and is returned to the blood
- Respiratory and muscular pumps promote flow of fluidà empties into subclavian veins.
Histology of Lymphatic system
Organs Involved:
- Red bone marrow = cells originate here.
- Encapusulated organs: lymph nodes, spleen, thymus.
- In axilla / groin = majority of nodes here, running along vasculature.
- Throughout organs / on surfaces exposed to outside world (urogenital tract, GI tract), have diffuse lymphatic tissue (not encapsulated). Include tonsils, adenoids, peyer’s patches, appendix.
Functions:
- Surface protection – non specific (keratin, mucus) MACs
- Drain excess interstitial fluid and plasma protein from tissue spaces
- Transport of dietery lipids / vitamins from GI tract.
- Facilitate immune response = specific to invading organisms. Depends on ability to recognize self / nonself. Immune system activated to neutralize / destroy antigen. B / T cells are activated by specific antigens to destroy those same antigens.
- Acute inflammation: nonspecific mediated by neutrophils, response is always the same.
Lymphatic organs / Tissues:
- Primary lymphatic organs = provide environment for stem cells to divide and mature into B and T lymphocytes. These are bone marrow and thymus. Involve changes in biochemistry / gene expression.
- B cells development completely in bone marrowà acquire B cell receptor from immunoglobulin M or D. IgM is the main one. These cells then divide into subclasses depending on which antigen they are exposed to. B memory cells seek out their specific antigenà reactà proliferate into plasma cells with antibody secretion.
- Undifferentiated noncompetent T cells go to thymus after leaving bone marrow. Here, they acquire their CD molecules that determine their development. Here, they recognize self/ non self as well.
- Secondary lymphatic organs = Sites where immune response occurs. Lymph nodes, spleen, lymphatic nodules.
Immune reactions:
- Cellular immunity = mediated by T cells, react to foreign cells or virus.
- Delayed hypersensitivity takes 1-2 days.
- No circulating factors found
- Inflammation at site
- Humoral immunity = Mediated by B cells
- immediate hypersensitivity
- Antibodies in circulation
- Antibodies inactivate or destroy foreign substances
Lymphocytes:
T cells = 65-75% of lymphocytes
- Helper cells = Regulatory. Identified by CD4. stimulate differentiation of B cells. Are destroyed by HIV.
- Suppressor (effector) cells = identified by CD8. inhibit action of Th cells and Tc cells.
- Cytotoxic cells = identified by CD8. perforin released for cell lysis.
B cells = 5-10%
Effector only – many IgM on surface, type corresponds to each antigen.
Natural killer cells = kill virus infected / malignant cells. No need activaton.
Maturation of T cells:
- Mature in thymus
- Cell mediated response: killer cells attack antigens
- T helper cells costimulate cytotoxic T / B cellsà plasma cells
- Effective against fungi, parasites, cancer, tissue transplants.
- Intercellular pathogens targeted
B cells:
- Antibody mediated response
- Plasma cells form antibodies.
- Extracellular pathogens targeted (bacteria)
Tissue Organization:
Specialized connective tissue
- Two tissue elements
-
- Reticular fibers form the stroma or famework for the tissue
- Cells in spaces between the reticular fibers = lymphocytes, MACs, plasma cells, antigen presenting cells
- Lymphatic vessels connect lymphatic system to the blood vascular system.
Thymus:
- 2 lobed organ located in mediastinum. Atrophies as an adult into fat.
- Capsule and trabeculae divide into lobules→ each lobule has cortex and medulla.
- Cortex: tightly packed lymphocytes and MACs
- Medulla: reticular epithelial cells produce thymic hormones. Hassall’s corpuscles→ special reticular cell (type 6) unknown function. These are diagnostic for thymus.
Function:
- T cells mature = Express surface protein
- T cells become competent
- Tolerance for self / vs nonself
- T cells proliferate:
- Thymosin = T cell maturation
- Thymopoietin = T cell differentiation and platelet formation
- Thymulin = synthesis of CD molecules
- Thymic humoral factor = clonal expansion of CD8 expressing cells à one cell becomes many to await antigen.
Cortex:
- T lymphocytes, MACs, epithelial reticular cells. Essentially a basket for lymphocytes.
- Type I = isolate cortex from the body = occluding junctions (tight junctions)
- Type II = divide cortex into lymphocyte filled pockets (desmosomes)
- Type III = corticonmedullary junction that isolates the cortex from medulla (tight junctions).
- Type II and III act as antigen presenting cells
Medulla:
- Epithelial reticular cells. Fewer lymphocytes, paler in color. Cells are killed off if they recognize “self” antigens.
- Type IV = corticomedullary junction
- Type V = framework of medulla
- Type VI = hassall’s corpuscles
Thymic capsule: within trabeculae that form lobules = find dense irregular CT with vasculature within. Arteries go to medullaà capillaries go to cortex. Don’t want cells in cortex to be exposed to body-derived antigens. Corticomedullary junction = where vessels come in and capillary bed forms.
Tolerance:
- Tolerance-recognizes self / nonself
- Do not have immune response to self antigens
- Tolerance occurs by 2 mechanisms
- Anergy = disabling of the immunocompetent cell
- Killing of immnocompetent cells that would reconigze self antigens (this occurs in the thymus)
- Thymic cortex is isolated from the body
- Type II and type III epithelial reticular cells: antigen presenting cells, self-antigens, MHC I and MHC II à these are docking molecules required for immune response (both types).
- Cells are killed if: TCR recognizes self antigens, or if T cell CD4 / CD8 can’t recognize MHC I / II.
Groupings to associate: MHC I, CD8, Cytotoxic T cells. MHCII, CD4, T helper cells.
MACs are antigen presenting cells.
Lymph nodes:
- Bean shaped organs up to an inch long, located along lymphatic vessels. Scattered throughout body but concentrated near mammary glands / axillae and groin.
- Stroma is capsule, trabeculae (capsule dips to form pockets for cells) and reticular fibers.
- Parenchyma = 2 regions
- Cortex = lymphatic nodules with germinal centers containing dendritic cells. Here, antigen presenting cells and MACs are located. Outer part = B cell region. Inner part = paracortex = T cell region.
- Medulla = contains B cells and plasma cells in medullary cords.
Lymph flow:
- Afferent lymph vessels take fluid to node, efferent lymph nodes take cleansed lymph fluid away from node
- The purpose is to clear out antigens etc.
