Lymphoid Organs PDF

Immunology Made by : Sarah Ahmed Them 5 | 223  LEARNING OBJECTIVES LO1: Importance of lymphoid organ LO2: Types lymphoid organs LO3: Structure and function of thymus gland/ its role inT cell maturation and selection LO4: Structure and function of lymph nodes LO5: Structure and f...

Immunology Made by : Sarah Ahmed Them 5 | 223  LEARNING OBJECTIVES LO1: Importance of lymphoid organ LO2: Types lymphoid organs LO3: Structure and function of thymus gland/ its role inT cell maturation and selection LO4: Structure and function of lymph nodes LO5: Structure and function of spleen LO6: Mucosa associated lymphoid organs MALT LO7: HEVs and lymphocyte recirculation 1  Lymphoid Organs Aggregates of a large, diverse population of Specialized for protection Mainly lymphocytes leukocytes and other immune cells Importance of Immune System 1 2 3 Defense "Protection" Inflammation Defense aginst infections Repair the immune system recognizes and responds to Defense aginst tumors learance of dead cells and tissue repair tissue grafts and newly intruduced proteins Immune system may abnormally attack normal cells causing inflammatory diseases (autoimmune diseases) Under normal conditions, our immune system doesn't react against self-antigens Sometimes, the immune system reacts against self-antigens causing autoimmune diseases. For example: Rheumatoid arthritis, systemic lupus erythematosus Self-tolerance means the immune system doesn't react against self-antigen 2  Classification of Lymphoid Organs Primary Lymphoid Organs Secondary Lymphoid Organs (Lymphocyte Differentiation) (Lymphocyte Activation) Also called central lymphoid organ Where antigens are localized for effective exposure to mature lymphocytes Where immature lymphocytes develop Initiate adaptive immune responses Organs where differentiation, proliferation, and maturation of stem cells take place Also called peripheral lymphoid organs Includes: Includes: Thymus Bone Marrow Spleen Lymph nodes Tonsils Appendix Peyer's patches Mucosa-associated Lymphoid Organs "MALT" Notes: Cells exit from the organs as Immuno-competent Notes: cells, capable of attacking any foreign antigen Sites where immune cells (B and T cells population) Maturation involves acquiring specific receptors to fight against any foreign body Lymph nodes monitor lymph, filtering it; Spleen fight against antigens Thymus is responsible for the maturation of T filters blood, and Mucosa-associated Lymphoid Organs (MALT) filter tracks and mucosal surfaces 3 lymphocytes, and Bone marrow for B lymphocytes  Thymus gland Site: Superior mediastinum behind the sternum Shape: Bilobed Present in children / atrophied in adults "involution after puberty" Function: Promote production and maturation of T lymphocytes Education of developing thymocytes by positive and negative selection Central tolerance (prevent autoimmunity) Selective removal of T cells reactive against self-antigens When the gland atrophied, the functioning cells are replaced by adipose tissue Appears blue under the microscope because the major cell is T lymphocyte, and its nucleus and cytoplasm are basophilic T cells that exit from the thymus gland should be functioning and immuno-competent, meaning their receptors are efficient (they can bind to foreign antigens but can't attack self-antigens) Central tolerance educates T lymphocytes to never attack self-antigens, preventing autoimmune reactions 4 The organs in our body are either compact or hollow. Thymus gland Hollow organs have layers. Compact organs, like spleen and liver, have a general frame: Structure: 1 Stroma 2 Parenchyma (thymic lobule) Thin vascularized CT capsule Functioning part in the thymus gland Septa Lobule "thymic lobule" Functioning cells in the organ (e.g., hepato cells in the liver, T lymphocytes in the thymus) Thymic epithelial cells (No reticular fibers or cells) Thymic lobule consists of T cells arranged in two places: cortex and Capsule around the organ to maintain medulla. shape Septa or trabeculae Inside the organs, there is supporting connective tissue (in most organs, it is loose, but in lymphoid organs, it is reticular, consisting of reticular fibers and reticular cells, a special type of fibroblast) Thymus gland DOES NOT have reticular 5 connective tissue Thymic Lobule: Thymic Lobule: Contains a dense cortex and a pale central medulla T lymphocytes Divide in the cortex T cells migrate into the medulla Mature T cells leave the thymus by medullary blood vessels Outer Cortex: 1 Thymocytes 2 Cortical Thymic Epithelial Cells (TECs) 3 Macrophages Tightly packed small highly a. Squamous TECs b. Stellate TECs Act as scavengers basophilic T cells Under the capsule and Cytoreticulum Originate in bone marrow along the septa (macrophage) Form the blood thymic Act as antigen- barrier and presenting cells (APCs) corticomedullary