Lymphoid Tissues Notes
Spleen
Located in the upper left quadrant of the abdominal cavity.
The size of a clenched fist; it’s the largest lymphoid organ.
It is the only lymphoid organ involved in blood filtration.
Gross Appearance:
Dark red color due to red pulp containing many red blood cells in sinusoids.
White spots indicate white pulp, consisting of numerous lymphocytes.
Histological Appearance:
Composed predominantly of splenic pulp.
Red pulp:
Splenic cords.
Splenic sinusoids containing red blood cells (acidophilic).
Macrophages and other Antigen Presenting Cells (APCs).
White pulp:
Lymphoid nodules.
Periarteriolar lymphatic sheaths (PALS).
Mainly lymphocytes (basophilic).
Very cellular composition:
Red pulp
White pulp is located along the arterial blood supply.
Minimal fibrous connective tissue (CT) present to support functional parenchyma.
If damaged, there is a high risk of hemorrhage.
Dense CT capsule and CT trabeculae with trabecular arteries.
Components of White Pulp
White pulp (lymph) nodules:
B lymphocytes.
PALS (periarteriolar lymphatic sheaths) surrounding arterioles:
Predominantly T lymphocytes.
Functions of White Pulp
Detects blood-borne antigens.
Initiates an immune response.
Produces antibodies and lymphocytes that enter venous blood.
Blood Circulation in the Spleen
Trabecular artery → Central artery
Peripheral white pulp (B cells)
Marginal zone sinuses
PALS (T cells)
Red pulp
Penicillar arteriole
Marginal zone sinuses
Sinusoid
Pulp vein
Trabecular vein
Two types of circulation:
Closed circulation
Open circulation
Blood Circulation & Splenic Function
Trabecular arteries → central arteries → smaller arteries in CT → in white pulp → in red pulp.
10% of blood flows to capillaries at the edge of PALS.
Splenic sinuses/sinusoids.
Defective RBCs are removed herein.
Blood-borne antigens initiate an immune response.
Veins.
Components of Red Pulp
Splenic cords, contain macrophages.
Splenic sinusoids.
Function of Red Pulp
Macrophages remove defective/effete RBCs.
Lysosomal digestion of hemoglobin.
Iron is stored as ferritin, hemosiderin.
Iron is recycled to bone marrow.
Bilirubin and biliverdin moved to the liver, enter bile, and are excreted in feces.
Macrophages in the Spleen
Red pulp macrophages are involved in the breakdown of erythrocytes.
Stain for iron (Fe) is confined to the red pulp.
Macrophages are also present in white pulp (brown stain) but do not contain Fe.
Involved in antigen presentation and other immune functions.
Spleen Key Point Summary
Parenchyma-rich organ that filters blood and is easily damaged.
White pulp:
Located along the arterial supply route.
Lymph nodules/follicles & PALS
Rich in lymphocytes
Site of immune responses.
Red pulp:
Composed of cords of cells & sinusoids.
Has abundant macrophages.
Site of removal of effete erythrocytes.
Thymus
Primary Lymphoid Organ.
Bilobed, incompletely lobulated organ.
Located in the mediastinum of the thoracic cavity, overlying the great vessels of the heart.
Largest size in newborn to puberty.
Undergoes involution in adults.
Histological Structure:
Organized into incomplete lobules with:
Densely stained outer cortex (many nuclei of T cell precursors/thymocytes).
Pale inner medulla.
CT septae separate lobules.
Cellular network supporting & isolating thymocytes.
Thymic Epithelial Reticular (ER) Cells
Lymph nodes & spleen have a framework of reticular cells (CT origin) to support lymphocytes.
Thymus has epithelial reticular cells (epithelial origin) that form a supporting framework for lymphocytes.
Adjacent cell processes are bound by desmosomes.
ER cells have different functions in different areas of the thymus, e.g., APCs, secrete cytokines.
Functions of Epithelial Reticular (ER) Cells
Produce growth factors & hormones that influence T cell maturation & proliferation in the thymus & other lymphoid organs.
In the thymic Cortex:
Promote proliferation & differentiation of developing T cells.
Initiate apoptosis (programmed cell death) in T cells that don't recognize any antigens.
Contribute to the blood-thymus barrier à isolate developing T cells from blood-borne antigens.
In the thymic Medulla:
Induce apoptosis in cells that recognize self-antigens.
Provide structural meshwork.
Form Hassall's corpuscles - whorls of ER cells that secrete cytokines.
Thymus: Location-Function Relationships
Precursor T cells (from bone marrow) enter the thymus from capsular & septal blood vessels at the corticomedullary junction.