- Vasculature: arterties form capillary bed within cortex = high endothelial venules à specific for the post capillary bed of cortex (paracortex). Through these venules, WBCs leave blood and enter the node.
- Vessels carry blood through sinuses at all timesà between cords. Sinuses are not lined by endothelial cells.
- Also in cortex: Nodules = B cells are activated and start to differentiate into plasma cells.
Pattern of flow:
- Flow is in one direction. Afferent vessels lead in, sinuses lead to efferent vessels that exit at the hilus
- Only filter lymph fluid, not blood.
- Fluid can leave at cortex / paracortex (where WBCs enter) / medulla.
- WBCs in paracortex for Ag presentationà go up to cortex to differentiate à back to medulla to enter lymph again.
- Interior of node segments will be lighter in color if B cells are actively proliferating. Normal circumstances = uniform color.
- Germinal centers: have active B cells = pale center of cord.
Spleen:
- 5 inch organ between stomach and diaphragm
- Hilus contains blood / lymphatic vessels
- Stroma consists of capsule with downward leading trabeculae, fibers, fibroblasts
- Parenchyma contains white / red pulp
- Each arteriole that enters the spleen acts as a center for a White pulp section of the spleen.
- White is lymphatic tissue (lymphocytes / MACs) around branches of splenic artery. Contains WBCs. Antigen presentation takes placeà have germinal centers forming.
- Red is venous sinuses filled with blood / splenic tissue (splenic cords). Made up of cords of Delrothà make up structure of the spleen.
- Sinusoids are vascular structures lined by epithelial cells and MACs. In the cords is where MACs destroy old RBCs.
- Spleen has 2 jobs: 1. filter blood in the parenchyma, RBCs are destroyed by MACs. 2. mount an immune response whenever blood supply is involved.
Artery→ surrouned by periarteriolar lymphatic sheath made of T cells→ surrounded by surrounded by marginal zone where B cells contact antigens. Along the sinus = MACs.
Sinusoids: endothelial lined, contain MACs.
Central artery→ branches into penicillar artery with 3 regions.
- Starts as pulp arteriole
- Becomes sheathed arteriole = surrounded by sheath of MACs
- Becomes terminal capillaryà goes directly into sinus or empties into red pulp cords of Delroth (thus determines open / closed circulation).
Blood leaves the central artery to enter red pulp by: 1. open circulation and 2. closed circulation. Blood must enter splenic cordsà then enters sinusoid to exit via trabecular veins.
Mucosa associated lymphatic tissue:
Locations:
- GI tract = GALT – gut associated lymphatic tissue
- Trachea
- Tonsils (waldeyer’s ring) has nodules
- Peyer’s patch has nodules
- Appendix has nodules
Respiratory tract: BALT bronchus…
Functions: Antigen presentation / phagocytosis.
Lymphatic nodules in diffuse tissues:
- Concentrations of lymphatic tissue not surrounded by a capsule. scattered throughout CT of mucous membranes.
- Mucosa associated lymphoid tissue = MALT
Tonsils:
- Form a ring at the top of the throat
- Adenoids = pharyngeal tonsils
- Palatine tonsils = on each side wall
- Lingual tonsil = in the back of the tongue
eyer’s patches:
- In the ilium of the small intestine.
- 2 T cell domains on outer portion of germinal center within the follicle (B cell area). M cells are on epithelium of gut lumen à are Ag presenting cell (a phagocyte).
- If it takes up an antigen from gutà it migrates into B cell domain to present antigen.
Lymphatic circulation
Capillaries that begin as closed-ended tubes found in spaces between cells.
- Lymphatic capillary is between arterioles and venules in capillary bed.
- Fluids and protein from capillaries is collected by lymphatic capillaries and is returned to the blood
- Respiratory and muscular pumps promote flow of fluidà empties into subclavian veins.
Histology of Lymphatic system
Organs Involved:
- Red bone marrow = cells originate here.
- Encapusulated organs: lymph nodes, spleen, thymus.
- In axilla / groin = majority of nodes here, running along vasculature.
- Throughout organs / on surfaces exposed to outside world (urogenital tract, GI tract), have diffuse lymphatic tissue (not encapsulated). Include tonsils, adenoids, peyer’s patches, appendix.
Functions:
- Surface protection – non specific (keratin, mucus) MACs
- Drain excess interstitial fluid and plasma protein from tissue spaces
- Transport of dietery lipids / vitamins from GI tract.
- Facilitate immune response = specific to invading organisms. Depends on ability to recognize self / nonself. Immune system activated to neutralize / destroy antigen. B / T cells are activated by specific antigens to destroy those same antigens.
- Acute inflammation: nonspecific mediated by neutrophils, response is always the same.
Lymphatic organs / Tissues:
- Primary lymphatic organs = provide environment for stem cells to divide and mature into B and T lymphocytes. These are bone marrow and thymus. Involve changes in biochemistry / gene expression.
- B cells development completely in bone marrowà acquire B cell receptor from immunoglobulin M or D. IgM is the main one. These cells then divide into subclasses depending on which antigen they are exposed to. B memory cells seek out their specific antigenà reactà proliferate into plasma cells with antibody secretion.
- Undifferentiated noncompetent T cells go to thymus after leaving bone marrow. Here, they acquire their CD molecules that determine their development. Here, they recognize self/ non self as well.
- Secondary lymphatic organs = Sites where immune response occurs. Lymph nodes, spleen, lymphatic nodules.
Immune reactions:
- Cellular immunity = mediated by T cells, react to foreign cells or virus.
- Delayed hypersensitivity takes 1-2 days.
- No circulating factors found
- Inflammation at site
- Humoral immunity = Mediated by B cells
- immediate hypersensitivity
- Antibodies in circulation
- Antibodies inactivate or destroy foreign substances
Lymphocytes:
T cells = 65-75% of lymphocytes
- Helper cells = Regulatory. Identified by CD4. stimulate differentiation of B cells. Are destroyed by HIV.
- Suppressor (effector) cells = identified by CD8. inhibit action of Th cells and Tc cells.
- Cytotoxic cells = identified by CD8. perforin released for cell lysis.
B cells = 5-10%
Effector only – many IgM on surface, type corresponds to each antigen.
