2. Biochemistry & Functions Dr Sara Mariyum
Immunoglobulin
Biochemistry & Functions
Dr Sara Mariyum

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

4. 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

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

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

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

9. Domains of Immunoglobulin

10. 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

11. 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

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

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

14. Mechanism of action of antibodies

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

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

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

18. 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.

19. 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

20. Five Classes of Immunoglobulin

21. 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

22. 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

23. Structure of IgM

24. 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

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

26.   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.

27. 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.

28. 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.

29. Secretory IgA

30. 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

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

32. 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.)

33. IgE-Induced Degranulation of Mast Cells In Allergy