for both MHCI and II barrier 6 Secrete cytokines for T cell development Note: Tight junctions /desmosomes present Note: Desmosomes present  Outer Cortex: Functional Details: Structural Insights: Stellate TECs (Branched Cells): Squamous TECs create a sheath The type of junction forming Among thymocytes, stellate TECs create a separating the cortex from the any barrier is a tight junction. cytoreticulum, forming a cellular net. capsule and septa. Junctions between cells are This net acts as mechanical support for Another layer exists between the desmosomes. thymocytes and serves as an antigen- cortex and medulla, forming presenting cell for both self and nonself- barriers to isolate the cortex antigens. completely from the blood and medulla. This creates an environment for optimal growth, differentiation, and maturation for T cells. 7  Inner Medulla: 1 2 3 4 Medullary Thymic Mature T Lymphocytes Macrophages Dendritic Cells Epithelial Cells (TECs) Fewer, less densely packed, APCs large, and lightly stained a. Squamous TECs b. Stellate TECs mature T lymphocytes. Form the 2nd layer of Supportive: the Corticomedullary Cytoreticulum Barrier. APCs: Express many specialized proteins specific to cells of other organs. c. Hassall Corpuscle Releases cytokines to control dendritic cell activity/regulatory T cell development ("peripheral tolerance"). 8  Inner Medulla: Functional Details: Hassall corpuscle is only present The medulla lacks a blood Mature T lymphocytes in the medulla and is a group of thymic barrier, allowing are functioning with Stellate TECs do not squamous cells important for the lymphocytes to easily effective receptors secrete cytokines. development of dendritic cells leave to the blood (e.g., CD4, CD8, TCR). (APCs) and the development and because they are mature. maturing of regulatory T cells. Difference between Central and Peripheral Tolerance: Central Tolerance Peripheral Tolerance Hassall corpuscle develops regulatory T The thymus is responsible for producing cells that stay in the blood circulation and efficient T cells that do not attack self- continuously prevent autoimmune antigens, preventing autoimmune diseases. diseases. 9  T cell selection and maturation To produce fully functional T cells that do not recognize and strongly bind MHC with self-antigens. Aim: The entire selection process is aimed at educating T cells and preventing autoimmune reactions. Negative Selection in the Medulla 1 Positive Selection in the Cortex: 2 (Critical Stage): Objective: T cells gain their own receptors (CD4, CD8, TCR). Dendritic cells present self and non-self antigens. Stellate TECs present self and non-self antigens to test If it binds to self-antigen If it binds to non-self antigen efficiency. Can it bind to the receptor? Apoptosis Kept Yes No Move to the medulla Apoptosis, cleaned by macrophages 3 Result: Helper T cells ➔ CD4 Each functioning T cell (about 2%) will have its own receptor. Cytotoxic T cells ➔ CD8 10  Lymph Node Structure: Site: Shape: Bean-shaped Surfaces: Convex & Concave Structure: 1 Stroma 2 Parenchyma (thymic lobule) Capsule / Trabeculae / Supporting reticular 3 Regions: tissue (reticular cells & fibers) 1 2 3 Paracortex (Inner or Deep Cortex) Cortex (B Cell Zone + FDCs): Medulla: (T Cell Zone + Dendritic Cells): Regular compartments (lymphoid Zone or band of diffuse T cell Irregular compartments having nodules) arranged in balls called population medullary cords (activated T and lymphoid nodules B, memory cells, plasma cells, antibodies, macrophages with Main Function: immune components) and medullary sinuses Filtration of lymph Present along the lymphatic vessels but more prominent in specific areas such as the neck, armpit, groin, mediastinum, mesentery 11  Lymph Node Structure: Immune Zones (Armies): 1 B Cell Army (Humoral Immunity): 2 T Cell Army (Cytotoxic Immunity): B cell (the leader) Cytotoxic T cell (the leader) T helper cell (to activate B cells) T helper cell (to activate T cells) Follicular dendritic cell (this type is not Dendritic cell APC) Macrophage (acts as a scavenger) Macrophage (acts as a scavenger) Results of Immune Reaction: In the medulla 12 Lymph node lymph & vascular supply High Endothelial Venules (HEVs): In paracortex Major source (90%) of lymphocytes within the lymph node The main source of lymphocytes (90%) by diapedesis; the other 10% comes from the lymph itself Responsible for the release of certain cytokines Filtration Steps: Non-filtered lymph flows under the capsule 1 (subcapsular sinus). Moves next to cortical sinus, presented to both armies 2 (B cell zone, T cell zone) for filtering from microbes and pathogens. 3 Filtered lymph moves to medullary sinus. 