Natural killer cells = kill virus infected / malignant cells. No need activaton.
Maturation of T cells:
- Mature in thymus
- Cell mediated response: killer cells attack antigens
- T helper cells costimulate cytotoxic T / B cellsà plasma cells
- Effective against fungi, parasites, cancer, tissue transplants.
- Intercellular pathogens targeted
B cells:
- Antibody mediated response
- Plasma cells form antibodies.
- Extracellular pathogens targeted (bacteria)
Tissue Organization:
Specialized connective tissue
- Two tissue elements
-
- Reticular fibers form the stroma or famework for the tissue
- Cells in spaces between the reticular fibers = lymphocytes, MACs, plasma cells, antigen presenting cells
- Lymphatic vessels connect lymphatic system to the blood vascular system.
Thymus:
- 2 lobed organ located in mediastinum. Atrophies as an adult into fat.
- Capsule and trabeculae divide into lobules→ each lobule has cortex and medulla.
- Cortex: tightly packed lymphocytes and MACs
- Medulla: reticular epithelial cells produce thymic hormones. Hassall’s corpuscles→ special reticular cell (type 6) unknown function. These are diagnostic for thymus.
Function:
- T cells mature = Express surface protein
- T cells become competent
- Tolerance for self / vs nonself
- T cells proliferate:
- Thymosin = T cell maturation
- Thymopoietin = T cell differentiation and platelet formation
- Thymulin = synthesis of CD molecules
- Thymic humoral factor = clonal expansion of CD8 expressing cells à one cell becomes many to await antigen.
Cortex:
- T lymphocytes, MACs, epithelial reticular cells. Essentially a basket for lymphocytes.
- Type I = isolate cortex from the body = occluding junctions (tight junctions)
- Type II = divide cortex into lymphocyte filled pockets (desmosomes)
- Type III = corticonmedullary junction that isolates the cortex from medulla (tight junctions).
- Type II and III act as antigen presenting cells
Medulla:
- Epithelial reticular cells. Fewer lymphocytes, paler in color. Cells are killed off if they recognize “self” antigens.
- Type IV = corticomedullary junction
- Type V = framework of medulla
- Type VI = hassall’s corpuscles
Thymic capsule: within trabeculae that form lobules = find dense irregular CT with vasculature within. Arteries go to medullaà capillaries go to cortex. Don’t want cells in cortex to be exposed to body-derived antigens. Corticomedullary junction = where vessels come in and capillary bed forms.
Tolerance:
- Tolerance-recognizes self / nonself
- Do not have immune response to self antigens
- Tolerance occurs by 2 mechanisms
- Anergy = disabling of the immunocompetent cell
- Killing of immnocompetent cells that would reconigze self antigens (this occurs in the thymus)
- Thymic cortex is isolated from the body
- Type II and type III epithelial reticular cells: antigen presenting cells, self-antigens, MHC I and MHC II à these are docking molecules required for immune response (both types).
- Cells are killed if: TCR recognizes self antigens, or if T cell CD4 / CD8 can’t recognize MHC I / II.
Groupings to associate: MHC I, CD8, Cytotoxic T cells. MHCII, CD4, T helper cells.
MACs are antigen presenting cells.
Lymph nodes:
- Bean shaped organs up to an inch long, located along lymphatic vessels. Scattered throughout body but concentrated near mammary glands / axillae and groin.
- Stroma is capsule, trabeculae (capsule dips to form pockets for cells) and reticular fibers.
- Parenchyma = 2 regions
- Cortex = lymphatic nodules with germinal centers containing dendritic cells. Here, antigen presenting cells and MACs are located. Outer part = B cell region. Inner part = paracortex = T cell region.
- Medulla = contains B cells and plasma cells in medullary cords.
Lymph flow:
- Afferent lymph vessels take fluid to node, efferent lymph nodes take cleansed lymph fluid away from node
- The purpose is to clear out antigens etc.
- Vasculature: arterties form capillary bed within cortex = high endothelial venules à specific for the post capillary bed of cortex (paracortex). Through these venules, WBCs leave blood and enter the node.
- Vessels carry blood through sinuses at all timesà between cords. Sinuses are not lined by endothelial cells.
- Also in cortex: Nodules = B cells are activated and start to differentiate into plasma cells.
Pattern of flow:
- Flow is in one direction. Afferent vessels lead in, sinuses lead to efferent vessels that exit at the hilus
- Only filter lymph fluid, not blood.
- Fluid can leave at cortex / paracortex (where WBCs enter) / medulla.
- WBCs in paracortex for Ag presentationà go up to cortex to differentiate à back to medulla to enter lymph again.
- Interior of node segments will be lighter in color if B cells are actively proliferating. Normal circumstances = uniform color.
- Germinal centers: have active B cells = pale center of cord.
Spleen:
- 5 inch organ between stomach and diaphragm
- Hilus contains blood / lymphatic vessels
- Stroma consists of capsule with downward leading trabeculae, fibers, fibroblasts
- Parenchyma contains white / red pulp
- Each arteriole that enters the spleen acts as a center for a White pulp section of the spleen.
- White is lymphatic tissue (lymphocytes / MACs) around branches of splenic artery. Contains WBCs. Antigen presentation takes placeà have germinal centers forming.
- Red is venous sinuses filled with blood / splenic tissue (splenic cords). Made up of cords of Delrothà make up structure of the spleen.
- Sinusoids are vascular structures lined by epithelial cells and MACs. In the cords is where MACs destroy old RBCs.
- Spleen has 2 jobs: 1. filter blood in the parenchyma, RBCs are destroyed by MACs. 2. mount an immune response whenever blood supply is involved.
Artery→ surrouned by periarteriolar lymphatic sheath made of T cells→ surrounded by surrounded by marginal zone where B cells contact antigens. Along the sinus = MACs.
Sinusoids: endothelial lined, contain MACs.
Central artery→ branches into penicillar artery with 3 regions.
- Starts as pulp arteriole
- Becomes sheathed arteriole = surrounded by sheath of MACs
- Becomes terminal capillaryà goes directly into sinus or empties into red pulp cords of Delroth (thus determines open / closed circulation).
Blood leaves the central artery to enter red pulp by: 1. open circulation and 2. closed circulation. Blood must enter splenic cordsà then enters sinusoid to exit via trabecular veins.
