Structure of immune system mbbs


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Structure of immune system mbbs

  2. 2. WHAT IS THIS ? Lymphoreticular system; Complex organization of cells with different morphology and distributed in all organs and tissues of the body and responsible for immunity.
  3. 3. 1.Reticuloendothelial component . a) Phagocytic cells. b) Plasma cells. 2.Lymphoid component. a) Lymphocytes (T & B). b) Plasma cells. Non specific Immune response Specific Immune response
  5. 5. Myeloblasts Monoblasts Megakaryoblast Proerythroblast Lymphoblasts
  6. 6. <ul><li>Production: </li></ul><ul><ul><ul><li>Yolk sac. </li></ul></ul></ul><ul><ul><ul><li>(Up to 6 th -8 th wks of gestation) </li></ul></ul></ul><ul><ul><ul><li>Fetal liver. </li></ul></ul></ul><ul><ul><ul><li>Bone marrow. </li></ul></ul></ul><ul><ul><ul><li>(From just before birth) </li></ul></ul></ul>Fetal Liver Bone marrow
  7. 7. Lymphopoiesis in central & Peripheral lymphoid organs and mix together constantly to maintain Lymphocyte traffic . Mucosa associated lymphoid tissue
  8. 8. <ul><li>Thymus: </li></ul><ul><ul><ul><li>Lymphoepithelial structure. </li></ul></ul></ul><ul><ul><ul><li>Behind the upper part of sternum </li></ul></ul></ul><ul><ul><ul><li>3 rd & 4 th pharyngeal pouches at </li></ul></ul></ul><ul><ul><ul><li>6 th week of IUL. </li></ul></ul></ul><ul><ul><ul><li>Maximum size just before birth. </li></ul></ul></ul><ul><ul><ul><li>Atrophied after puberty. </li></ul></ul></ul>
  9. 9. T-stem cells migrate into Thymic rudiment (During 3 rd month of I U L) Thymus develop into…………. Cortex Medulla . (Immature T-cells) (Mature T- cells ) In thymic epithelial cells Peptidic hormones. Thymulin, α & β4 thymosin, Thymopoietin. Matured into immuno competent T- cells . <ul><li>Maturation process is more vigorous during….. </li></ul><ul><ul><ul><li>Fetal age ,Neonatal stage, Puberty. </li></ul></ul></ul>
  10. 10. <ul><li>Functions of Thymus </li></ul><ul><li>Production, maturation & differentiation of </li></ul><ul><li>T – cells. </li></ul><ul><li>Death of T- cells that cannot recognize antigen- </li></ul><ul><li>MHCs and T- cells react with self-antigen-MHC. </li></ul><ul><ul><li>Thymectomised mice: Deficient CMI </li></ul></ul><ul><ul><li>Lymphopenia,Deficient Graft rejection </li></ul></ul><ul><ul><li>Runting disease. </li></ul></ul><ul><ul><li>Congenital aplasia: </li></ul></ul><ul><ul><li>Di-George syndrome (CMI deficient) </li></ul></ul>
  11. 11. <ul><li>Bone marrow </li></ul><ul><ul><ul><li>Some of the lymphoid stem cells </li></ul></ul></ul><ul><ul><ul><li>retained and converted into </li></ul></ul></ul><ul><ul><ul><li>B – lymphocytes . </li></ul></ul></ul><ul><li> by </li></ul><ul><ul><ul><li>Interaction with Marrow stromal cells </li></ul></ul></ul><ul><ul><ul><li>and production of cytokines (IL-7) . </li></ul></ul></ul>
  12. 12. Acts as Filters or traps for antigens, become inflamed or enlarged in various conditions distributed widely throughout the body including the armpit and stomach/gut and linked by lymphatic vessels. Garrisons of B, T, and other immune cells dendritic cells, macrophages Lymph node is a small ball-shaped organ of the immune system ,
  13. 13. Naive lymphocytes (cells,not yet encountered an antigen) enter the node from the bloodstream, through specialized capillary venules, known as high endothelial venules. After the lymphocytes specialize they will exit the lymph node through the efferent lymphatic vessel with the rest of the lymph. Clinical significance of lymphnode
  14. 14. While most of the gut viscera are endodermally the spleen is derived from mesenchymal tissue. The spleen is purple and gray. The spleen is unique in respect to its development within the gut.