13  Lymph Node Function "Antigen Supply" Filtration of lymph B Lymphocyte activation / Plasma cells production (humoral immunity) Distributor of antibodies and other immune substances T cell activation Humoral Immune Response "Types of Lymphoid Nodules" Two types of lymphoid nodules (primary, secondary) Primary Lymphoid Secondary Lymphoid Nodule (Follicles): Nodule (Follicles): Small amount of Naive B cells that After exposure to antigens, the are mature but not exposed to battle area inside the follicles is antigens yet. called the germinal center. 14 Humoral Immune Response Lymph node function / T cell activation 15  Lymphocyte Recirculation: HEVS and lymphocyte recirculation HEVs consist of cuboidal epithelial cells responsible for the diapedesis process Lymphocytes constantly recirculate from blood to (lymphocytes migrate from the HEVs by spleen, lymph node, and other lymphoid organs. diapedesis). Continuous circulation provides constant Only present in the paracortex of the lymph node. monitoring of our body and a greater opportunity to catch foreign antigens. 16  Spleen and Its Structure: Site: Left upper quadrant of the abdomen Structure: 1 Stroma 2 Parenchyma (Splenic Pulp): Capsule / Trabeculae / Supporting reticular tissue White Pulp (20%): Lymphoid nodules / PALS Splenic cords (of Billroth) + Red Pulp: Splenic sinusoids Function: Responsible for the red color Filtration of blood Contains actual blood Removal of damaged RBCs Lymphocyte activation and antibody production 17  Spleen vascular supply and function Blood circulation : 1 Splenic artery (main) enter through the capsule 2 transform to trabecular artery (within the spleen) next the central Artery is within the T cell zone 3 (PALS) then it branches to get to the peripheral white pulp (Lymphoid nodules) where B cells are located Spleen Vascular Supply and Function: Filtration of blood In the white pulp the filtration process takes place. and then the penicillar Destruction of old, effete or damaged RBCs arteriole will carry the filtered blood Lymphocyte activation and antibody production What are the contents of the red pulp ? In closed circulation In open circulation All blood related contents E.g. plasma, platelets, leukocytes. As well as Activated T, B cells. Antibodies, filtered blood will communicate the blood will spread ( diffuse) to and all immune components with spleen sinusoid (they are filled the spleen. with blood) and they will drain the What is the idea behind the open circulation? filtered blood to the trabecular vein To check the efficiency of the RBCs if they are (splenic vein) normal they go back to the blood circulation with other components, if not they stay in the spleen and 18 get cleared by macrophages.  Spleen vascular supply and function Spleen - Blood Circulation: Handling Damaged (Abnormal) RBCs: All normal oozing blood goes back to circulation Damaged RBCs are disposed of in the splenic and is reuptaken by splenic sinusoids. cords by macrophages. Splenic sinusoids are lined with epithelial cells Their iron passes through stave cells and is called stave cells, acting like bodyguards. reused in the formation of new RBCs. Stave cells allow normal blood to pass and return Heme-free protein goes to the liver to form for circulation. bilirubin. 19  Mucosa associated lymphoid tissue“MALT” Non-capsulated large and diffuse collections of lymphocytes, plasma cells, APCs, Definition: and lymphoid nodules. Site: Respiratory/genitourinary/GIT Tracts Protected: Respiratory, digestive, urinary, genital tracts Non-capsulated (except tonsils, partially capsulated in Composition: mucosa) Lymphoid nodules (B cells zone) + diffuse lymphoid tissue (T cells zone) Dominant Cell Type: B cell, producing secretory IgA, antagonizing pathogens or foreign antigens. 20  Non-Capsulated Lymphoid Tissue: D-MALT O-MALT (Diffuse Mucosa-Associated Lymphoid Tissue): (Organized Mucosa-Associated Lymphoid Tissue): Diffuse cells in GIT Tonsils Different names depending on location: GALT (Gut-ALT) in GIT: Appendix (in GIT) The largest immune organ Peyer’s Patches in the Ileum (in GIT) Solitary lymphoid nodules aggregates Called organized because it is in specific places for NALT (Nose-ALT) in Nasal Cavity all humans, like tonsils. BALT (Bronchus-ALT) in Lower Respiratory Tract: Diffuse and scattered in any part of the tract 21  Peyer’s Patches & antigen processing Peyer’s patches in the ileum are made by absorptive cells. In Peyer’s patches, there is an M cell, which is a modified primary absorptive cell. The M cell contains intraepithelial lymphocytes present in the cortex of the M cells. The M cell has a bucket containing lymphocytes and dendritic cells. The M cell allows any toxin or foreign bodies to pass and enter the bucket. Lymphocytes and dendritic cells already present in the bucket take up these materials. Finally, the immune reaction starts and produces secretory IgA, which gets back to the mucosa by absorptive cells. 22 Remember ! 23  Immunology Made by : Sarah Ahmed