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Immunology (elective) MLIM-101

Immunology (elective) MLIM-101. Prepared by: Dr. Mohamed S. Abdel- Latif. Immunoglobulins : Structure and Function. Learning Outcome:. At this time you should know the following: 1. To discuss the general properties of all immunoglobulins

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Immunology (elective) MLIM-101

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  1. Immunology (elective) MLIM-101 Prepared by: Dr. Mohamed S. Abdel-Latif

  2. Immunoglobulins:Structure and Function

  3. Learning Outcome: At this time you should know the following: 1. To discuss the general properties of all immunoglobulins 2. To describe the basic structure of immunoglobulins 3. To relate immunoglobulin structure with function 4. To define immunoglobulin hypervariable and framework regions 5. To define immunoglobulin classes and subclasses, types and subtypes 6. To describe the structures and properties of immunoglobulin classes

  4. - + albumin Amount of protein globulins   1 2 Immune serum Ag adsorbed serum Mobility Immunoglobulins:Structure and Function • Definition: Glycoprotein molecules that are produced by plasma cells in response to an immunogen and which function as antibodies

  5. General Functions of Immunoglobulins • Ag binding • Can result in protection • Valency • Effector functions • Fixation of complement • Binding to various cells (Usually require Ag binding)

  6. Basic Immunoglobulin Structure • Immunoglobulins - heterogeneous • Myeloma proteins - homogeneous immunoglobulins

  7. Disulfide bond Carbohydrate CL VL CH2 CH3 CH1 Hinge Region VH Immunoglobulin Structure • Heavy & Light Chains • Disulfide bonds • Inter-chain • Intra-chain

  8. Disulfide bond Carbohydrate CL VL CH2 CH3 CH1 Hinge Region VH Immunoglobulin Structure • Variable & Constant Regions • VL & CL • VH & CH • Hinge Region

  9. Disulfide bond Carbohydrate CL VL CH2 CH3 CH1 Hinge Region VH Immunoglobulin Structure • Domains • VL & CL • VH & CH1 - CH3 (or CH4) • Oligosaccharides

  10. IgG molecule Used with permission from: Dr. Mike Clark, Immunology Division, Department of Pathology Cambridge University, Cambridge, England

  11. HVR3 150 Variability Index 100 HVR2 HVR1 50 FR2 FR1 FR4 FR3 0 25 75 100 50 Amino acid residue Structure of the Variable Region • Hypervariable (HVR) or complimentarity determining regions (CDR) • Framework regions

  12. Papain Fc Fab Immunoglobulin Fragments: Structure/Function Relationships • Fab • Ag binding • Valence = 1 • Specificty determined by VH and VL • Fc • Effector functions

  13. Ag Binding Complement Binding Site Binding to Fc Receptors Placental Transfer Immunoglobulin Fragments: Structure/Function Relationships

  14. Pepsin Fc Peptides F(ab’)2 Immunoglobulin Fragments: Structure/Function Relationships • Fab • Ag binding • Fc • Effector functions • F(ab’)2

  15. Human Immunoglobulin Classes • IgG - Gamma () heavy chains • IgM - Mu () heavy chains • IgA - Alpha () heavy chains • IgD - Delta () heavy chains • IgE - Epsilon () heavy chains

  16. Human Immunoglobulin Subclasses • IgG Subclasses • IgG1 - Gamma 1 (1) heavy chains • IgG2 - Gamma 2 (2) heavy chains • IgG3 - Gamma 3 (3) heavy chains • IgG4 - Gamma 4 (4) heavy chains • IgA subclasses • IgA1 - Alpha 1 (1) heavy chains • IgA2 - Alpha 2 (2) heavy chains

  17. Human ImmunoglobulinLight Chain Types • Kappa () • Lambda ()

  18. Human ImmunoglobulinLight Chain Subtypes • Lambda light chains • Lambda 1 (1) • Lambda 2 (2) • Lambda 3 (3) • Lambda 4 (4)

  19. Immunoglobulins • Nomenclature • IgM (kappa) • IgA1(lambda 2) • IgG • Heterogeneity

  20. IgG1, IgG2 and IgG4 IgG3 IgG • Structure • Monomer (7S)

  21. IgG • Structure • Properties • Major serum Ig • Major Ig in extravascular spaces • Placental transfer – Does not require Ag binding ( IgG2) • Fixes complement ( IgG4) • Binds to Fc receptors ( IgG2, IgG4) • Phagocytes - opsonization • K cells - ADCC

  22. J Chain C4 IgM • Structure • Pentamer (19S) • Extra domain (CH4) • J chain

  23. IgM • Structure • Properties • 3rd highest serum Ig • First Ig made by fetus and B cells • Fixes complement

  24. C1r C1r C1s C1s C1q C1q Fixation of C1 by IgG and IgM Abs No activation Activation

  25. Tail Piece IgM • Structure • Properties • 3rd highest serum Ig • First Ig made by fetus and B cells • Fixes complement • Agglutinating Ig • Binds to Fc receptors • B cell surface Ig

  26. Ig- Ig- Ig- Ig- B Cell Antigen Receptor (BcR)

  27. Secretory Piece J Chain IgA • Structure • Serum - monomer • Secretions (sIgA) • Dimer (11S) • J chain • Secretory component

  28. Y Y Y Y Y Y Origin of Secretory Component of sIgA

  29. IgA • Structure • Properties • 2nd highest serum Ig • Major secretory Ig (Mucosal or Local Immunity) • Tears, saliva, gastric and pulmonary secretions • Does not fix complement (unless aggregated) • Binds to Fc receptors on some cells

  30. Tail Piece IgD • Structure • Monomer • Tail piece

  31. IgD • Structure • Properties • 4th highest serum Ig • B cell surface Ig • Does not bind complement

  32. C4 IgE • Structure • Monomer • Extra domain (CH4)

  33. IgE • Structure • Properties • Least common serum Ig • Binds to basophils and mast cells (Does not require Ag binding) • Allergic reactions • Parasitic infections (Helminths) • Binds to Fc receptor on eosinophils • Does not fix complement

  34. Assignment: As a part of the semester activity, group of students are selected every week to prepare a short seminar about his/her point of interest in one of the lecture topics. That to be discussed and evaluated during the next lecture.

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