Migrate into the cortex = where proliferation, initial selection & maturation of “thymocytes” occurs.
Thymocytes passing selection move to the medulla.
Further selection & “education” occur in the medulla.
Successful cells exit the thymus as CD4 helper or CD8 cytotoxic T cells.
Thymic Function = ‘Education’ of T cells
Positive Selection in the cortex
Lymphocytes presented with self & foreign antigens.
Pass → proceed to medulla (DP cells).
Fail → apoptotic death.
Negative Selection in the medulla
Lymphocytes presented with self-antigens.
Responders → eliminated; ER cells induce apoptosis.
Non-responders → self-tolerant SP cells enter venules at CMJ.
Blood-Thymic Barrier
Present in the cortex; prevents unregulated exposure of thymocytes (developing T cells) to antigens.
Components include:
Continuous endothelium, highly impermeable to macromolecules.
Thick basal lamina.
Perivascular CT with many macrophages to phagocytose antigenic material.
Basal lamina of ER cells.
Sheath of ER (epithelioreticular) cells.
No afferent lymph vessels are present in the thymus.
Hassall’s (aka Thymic) Corpuscles
Whorls/aggregates of ER cells in the medulla.
Release cytokines important in:
Dendritic cell (an antigen-presenting cell) activation.
Differentiation of regulatory T cells.
Involution of the Thymus
The size of the thymus decreases from birth onwards, particularly after puberty.
A small thymus persists in adults.
Trabeculae increase in thickness and accumulate adipose tissue.
Lymphocyte numbers decrease.
The junction between the cortex & medulla becomes less distinct.
Calcification of Hassall’s corpuscles.
Mucosal Associated Lymphoid Tissue (MALT)
Non-capsulated lymphoid tissue in the lamina propria of mucosal linings.
Collectively, MALT forms the largest mass of lymphoid tissue.
Intercepts & reacts with antigens.
Large aggregations include:
Tonsils
Appendix
Peyer's patches
Increased numbers of lymphocytes in the lamina propria à diffuse MALT.
Thousands of lymph nodules in the mucosa of the digestive tract, also in the respiratory tract.
Lymphocytes monitor the lining for the presence of antigenic material & respond via both antibody & cellular immune reactions.
Defense Role of MALT
Provides surveillance of mucous membranes for potential invaders.
Palatine tonsils have crypts surrounded by abundant lymphoid tissue.
Ducts from mucoserous glands in the lingual tonsils & adenoids enter crypts at the bottom of ducts & keep them flushed clean of pathogens.
In palatine tonsils, ducts are adjacent to tonsils.
Bacteria can lodge in crypts & overwhelm the lymphoid tissue.
Inflammation & infection occur.
Secretion from glands here does not flush crypts.
Lymph Nodes
Size: 2mm - 10mm
Located along lymph vessels
Bean-shaped
Indentation = hilus
Two main histological regions: outer cortex, inner medulla
Functions of Lymph Nodes
One-way lymph flow through nodes enables:
Monitoring of antigenic content of lymph
Filtering out of particles, rogue cells, etc.
Elimination of antigens by antibody & cell-mediated responses.
Lymph Circulation through Lymph Nodes
Several afferent lymph vessels on the convex surface take lymph to the node.
Lymph percolates through sinuses within the node.
1 or 2 efferent lymph vessels at the hilus drain lymph from the node.
Lymph Node Sinuses
Afferent vessels drain into subcapsular sinus.
Leads to trabecular/cortical sinuses that connect with centrally located medullary sinuses.
Sinuses = irregular spaces spanned by reticular & dendritic cells.
Lymph in medullary sinuses flows into the efferent lymph vessel that leaves the node.
Lymph Node – Tissue Components
Capsule (dense CT):
Dense CT covering.
Trabeculae provide dense CT support for cellular contents.
The fine network of reticular fibers holds cells in place.
Cortex:
Densely arranged lymphocytes.
Medulla:
Loosely arranged lymphocytes & other cells.
Lymph Node Cortex & Medulla
Cortex:
B lymphocytes densely arranged as spherical nodules (aka follicles).
Immunologically active nodule (secondary nodule) has a pale center (germinal center) where larger lymphoblasts are present.
The inner region of the cortex has a band of T lymphocytes (= paracortex).
Medulla:
Medullary sinuses – paler, contain lymph.
Medullary cords - consist of lymphocytes & plasma cells.
Lymph Node Structure
Medullary cord
More cellular (denser) region of the medulla that contains:
Lymphocytes
Macrophages
Plasma cells → release antibody into lymph in sinuses
Medullary sinus
Channel for lymph that contains
Macrophages
Reticular cells with long processes & elongated nuclei = final filter of lymph.
