lect 5- biochemistry- Immunoglobulin structure (1)_.pdf

1 Immunoglobulin (IG)  IMMUNOGLOBULINS (Antibodies)  Glycoproteins present in gamma globulin fraction of plasma (Gamma-globulin).  Produced by B-Lymphocytes (plasma cells) in response to exposure to an antigen to react specifically with antigen.  Each Antibody has at least...

1 Immunoglobulin (IG)  IMMUNOGLOBULINS (Antibodies)  Glycoproteins present in gamma globulin fraction of plasma (Gamma-globulin).  Produced by B-Lymphocytes (plasma cells) in response to exposure to an antigen to react specifically with antigen.  Each Antibody has at least 2 antigen binding sites. 3  Basic unit (monomer) of the Immunoglobulin Four polypeptide chains (Y-shaped tetramer):  Two identical heavy (H) polypeptide chains  Two identical light (L) polypeptide chains. 4  Heavy chains (H) -They have a molecular weight 50-75 kDa (400 amino- acids) approximately twice of that of the light chain. -The amino acid differences in the carboxyl terminal portion of the H chains identify five different classes (isotypes). -These classes (isotypes) are: IgG = ( γ ), IgA = ( α ), IgM = ( μ ), IgD = ( δ ), and IgE = ( ε ). 5  Light chains (L) -have a molecular weight of approximately 23 kDa and are composed of about 212 amino acids. - L chains are of two types κ (kappa) and λ (Lambda) based on their structural differences. -All immunoglobulins classes have both κ and λ chains 6  Disulfide bonds Interchain bonds :  between H chains (H-H)  between H and L chains (H-L) Intrachain bonds :  within an individual chain 7  IG domains  Each H chain has four or five domains, one in the variable region (VH) and three or four in the constant region (CH1, CH2, CH3, and CH4).  Each L chain has two domains, one in the variable region (VL) and one in the constant region (CL). 8  Antigen binding site (paratope)  Area of the immunoglobulin molecule which interacts specifically with the epitope of the antigen.  The two antigen-binding sites are formed by the paired VH and VL domains at the ends of the two arms of the Y tetramer 9  Immunoglobulin classes Ig G IgM IgA IgD IgE Type of Heavy γ (Gamma) μ (Meu) α (alpha) δ (delta) ε (epsilon) chain Structure Monomer Pentamer Monomer Monomer Monomer (serum) , Dimeric (secretory ) Placental Pass Not pass Not pass Not pass Not pass transfer 10 Immunoglobulin classes 11  Immunoglobulin digestion 2 enzymes can digest the immunoglobulin molecule: a) Papain enzyme: digest Ig into 2 antigen binding fragment (2 Fab) and 1 crystallizable fragment (Fc) b) Pepsin enzyme: digest Ig into1 antigen binding fragment F(ab)2 and digested fragments of Fc. 12  Clinical correlates 1- Multiple Myeloma  Plasma cell cancer (plasmacytoma)  Females are mor susceptible than males  This results in overproduction of abnormal Ig mostly IgG (75%) , and in some cases (25 %) IgA or IgM. 13  Clinical correlates Bence jones proteinuria  free light chain proteinuria (Bence Jones proteinuria)  is seen in patients with light chain myeloma (where there is a monoclonal expression of the light chain without a coexisting heavy chain), in approximately 50% of those with IgG and IgA myeloma 14