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IMMUNOGLOBULINS Immunoglobulin Classes I. IgG Structure: Monomer (m.wt 150,000) Percentage serum antibodies: 75-80% Is the major Ig in extra vascular spaces Location: Blood, lymph, intestine Half-life in serum: 23 days Complement Fixation: Yes (IgG4 does not fix complement.) Placental Transfer: Yes Known Functions:is the most versatile immunoglobulin, because it is capable of carrying out all of the functions of IG molecules: •Enhances phagocytosis •Neutralizes toxins and viruses, •Protects fetus and newborn. IgG II. IgM Structure: Pentamer (m.wt 900,000) Has an extra domain on the μ chain (CH4) & it has another protein covalently bound via an S-S bond called the J chain, This chain functions in polymerization of the molecule into a pentamer Percentage serum antibodies: 5-10% Location: Blood, lymph Half-life in serum: 5 days Complement Fixation: Yes Placental Transfer: No Known Functions: • First antibodies produced during an infection. • Effective against microbes and agglutinating antigens. III. IgA Structure: Dimer (m.wt 150,000-350,000) When IgA exits as a dimer, a J chain is associated with it. Percentage serum antibodies: 10-15% Location: Secretions (tears, saliva, intestine, milk), blood and lymph. Half-life in serum: 6 days Complement Fixation: Normally does not fix complement, unless aggregated. Placental Transfer: No Known Functions: •Localized protection of mucosal surfaces. •Provides immunity to infant digestive tract. IV. IgD u u u u u u u Structure: Monomer (m.wt 180,000) Percentage serum antibodies: 0.2% Location: B-cell surface, blood, and lymph Half-life in serum: 3 days Complement Fixation: No Placental Transfer: No Known Functions: In serum function is unknown. On B cell surface, initiate immune response. V. IgE u Structure: Monomer(m.wt 190,000) u Percentage serum antibodies: 0.002% u IgE is the least common serum Ig since it binds very tightly to Fc receptors on basophils & Mast cells even before interacting with Ag. u Location: Bound to mast cells and basophils throughout body. u Half-life in serum: 2 days u Complement Fixation: No u Placental Transfer: No u Known Functions: Allergic reactions. Possibly lysis of worms. CLINICAL IMPLICATIONS OF HUMAN IMMUNOGLOBULIN CLASSES IgG Increases in: 1) Chronic granulomatous infections. 2) Infections of all types. 3) Hyperimmunization. 4) Liver disease. 5) Severe Malnutrition. 6) Dysproteinemia. 7) Rheumatoid arthritis. Decreases in: 1) Agammaglobulinemia. 2) Lymphoid aplasia. 3) Selective IgG & IgA deficiency 4) IgA myeloma. 5) Bence Jones proteinemia. 6) Chronic lymphocytic leukemia. IgM IgM increases (in newborns) - A level of IgM above 20 mg/dl is an indication of in utero infection: 1)- rubella virus. 2)- cytomegalovirus. 3)- syphilis. 4)- toxoplasmosis. IgM increases (in adults) in: 1) Waldenström’s macroglobulinemia. 2) Trypanosomiasis. 3) Actinomycosis. 4) Malaria 5)Infectious mononucleosis. 6) Lupus erythematosus. 7) Rheumatoid arthritis. IgM decreases in: 1) Agammaglobulinemia. 2). Lymphoid aplasia. 3) IgG & IgA myeloma. 4) Dysgammaglobulinemia. 5) Chronic lymphocytic leukemia. IgA IgA increases in: 1) Wiskott-Aldrich syndrome. 2) Most cases of liver Cirrhosis 3) Certain stages of collagen & other autoimmune disorders such as rheumatoid arthritis & lupus erythematosus. 4) IgA myeloma. IgA decreases in: 1) Hereditary ataxia telangiectasia. 2) Immunologic deficiency states (e.g.:dysgammaglobulinemi a, congenital & acquired agammaglobulinemia, & hypogammaglobulinemia). 3) Malabsorption syndromes. 4) Lymphoid aplasia. 5) IgG myeloma. 6) Acute & Chronic lymphoblastic leukemia. IgD increases in: 1) Chronic infections. 2) IgD myelomas. IgE increases in: 1) Atopic skin diseases such as eczema. 2) Hay fever. 3) Asthma. 4) Anaphylactic shock. 5) IgE-myeloma. IgE decreases in: - Congenital agammaglobulinemia Immunoglobulin Structure Disulfide bond Carbohydrate CL VL CH2 CH1 VH Hinge Region CH3