Lymphocytes may exit the node via lymph to distant sites.
Adjacent CT Trabeculae (3)
Sites of Functions in Lymph Nodes
Antigens are filtered out by macrophages mainly in the subcapsular sinus.
B cells in the cortex are activated by helper T cells from the paracortical region.
Activated B cells proliferate in the germinal center of nodules.
Some B lymphocytes differentiate into plasma cells that migrate to medullary cords where they release antibodies into the lymph.
Memory B cells and memory T cells increase in numbers, and some leave via the efferent lymph vessel.
Blood Supply to Lymph Nodes
Blood vessels enter & leave at the hilum.
Lymphocytes leave the blood circulatory system at postcapillary/high endothelial lined venules (HEVs) in the deep cortex, i.e., paracortex - the one-directional cellular route, IN ONLY.
Lymphocytes entering via blood exit the lymph node by the efferent lymph vessel.
Lymph Node High Endothelial Venules (HEVs)
HEVs are located in the paracortex; modified endothelium attracts the entry of lymphocytes into the node via diapedesis.
Lymphocyte Locations & Movement in a Lymph Node
Some lymphocytes enter via afferent lymph vessels.
Some lymphocytes are produced in the lymph node (germinal centers).
Lymphocytes from blood enter the lymph node via high endothelial venules (HEV).
All lymphocytes leave via the efferent lymph vessel in the hilus.
Function: antigens are concentrated in the node; lymphocytes respond to the presence of antigens.
Metastases in Lymph Nodes
Particles & cells enter the subcapsular sinus.
Phagocytosed by macrophages
Indigestible components, e.g., carbon in dust, remain in macrophages BUT:
Cancer cells can overwhelm macrophages & divide in the node – form secondary tumor or metastasis.
Lymph nodes with metastases are swollen, firm to the touch but not painful; lymph nodes with infections are swollen, soft to the touch, ‘moveable,’ & painful.
Lymph Node Key Point Summary
Cortex = site of B lymphocytes in nodules; germinal centers in activated nodules where lymphoblasts proliferate
Paracortex/deep cortex = site of T lymphocytes
The medulla has cords & sinuses; plasma cells in cords release antibodies into sinuses
High endothelial venules (HEVs) enable entry of lymphocytes from blood & transfer fluid from the node to blood
Sinuses = sites of filtration
Metastasis of tumors in lymph nodes when the filtration function is overwhelmed
Immunity
Immunocompetence:
The ability to distinguish between "self" (molecules normally present within the body) & "non-self," i.e., foreign molecules.
Represents balance between responsiveness to antigens & tolerance of them
Antigen:
Any substance that can induce an immune response, e.g., foreign protein, polysaccharide, toxin, infectious organism, foreign tissue, transformed tissue
Antibody:
Proteins that mark invaders for destruction by other immune cells
Non-specific (Innate) Defenses
Pre-existing, first line of defense
Localized in action
Include:
Physical barriers, - skin & mucous membranes
Chemical defenses, e.g., low pH
Secretory substances, e.g., lysozyme, fibronectin, interferon, complement
Phagocytic cells, e.g., macrophages, neutrophils
Natural killer (NK) cells
Inflammatory reaction
Specific Defenses - Adaptive Immunity
Exposure to foreign antigenic material brings about a series of steps, an immune response, that results in the elimination of the antigen/s
The immune reaction is not restricted to the initial site of entry of foreign material into the body → systemic.
The immune response generates ‘immune memory’ for the antigen. In subsequent exposures to the antigen, it will be eliminated before it can cause disease.
