1 / 77

Structure & Function of Immune System

Structure & Function of Immune System. Cells of the Acquired Immune System. Lymphocytes Antigen presenting cells (APCs). Subsets of Lymphocytes. 2 subsets : T cells B cells T cells are thymus derived. B cells are bone marrow derived.

beckyperez
Download Presentation

Structure & Function of Immune System

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Structure & Function of Immune System

  2. Cells of the Acquired Immune System • Lymphocytes • Antigen presenting cells (APCs)

  3. Subsets of Lymphocytes • 2 subsets : T cells B cells • T cells are thymus derived. • B cells are bone marrow derived. • B cells : ability to synthesise proteins called Immunoglobulins (Igs). Each Ig can bind specifically & with high affinity to a particular Ag.

  4. Lymphopoiesis • Occurs in yolk sac, fetal liver then bone marrow throughout rest of life • Mature, naïve B cells released into circulation • B cell production occurs throughout life; does not wane as does T cell production • About 5 million produced per day • Only 10% of B cells mature • Naïve B cells survive about one week • Undergo negative selection

  5. B Cell Development Maturation-Stem cells to mature, naïve B cells Activation-Ag binding; initiation of cell changes Differentiation-Cell division and changes into effector B cells (plasma cells) and memory B cells

  6. B Cell Changes • Pro B cells • Rearrangement of Ig heavy chaingenes • Expression of CD45R and CD19 • Further maturation is dependent on direct interaction with BM stromal cells

  7. B Cell Changes • Pre B cells • Cell division occurs • Rearrangement of Ig light chaingenes • Expression of IL7 receptor • Expression of mu heavy chains • Shuts down further Ig gene rearrangement

  8. B Cell Changes • Immature B cells • IgM expressed on surface • B cell receptor appears • Cells interact with self Ags • Negative selection (clonal deletion) occurs

  9. B Cell Changes • Mature B cells • Migrate out of bone marrow • Both IgM and IgD expressed on surface • Cell division occurs

  10. B Cell Activation • Triggered by combining with Ag • Two types of Ags that activate B cells • Thymus dependent Ag e.g. soluble proteins • Thymus independent Ag • Type 1, e.g. LPS • Type 2, e.g. capsular polysaccharides

  11. B Cell/T Cell Interaction

  12. B Cell Subsets • B1 • CD5 marker • Seen in peritoneum IN NEONATES • Produce natural IgM antibacterial antibodies • B2 • Most B cells (95%) • Drive the Ag response in secondary lymphoid organs

  13. Functions of B cells • Chief cell type in humoral immunity. • Function as Ag Presenting Cells. • Secrete lymphokines & other factors that influence the growth and activities of other immunologically important cells.

  14. LYMPHOCYTES • Small, round cells present in the peripheral blood, lymph, lymphoid organs and in many other tissues. • Constitute 20-45% of leucocytes in the peripheral blood. • Major cell types in lymphoid organs. • 1012 lymphocytes in human body & only 1% of it is present in the blood.

  15. ‘T’ CELL MATURATION

  16. Thymic Selection Processes • Thymocytes are in the Double Positive State (i.e. express both co receptors. • Positive and Negative Selection necessary to produce an effective T-Cell repertoire. MHC Restriction - T cells responds to processed Ags on APC ONLY when they are presented along with the SELF- MHC Ag

  17. Positive Selection • Results in MHC restriction • Mechanism: • Immature thymocytes cluster with MHC molecules on the cortical cells of the thymus • If TCR interacts with MHC  protective signal results that prevents apoptosis. • If TCR does not interact with MHC  no protective signal and apoptosis occurs.