Mucosa associated lymphatic tissue:
Locations:
- GI tract = GALT – gut associated lymphatic tissue
- Trachea
- Tonsils (waldeyer’s ring) has nodules
- Peyer’s patch has nodules
- Appendix has nodules
Respiratory tract: BALT bronchus…
Functions: Antigen presentation / phagocytosis.
Lymphatic nodules in diffuse tissues:
- Concentrations of lymphatic tissue not surrounded by a capsule. scattered throughout CT of mucous membranes.
- Mucosa associated lymphoid tissue = MALT
Tonsils:
- Form a ring at the top of the throat
- Adenoids = pharyngeal tonsils
- Palatine tonsils = on each side wall
- Lingual tonsil = in the back of the tongue
eyer’s patches:
- In the ilium of the small intestine.
- 2 T cell domains on outer portion of germinal center within the follicle (B cell area). M cells are on epithelium of gut lumen à are Ag presenting cell (a phagocyte).
- If it takes up an antigen from gutà it migrates into B cell domain to present antigen.
Lymphatic circulation
Capillaries that begin as closed-ended tubes found in spaces between cells.
- Lymphatic capillary is between arterioles and venules in capillary bed.
- Fluids and protein from capillaries is collected by lymphatic capillaries and is returned to the blood
- Respiratory and muscular pumps promote flow of fluidà empties into subclavian veins.
Histology of Lymphatic system
Organs Involved:
- Red bone marrow = cells originate here.
- Encapusulated organs: lymph nodes, spleen, thymus.
- In axilla / groin = majority of nodes here, running along vasculature.
- Throughout organs / on surfaces exposed to outside world (urogenital tract, GI tract), have diffuse lymphatic tissue (not encapsulated). Include tonsils, adenoids, peyer’s patches, appendix.
Functions:
- Surface protection – non specific (keratin, mucus) MACs
- Drain excess interstitial fluid and plasma protein from tissue spaces
- Transport of dietery lipids / vitamins from GI tract.
- Facilitate immune response = specific to invading organisms. Depends on ability to recognize self / nonself. Immune system activated to neutralize / destroy antigen. B / T cells are activated by specific antigens to destroy those same antigens.
- Acute inflammation: nonspecific mediated by neutrophils, response is always the same.
Lymphatic organs / Tissues:
- Primary lymphatic organs = provide environment for stem cells to divide and mature into B and T lymphocytes. These are bone marrow and thymus. Involve changes in biochemistry / gene expression.
- B cells development completely in bone marrowà acquire B cell receptor from immunoglobulin M or D. IgM is the main one. These cells then divide into subclasses depending on which antigen they are exposed to. B memory cells seek out their specific antigenà reactà proliferate into plasma cells with antibody secretion.
- Undifferentiated noncompetent T cells go to thymus after leaving bone marrow. Here, they acquire their CD molecules that determine their development. Here, they recognize self/ non self as well.
- Secondary lymphatic organs = Sites where immune response occurs. Lymph nodes, spleen, lymphatic nodules.
Immune reactions:
- Cellular immunity = mediated by T cells, react to foreign cells or virus.
- Delayed hypersensitivity takes 1-2 days.
- No circulating factors found
- Inflammation at site
- Humoral immunity = Mediated by B cells
- immediate hypersensitivity
- Antibodies in circulation
- Antibodies inactivate or destroy foreign substances
Lymphocytes:
T cells = 65-75% of lymphocytes
- Helper cells = Regulatory. Identified by CD4. stimulate differentiation of B cells. Are destroyed by HIV.
- Suppressor (effector) cells = identified by CD8. inhibit action of Th cells and Tc cells.
- Cytotoxic cells = identified by CD8. perforin released for cell lysis.
B cells = 5-10%
Effector only – many IgM on surface, type corresponds to each antigen.
Natural killer cells = kill virus infected / malignant cells. No need activaton.
Maturation of T cells:
- Mature in thymus
- Cell mediated response: killer cells attack antigens
- T helper cells costimulate cytotoxic T / B cellsà plasma cells
- Effective against fungi, parasites, cancer, tissue transplants.
- Intercellular pathogens targeted
B cells:
- Antibody mediated response
- Plasma cells form antibodies.
- Extracellular pathogens targeted (bacteria)
Tissue Organization:
Specialized connective tissue
- Two tissue elements
-
- Reticular fibers form the stroma or famework for the tissue
- Cells in spaces between the reticular fibers = lymphocytes, MACs, plasma cells, antigen presenting cells
- Lymphatic vessels connect lymphatic system to the blood vascular system.
Thymus:
- 2 lobed organ located in mediastinum. Atrophies as an adult into fat.
- Capsule and trabeculae divide into lobules→ each lobule has cortex and medulla.
- Cortex: tightly packed lymphocytes and MACs
- Medulla: reticular epithelial cells produce thymic hormones. Hassall’s corpuscles→ special reticular cell (type 6) unknown function. These are diagnostic for thymus.
Function:
- T cells mature = Express surface protein
- T cells become competent
- Tolerance for self / vs nonself
- T cells proliferate:
- Thymosin = T cell maturation
- Thymopoietin = T cell differentiation and platelet formation
- Thymulin = synthesis of CD molecules
- Thymic humoral factor = clonal expansion of CD8 expressing cells à one cell becomes many to await antigen.
Cortex:
- T lymphocytes, MACs, epithelial reticular cells. Essentially a basket for lymphocytes.
- Type I = isolate cortex from the body = occluding junctions (tight junctions)
- Type II = divide cortex into lymphocyte filled pockets (desmosomes)
- Type III = corticonmedullary junction that isolates the cortex from medulla (tight junctions).
- Type II and III act as antigen presenting cells
Medulla:
- Epithelial reticular cells. Fewer lymphocytes, paler in color. Cells are killed off if they recognize “self” antigens.
- Type IV = corticomedullary junction
- Type V = framework of medulla
- Type VI = hassall’s corpuscles
Thymic capsule: within trabeculae that form lobules = find dense irregular CT with vasculature within. Arteries go to medullaà capillaries go to cortex. Don’t want cells in cortex to be exposed to body-derived antigens. Corticomedullary junction = where vessels come in and capillary bed forms.