Major Cells of the Immune Response: B lymphocytes, T lymphocytes, Natural Killer (NK) Cells & Antigen Presenting Cells (various cells including macrophages & some B lymphocytes)
Subsets of Lymphocytes
Two subsets of lymphocytes derived from the same stem cell in bone marrow:
Cells migrate to the thymus - become T cells – Cell-mediated immunity
A subset remains in the bone marrow to finish development - become B cells & Natural Killer (NK) cells
B cells differentiate into plasma cells—produce antibodies = humoral immunity
NK cells: kill virus-infected cells & secrete IFN-γ
Types of Lymphocytes
B lymphocytes & natural killer (NK) lymphocytes
Formed in bone marrow & leave bone marrow already mature
Seed secondary lymphoid organs & transit through the blood, epithelia, & connective tissues
Immature CD4- and CD8- T lymphocyte precursors
Transported by blood circulation from bone marrow to the thymus
Complete maturation in the thymus & leave as either CD4+ or CD8+ T cells
Immune Responses
B lymphocyte:
antibody-mediated (humoral) response
T lymphocyte:
cell-mediated response
Lymphocyte Histology
Non–granular, basophilic staining cytoplasm
Large range of sizes
Small ~8 μm, large ~16 μm
Many ribosomes (visible with EM)
Recirculating immunocompetent cells
Functionally distinct sub-classes, but …
B-cells & T-cells are indistinguishable in blood smears & histological sections - have the same histological appearance
Lymph & Lymph Circulation
Roles of the lymphoid system:
Monitor body surfaces & internal fluid compartments = surveillance
React to the presence of potentially harmful substances = defense
The definitive cell type = lymphocyte
Lymphatic tissues & organs = sites where lymphocytes proliferate, differentiate & mature
Lymphatic vessels – drain lymph & connect parts of the lymphoid system to the blood vascular system → circulation route for lymphocytes
Lymphoid System Components
Lymph
Lymph capillaries (lacteals in GIT mucosa)
Lymph vessels
Lymph nodes
Spleen
Thymus
MALT = mucosal associated lymphoid tissue (diffuse lymphocytes & lymphatic nodules)
Bone marrow
What is Lymph
Fluid contained within lymph vessels that is derived from the extracellular environment, i.e., a derivative of interstitial fluid.
Contains lymphocytes, ions, antigens, particles, rogue cells …. (any small molecules in the extracellular spaces have the potential to enter lymph)
Lymph from GIT also contains lipids and some proteins = chyle
Lymph & Blood Circulation
Cardiovascular system is closed
The heart pumps blood around the body
The Lymph system is open
Starts as blind-ending lymph capillaries in tissues
Lymph nodes filter lymph
Lymph returned via lymphatic vessels to blood circulation at major veins near the heart
Lymph Capillaries
Present in all tissues except CNS, thymus, spleen
Tissue fluid, large molecules, antigens, & some lymphocytes drain into lymph capillaries to form lymph
In intestines, absorbed lipid drains into lymph vessels – lacteals
Lymph capillaries drain into lymph vessels that pass through several lymph nodes before flowing into major veins
Fluid Collection by Lymph Capillaries
When the pressure of fluid is greater in the interstitial spaces than in the capillary, cells separate slightly & fluid flows in.
When the pressure is greater in the capillary than in the interstitial spaces, cells tightly adhere & lymph cannot escape valves.
Lymph Circulation
Lymph capillaries → Lymph vessels → Lymph nodes → Lymph trunks → 2 main channels: thoracic (left lymphatic) duct (most of the body) and right lymphatic duct (right & superior to dotted lines) → Venous blood
Vessel Features & Lymph Flow:
Not easily detected with the naked eye
Mainly accompany arteries & veins
Very thin wall, endothelial lining
Outer layer of dense connective tissue, collagen fibres, minimal smooth muscle
Valves prevent backflow of lymph
Collapse if empty of lymph
Sluggish lymph flow towards the heart; mainly relies on the movement of surrounding skeletal muscle & valves to prevent backflow (i.e., similar to veins)
Mechanics of Lymph Circulation
Respiratory pump: Lymph flow is maintained by pressure changes that occur during inhalation
Lymph flows from the abdominal region (high pressure) to the thoracic region (low pressure)
When pressures reverse during exhalation, valves prevent backflow
Lymph Key Point Summary
Lymph is:
Derived from extracellular tissue fluid & contains antigens, lipid & lymphocytes
Collected into lymph capillaries
Has a slow passage through lymph vessels
Passes through several lymph nodes, where it is filtered (details to come)
Returned to venous circulation close to the heart
Spleen
Located in the upper left quadrant of the abdominal cavity.
The size of a clenched fist; it’s the largest lymphoid organ.
It is the only lymphoid organ involved in blood filtration.
Gross Appearance:
Dark red color due to red pulp containing many red blood cells in sinusoids. This facilitates the spleen's role in filtering blood and removing damaged red blood cells.
White spots indicate white pulp, consisting of numerous lymphocytes. These areas are crucial for immune responses.
Histological Appearance:
Composed predominantly of splenic pulp.
Red pulp:
Splenic cords: These contain a network of reticular fibers and cells, including macrophages and lymphocytes.
Splenic sinusoids containing red blood cells (acidophilic): Their structure allows for the easy passage of red blood cells and facilitates the removal of defective cells.
Macrophages and other Antigen Presenting Cells (APCs): Essential for capturing and presenting antigens to initiate immune responses.
