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Transcript
Immunogenetics The immune system has two ways of recognizing antigens: B-cells recognize intact antigens using immunoglobulin (antibody) as their receptor T-cells have evolved to recognize antigens originating from within other cells using their T-cell antigen receptors (TCRs) Red blood cells have antigens on their surface known as red-cell antigens made up mainly of glycoproteins Each blood group belongs to a different locus Antibodies against most red blood cell groups are produced only following a challenge with the appropriate antigen. Exceptions are: J system in cattle AB system in cats transfusions were inconsistent with many recipients in that their body had strong rejection responses to the transfused blood Only later was blood correctly matched from donor to recipient due to the discovery of blood group systems Blood systems include the ABO group, Rh factor etc. Our knowledge of the ABO and Rhesus blood groups has resulted in safe blood transfusion This has also prevented Rhesus haemolytic disease of the newborn THE ABO BLOOD GROUPS ----------------------------------------------------------------------------------------------- ABO blood group phenotypes and genotypes ----------------------------------------------------------------------------------------------Red blood cells React with antiserum Phenotype Genotype Antibodies Antigen – A Antigen – B ----------------------------------------------------------------------------------------------O OO anti – A,B A AA, AO anti – B + B BB, BO anti – A + AB AB + + ------------------------------------------------------------------------------------------------ The rhesus (Rh) blood group system involves three sets of closely linked antigens D is very strongly antigenic and persons are either Rh positive (possessing the D antigen) or Rh negative (lacking the D antigen). A proportion of women who are Rh negative have an increased chance of having a child who will either die in utero or be born severely anemic because of haemolysis unless transfused in utero (i.e.. lysis of red blood cells) an Rh-negative mother carrying an Rh positive fetus can induce the formation of Rh antibodies in the mother. In pregnancy these antibodies can cross the placenta and enter the fetal circulation. This leads to haemolysis of the fetal red blood cells if the fetus is Rh positive Therefore Rh-compatible blood must be always be used in any blood transfusion 1. 2. 3. The MHC plays a central role in the immune system MHC molecules occur in three classes: class I molecules occurring on virtually all cells and which are responsible for recruiting cytotoxic T cells class II molecules that occur on B cells and macrophages and are involved in signaling T helper cells to recruit further B cells and macrophages class III molecules that include a number of other proteins with a variety of other immunological functions. Name Function Expression MHC class I Encodes heterodimeric peptide-binding proteins, as well as antigen-processing molecules such as TAP and Tapasin. All nucleated cells. MHC class I proteins contain an α chain & β2-micro-globulin (not part of the MHC). They present antigen fragments to cytotoxic T-cells via the CD8 molecule and also bind inhibitory receptors on NK cells. MHC class II Encodes heterodimeric peptide-binding proteins and proteins that modulate antigen loading onto MHC class II proteins in the lysosomal compartment such as MHC II DM, MHC II DQ, MHC II DR, and MHC II DP. On most immune system cells, specifically on antigen-presenting cells. MHC class II proteins contain α & β chains and they present antigen fragments to T-helper cells by binding to the CD4 receptor on the T-helper cells. MHC class III regi on Encodes for other immune components, such as complement components (e.g., C2, C4, factor B) and some that encode cytokines (e.g., TNF-α) and also hsp. Variable • The genes encoding class I, II and III molecules are known as the Human Leukocyte Antigen (HLA) system •success of transplants depends on the degree of antigenic similarity between the donor and recipient •antigenic similarity of donor and recipient has to be assessed by testing them with suitable antisera •The HLA system is highly polymorphic, two unrelated individuals are therefore very unlikely to have identical HLA phenotypes •A finding which helps to throw light on the pathogenesis of certain diseases is the demonstration of their association with certain HLA types • e.g. In the case of narcolepsy (a sleeping sickness) almost all affected individuals are HLA DR2. •In general, the mechanisms involved in most HLA disease associations are not well understood. Innate immunity system - is a roving military patrol unit that is continuously observing and circling the body’s system for any imbalances The adaptive immunity system - is like a sniper that has specific targets, plans an attack, and has learned from prior experience with the targets how to assassinate them. Searches for antigens continuously by identifying infectious organisms that have entered the body Works rapidly to destroy the organisms in the same manner each time the innate immune system comes across a foreign organism No increase in the amount of time that it takes to destroy the infectious organism based upon the frequency of encounters. Uses skin and mucous membranes, bloodborn molecular enzymes, lymphocyte cells, inflammatory properties, and phagocyte cells on order to scan and destroy the organisms. more rapid immune response as they specifically target the area needing attention immune response takes place upon exposure to an antigen that is familiar and this is the reason why immunizations are given to children prior to exposure to life threatening diseases such as polio unclear if there has been a determining factor as to why there is an ability of T-cells to gain memory in the adaptive immunity process the humoral response - B cells secreting antibodies to neutralize, clump, and stimulate the destruction of pathogens by recognizing and binding specific foreign antigens. Antibodies - Y-shaped polypeptides with constant and variable regions. the cellular immune response - helper T cells that stimulate B cells to produce antibodies and cytotoxic T cells to secrete cytokines. Some T cells bind to non-self cells and virus covered cells and allow them to burst. AIDS- Acquired virus replicates and kills Tcells important for immune function FIV in cats- lentivirus causing immunosuppression Transmitted via biting (fights) Recurrent absesses, mouth infections etc Arabian foals (SCID) Abnormal reaction to allergens Histamines and leucotrienes Mast cell inhibitors Feline rhinotracheitis, skin dermatitis in dogs (food allergy related) Special diets formulated (eg Hill’s Prescription Diet z/d) Immune system of animal attacks organs and tissues of that animal Antigens, antibodies or immunogenesis Retained fetal cells Mutations in certain genes may show as an autoimmune disease Hemolytic anaemia, lupus erythematosis, polyarthritis, immune-mediated thrombocytopenia where immune system destroys cells responsible for blood clotting Vaccines: These are disabled pathogens or their parts that elicit an immune response, protecting against infection by the active pathogen Uses immune system component to fight disease. Hybridomas are artificial cells that consists of a B-cell fused with a cancer cell and produce monoclonal antibodies (Mabs) that can target specific antigens. Cytokines boost immune function and destroy cancer cell. Organ transplant is the moving of an organ from one body to another or from one part to the other in the same body, for the purpose of replacing the recipient’s damaged organ. Problem: Organ Rejection where the body has an immune response to an organ which causes failure to the transplant. Types of Transplants Autograft transplant of tissue to the same person, e.g. skin graft. Allograft transplant of an organ or tissue between two non-identical members of the same species Isograft transplant of organ or tissue between genetically identical twins. Xenograft transplant from one species to another The success rate of transplants is improved by the use of immunosuppressor drugs, by stripping antigens from donor tissue, and by matching donor to the recipient. Examples of immunosuppressor drugs Calcineurin inhibitors- Cyclosporin It is an adaptive immune response and is mediated through both T-cell mediate and humoral immune (antibodies) mechanism. 1. Innate Anatomical features - function as a barrier to infection. Mediated by phagocytes. 2. Acquired Elimination of pathogens - late phase of infection. Generation of immunological memory. 1. 2. 3. Mutual evolution of microbe-victim ecological system. 3 systems of Immunogenesis Constitutional Phagocytic Lymphatic Pathogenicity of microbes – depends on genetically-determined molecular structure of targets in the potential victim. Evolution of an epidemic process: transformation of a population in the fight against infectious agent (Rumyantsev, 2002, modified).