Tolerance:
- Tolerance-recognizes self / nonself
- Do not have immune response to self antigens
- Tolerance occurs by 2 mechanisms
- Anergy = disabling of the immunocompetent cell
- Killing of immnocompetent cells that would reconigze self antigens (this occurs in the thymus)
- Thymic cortex is isolated from the body
- Type II and type III epithelial reticular cells: antigen presenting cells, self-antigens, MHC I and MHC II à these are docking molecules required for immune response (both types).
- Cells are killed if: TCR recognizes self antigens, or if T cell CD4 / CD8 can’t recognize MHC I / II.
Groupings to associate: MHC I, CD8, Cytotoxic T cells. MHCII, CD4, T helper cells.
MACs are antigen presenting cells.
Lymph nodes:
- Bean shaped organs up to an inch long, located along lymphatic vessels. Scattered throughout body but concentrated near mammary glands / axillae and groin.
- Stroma is capsule, trabeculae (capsule dips to form pockets for cells) and reticular fibers.
- Parenchyma = 2 regions
- Cortex = lymphatic nodules with germinal centers containing dendritic cells. Here, antigen presenting cells and MACs are located. Outer part = B cell region. Inner part = paracortex = T cell region.
- Medulla = contains B cells and plasma cells in medullary cords.
Lymph flow:
- Afferent lymph vessels take fluid to node, efferent lymph nodes take cleansed lymph fluid away from node
- The purpose is to clear out antigens etc.
- Vasculature: arterties form capillary bed within cortex = high endothelial venules à specific for the post capillary bed of cortex (paracortex). Through these venules, WBCs leave blood and enter the node.
- Vessels carry blood through sinuses at all timesà between cords. Sinuses are not lined by endothelial cells.
- Also in cortex: Nodules = B cells are activated and start to differentiate into plasma cells.
Pattern of flow:
- Flow is in one direction. Afferent vessels lead in, sinuses lead to efferent vessels that exit at the hilus
- Only filter lymph fluid, not blood.
- Fluid can leave at cortex / paracortex (where WBCs enter) / medulla.
- WBCs in paracortex for Ag presentationà go up to cortex to differentiate à back to medulla to enter lymph again.
- Interior of node segments will be lighter in color if B cells are actively proliferating. Normal circumstances = uniform color.
- Germinal centers: have active B cells = pale center of cord.
Spleen:
- 5 inch organ between stomach and diaphragm
- Hilus contains blood / lymphatic vessels
- Stroma consists of capsule with downward leading trabeculae, fibers, fibroblasts
- Parenchyma contains white / red pulp
- Each arteriole that enters the spleen acts as a center for a White pulp section of the spleen.
- White is lymphatic tissue (lymphocytes / MACs) around branches of splenic artery. Contains WBCs. Antigen presentation takes placeà have germinal centers forming.
- Red is venous sinuses filled with blood / splenic tissue (splenic cords). Made up of cords of Delrothà make up structure of the spleen.
- Sinusoids are vascular structures lined by epithelial cells and MACs. In the cords is where MACs destroy old RBCs.
- Spleen has 2 jobs: 1. filter blood in the parenchyma, RBCs are destroyed by MACs. 2. mount an immune response whenever blood supply is involved.
Artery→ surrouned by periarteriolar lymphatic sheath made of T cells→ surrounded by surrounded by marginal zone where B cells contact antigens. Along the sinus = MACs.
Sinusoids: endothelial lined, contain MACs.
Central artery→ branches into penicillar artery with 3 regions.
- Starts as pulp arteriole
- Becomes sheathed arteriole = surrounded by sheath of MACs
- Becomes terminal capillaryà goes directly into sinus or empties into red pulp cords of Delroth (thus determines open / closed circulation).
Blood leaves the central artery to enter red pulp by: 1. open circulation and 2. closed circulation. Blood must enter splenic cordsà then enters sinusoid to exit via trabecular veins.
Mucosa associated lymphatic tissue:
Locations:
- GI tract = GALT – gut associated lymphatic tissue
- Trachea
- Tonsils (waldeyer’s ring) has nodules
- Peyer’s patch has nodules
- Appendix has nodules
Respiratory tract: BALT bronchus…
Functions: Antigen presentation / phagocytosis.
Lymphatic nodules in diffuse tissues:
- Concentrations of lymphatic tissue not surrounded by a capsule. scattered throughout CT of mucous membranes.
- Mucosa associated lymphoid tissue = MALT
Tonsils:
- Form a ring at the top of the throat
- Adenoids = pharyngeal tonsils
- Palatine tonsils = on each side wall
- Lingual tonsil = in the back of the tongue
eyer’s patches:
- In the ilium of the small intestine.
- 2 T cell domains on outer portion of germinal center within the follicle (B cell area). M cells are on epithelium of gut lumen à are Ag presenting cell (a phagocyte).
- If it takes up an antigen from gutà it migrates into B cell domain to present antigen.
Lymphatic circulation
Capillaries that begin as closed-ended tubes found in spaces between cells.
- Lymphatic capillary is between arterioles and venules in capillary bed.
- Fluids and protein from capillaries is collected by lymphatic capillaries and is returned to the blood
- Respiratory and muscular pumps promote flow of fluidà empties into subclavian veins.
Histology of Lymphatic system
Organs Involved:
- Red bone marrow = cells originate here.
- Encapusulated organs: lymph nodes, spleen, thymus.
- In axilla / groin = majority of nodes here, running along vasculature.
- Throughout organs / on surfaces exposed to outside world (urogenital tract, GI tract), have diffuse lymphatic tissue (not encapsulated). Include tonsils, adenoids, peyer’s patches, appendix.
Functions:
- Surface protection – non specific (keratin, mucus) MACs
- Drain excess interstitial fluid and plasma protein from tissue spaces
- Transport of dietery lipids / vitamins from GI tract.
- Facilitate immune response = specific to invading organisms. Depends on ability to recognize self / nonself. Immune system activated to neutralize / destroy antigen. B / T cells are activated by specific antigens to destroy those same antigens.
- Acute inflammation: nonspecific mediated by neutrophils, response is always the same.
Lymphatic organs / Tissues:
- Primary lymphatic organs = provide environment for stem cells to divide and mature into B and T lymphocytes. These are bone marrow and thymus. Involve changes in biochemistry / gene expression.