White pulp:
Lymphoid nodules: Primarily B lymphocytes, which are key for antibody production.
Periarteriolar lymphatic sheaths (PALS): Mostly T lymphocytes, which are vital for cell-mediated immunity.
Mainly lymphocytes (basophilic).
Very cellular composition:
Red pulp: High concentration of red blood cells and macrophages for filtration.
White pulp is located along the arterial blood supply: Allows for quick immune response to blood-borne antigens.
Minimal fibrous connective tissue (CT) present to support functional parenchyma.
If damaged, there is a high risk of hemorrhage due to the spleen's role in blood filtration and the absence of extensive supportive tissue.
Dense CT capsule and CT trabeculae with trabecular arteries: Provides some structural support and allows for the entry of blood vessels.
Components of White Pulp
White pulp (lymph) nodules:
B lymphocytes: Responsible for producing antibodies.
PALS (periarteriolar lymphatic sheaths) surrounding arterioles:
Predominantly T lymphocytes: Key for cell-mediated immune responses.
Functions of White Pulp
Detects blood-borne antigens.
Initiates an immune response: B and T lymphocytes work together to recognize and respond to antigens.
Produces antibodies and lymphocytes that enter venous blood: Contributes to systemic immunity.
Blood Circulation in the Spleen
Trabecular artery → Central artery
Peripheral white pulp (B cells)
Marginal zone sinuses
PALS (T cells)
Red pulp
Penicillar arteriole
Marginal zone sinuses
Sinusoid
Pulp vein
Trabecular vein
Two types of circulation:
Closed circulation: Blood remains within vessels.
Open circulation: Blood passes through the splenic cords, enhancing filtration by macrophages.
Blood Circulation & Splenic Function
Trabecular arteries → central arteries → smaller arteries in CT → in white pulp → in red pulp.
10% of blood flows to capillaries at the edge of PALS.
Splenic sinuses/sinusoids: Specialized structure facilitates filtration and removal of damaged cells.
Defective RBCs are removed herein.
Blood-borne antigens initiate an immune response.
Veins.
Components of Red Pulp
Splenic cords, contain macrophages: Macrophages efficiently remove debris and damaged cells.
Splenic sinusoids.
Function of Red Pulp
Macrophages remove defective/effete RBCs: Essential for maintaining healthy blood.
Lysosomal digestion of hemoglobin: Breaks down hemoglobin for recycling.
Iron is stored as ferritin, hemosiderin.
Iron is recycled to bone marrow.
Bilirubin and biliverdin moved to the liver, enter bile, and are excreted in feces.
Macrophages in the Spleen
Red pulp macrophages are involved in the breakdown of erythrocytes.
Stain for iron (Fe) is confined to the red pulp: Indicates the site of iron storage and recycling.
Macrophages are also present in white pulp (brown stain) but do not contain Fe.
Involved in antigen presentation and other immune functions.
Spleen Key Point Summary
Parenchyma-rich organ that filters blood and is easily damaged.
White pulp:
Located along the arterial supply route: Ensures immediate immune response to blood-borne antigens.
Lymph nodules/follicles & PALS
Rich in lymphocytes
Site of immune responses.
Red pulp:
Composed of cords of cells & sinusoids.
Has abundant macrophages: Facilitates efficient removal of damaged cells and debris.
Site of removal of effete erythrocytes.
Thymus
Primary Lymphoid Organ.
Bilobed, incompletely lobulated organ.
Located in the mediastinum of the thoracic cavity, overlying the great vessels of the heart.
Largest size in newborn to puberty.
Undergoes involution in adults.
Histological Structure:
Organized into incomplete lobules with:
Densely stained outer cortex (many nuclei of T cell precursors/thymocytes): Indicates high cellular activity and T cell development.
Pale inner medulla: Site of more mature T cells.
CT septae separate lobules.
Cellular network supporting & isolating thymocytes.
Thymic Epithelial Reticular (ER) Cells
Lymph nodes & spleen have a framework of reticular cells (CT origin) to support lymphocytes.
Thymus has epithelial reticular cells (epithelial origin) that form a supporting framework for lymphocytes: These cells are unique to the thymus and crucial for T cell maturation.
Adjacent cell processes are bound by desmosomes.
ER cells have different functions in different areas of the thymus, e.g., APCs, secrete cytokines.
Functions of Epithelial Reticular (ER) Cells
Produce growth factors & hormones that influence T cell maturation & proliferation in the thymus & other lymphoid organs.
In the thymic Cortex:
Promote proliferation & differentiation of developing T cells.
Initiate apoptosis (programmed cell death) in T cells that don't recognize any antigens: Ensures only useful T cells survive.