  15. 15. Area Function Composition Red pulp Mechanical filtration of red blood cells. <ul><li>&quot;sinusoids ” which are filled with blood. </li></ul><ul><li>&quot;splenic cords&quot; of reticular fibers. </li></ul><ul><li>&quot;marginal zone&quot; bordering on white pulp </li></ul>White pulp Active immune response through humoral and cell-mediated pathways. <ul><li>Composed of nodules, called Malpighian corpuscles. These are composed of &quot;lymphoid follicles&quot; , rich in B- cells </li></ul><ul><li>“ Periarteriolar lymphoid sheaths&quot; (PALS) , rich in T-lymphocytes. </li></ul>
  16. 16.
  17. 17. Functions of spleen: <ul><ul><li>It is a part of reticulo endothelial system. </li></ul></ul><ul><ul><li>It synthesizes antibodies in its white pulp and removes antibody-coated bacteria along with antibody-coated blood cells by way of blood and lymph node circulation. </li></ul></ul><ul><ul><li>Removal of aged elements, elimination of particulate matter from blood. </li></ul></ul>
  18. 18. <ul><ul><li>Depends on age. </li></ul></ul><ul><ul><ul><li>In children : Bacterial sepsis is common with Str.pneumoniae, N.meningitidis, H.influenzae </li></ul></ul></ul><ul><ul><ul><li>In adults : Susceptibility to Blood borne bacterial infections. </li></ul></ul></ul>Effect of Splenectomy on Immune response .
  19. 19. <ul><li>MALT (Mucosa Associated Lymphoid Tissue). </li></ul><ul><ul><ul><li>Sub epithelial accumulations of lymphoid tissue in </li></ul></ul></ul><ul><ul><ul><li>the mucosa of various secretary systems. </li></ul></ul></ul><ul><li>Sites: Respiratory tract. (BALT) </li></ul><ul><li> Alimentary tract (GALT) </li></ul><ul><li> Genitourinary tract </li></ul><ul><ul><ul><ul><ul><li>Consists of T & B lymphocytes, Macrophages. </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Produces Ig A , Ig M & Ig E antibodies. </li></ul></ul></ul></ul></ul>
  20. 20. Distributed as: 1).Diffuse collections. 2).Specialized aggregations Lingual, Palatine, Pharyngeal tonsils. Payer's patches.
  21. 21. T cell maturation T - cell precursors Migrate in to thymus Thymic epithelial cells. ( Attains self tolerance , Capacity to recognize Ag- MHC complex ) Synthesis CD3 & acquire new surface Ag ( Thy ag.) Pre T – cells With T- cells receptor ( T C R) Becomes Antigen recognition unit ( I C C ) . (TCR & CD3, Thy proteins)
  22. 22. Most can be distinguished by the presence of either CD4 or CD8 membrane molecules. <ul><li>CD4 (65%): </li></ul><ul><li>Perform helper </li></ul><ul><li>function; </li></ul><ul><li>Transformation of B </li></ul><ul><li>cells to plasma cells. </li></ul><ul><li>Present in thymic </li></ul><ul><li>medulla, tonsil and </li></ul><ul><li>blood. </li></ul><ul><li>Recognizes Ag by MHC </li></ul><ul><li>class II molecules. </li></ul>CD8(35%): Cytotoxic activity on virus- infected cells, Allograft cells and tumor cells.