- B cells development completely in bone marrowà acquire B cell receptor from immunoglobulin M or D. IgM is the main one. These cells then divide into subclasses depending on which antigen they are exposed to. B memory cells seek out their specific antigenà reactà proliferate into plasma cells with antibody secretion.
- Undifferentiated noncompetent T cells go to thymus after leaving bone marrow. Here, they acquire their CD molecules that determine their development. Here, they recognize self/ non self as well.
- Secondary lymphatic organs = Sites where immune response occurs. Lymph nodes, spleen, lymphatic nodules.
Immune reactions:
- Cellular immunity = mediated by T cells, react to foreign cells or virus.
- Delayed hypersensitivity takes 1-2 days.
- No circulating factors found
- Inflammation at site
- Humoral immunity = Mediated by B cells
- immediate hypersensitivity
- Antibodies in circulation
- Antibodies inactivate or destroy foreign substances
Lymphocytes:
T cells = 65-75% of lymphocytes
- Helper cells = Regulatory. Identified by CD4. stimulate differentiation of B cells. Are destroyed by HIV.
- Suppressor (effector) cells = identified by CD8. inhibit action of Th cells and Tc cells.
- Cytotoxic cells = identified by CD8. perforin released for cell lysis.
B cells = 5-10%
Effector only – many IgM on surface, type corresponds to each antigen.
Natural killer cells = kill virus infected / malignant cells. No need activaton.
Maturation of T cells:
- Mature in thymus
- Cell mediated response: killer cells attack antigens
- T helper cells costimulate cytotoxic T / B cellsà plasma cells
- Effective against fungi, parasites, cancer, tissue transplants.
- Intercellular pathogens targeted
B cells:
- Antibody mediated response
- Plasma cells form antibodies.
- Extracellular pathogens targeted (bacteria)
Tissue Organization:
Specialized connective tissue
- Two tissue elements
-
- Reticular fibers form the stroma or famework for the tissue
- Cells in spaces between the reticular fibers = lymphocytes, MACs, plasma cells, antigen presenting cells
- Lymphatic vessels connect lymphatic system to the blood vascular system.
Thymus:
- 2 lobed organ located in mediastinum. Atrophies as an adult into fat.
- Capsule and trabeculae divide into lobules→ each lobule has cortex and medulla.
- Cortex: tightly packed lymphocytes and MACs
- Medulla: reticular epithelial cells produce thymic hormones. Hassall’s corpuscles→ special reticular cell (type 6) unknown function. These are diagnostic for thymus.
Function:
- T cells mature = Express surface protein
- T cells become competent
- Tolerance for self / vs nonself
- T cells proliferate:
- Thymosin = T cell maturation
- Thymopoietin = T cell differentiation and platelet formation
- Thymulin = synthesis of CD molecules
- Thymic humoral factor = clonal expansion of CD8 expressing cells à one cell becomes many to await antigen.
Cortex:
- T lymphocytes, MACs, epithelial reticular cells. Essentially a basket for lymphocytes.
- Type I = isolate cortex from the body = occluding junctions (tight junctions)
- Type II = divide cortex into lymphocyte filled pockets (desmosomes)
- Type III = corticonmedullary junction that isolates the cortex from medulla (tight junctions).
- Type II and III act as antigen presenting cells
Medulla:
- Epithelial reticular cells. Fewer lymphocytes, paler in color. Cells are killed off if they recognize “self” antigens.
- Type IV = corticomedullary junction
- Type V = framework of medulla
- Type VI = hassall’s corpuscles
Thymic capsule: within trabeculae that form lobules = find dense irregular CT with vasculature within. Arteries go to medullaà capillaries go to cortex. Don’t want cells in cortex to be exposed to body-derived antigens. Corticomedullary junction = where vessels come in and capillary bed forms.
Tolerance:
- Tolerance-recognizes self / nonself
- Do not have immune response to self antigens
- Tolerance occurs by 2 mechanisms
- Anergy = disabling of the immunocompetent cell
- Killing of immnocompetent cells that would reconigze self antigens (this occurs in the thymus)
- Thymic cortex is isolated from the body
- Type II and type III epithelial reticular cells: antigen presenting cells, self-antigens, MHC I and MHC II à these are docking molecules required for immune response (both types).
- Cells are killed if: TCR recognizes self antigens, or if T cell CD4 / CD8 can’t recognize MHC I / II.
Groupings to associate: MHC I, CD8, Cytotoxic T cells. MHCII, CD4, T helper cells.
MACs are antigen presenting cells.
Lymph nodes:
- Bean shaped organs up to an inch long, located along lymphatic vessels. Scattered throughout body but concentrated near mammary glands / axillae and groin.
- Stroma is capsule, trabeculae (capsule dips to form pockets for cells) and reticular fibers.
- Parenchyma = 2 regions
- Cortex = lymphatic nodules with germinal centers containing dendritic cells. Here, antigen presenting cells and MACs are located. Outer part = B cell region. Inner part = paracortex = T cell region.
- Medulla = contains B cells and plasma cells in medullary cords.
Lymph flow:
- Afferent lymph vessels take fluid to node, efferent lymph nodes take cleansed lymph fluid away from node
- The purpose is to clear out antigens etc.
- Vasculature: arterties form capillary bed within cortex = high endothelial venules à specific for the post capillary bed of cortex (paracortex). Through these venules, WBCs leave blood and enter the node.
- Vessels carry blood through sinuses at all timesà between cords. Sinuses are not lined by endothelial cells.
- Also in cortex: Nodules = B cells are activated and start to differentiate into plasma cells.
Pattern of flow:
- Flow is in one direction. Afferent vessels lead in, sinuses lead to efferent vessels that exit at the hilus
- Only filter lymph fluid, not blood.
- Fluid can leave at cortex / paracortex (where WBCs enter) / medulla.
- WBCs in paracortex for Ag presentationà go up to cortex to differentiate à back to medulla to enter lymph again.
- Interior of node segments will be lighter in color if B cells are actively proliferating. Normal circumstances = uniform color.
- Germinal centers: have active B cells = pale center of cord.
Spleen:
- 5 inch organ between stomach and diaphragm
- Hilus contains blood / lymphatic vessels
- Stroma consists of capsule with downward leading trabeculae, fibers, fibroblasts
- Parenchyma contains white / red pulp
- Each arteriole that enters the spleen acts as a center for a White pulp section of the spleen.