Contribute to the blood-thymus barrier à isolate developing T cells from blood-borne antigens.
In the thymic Medulla:
Induce apoptosis in cells that recognize self-antigens.
Provide structural meshwork.
Form Hassall's corpuscles - whorls of ER cells that secrete cytokines.
Thymus: Location-Function Relationships
Precursor T cells (from bone marrow) enter the thymus from capsular & septal blood vessels at the corticomedullary junction.
Migrate into the cortex = where proliferation, initial selection & maturation of “thymocytes” occurs.
Thymocytes passing selection move to the medulla.
Further selection & “education” occur in the medulla.
Successful cells exit the thymus as CD4 helper or CD8 cytotoxic T cells.
Thymic Function = ‘Education’ of T cells
Positive Selection in the cortex:
Lymphocytes presented with self & foreign antigens.
Pass → proceed to medulla (DP cells).
Fail → apoptotic death.
Negative Selection in the medulla:
Lymphocytes presented with self-antigens.
Responders → eliminated; ER cells induce apoptosis.
Non-responders → self-tolerant SP cells enter venules at CMJ.
Blood-Thymic Barrier
Present in the cortex; prevents unregulated exposure of thymocytes (developing T cells) to antigens: Protects developing T cells from premature activation.
Components include:
Continuous endothelium, highly impermeable to macromolecules.
Thick basal lamina.
Perivascular CT with many macrophages to phagocytose antigenic material.
Basal lamina of ER cells.
Sheath of ER (epithelioreticular) cells.
No afferent lymph vessels are present in the thymus.
Hassall’s (aka Thymic) Corpuscles
Whorls/aggregates of ER cells in the medulla.
Release cytokines important in:
Dendritic cell (an antigen-presenting cell) activation.
Differentiation of regulatory T cells.
Involution of the Thymus
The size of the thymus decreases from birth onwards, particularly after puberty.
A small thymus persists in adults.
Trabeculae increase in thickness and accumulate adipose tissue.
Lymphocyte numbers decrease.
The junction between the cortex & medulla becomes less distinct.
Calcification of Hassall’s corpuscles.
Mucosal Associated Lymphoid Tissue (MALT)
Non-capsulated lymphoid tissue in the lamina propria of mucosal linings: Its location allows it to efficiently intercept antigens at mucosal surfaces.
Collectively, MALT forms the largest mass of lymphoid tissue.
Intercepts & reacts with antigens.
Large aggregations include:
Tonsils
Appendix
Peyer's patches
Increased numbers of lymphocytes in the lamina propria à diffuse MALT.
Thousands of lymph nodules in the mucosa of the digestive tract, also in the respiratory tract.
Lymphocytes monitor the lining for the presence of antigenic material & respond via both antibody & cellular immune reactions.
Defense Role of MALT
Provides surveillance of mucous membranes for potential invaders.
Palatine tonsils have crypts surrounded by abundant lymphoid tissue: The crypts increase surface area for antigen sampling.
Ducts from mucoserous glands in the lingual tonsils & adenoids enter crypts at the bottom of ducts & keep them flushed clean of pathogens.
In palatine tonsils, ducts are adjacent to tonsils.
Bacteria can lodge in crypts & overwhelm the lymphoid tissue.
Inflammation & infection occur.
Secretion from glands here does not flush crypts.
Lymph Nodes
Size: 2mm - 10mm
Located along lymph vessels: Strategic placement allows for efficient filtering of lymph.
Bean-shaped
Indentation = hilus
Two main histological regions: outer cortex, inner medulla
Functions of Lymph Nodes
One-way lymph flow through nodes enables:
Monitoring of antigenic content of lymph
Filtering out of particles, rogue cells, etc.
Elimination of antigens by antibody & cell-mediated responses.
Lymph Circulation through Lymph Nodes
Several afferent lymph vessels on the convex surface take lymph to the node.
Lymph percolates through sinuses within the node: Allows for interaction with immune cells and filtration.
1 or 2 efferent lymph vessels at the hilus drain lymph from the node.
Lymph Node Sinuses
Afferent vessels drain into subcapsular sinus.
Leads to trabecular/cortical sinuses that connect with centrally located medullary sinuses.
Sinuses = irregular spaces spanned by reticular & dendritic cells: Facilitates the capture and presentation of antigens.
Lymph in medullary sinuses flows into the efferent lymph vessel that leaves the node.
Lymph Node – Tissue Components
Capsule (dense CT):
Dense CT covering: Provides structural support and protection.
Trabeculae provide dense CT support for cellular contents.
The fine network of reticular fibers holds cells in place.
