Biochemistry & Functions Dr Sara Mariyum Immunoglobulin Biochemistry & Functions Dr Sara Mariyum

Immunity Latin word ….immunis Two types Cellular Immunity Humoral Immunity

Immunoglobulin The immunoglobulins are a group of glycoproteins present in the serum and tissue fluids of all mammals. Definition: Glycoprotein molecules that are produced by plasma cells in response to an immunogen and which function as antibodies

Structure of immunoglobulin Two identical heavy (H) chains and two identical light (L) chains combine to form this Y-shaped antibody molecule

Heavy chains The heavy chains each have four domains Variable domains (VH) Constant domains (CH1,2,3)

Light chain The light chains are constructed of two domains Variable (VL) Constant (CL)

Domains of Immunoglobulin

Fragments of antibody Fab: Antigen-binding fragment. Antibodies bind to antigens by reversible, noncovalent interactions, including hydrogen bonds and charge interactions Fc: Constant fragment. Portion of molecule carrying out the biological activities of antibody. Binding to receptors on phagocytes Adherence to the tissues Activating the classical complement pathway Passing through the membranes

Hinge Two disulfide bonds in the hinge region unite the two heavy chains The hinge allows the two antigen-binding Fab regions of each antibody molecule to move

Functions of Immunoglobulins Recognition of antigen Activation of complement Opsonization Antibody-dependent cell-mediated cytotoxicity

Mechanism of action of antibodies Neutralization Agglutination Precipitation Opsonization & enhancement of Phagocytosis Stimulation of Killer cells Activation of complement system (indirect attack)

Mechanism of action of antibodies

Opsonization Extracellular bacteria Opsonization Macrophage Ingestion by macrophage Digestion in lysosome

Complement Activation Digestion in lysosome Bacteria in plasma Complement activation Lysis and ingestion

Antibody-Dependent Cell-Mediated Cytotoxicity(ADCC)

Immunoglobulin Classes and Subclasses Immunglobulin molecules are divided into distinct classes and subclasses in terms of the differences in amino acid sequence of constant region of heavy chain, i.e.γ,α,μ,δ,andεchains.

Immunoglobulin Classes IgG - Gamma (γ) heavy chains IgM - Mu (µ) heavy chains IgA - Alpha (α) heavy chains IgD - Delta (δ) heavy chains IgE - Epsilon (ε) heavy chains

Five Classes of Immunoglobulin

Light Chain Types of Immunoglobulin Kappa (κ) Lambda (λ) All light chains have protein molecular weights of approximately 23,000 but can be divided into two distinct types, namely λchain, κchain, respectively

Immunoglobulin M (IgM) Largest antibody Five Y structures being joined by their Fc regions in a circular configuration. A J chain links the five antibodies 10 % of antibodies in the blood. Agglutinate antigens More efficient than IgG at activating the complement Synthesized early in a primary immune response

Structure of IgM

Functions of IgM 3rd highest serum Ig. IgM cannot traverse blood vessels, hence it is restricted to the blood stream. 1st Ig produced in a primary response to an antigen and serve as first line of defense. a good complement activation Ig. Thus, IgM is the most effective in leading to the lysis of microorganisms. Binds to Fc receptors

Immunoglobulin G (IgG) Predominant Ig of blood Found in all body fluids 1 unit, smallest Longest half-life Passive transfer Agglutination Opsonization Complement Actn.

  IgG IgG1, IgG2, IgG4 IgG3 It is the most abundant class in serum, constitutes about 80% of the total serum Ig. 4 subclasses, IgG1, IgG2, IgG3, and IgG4. All IgG's are monomers. The subclasses differ in the number of disulfide bonds and length of the hinge region.

Functions of IgG 1. Major Ig in extravascular spaces. 2. Placental transfer: IgG is the only class of Ig that crosses the placenta. 3. Complement activation. 4. Binding to cells - Macrophages, monocytes, PMNs (polymorphonuclear leukocyte), and some lymphocytes have Fc receptors for the Fc region of IgG.

Immunoglobulin A (Ig A) Secretory antibody Present in serum, mucus, saliva, tears, sweat and milk. IgA in breast milk- Passive immunity The newborn develops its own immunity while being partially protected by the mother. Do not activate the classical complement pathway May activate the alternative complement pathway.

Secretory IgA

IgA Function 2nd highest serum Ig Major secretory Ig (Mucosal or Local Immunity) Found in the body secretions: tears, breast milk, saliva, mucus of the bronchial, genitourinary, and digestive tract IgA is the most predominant antibody in the colostrum, the initial secretion from the mother’ breast after a baby is born. Does not activate complement (unless aggregated) Binds to Fc receptors on some cells

Immunoglobulin (Ig D) Found on the surface of B-lymphocytes Serves as antigen receptor for the activation of B cell IgD is monovalent.

Immunoglobulin E (Ig E) Polyvalent antibody- like Ig M 0.002 % of the total serum antibodies. Bound to tissue cells especially mast cells and eosinophils. Cause release of histamine from the mast cells Responsible for allergic reactions (e.g., anaphylaxis, asthma, hay fever etc.)

IgE-Induced Degranulation of Mast Cells In Allergy