- White is lymphatic tissue (lymphocytes / MACs) around branches of splenic artery. Contains WBCs. Antigen presentation takes placeà have germinal centers forming.
- Red is venous sinuses filled with blood / splenic tissue (splenic cords). Made up of cords of Delrothà make up structure of the spleen.
- Sinusoids are vascular structures lined by epithelial cells and MACs. In the cords is where MACs destroy old RBCs.
- Spleen has 2 jobs: 1. filter blood in the parenchyma, RBCs are destroyed by MACs. 2. mount an immune response whenever blood supply is involved.
Artery→ surrouned by periarteriolar lymphatic sheath made of T cells→ surrounded by surrounded by marginal zone where B cells contact antigens. Along the sinus = MACs.
Sinusoids: endothelial lined, contain MACs.
Central artery→ branches into penicillar artery with 3 regions.
- Starts as pulp arteriole
- Becomes sheathed arteriole = surrounded by sheath of MACs
- Becomes terminal capillaryà goes directly into sinus or empties into red pulp cords of Delroth (thus determines open / closed circulation).
Blood leaves the central artery to enter red pulp by: 1. open circulation and 2. closed circulation. Blood must enter splenic cordsà then enters sinusoid to exit via trabecular veins.
Mucosa associated lymphatic tissue:
Locations:
- GI tract = GALT – gut associated lymphatic tissue
- Trachea
- Tonsils (waldeyer’s ring) has nodules
- Peyer’s patch has nodules
- Appendix has nodules
Respiratory tract: BALT bronchus…
Functions: Antigen presentation / phagocytosis.
Lymphatic nodules in diffuse tissues:
- Concentrations of lymphatic tissue not surrounded by a capsule. scattered throughout CT of mucous membranes.
- Mucosa associated lymphoid tissue = MALT
Tonsils:
- Form a ring at the top of the throat
- Adenoids = pharyngeal tonsils
- Palatine tonsils = on each side wall
- Lingual tonsil = in the back of the tongue
eyer’s patches:
- In the ilium of the small intestine.
- 2 T cell domains on outer portion of germinal center within the follicle (B cell area). M cells are on epithelium of gut lumen à are Ag presenting cell (a phagocyte).
- If it takes up an antigen from gutà it migrates into B cell domain to present antigen.
Lymphatic circulation
Capillaries that begin as closed-ended tubes found in spaces between cells.
- Lymphatic capillary is between arterioles and venules in capillary bed.
- Fluids and protein from capillaries is collected by lymphatic capillaries and is returned to the blood
- Respiratory and muscular pumps promote flow of fluidà empties into subclavian veins.
Histology of Lymphatic system
Organs Involved:
- Red bone marrow = cells originate here.
- Encapusulated organs: lymph nodes, spleen, thymus.
- In axilla / groin = majority of nodes here, running along vasculature.
- Throughout organs / on surfaces exposed to outside world (urogenital tract, GI tract), have diffuse lymphatic tissue (not encapsulated). Include tonsils, adenoids, peyer’s patches, appendix.
Functions:
- Surface protection – non specific (keratin, mucus) MACs
- Drain excess interstitial fluid and plasma protein from tissue spaces
- Transport of dietery lipids / vitamins from GI tract.
- Facilitate immune response = specific to invading organisms. Depends on ability to recognize self / nonself. Immune system activated to neutralize / destroy antigen. B / T cells are activated by specific antigens to destroy those same antigens.
- Acute inflammation: nonspecific mediated by neutrophils, response is always the same.
Lymphatic organs / Tissues:
- Primary lymphatic organs = provide environment for stem cells to divide and mature into B and T lymphocytes. These are bone marrow and thymus. Involve changes in biochemistry / gene expression.
- B cells development completely in bone marrowà acquire B cell receptor from immunoglobulin M or D. IgM is the main one. These cells then divide into subclasses depending on which antigen they are exposed to. B memory cells seek out their specific antigenà reactà proliferate into plasma cells with antibody secretion.
- Undifferentiated noncompetent T cells go to thymus after leaving bone marrow. Here, they acquire their CD molecules that determine their development. Here, they recognize self/ non self as well.
- Secondary lymphatic organs = Sites where immune response occurs. Lymph nodes, spleen, lymphatic nodules.
Immune reactions:
- Cellular immunity = mediated by T cells, react to foreign cells or virus.
- Delayed hypersensitivity takes 1-2 days.
- No circulating factors found
- Inflammation at site
- Humoral immunity = Mediated by B cells
- immediate hypersensitivity
- Antibodies in circulation
- Antibodies inactivate or destroy foreign substances
Lymphocytes:
T cells = 65-75% of lymphocytes
- Helper cells = Regulatory. Identified by CD4. stimulate differentiation of B cells. Are destroyed by HIV.
- Suppressor (effector) cells = identified by CD8. inhibit action of Th cells and Tc cells.
- Cytotoxic cells = identified by CD8. perforin released for cell lysis.
B cells = 5-10%
Effector only – many IgM on surface, type corresponds to each antigen.
Natural killer cells = kill virus infected / malignant cells. No need activaton.
Maturation of T cells:
- Mature in thymus
- Cell mediated response: killer cells attack antigens
- T helper cells costimulate cytotoxic T / B cellsà plasma cells
- Effective against fungi, parasites, cancer, tissue transplants.
- Intercellular pathogens targeted
B cells:
- Antibody mediated response
- Plasma cells form antibodies.
- Extracellular pathogens targeted (bacteria)
Tissue Organization:
Specialized connective tissue
- Two tissue elements
-
- Reticular fibers form the stroma or famework for the tissue
- Cells in spaces between the reticular fibers = lymphocytes, MACs, plasma cells, antigen presenting cells
- Lymphatic vessels connect lymphatic system to the blood vascular system.
Thymus:
- 2 lobed organ located in mediastinum. Atrophies as an adult into fat.
- Capsule and trabeculae divide into lobules→ each lobule has cortex and medulla.
- Cortex: tightly packed lymphocytes and MACs
- Medulla: reticular epithelial cells produce thymic hormones. Hassall’s corpuscles→ special reticular cell (type 6) unknown function. These are diagnostic for thymus.
