Ab 4.24.45 PM - Antibodies or Immunoglobulins Antibodies...

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Unformatted text preview: Antibodies or Immunoglobulins Antibodies * Definition: Glycoprotein in serum and tissue fluid * Produced by: B­lymphocytes in response to exposure to antigen * React specifically with antigen * Five classes of Antibodies: IgG IgM IgA IgD IgE IgG IgG Properties • • • • • Major serum Ig Major Ig in extravascular spaces The only Placental transfer Ig Fixes complement Phagocytes ­ opsonization IgM IgM Properties First Ig made by fetus and B cells Present in colostrum and mother milk protect newly born. • Fixes complement • • IgA IgA ­Found in serum and body secretion: Tears, saliva, gastric and pulmonary secretions • Major secretory Ig on Mucous surfaces give Local Immunity by coating m.o, bacteria or viruses preventing their adherence to mucosal cells • Does not fix complement (unless aggregated) • Present in colostrum and mother milk protect newly born. IgE IgE • Least common serum Ig • • Binds to basophils and mast cells (Does not require Ag binding) Allergic and hypersensitivity reactions Parasitic infections (Helminths) Binds to Fc receptor on eosinophils • Does not fix complement IgD IgD • • • Present in very small amount in serum B cell surface Ig Does not bind complement Antibody Production Antibody Clonal selection theory: *B­cells display immunoglobulin molecules on surfaces *Immunoglobulin serve as receptors for specific antigen *The antigen binds to immunoglobulin receptor of B­cells *B­cells is stimulated to divide and form a clone *B­cells become plasma cells and secrete antibodies *Some stimulated B­cells revert to small lymphocyte (memory cells) *Memory cells proliferate on re­exposure to same antigen Activation of B-cells Activation Two mechanisms: 1) T­dependent antigen: . Most antigen require T­helper cells to activate B­cells . Antigen is phagocytosed by macrophages or B­cells . Macrophages or B process present Ag to T­cells . These activate T­cells to produce lymphokines . lymphokines (IL­2,IL­4,IL,5) stimulate B­cells to divide and differentiate into plasma cells specific antibody . Plasma cells form or differentiate into memory cells . All classes of antibody (IgG,IgM,IgA,IgD,IgE) are T­cell dependant Activation of B-cells Activation 2) T­independent antigens: . Activation of B­cells directly without help of T­cells (e.g. bacterial capsular polysaccharides) . IgM antibody is primarily produced Antibody Structure Antibody Immunoglobulins are glycoproteins made up of ­ Four polypeptid chains (IgG): a­ Two light (L) polypeptide chains b­ Two heavy (H) polypeptide chains ­ The four chains are linked by disulfide bonds ­ Terminal portion of L­chain contains part of antigen binding site ­ H­chains are distinct for each of the five immunoglobulins ­ Terminal portion of H­chain participate in antigen binding site ­ The other (Carboxyl) terminal portion forms Fc fragment ANTIBODY STRUCTURE ANTIBODY An antibody molecule is composed of two identical Ig heavy chains (H) and two identical light chains (L), each light with a variable region (V) & constant region (C). Amino acid sequences were determined from myeloma proteins. Fig. 1-17,1-16 Variable(V) and Constant (C) Regions ­ Each H­chain and each L­chain has V­region and C­region ­ V­region lies in terminal portion of molecule ­ V­region shows wide variation in amino a. sequences ­ Hypervariable region form region complementary to Ag determinant ­ It is responsible for antigen binding ­ C­region lies in carboxyl or terminal portion of molecule ­ C­region shows an unvarying amino acid sequence ­ It is responsible for biologic functions Antibody Fragments Antibody Fab fragment: antigen binding site Fc (crystallizable fragment): a­ Complement fixation (IgM and IgG) b­ Opsonization (IgG) C­ Placental attachment (IgG) d­ Mucosal attachment (IgA) e­ Binding to mast cells (IgE) Properties of Immunoglobulins Properties Property IgG IgA IgM IgE IgD µ ε δ γ α symbol Molecular 150 170­400 900 190 180 weight KDa KDa KDa KDa KDa Percentage 75 % 15 % 10 % 0.004 % % 0.2 in serum Complement Yes No Yes No No fixation Transplacental Yes No No No No passage Opsonization No No No No Heavy chain Yes Antibody Diversity Antibody *Immunoglobulins are protein (antigenic) *Immunoglobulins subdivided into : a­ Isotypes: Antigenic difference in C­region five immunogl. classes are different isotypes b­ Idiotypes: Ag difference in V­region of immunogl. c­ Allotypes: Antigenic feature of immunogl. that vary among individual under genetic control Ag difference in C­region of H and L chain Primary and Secondary antibody response Primary Primary antibody respone Secondary antibody response * first exposure to antigen * Subsequent exposure * lag period: days or weeks * Lag period: hours (slow onset) (rapid onset) * Small amount immunogl. * large amount immunogl. low Ab level with gradual increase high Ab with rapid increas * Ab Persist for short duration * Persist for long periods Weeks then decline rapidly (monthes or years) * Antibody is IgM * Antibody is IgG Primary and Secondary antibody response Primary Secondary response to Ag Amount of antibodies in serum Primary response to Ag 1 2 3 4 5 6 Time (months) 1st injection of Ag 2nd injection of Ag ...
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