  23. 23. <ul><li>Immunologically competent cells ( I C C ) : </li></ul><ul><ul><li>Lymphocytes which are educated by central </li></ul></ul><ul><ul><li>lymphoid organs. </li></ul></ul><ul><ul><ul><li>Recognizing capacity of antigen. </li></ul></ul></ul><ul><ul><ul><li>Storage of immunological memory. </li></ul></ul></ul><ul><ul><ul><li>Immune response to specific antigen. </li></ul></ul></ul>
  24. 24. Functional cell
  25. 25. <ul><li>Regulatory functions of T cells. </li></ul><ul><li>Regulation of antibody production by </li></ul><ul><li>B- cells. </li></ul><ul><li>Stimulation of helper and cytotoxic T cells to participate in CMI by the production of IL-2. </li></ul><ul><li>Imbalance between T4 and T8 cells results in Autoimmunity or immunodeficiency. </li></ul>
  26. 26. <ul><li>Effector functions: </li></ul><ul><li>Cytotoxicity of CD8 cells. </li></ul><ul><li>Activates macrophages to mediate delayed </li></ul><ul><li>hypersensitivity. </li></ul><ul><li>To produce memory T cells. </li></ul><ul><li>Destroy the virus- infected cells. </li></ul><ul><li>Graft rejection, tumor destruction. </li></ul>
  27. 27. Cells, with ability to respond rapidly for many years after the initial exposure to an antigen. <ul><li>Characteristic features: </li></ul><ul><li>Live for many years. </li></ul><ul><li>Enhanced secondary </li></ul><ul><li>response. </li></ul><ul><li>Activated by small quantity of antigen. </li></ul><ul><li>Activated memory cells </li></ul><ul><li>produce large quantities of interleukins. </li></ul>Memory cells
  28. 28. Ag + MHC protein on APC TCR on T-cell Production of IL-1 from macrophages. B7 protein on APC + CD28 on helper T-cell Production of IL-2 from T4 - cells. IL-2 is responsible for regulatory,effector and memory functions of t4 cells T-cell activation Responsible for regulatory , effector and memory functions of T-cells. CTLA-4 (Cytotoxic T-lymphocyte antigen-4 ) protein appears on T-cell surface and binds to B7 by displacing CD28 , results in inhibition of IL-2 production. T-cell homeostasis Mutant T-cells which lack CTLA-4 & responsible for autoimmune disease.
  29. 29. B – cell maturation Pro – B cell ( From Lymphoid progenitor) Pre – B cell Mature B – Cell (Virgin B-cell) Migrate to peripheral lymphoid tissue Transformed into PLASMA CELL Contact with Antigen Rearrangement of DNA . Express receptors for IgM, IgG, IgA, IgE & for hormones. . Self tolerance .
  30. 30. <ul><li>PLASMA CELLS: </li></ul><ul><ul><ul><li>Antibody secreting cell (Ig factory) </li></ul></ul></ul><ul><ul><ul><li>Usually found in the Bone Marrow, </li></ul></ul></ul><ul><ul><ul><li>Perimucosal lymphoid tissue . </li></ul></ul></ul><ul><ul><ul><li>Life span 30 days. </li></ul></ul></ul><ul><li>Some B-cells express T- cell </li></ul><ul><li>marker (CD5) on their surface – B1 cells . </li></ul><ul><li>Responsible for T -independent antibody ” </li></ul><ul><li>production in neonates. </li></ul><ul><li>Responsible for Autoimmune diseases. </li></ul>
  31. 31. T – Cell B – Cell 1). Location : Thoracic duct Spleen Thymus. 55 – 60% 96% Production, maturation: BM, Thymus B M 2). Thy antigen + - 3). CD3 receptor + - 4). Surface Ig - + 5). S RBC rosette + - 6). E A C rosette - + 7). Blast transformation with anti – CD3 + - anti – Ig - + Endotoxin - +
