Immunology Study Notes: Understanding Immunoglobulins and Their Functions, Summaries of Immunology

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GENERAL IMMUNOLOGY

STUDY MATERIAL & NOTES DECEMER 2021

Immunoglobulins (Igs)

(Antibodies)

Undergraduate student

Definition: Immunoglobulins are glycoproteins which mediate humeral or

antibody mediated immunity Production & distribution of antibodies a. In lymph node→ antigenic stimulation of B cells with help of T helper cytokines →B cell proliferate → differentiation to plasma cell which secrete antibodies → enter circulation →site of infection b. Also mature B cell in Bone Marrow express membrane bound antibodies (BCR)

Structure of immunoglobulin

Y shaped molecules of 4 polypeptide chains

• 2 identical heavy chain → each chain → 1 variable domain (VH) & 3 or 4 constant domains (CH)
• 2 identical light chain → each chain → 1 variable domain (VL) & 1 constant domains (CL)
• Each variable domain (VL or VH) contains 3 hypervariable regions called complementary determining repeats (CDR)
  • Disulfide bond connect heavy chain with light chain & heavy chain with heavy chain

Fab=fragment Ag

binding

Hinge region

Fc=fragment crystalline

CHO

Heavy chain class (isotype) switching: is the switch from one Ig isotype to another. After activation of B lymphocytes, the antigen-specific clone of B cells proliferate and differentiate into progeny that secrete antibodies; some of the progeny secrete IgM, and other progeny of the same B cells produce antibodies of different isotypes to mediate different functions and combat different types of microbes. Isotype Subtyp es

H

chain Serum conc. mg/ml Secreted form Functions IgA IgA IgA α α 3.5 Monomer, dimer, trimer Mucosal(local)immunity IgD None δ Trace None Naïve Bcell antigen receptor BCR IgE None ε 0.05 Monomer 1.Defenseagainsthelminthi cparasites 2.Immediatehypersensitivi ty IgG IgG IgG IgG IgG γ γ γ γ 13.5 Monomer 1.Opsonization, 2.Complementactivation 3.ADCC 4.2ryimmuneresponse IgM None μ 1.5 Pen tamer 1.NaïveBCR 2.1ryimmuneresponse 3.Complementactivation

IgM

• 5-10% of serum immunoglobulin
• IgM (also IgD) expressed on B-cells as BCR
• Pentameric is secreted
• First Ig of primary immune response
• High valence Ig
• More efficient than IgG in complement activation
• Not Cross the placenta IgG
• 70% of serum immunoglobulin
• Predominant Ig in blood
• monomeric is secreted(low mw)
• it found in secondary immune response
• Has a molecular weight of 150 kd.
• Crosses the placenta (except for subclass IgG4).
• Fixes complement (except for IgG4).
• Contains 3% carbohydrate.
• Consists of four subclasses (isotypes): IgG1, 70% of IgG; IgG2, 19%; IgG3, 8%; and IgG4, 3%.
• act as opsonizing agent
• ADCC(antibody dependent cell cytotoxicity) function

Function of antibody

1. Neutralization
2. Opsonization and phagocytosis: Antibodies of IgG isotype opsonize (coat) microbes and promote their phagocytosis by binding to Fc receptors on phagocytic cell
3. Element the extracellular antigen
4. targeting and enhancing complement-lysis of bacteria
5. ADCC (antibody-dependent cellular cytotoxicity): Via their Fc-receptors, NK cells are able to sense cells carrying bound antibodies, which they proceed to kill. For example, these may be virus-infected cells exposing viral envelope proteins in their cell membrane. a. IgG antibodies bind to infected cells are recognized by Fc receptors on NK cells. → Activation of NK cells → killing of antibody - coated cells. b. IgE antibodies bind to helminthic parasites, and are recognized by Fc receptors on eosinophils → activation of eosinophils →release their granule contents, → killing of parasites.

Functions of antibodies at special sites:

a. Mucosal immunity : IgA is the major class produced by the mucosa-associated lymphoid tissues (MALT) in the GIT and RT and transported to the lumen so Forgan’s .In mucosal secretions, IgA binds to microbes and toxins present in the lumen and neutralize them by blocking their entry into the host. b. Neonatal immunity: neonates are protected from infection by maternal antibodies (IgG) transported across the placenta into the

fetal circulation and by antibodies in ingested milk transported across the gut epithelium of newborns. c. The primary response When were exposed to an antigen for the first time ,there is algae of several days (10days) before specific antibody becomes detectable .This antibody is IgM .After a short time, the antibody level declines. d. The secondary response e. Activation of the complement by IgG and IgM Monoclonal antibodies.