Microbiology - Adaptive Immunity and MHC - PDF

Adaptive immunity and MHC LECTURE (5) Adaptive immunity & MHC 1  Adaptive immunity and MHC  Secreted antibodies.  Defense against extracellular...

Adaptive immunity and MHC LECTURE (5) Adaptive immunity & MHC 1  Adaptive immunity and MHC  Secreted antibodies.  Defense against extracellular microbes and microbial toxins.  Blocks and prevent binding of microbe to cells i.e. prevent infection of cells.  Block binding of toxin to cellular receptors → inhibit pathologic effects of toxin.  Inhibit spread of microbes from an infected cell to an adjacent cell.  Antibodies of IgG isotype opsonize (coat) microbes.  Bind to infected cells by Fab regions, and bind by Fc to Fc receptors on NK.  NK cells are activated → kill the cells.  Bind to helminthic parasites by Fab regions, and bind by Fc to Fc receptors on eosinophils.  Eosinophils are activated to release their granule contents → kill parasites. 2  Adaptive immunity and MHC  IgA is the major class that is produced  Neonates are protected from infection by mucosa-associated lymphoid by maternal antibodies (IgG) tissues (MALT) in GIT and RT and transported across placenta into fetal transported to lumens of organs. circulation and by antibodies in ingestd  In mucosal secretions, IgA binds to milk transported across the gut microbes and toxins present in the epithelium of newborns. lumen and neutralize them by blocking their entry. 3  Adaptive immunity and MHC  When we are exposed to an antigen  If at a later date we are re-exposed to for the first time: the same antigen, there is: Lag of several days (10 days) before More rapid appearance of antibody, specific antibody becomes Greater amount. detectable. This antibody is IgM. IgG class. After a short time, the antibody Remains detectable for months or level declines. years. Slow in Onset Rapid in Onset Low in Magnitude High in Magnitude Short Lived Long Lived IgM IgG (Or IgA, or IgE) 1. If at the same time that we are re-exposed to an antigen, we are exposed to a different antigen for the first time, the properties of the specific response to this antigen are those of the primary response. ‫يف اإلعادة افادة‬ 2. This phenomenon is possible because the immune system possesses specific immunologic memory for antigens. 3. During primary response, some B lymphocytes, become memory cells which are long lived. 4. Secondary response requires the phenomen known as class switching (IgM to IgG). 4  Adaptive immunity and MHC Eradicates infections by intracellular microbes. Consist of the activation of naïve T cells to proliferate and differentiate into effector cells (CD4+ T helper cells and CD8+ cytolytic cells; CTLs) and the elimination of the intracellular microbes.  Differentiate into 2 effector cells according to cytokine production by antigen presenting cell:  Th1 secrets: IFN-g activates  Th2 secrets: IL-4 and IL-5 which phagocytes to kill microbes. stimulate eosinophil and mast cell degranulation in allergy and helminthic infection  Kill any cell containing microbes or microbial proteins in the cytoplasm (intracellular) by direct cell cytotoxicity, eliminating the reservoir of infection.  Peptide + MHC on the surface of APCs recognized by TCR-CD3.  Is the interaction of B7 molecule on APCs with CD28 on T cells.  In absence of 2nd signal, exposure of T cells to antigen lead to anergy (unresponsiveness). 5  Adaptive immunity and MHC 1. CTLs recognize class I MHC + peptides on the surface of infected “target” cell”. 2. Formation of tight adhesions “conjugates” with these cells. 3. CTLs are activated by IL-2 & IFN-γ to release their granule contents toward the target cell i.e. granule exocytosis. 4. The granules contents include: Perforin: which form pores in the target cell membrane Granzymes: enter the target cells through these pores and induce apoptosis through the activation of caspases. 5. Detachment of CTL from target cells to kill other target cell. 6. Death of target cell. 6  Adaptive immunity and MHC  Group of genes on short arm of chromosome 6  Produce MHC molecules present on cell surfaces and responsible for display of protein Ag to T cell Also called human leucocytic Ag = HLA  HLA-A & HLA-B & HLA-C → role in Ag presentation to Tc.  HLA-D region (HLA-DR & HLA-DP & HLA-DQ) → role in Ag presentation to Th.  Lies between class I & II & not produce MHC but produce some complement components & TNF-α.  Membrane proteins expressed on cells.  Each class I & II molecule consist of extracellular part, a transmembrane and a cytoplasmic part to anchore the molecule to the cell. 7  Adaptive immunity and MHC  2 polypeptide chains, α chain  2 polypeptide chains α chain formed of 3 domains (α1, α2, α3), (α1 & α2) and β chain (β1 & attached to a polypeptide chain β2). called β2 microglobulin encoded by a gene outside MHC.  α1 and α2 domains form the cleft  α1 and β1 domains form the or groove which bind peptide. peptide binding cleft.  Present antigen to CD8+ cells.  Present antigen to CD4+ cells.  Class I molecules are expressed  Class II is expressed on APCs on all nucleated cells. only. 8  Adaptive immunity and MHC  A 65 years old man suffering from chronic renal failure. He undergone kidney transplantation from his blood group matched friend.  After 2 weeks suffering from continuous rises in creatinine level, he was told that he will be subjected to renal dialysis again. What is the proper diagnosis. What test should you concentrate on next operation for this man? 9