Cortex:
Densely arranged lymphocytes.
Medulla:
Loosely arranged lymphocytes & other cells.
Lymph Node Cortex & Medulla
Cortex:
B lymphocytes densely arranged as spherical nodules (aka follicles): Sites for B cell activation and antibody production.
Immunologically active nodule (secondary nodule) has a pale center (germinal center) where larger lymphoblasts are present: Indicates active B cell proliferation.
The inner region of the cortex has a band of T lymphocytes (= paracortex).
Medulla:
Medullary sinuses – paler, contain lymph.
Medullary cords - consist of lymphocytes & plasma cells: Plasma cells here secrete antibodies into the lymph.
Lymph Node Structure
Medullary cord:
More cellular (denser) region of the medulla that contains:
Lymphocytes
Macrophages
Plasma cells → release antibody into lymph in sinuses
Medullary sinus:
Channel for lymph that contains:
Macrophages
Reticular cells with long processes & elongated nuclei = final filter of lymph.
Lymphocytes may exit the node via lymph to distant sites.
Adjacent CT Trabeculae (3)
Sites of Functions in Lymph Nodes
Antigens are filtered out by macrophages mainly in the subcapsular sinus.
B cells in the cortex are activated by helper T cells from the paracortical region.
Activated B cells proliferate in the germinal center of nodules.
Some B lymphocytes differentiate into plasma cells that migrate to medullary cords where they release antibodies into the lymph.
Memory B cells and memory T cells increase in numbers, and some leave via the efferent lymph vessel.
Blood Supply to Lymph Nodes
Blood vessels enter & leave at the hilum.
Lymphocytes leave the blood circulatory system at postcapillary/high endothelial lined venules (HEVs) in the deep cortex, i.e., paracortex - the one-directional cellular route, IN ONLY: HEVs allow lymphocytes to efficiently enter the lymph node from the bloodstream.
Lymphocytes entering via blood exit the lymph node by the efferent lymph vessel.
Lymph Node High Endothelial Venules (HEVs)
HEVs are located in the paracortex; modified endothelium attracts the entry of lymphocytes into the node via diapedesis.
Lymphocyte Locations & Movement in a Lymph Node
Some lymphocytes enter via afferent lymph vessels.
Some lymphocytes are produced in the lymph node (germinal centers).
Lymphocytes from blood enter the lymph node via high endothelial venules (HEV).
All lymphocytes leave via the efferent lymph vessel in the hilus.
Function: antigens are concentrated in the node; lymphocytes respond to the presence of antigens.
Metastases in Lymph Nodes
Particles & cells enter the subcapsular sinus.
Phagocytosed by macrophages
Indigestible components, e.g., carbon in dust, remain in macrophages BUT:
Cancer cells can overwhelm macrophages & divide in the node – form secondary tumor or metastasis.
Lymph nodes with metastases are swollen, firm to the touch but not painful; lymph nodes with infections are swollen, soft to the touch, ‘moveable,’ & painful.
Lymph Node Key Point Summary
Cortex = site of B lymphocytes in nodules; germinal centers in activated nodules where lymphoblasts proliferate
Paracortex/deep cortex = site of T lymphocytes
The medulla has cords & sinuses; plasma cells in cords release antibodies into sinuses
High endothelial venules (HEVs) enable entry of lymphocytes from blood & transfer fluid from the node to blood
Sinuses = sites of filtration
Metastasis of tumors in lymph nodes when the filtration function is overwhelmed
Immunity
Immunocompetence:
The ability to distinguish between "self" (molecules normally present within the body) & "non-self," i.e., foreign molecules.
Represents balance between responsiveness to antigens & tolerance of them
Antigen: Any substance that can induce an immune response, e.g., foreign protein, polysaccharide, toxin, infectious organism, foreign tissue, transformed tissue
Antibody: Proteins that mark invaders for destruction by other immune cells
Non-specific (Innate) Defenses
Pre-existing, first line of defense
Localized in action
Include:
Physical barriers, - skin & mucous membranes
Chemical defenses, e.g., low pH
Secretory substances, e.g., lysozyme, fibronectin, interferon, complement
Phagocytic cells, e.g., macrophages, neutrophils
Natural killer (NK) cells
Inflammatory reaction
Specific Defenses - Adaptive Immunity
Exposure to foreign antigenic material brings about a series of steps, an immune response, that results in the elimination of the antigen/s
The immune reaction is not restricted to the initial site of entry of foreign material into the body → systemic.
The immune response generates ‘immune memory’ for the antigen. In subsequent exposures to the antigen, it will be eliminated before it can cause disease.