  18. Express MHC I 4- 8- 4+/- 8+ 4+ 8+ TCR low 4+ 8+ TCR low 4+ 8+ TCR low 4+ 8+ TCR low 8+ TCR high 8+ TCR high 4+ TCR high 4+ TCR high Express MHC II No MHC engagement apoptosis Self MHC Restriction in the Thymus

  19. T cell types Based on their surface markers, MHC restriction, target cells & function; following T cell subtypes are recognised- • Regulatory cells- Helper cells (CD4 cells) Suppressor cells (CD8 cells) - balanced activity results in optimal response. - over activity of helper T cells & low suppressor cell activity – Autoimmunity - decreased helper T cell activity & increased suppressor T cell activity – Immunodeficiency • Effector T cells – Cytotoxic T cells - Delayed type hypersensitivity (DTH) cells - Mixed lymphocyte reactivity cells (MLR) cells

  20. Helper T cells CD4 marker and MHC II restriction TH1 cells: • Produce Cytokines Interferon gamma (IFNγ) & IL2, which activate macrophages and T cells promoting CMI, • Destruction of target cells and killing intracellular microbes. TH2 cells: • Produce cytokines IL 4, 5 & 6 which stimulate B cells to form antibodies

  21. Cytotoxic T cells: - CD8surface marker and MHC class I restriction. - Can kill and lyse specific target cells eg. Viral infected cells, tumor cells, allograft.

  22. T supressor cells (Ts): CD8 marker • block immune response by their action on T-helper or B-cells DTH cells: -Type of Th1 cells - secretes different lymphokines (γ-interferon) - Responsible for Type IV hypersensitivity

  23. Null cells • Also called large granular lymhocytes (LGL) • Double the size of small lymphocytes • Indented nuclei & abundant cytoplasm • Several azurophilic granules composed of mitochondria, ER, GA & ribosomes • Three types - Natural Killer cells (NK cells) - Ag dependent Cytotoxic cells (ADCC) - Lymphokines activated killer (LAK) cells

  24. Natural killer cells • Cytotoxicity towards various target cells mainly tumor & virus infected • Cytotoxicity not Ab dependent or MHC restricted • Normally active in SCID • Their activity is augmented by interferon • Important in immune surveillance & natural defence against virus infected & malignant mutant cell

  25. CD16 & CD56 Bind to GP receptor on the surface of target cells Release of cytolytic factor, PERFORIN Transmembrane pore Cytotoxic factors mainly TNFβ enter to cell Apoptosis of cells

  26. Antigen dependent cytotoxic cells (ADCC) • Subpopulation of LGL • Surface receptor for Fc part of Ig • Capable to kill target cell sensitized with IgG

  27. Lymphokine activated killer cell (LAK) • NK lymphocytes treated with IL2 • Cytotoxic to wide range of tumor cells without affecting normal cells

  28. Phagocytic cells: • Mono nuclear Macrophages, • Polymorpho nuclear microphages eg. Neutro, Eosino, Basophil • Mono nuclear Macrophages • -Originate in BM & become monocytes in six days • -Monocytes: - In blood, 12-15μm, half life 3 days - Macrophages • Named Based on Tissue They Reside • Alveolar (lungs), Kupffer (liver), • Microglial (brain), Osteoclasts (bone)

  29. Function of Macrophage • Phagocytic response: • Fusion of phagosome with lysozomes forming phagolysosome • Lysosmal enzymes digest the particles,. some bacteria resist (Myc Tub, myc Leprae etc.) • Antigen processing and presentation: • ‘T’ dependant Ag need to be presented by APC

  30. Function of Macrophage (Contd.) • Cleaved particles along with MHC Mol. (MHC I and II) attract ‘T’ cells with complementary receptor (MHC restricted) • Cytokine Production: • Secrete a number of biologically active substances (IL-1, IL-6, CSF hydrolytic enzymes etc.). • Initiates inflammation (Pyrogen, prostaglandin, compliment, and clotting factors) • Tissue repair (enzymes and growth factor)

  31. Antigen Presenting Cells • Heterogenous group of cells which process & present Ags to the T cells. • Major APCs : Macrophages • Others : Dendritic cells, B cells, Langerhans cells in skin.