  32. 32. <ul><li>NULL CELLS ( Natural killer cells). </li></ul><ul><li>Large granular lymphocytes, </li></ul><ul><li>Lack CD3, surface </li></ul><ul><li>immunoglobulin markers & TCR </li></ul><ul><li>Constitutes 3-5% of </li></ul><ul><li>peripheral lymphocytes </li></ul><ul><li>Thymus not required for </li></ul><ul><li>development. </li></ul>
  33. 33. <ul><li>Functions: </li></ul><ul><li>Kills malignant cells & virus infected cells by </li></ul><ul><li>apoptosis. </li></ul><ul><li>Cytotoxicity is not M H C restricted. </li></ul><ul><li>Mechanism of killing is by cytotoxins like perforins </li></ul><ul><li>and granzymes. </li></ul><ul><li>Active in severe combined immunodeficiencies. </li></ul><ul><li>Activated by IL-2 and Interferons. </li></ul>
  34. 34. <ul><li>Antigen Presenting Cells (APC) </li></ul><ul><li>1.Macrophages: </li></ul><ul><ul><ul><li>Blood: Monocytes. </li></ul></ul></ul><ul><ul><ul><li>Tissues: Lungs - Alveolar macrophages. </li></ul></ul></ul><ul><ul><ul><li> Liver- Kupffer cells </li></ul></ul></ul><ul><ul><ul><li> Skin- Langerhans cells </li></ul></ul></ul><ul><ul><ul><li> Spleen- Sinusoidal cells. </li></ul></ul></ul><ul><ul><ul><li> Brain - Microglial cells. </li></ul></ul></ul><ul><ul><ul><li> Joints - Synovial cells. </li></ul></ul></ul>
  36. 36. <ul><li>Another variety of </li></ul><ul><li>antigen presenting </li></ul><ul><li>cells to T – cells. </li></ul><ul><li>Derived from BM. </li></ul><ul><li>Present in </li></ul><ul><li>1.Peripheral blood. </li></ul><ul><li>2.Lymph node. </li></ul>Dendritic cells.
  37. 37. Granulocytes (Microphages) Neutrophil: Phagocytic role in acute inflammation Eosinophil: Phagocytic & motile. Parasite killing with hydrolytic enzymes. Basophil: Blood and tissues(Mast cells) Not phagocytic. Receptors for Fc portion of Ig E .
  38. 38. <ul><li>TCR are unable to recognize free antigens. </li></ul><ul><li>To be cleaved into small peptides and must </li></ul><ul><li>be embedded within a specific “molecular </li></ul><ul><li>groove” (located on MHC molecule) for T-cell </li></ul><ul><li>response….. MHC restriction. </li></ul>HLA complex
  39. 39. <ul><li>HLA complex located on </li></ul><ul><li>short arm of chromosome-6 </li></ul><ul><li>Molecules coded by MHC </li></ul><ul><li>are classified into three </li></ul><ul><li>groups Class I,II and III. </li></ul>
  40. 40. 1.MHC class I molecules Fibroblasts, Hepatocytes Lymphocytes, Neuron 2.MHC class II molecules Stromal cells in BM Dendritic cells,Macrophages
  41. 41. <ul><li>Cytokines: </li></ul><ul><li>Non antibody molecules. </li></ul><ul><li>Produced by …… </li></ul><ul><li>Lymphocytes, monocytes, keratinocytes, </li></ul><ul><li>Endothelial cells and thymic epithelial cells. </li></ul><ul><li>Glycoproteins. </li></ul><ul><li>Target cells : Neutrophils </li></ul><ul><li> Macrophages </li></ul><ul><li> Lymphocytes </li></ul><ul><li> Endothelial cells </li></ul><ul><li> Fibroblasts. </li></ul>
  42. 42. <ul><li>Types: </li></ul><ul><ul><ul><li>Interleukins </li></ul></ul></ul><ul><ul><ul><li>TNF </li></ul></ul></ul><ul><ul><ul><li>Interferons </li></ul></ul></ul><ul><ul><ul><li>Colony stimulating factors . </li></ul></ul></ul><ul><li>Functions: </li></ul><ul><ul><ul><li>Control of lymphocyte growth. </li></ul></ul></ul><ul><ul><ul><li>Activation of innate immunity. </li></ul></ul></ul><ul><ul><ul><li>Control of hemopoiesis. </li></ul></ul></ul>
  43. 43. Further proceed to understand the basis of immune response