Major Cells of the Immune Response: B lymphocytes, T lymphocytes, Natural Killer (NK) Cells & Antigen Presenting Cells (various cells including macrophages & some B lymphocytes)
Subsets of Lymphocytes
Two subsets of lymphocytes derived from the same stem cell in bone marrow:
Cells migrate to the thymus - become T cells – Cell-mediated immunity
A subset remains in the bone marrow to finish development - become B cells & Natural Killer (NK) cells
B cells differentiate into plasma cells—produce antibodies = humoral immunity
NK cells: kill virus-infected cells & secrete IFN-γ
Types of Lymphocytes
B lymphocytes & natural killer (NK) lymphocytes
Formed in bone marrow & leave bone marrow already mature
Seed secondary lymphoid organs & transit through the blood, epithelia, & connective tissues
Immature CD4- and CD8- T lymphocyte precursors
Transported by blood circulation from bone marrow to the thymus
Complete maturation in the thymus & leave as either CD4+ or CD8+ T cells
Immune Responses
B lymphocyte: antibody-mediated (humoral) response
T lymphocyte: cell-mediated response
Lymphocyte Histology
Non–granular, basophilic staining cytoplasm
Large range of sizes:
Small ilda 8 μm, large ilda 16 μm
Many ribosomes (visible with EM)
Recirculating immunocompetent cells
Functionally distinct sub-classes, but …
B-cells & T-cells are indistinguishable in blood smears & histological sections - have the same histological appearance
Lymph & Lymph Circulation
Roles of the lymphoid system:
Monitor body surfaces & internal fluid compartments = surveillance
React to the presence of potentially harmful substances = defense
The definitive cell type = lymphocyte
Lymphatic tissues & organs = sites where lymphocytes proliferate, differentiate & mature
Lymphatic vessels – drain lymph & connect parts of the lymphoid system to the blood vascular system → circulation route for lymphocytes
Lymphoid System Components
Lymph
Lymph capillaries (lacteals in GIT mucosa)
Lymph vessels
Lymph nodes
Spleen
Thymus
MALT = mucosal associated lymphoid tissue (diffuse lymphocytes & lymphatic nodules)
Bone marrow
What is Lymph
Fluid contained within lymph vessels that is derived from the extracellular environment, i.e., a derivative of interstitial fluid.
Contains lymphocytes, ions, antigens, particles, rogue cells …. (any small molecules in the extracellular spaces have the potential to enter lymph)
Lymph from GIT also contains lipids and some proteins = chyle
Lymph & Blood Circulation
Cardiovascular system is closed
The heart pumps blood around the body
The Lymph system is open
Starts as blind-ending lymph capillaries in tissues
Lymph nodes filter lymph
Lymph returned via lymphatic vessels to blood circulation at major veins near the heart
Lymph Capillaries
Present in all tissues except CNS, thymus, spleen
Tissue fluid, large molecules, antigens, & some lymphocytes drain into lymph capillaries to form lymph
In intestines, absorbed lipid drains into lymph vessels – lacteals
Lymph capillaries drain into lymph vessels that pass through several lymph nodes before flowing into major veins
Fluid Collection by Lymph Capillaries
When the pressure of fluid is greater in the interstitial spaces than in the capillary, cells separate slightly & fluid flows in.
When the pressure is greater in the capillary than in the interstitial spaces, cells tightly adhere & lymph cannot escape valves.
Lymph Circulation
Lymph capillaries → Lymph vessels → Lymph nodes → Lymph trunks → 2 main channels: thoracic (left lymphatic) duct (most of the body) and right lymphatic duct (right & superior to dotted lines) → Venous blood
Vessel Features & Lymph Flow:
Not easily detected with the naked eye
Mainly accompany arteries & veins
Very thin wall, endothelial lining
Outer layer of dense connective tissue, collagen fibres, minimal smooth muscle
Valves prevent backflow of lymph
Collapse if empty of lymph
Sluggish lymph flow towards the heart; mainly relies on the movement of surrounding skeletal muscle & valves to prevent backflow (i.e., similar to veins)
Mechanics of Lymph Circulation
Respiratory pump: Lymph flow is maintained by pressure changes that occur during inhalation
Lymph flows from the abdominal region (high pressure) to the thoracic region (low pressure)
When pressures reverse during exhalation, valves prevent backflow
Lymph Key Point Summary
Lymph is:
Derived from extracellular tissue fluid & contains antigens, lipid & lymphocytes
Collected into lymph capillaries
Has a slow passage through lymph vessels
Passes through several lymph nodes, where it is filtered (details to come)
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