Normal level of plasma protein Site of synthesis of plasma protein

3. Normal level of plasma protein • Site of synthesis of plasma protein • Classification of plasma protein • Functions of plasma protein

4. Immunoglobulin Biochemistry & Functions Dr Sara Mariyum

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

7. 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

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

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

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

12. Domains of Immunoglobulin

13. 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

14. 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

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

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

17. Mechanism of action of antibodies

18. Extracellular bacteria Opsonization Macrophage Ingestion by macrophage Digestion in lysosome Opsonization

19. Bacteria in plasma Lysis and ingestion C1 C1 C2 C4 Complement activation C2 C4 Digestion in lysosome Complement Activation

20. Antibody-Dependent Cell-Mediated Cytotoxicity(ADCC)

21. 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.

22. 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

23. Five Classes of Immunoglobulin

24. 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

25. 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

26. Structure of IgM

27. 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

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

29. IgG1, IgG2, IgG4 IgG3 IgG • 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.

30. 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.

31. 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.

32. Secretory IgA

33. 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

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

35. 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.)

36. IgE-Induced Degranulation of Mast CellsIn Allergy

38. Classify immunoglobulin's • Draw structure of IgG , IgM and IgA • Write down five differences between IgA and IgG