Function:
- T cells mature = Express surface protein
- T cells become competent
- Tolerance for self / vs nonself
- T cells proliferate:
- Thymosin = T cell maturation
- Thymopoietin = T cell differentiation and platelet formation
- Thymulin = synthesis of CD molecules
- Thymic humoral factor = clonal expansion of CD8 expressing cells à one cell becomes many to await antigen.
Cortex:
- T lymphocytes, MACs, epithelial reticular cells. Essentially a basket for lymphocytes.
- Type I = isolate cortex from the body = occluding junctions (tight junctions)
- Type II = divide cortex into lymphocyte filled pockets (desmosomes)
- Type III = corticonmedullary junction that isolates the cortex from medulla (tight junctions).
- Type II and III act as antigen presenting cells
Medulla:
- Epithelial reticular cells. Fewer lymphocytes, paler in color. Cells are killed off if they recognize “self” antigens.
- Type IV = corticomedullary junction
- Type V = framework of medulla
- Type VI = hassall’s corpuscles
Thymic capsule: within trabeculae that form lobules = find dense irregular CT with vasculature within. Arteries go to medullaà capillaries go to cortex. Don’t want cells in cortex to be exposed to body-derived antigens. Corticomedullary junction = where vessels come in and capillary bed forms.
Tolerance:
- Tolerance-recognizes self / nonself
- Do not have immune response to self antigens
- Tolerance occurs by 2 mechanisms
- Anergy = disabling of the immunocompetent cell
- Killing of immnocompetent cells that would reconigze self antigens (this occurs in the thymus)
- Thymic cortex is isolated from the body
- Type II and type III epithelial reticular cells: antigen presenting cells, self-antigens, MHC I and MHC II à these are docking molecules required for immune response (both types).
- Cells are killed if: TCR recognizes self antigens, or if T cell CD4 / CD8 can’t recognize MHC I / II.
Groupings to associate: MHC I, CD8, Cytotoxic T cells. MHCII, CD4, T helper cells.
MACs are antigen presenting cells.
Lymph nodes:
- Bean shaped organs up to an inch long, located along lymphatic vessels. Scattered throughout body but concentrated near mammary glands / axillae and groin.
- Stroma is capsule, trabeculae (capsule dips to form pockets for cells) and reticular fibers.
- Parenchyma = 2 regions
- Cortex = lymphatic nodules with germinal centers containing dendritic cells. Here, antigen presenting cells and MACs are located. Outer part = B cell region. Inner part = paracortex = T cell region.
- Medulla = contains B cells and plasma cells in medullary cords.
Lymph flow:
- Afferent lymph vessels take fluid to node, efferent lymph nodes take cleansed lymph fluid away from node
- The purpose is to clear out antigens etc.
- Vasculature: arterties form capillary bed within cortex = high endothelial venules à specific for the post capillary bed of cortex (paracortex). Through these venules, WBCs leave blood and enter the node.
- Vessels carry blood through sinuses at all timesà between cords. Sinuses are not lined by endothelial cells.
- Also in cortex: Nodules = B cells are activated and start to differentiate into plasma cells.
Pattern of flow:
- Flow is in one direction. Afferent vessels lead in, sinuses lead to efferent vessels that exit at the hilus
- Only filter lymph fluid, not blood.
- Fluid can leave at cortex / paracortex (where WBCs enter) / medulla.
- WBCs in paracortex for Ag presentationà go up to cortex to differentiate à back to medulla to enter lymph again.
- Interior of node segments will be lighter in color if B cells are actively proliferating. Normal circumstances = uniform color.
- Germinal centers: have active B cells = pale center of cord.
Spleen:
- 5 inch organ between stomach and diaphragm
- Hilus contains blood / lymphatic vessels
- Stroma consists of capsule with downward leading trabeculae, fibers, fibroblasts
- Parenchyma contains white / red pulp
- Each arteriole that enters the spleen acts as a center for a White pulp section of the spleen.
- White is lymphatic tissue (lymphocytes / MACs) around branches of splenic artery. Contains WBCs. Antigen presentation takes placeà have germinal centers forming.
- Red is venous sinuses filled with blood / splenic tissue (splenic cords). Made up of cords of Delrothà make up structure of the spleen.
- Sinusoids are vascular structures lined by epithelial cells and MACs. In the cords is where MACs destroy old RBCs.
- Spleen has 2 jobs: 1. filter blood in the parenchyma, RBCs are destroyed by MACs. 2. mount an immune response whenever blood supply is involved.
Artery→ surrouned by periarteriolar lymphatic sheath made of T cells→ surrounded by surrounded by marginal zone where B cells contact antigens. Along the sinus = MACs.
Sinusoids: endothelial lined, contain MACs.
Central artery→ branches into penicillar artery with 3 regions.
- Starts as pulp arteriole
- Becomes sheathed arteriole = surrounded by sheath of MACs
- Becomes terminal capillaryà goes directly into sinus or empties into red pulp cords of Delroth (thus determines open / closed circulation).
Blood leaves the central artery to enter red pulp by: 1. open circulation and 2. closed circulation. Blood must enter splenic cordsà then enters sinusoid to exit via trabecular veins.
Mucosa associated lymphatic tissue:
Locations:
- GI tract = GALT – gut associated lymphatic tissue
- Trachea
- Tonsils (waldeyer’s ring) has nodules
- Peyer’s patch has nodules
- Appendix has nodules
Respiratory tract: BALT bronchus…
Functions: Antigen presentation / phagocytosis.
Lymphatic nodules in diffuse tissues:
- Concentrations of lymphatic tissue not surrounded by a capsule. scattered throughout CT of mucous membranes.
- Mucosa associated lymphoid tissue = MALT
Tonsils:
- Form a ring at the top of the throat
- Adenoids = pharyngeal tonsils
- Palatine tonsils = on each side wall
- Lingual tonsil = in the back of the tongue
eyer’s patches:
- In the ilium of the small intestine.
- 2 T cell domains on outer portion of germinal center within the follicle (B cell area). M cells are on epithelium of gut lumen à are Ag presenting cell (a phagocyte).
- If it takes up an antigen from gutà it migrates into B cell domain to present antigen.
Lymphatic circulation
Capillaries that begin as closed-ended tubes found in spaces between cells.
- Lymphatic capillary is between arterioles and venules in capillary bed.
- Fluids and protein from capillaries is collected by lymphatic capillaries and is returned to the blood
- Respiratory and muscular pumps promote flow of fluidà empties into subclavian veins.