humoral immunity.pdf

Basic immunology Done by Dr Radwa Mahmoud Elsharaby Assistant professor of clinical pathology Infection control specialist in Tanta university hospitals Faculty of medicine Tanta university Humoral immunity (HI) ilos Define immunoglo...

Basic immunology Done by Dr Radwa Mahmoud Elsharaby Assistant professor of clinical pathology Infection control specialist in Tanta university hospitals Faculty of medicine Tanta university Humoral immunity (HI) ilos Define immunoglobulin Describe structure of antibodies Enumerate function of immunoglobulin Discuss primary and secondary immune response Define monoclonal antibodies Definition of Antibody Group of glycoproteins present in the serum and tissue fluids of all mammals. They bind specifically to the antigen that induced their production Humoral immunity Mediated by antibodies synthesized by B lymphocytes and secreted by their fully differentiated end cells, the plasma cells.  B cell activation & production of antibodies T cell dependent activation Occurred when antigen is protein in nature (Most antigens), here, B cell acts as APC. B cell needs the help of T lymphocyte to be activated. T cell independent activation(without the help of T cell): Occurred when antigen is non protein in nature because these molecules are not processed and presented by APCs and hence do not activate Th cells. These polysaccharides act as a multivalent antigen that cross-links the IgM antigen receptors on the B cell and activates it (no memory cells). Structure of Immunoglobulins or Antibodies:  Light chains: There are two antigenic types called kappa (K) and lambda (A.). Only one type of light chain is found in any individual molecule The basic immunoglobulin unit (monomer) consists of Heavy chains: There are five main types; gamma (γ), alpha 4 polypeptide chains (α), mu (µ), delta (δ) and epsilon (ε) 1.between the heavy and light chains, the two heavy chains and within each of the polypeptide chains. Disulfide bonds  a.Light Chain - VL and CL Variable (V) Heavy Chain - VH and 3 CH and Constant (C) Regions region at which the arms of the antibody molecule form a Y. a) Fab: This fragment (whole L & 1/2 of H) is called the Fab fragments because it contains the antigen binding sites of the antibody. b) Fc: This fragment (remainder of the two H chains) is called Fc Hinge Region because it was easily crystallized. The effector functions of immunoglobulins are mediated by this part of the molecule. General functions of immunoglobulins: Ag binding Activation of complement → lysis of cells (Ag). Opsonization: if the organism is coated by its specific antibody ). Antibody dependent cellular cytotoxicity (ADCC): destruction of antibody coated target cells by NK cells, macrophages or polymorphs (receptors for IgG) and eosinophils (receptors for IgE; anti-parasite). Different classes of immunoglobulins Dimer Monomer Pentamer  Human immunoglobulin classes 1- IgG - Gamma heavy chains Structure Properties and functions A)The major Ig in serum (75% of serum Ig) monomeric unit. b) The major Ig in 2ry immune response c) It is the only class of Ig that crosses the placenta through Fc receptor on placental cells. d) Activate complement. e) Opsonisation: by Macrophages, PMN's and NK cells (Fc receptors for IgG). f) Rh antibodies are IgG. 2- IgM - Mu heavy chains Structure Properties and functions a) The 3rd most common serum Ig (7% of IgM normally exists as a serum Ig). pentamer with extra structure b) The major Ig in 1ry immune response termed J chain (on B- c) Cannot cross the placenta lymphocytes it is present as a monomer for Ag receptor). d) Activate complement e) Good agglutinating Ig.. f) The antibodies of ABO blood groups. 3- IgA - Alpha heavy chains Structure Properties and functions Serum IgA is a monomer IgA found in secretions is a a) Serum IgA is the 2nd most common dimer with a J chain and serum Ig (15% of serum Ig). secretory piece, synthesized in b) Secretory IgA present in all secretions epithelial cells, which protects as tears, saliva, colostrum, mucus and is it from the digestive effects of important in local (mucosal) immunity the enzymes. by inhibiting binding of the pathogens to the mucosal cells. 4- IgD - Delta heavy chains Structure Properties and functions a) IgD is found in low levels in serum. monomer. b) IgD is found on B cell surfaces where it acts as a receptor for antigen. 5- IgE - Epsilon heavy chains Structure Properties and functions a) IgE is the least serum Ig since it binds very tightly to Fc receptors on basophils monomer. and mast cells. b) Type I hypersensitivity. c) IgE also plays a role in the immunity against parasitic infections. Eosinophils have Fc receptors for IgE and binding of eosinophils to IgE-coated helminths results in killing of the parasite (ADCC).  primary immune response The first exposure of an individual to a foreign antigen result in the development of an immune response that takes an induction period of a week or two (lag phase )to provide detectable levels of antibody (IgM mainly), then declines rapidly to undetectable levels  Secondary immune response A second exposure to the same antigen after the primary immunity has developed leads to a very rapid and steeply rising level of antibody (IgG mainly) that persists at a plateau for weeks or months, this is due to the presence of immunological memory cells Monoclonal antibodies DIFENETION highly specific antibodies produced against single epitope. FORMATION They are obtained by fusion of a B-cell producing antibody against a single epitope and a myeloma cell (malignant plasma cell).The resulting fused cell is called hybridoma cell. This hybridoma cell has the ability to produce unlimited quantities of highly specific monoclonal antibodies  Applications: 1- Lymphocyte subsets determination. 2- HLA typing. 3- Anti-tumor therapy by using monoclonal antibodies to tumor markers (Magic bullet therapy). 4- Specific immunosuppressive therapy to prevent graft rejection.