L5 immunoglobulins
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Immunoglobulins, also known as antibodies, are glycoprotein molecules produced by plasma cells in response to antigens. They function to bind to antigens. The basic immunoglobulin structure consists of two heavy chains and two light chains held together by disulfide bonds. The heavy and light chains each contain a variable region for antigen binding and constant regions that determine the class and subclass. The five major classes in humans are IgG, IgM, IgA, IgD, and IgE, which have different structures and functions such as complement activation, opsonization, and roles in allergic reactions. Immunoglobulins can be further broken down into fragments like Fab and Fc that retain specific functions. Variants within
L5 immunoglobulins
- 1. Immunoglobulins: Structure and Function Immunology Lecture Dr.Jassim M.Abdo
- 3. Immunoglobulins:Structure and Function • Definition: Glycoprotein molecules that are produced by plasma cells in response to an immunogen and which function as antibodies Immune serum Ag adsorbed serum α1 α2 β γ + - albumin globulins Mobility Amountofprotein
- 4. General Functions of Immunoglobulins • Effector functions – Fixation of complement – Binding to various cells (Usually require Ag binding) • Ag binding – Can result in protection – Valence
- 5. Basic Immunoglobulin Structure • Immunoglobulins - heterogeneous • Myeloma proteins - homogeneous immunoglobulins
- 6. Immunoglobulin Structure • Heavy & Light Chains • Disulfide bonds – Inter-chain – Intra-chain CH1 VL CL VH CH2 CH3 Hinge Region Carbohydrate Disulfide bond
- 7. Immunoglobulin Structure • Variable & Constant Regions – VL & CL – VH & CH • Hinge Region CH1 VL CL VH CH2 CH3 Hinge Region Carbohydrate Disulfide bond
- 8. Immunoglobulin Structure • Domains – VL & CL – VH & CH1 - CH3 (or CH4) • Oligosaccharides CH1 VL CL VH CH2 CH3 Hinge Region Carbohydrate Disulfide bond
- 9. Structure of the Variable Region • Hypervariable (HVR) or complimentarity determining regions (CDR) HVR3 FR1 FR2 FR3 FR4 HVR1 HVR2 VariabilityIndex 25 7550 100 Amino acid residue 150 100 50 0 • Framework regions
- 10. Immunoglobulin Fragments: Structure/Function Relationships • Fab – Ag binding – Valence = 1 – Specificity determined by VH and VL Papain Fc Fab • Fc – Effector functions
- 11. Immunoglobulin Fragments: Structure/Function Relationships Ag Binding Complement Binding Site Placental Transfer Binding to Fc Receptors
- 12. Immunoglobulin Fragments: Structure/Function Relationships • Fab – Ag binding • Fc – Effector functions • F(ab’)2 Pepsin Fc Peptides F(ab’)2
- 15. Human 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
- 16. Human Immunoglobulin Subclasses • IgG Subclasses – IgG1 - Gamma 1 (γ1) heavy chains – IgG2 - Gamma 2 (γ2) heavy chains – IgG3 - Gamma 3 (γ3) heavy chains – IgG4 - Gamma 4 (γ4) heavy chains • IgA subclasses – IgA1 - Alpha 1 (α1) heavy chains – IgA2 - Alpha 2 (α2) heavy chains
- 17. Human Immunoglobulin Light Chain Types • Kappa (κ) • Lambda (λ)
- 18. Immunoglobulins • Nomenclature – IgM (kappa) – IgA1(lambda 2) – IgG • Heterogeneity
- 19. IgG • Structure • Properties – Major serum Ig (systemic immunity) – Major Ig in extravascular spaces – Placental transfer – Does not require Ag binding – Fixes complement(IgG Ab can activate the clasical complement pathway . – Binds to Fc receptors • Phagocytes - opsonization • K cells - ADCC
- 20. IgG • Typical BCR structure with two identical light chains and two identical γ heavy chains. • It is made and secreted by plasma cells in the spleen, lymph node ,nd bone marrow. • Highest concentration in the Blood plays a major role in the antibody –mediated defense mechanism . • Molecular weight 180 kD
- 21. IgG • Structure – Monomer (7S) CH1 VL CL VH CH2 CH3 Hinge Region Carbohydrate Disulfide bond
- 22. IgM• Produced by plasma cells in the spleen ,lymph node ,and bone marrow. • It is second highest concentration in the most mammalian serum . • Consist from 5 180 kDa subunit linked by disulfide bonds in circular, j chains joint two of the unit to complete the circle . • It is the major immunoglobulin produced during a primary immune response ,it also produced in secondary response but in small amount . • it is rarely to inter tissue site because of their very large size
- 23. IgM • Structure – Pentamer (19S) – Extra domain (CH4) – J chain Cµ4 J Chain
- 24. IgM • Structure • Properties – First Ig made by fetus and B cells – Fixes complement – More efficient than IgG at a complement activation ,opsonization, neutralization of viruses and agglutination.
- 25. IgM • Structure • Properties – First Ig made by fetus and B cells – Fixes complement Tail Piece – Agglutinating Ig – Binds to Fc receptors – B cell surface Ig
- 26. IgA • Molecular weight 360 kDa. • It can act in inside cells • Synthesized and Secreted by plasma cells in the intestinal submucosa. • IgA bind to glycoprotein receptors (pIgR) to make complex in the Basel surface of enterocyte .
- 27. IgA
- 28. IgA • It made in the walls of the intestine ,respiratory tract ,urinary system , skin and mammary gland
- 29. IgA • Structure – Serum - monomer – Secretions (sIgA) • Dimer (11S) • J chain • Secretory component J ChainSecretory Piece
- 30. IgA • Structure • Properties – 3nd highest serum Ig – Does not fix complement (unless aggregated) – Binds to Fc receptors on some cells
- 31. IgE • Structure – Monomer – Extra domain (CH4) Cε4
- 32. IgE • Structure • 200 kDa • Properties – Least common serum Ig(low conc in serum thefore can’t bined to Ag • Binds to basophils and mast cells (Does not require Ag binding) – Allergic reactions(mediated Type I hypersensitivity reaction). – Short life 2-3 days. – Parasitic infections (Helminths) • Binds to Fc receptor on eosinophils – Does not fix complement
- 33. IgD • Structure – Monomer – Tail piece – 180 kDa Tail Piece
- 34. IgD • IgD has been not detected in in all mammals. • Found in rodents, cattle ,sheep and pigs and probably present in dog. • It has been not detected in horses,rabbits. • It has been identified in certain fish(catfish,salmon,cod) but not been found in chickens. • Like IgE,IgD. Is destroyed by mild heat treatment. • IgD doesn't found in serum but in plasma .
- 35. IgD • Structure • Properties – 4th highest serum Ig – Mainly attached B cell(B cell surface Ig) – Does not bind complement
- 36. IMMUNOGLOBULIN VARIANTS isotype, Allotypes Idiotypes • Subclasses: immunoglobuline classes consist of a mixture of molecules with structurally different heavy chains. • Allotypes: inherited sequence variation in in heavy chain genes (inherited variation in in immunoglobulin amino acid sequences ) in individual animal . Homozygous: individual have the same allotype in all immunoglobulin in a class. Hetrozygous halve of immunoglobulin molecules will be of one allotype and half will be the other.
- 37. Idiotypes • Variation in the amino acid in sequence within the variable domain in light and heavy chains.