  32. MAJOR HISTOCOMPATIBILITY COMPLEX • Its discovery was based on transplantation experiments • First work done by GORER in 1930 on the Ag responsible for allograft rejection in inbreed mice • Snell, Dausset and Benacerraf was awarded the Nobel Prize for their work on MHC and the genetic control of immune system

  33. This is cell surface Ag that evoke immune response to an incompatible host resulting in allograft rejection • The H2 Ag system are found to be the major histocompatibility Ag for mice • This Ag is coded for by a closely linked multiallelic cluster of genes called MHC

  34. These alloantigens are present on surface of leucocyte in man are called human leucocyte Ag (HLA) and set of genes coding for them is called the HLA complex

  35. HLA COMPLEX • Gene for this complex are located on chromosome 6 • Pleomorphic • HLA loci are multiallelic • It consists of three separate cluster of gene - Class I: A, B & C loci - Class II: DR, DQ, & DP loci - Class III: Genes for C2, C4, Properdin factor B, Heat shock proteins & TNF α and β

  36. HLA complex loci on chromosome

  37. Human HLA Loci Class I Loci Equivalent toK, D, and L in Mice Kuby, 6th Edition, Figure 8.01, Bottom Half

  38. Structure of MHC I and MHCII Class II Class I Ch. 8

  39. MHC-encoded -chain of 43kDa • -chain anchored to the cell membrane 2 1 2m • Peptide antigen in a groove formed from a pair of a-helicies on a floor of anti-parallel b strands 3 • 2-microglobulin, 12kDa, non-MHC encoded, non-transmembrane, non covalently bound to -chain Overall structure of MHC class I molecules • 3 domain & 2m have structural & amino acid sequence homology with Ig C domains Ig GENE SUPERFAMILY

  40. MHC I: Biological function 44

  41. HLA class I Ag present on surface of all nucleated cell. • Ags recognisation to CD8 cell • Principal Ags involved in graft rejection & cell mediated cytolysis • May functions as component of hormone receptor

  42. HLA II • More restricted in distribution being found only on macrophages, dendritic cells, activated T cells & B cells • Ags recognisation to CD4 cell • Regulate the immune response • Responsible for graft Vs host reaction & mixed leucocyte reaction

  43. MHC-encoded, -chain of 34kDa and a -chain of 29kDa 1 1 a and b chains anchored to the cell membrane 2 2 Peptide antigen in a groove formed from a pair of a-helicies on a floor of anti-parallel b strands Overall structure of MHC class II molecules No b-2 microglobulin 2 & 2 domains have structural & amino acid sequence homology with Ig C domains Ig GENE SUPERFAMILY

  44. MHCII: Function 50

  45. Tissue MHC class I MHC class II T cells +++ +/- B cells +++ +++ Macrophages +++ ++ Other APC +++ +++ Thymus epithelium + +++ Neutrophils +++ - Hepatocytes + - Kidney + - Brain + - Erythrocytes - - Differential distribution of MHC molecules • Cell activation affects the level of MHC expression. • The pattern of expression reflects the function of MHC molecules: • Class I is involved in the regulation of anti-viral immune responses • Class II involved in regulation of the cells of the immune system • Anucleate erythrocytes can not support virus replication - hence no MHC class I. • Some pathogens exploit this - e.g. Plasmodium species.

  46. MHC III • Collection of genes associated with MHC • Do not code for MHC I or MHC II • Code for associated immunological molecules • complement • interferon • Tumour necrosis factor

  47. Gene C2, C4a,C4b, Bf COL11A2 CYP21,CYP21P G7a/b HSP LMP2, LMP7 TAP1,TAP2 TNF-a, TNF-b Encoded Protein Complement collagen Steroid 21-hydroxylases Valyl-tRNAsynthetase Heat Shock Protein Proteasome-like subunits Peptide transports subunits Tumour Necrosis factor Class III MHC Products

More Related