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HUMORAL IMMUNITY

HUMORAL IMMUNITY. By. Dr. Emad AbdElhameed Morad. Lecturer of Medical Microbiology and Immunology. ANTIBODIES. Definition Mechanism of antibody production Clonal selection Activation of B lymphocytes T cell dependent antigens T cell independent antigens

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HUMORAL IMMUNITY

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  1. HUMORAL IMMUNITY By Dr. Emad AbdElhameed Morad Lecturer of Medical Microbiology and Immunology

  2. ANTIBODIES Dr. Emad AbdElhameed Morad

  3. Definition • Mechanism of antibody production • Clonal selection • Activation of B lymphocytes • T cell dependent antigens • T cell independent antigens • Comparison between primary and secondary immune response. • Structure of immunoglobulins: • Basic structure • Domains of immunoglobulins • Paratope • Isotype (class of immunoglobulins) • Idiotype • Fragments of immunoglobulin molecule • Classes of immunoglobulins (M, A, G, E, D) Dr. Emad AbdElhameed Morad

  4. Definition: • Antibodies are gamma-globulins. • They are also called immunoglobulins. • They react specifically with the antigen that stimulated their production. • Mechanism of antibody production: • Clonal selection: • The immune system has a large pool of B lymphocytes. • Each B cell carries on its surface a specific receptor (IgM and IgD) that recognize a specific antigen. • When an antigen enters the body, only one B lymphocyte will proliferate to form a clone of antigen specific B lymphocytes. Dr. Emad AbdElhameed Morad

  5. Activation of B lymphocytes: • Mechanism of activation of B cells differ according to the type of antigen: • The antigen first binds to the B cell receptor (IgM, IgD). • Then, the antigen is internalized inside the B lymphocyte to be processed and presented on the surface of the B cell in association with MHC class ІІ. • TH0 cell will then bind to MHC-peptide complex by its TCR. • B7 molecule on B cell interacts with CD28 on TH0 cell. • CD40 on B cells will interacts with CD40L on TH0. • Now, TH0 cells will be activated and differentiate into TH2 cells under the effect of IL-4 which is secreted from mast cells. T cell dependent antigens Dr. Emad AbdElhameed Morad

  6. TH2 cells will secrete IL-2, 4, 5, 6, 10, 13 that will activate B lymphocyte to differentiate into: • Plasma cell which will secrete antibody specific for the antigen. This antibody will be IgM on first exposure to the antigen (Primary immune response). • Memory cell that will secrete IgG on next exposure to the same antigen (Secondary immune response). • Development of memory cells and immunoglobulin class switch (from IgM to IgG) occurs under the effect of: • Cytokines secreted from TH2 cells. • Interaction between CD40 on B cells and CD40L on T lymphocytes. Dr. Emad AbdElhameed Morad

  7. T cell independent antigens • These antigens are polysaccharide with repeated subunits of sugars. • These antigens interact with IgM receptor on B lymphocyte surface stimulating it directly to produce specific antibodies. • Due to absence of T cell help (cytokines, CD40-CD40L interaction): • No development of memory cells. • No immunoglobulin class switch (Only IgM is produced from B lymphocytes) Dr. Emad AbdElhameed Morad

  8. Dr. Emad AbdElhameed Morad

  9. T cell dependent and independent antigens Dr. Emad AbdElhameed Morad

  10. Dr. Emad AbdElhameed Morad

  11. Primary and secondary immune responses Dr. Emad AbdElhameed Morad

  12. Structure of immunoglobulins. • Basic structure: • Immunoglobulin molecule is formed of 4 polypeptide chains (2 identical heavy chains *H* and 2 identical light chains *L*) • Each antibody molecule has a hinge region in its middle. • The 4 chains are connected together by disulphide bonds. • Light chain (L chain) has two antigenic types kappa (κ) and lambda (λ). • The immunoglobulin molecule contains either κ or λ but never both. • Heavy chain (H chain) has five types: gamma (γ), alpha (α), mu (μ), delta (δ) and epsilon (ε) corresponding to the five classes of immunoglobulins: IgG, IgA, IgM, IgD, IgE. Dr. Emad AbdElhameed Morad

  13. Domains or regions of immunoglobulin molecule: • Every light chain has two domains: • VL (variable domain of light chain). This domain is present at the amino terminal end of the immunoglobulin molecule. It shows marked variation in its amino acid sequence. • CL (constant domain of light chain). This domain is present near the carboxy terminal end of the immunoglobulin molecule. It shows little variation in its amino acid sequence. • Every heavy chain has four domains: • VH (variable domain of heavy chain). • CH1, CH2, CH3 (constant domains of heavy chain). Dr. Emad AbdElhameed Morad

  14. Basic structure and domains of immunoglobulins Dr. Emad AbdElhameed Morad

  15. Paratope: • It is the area of immunoglobulin that interact with the epitope of the antigen. • It is formed of VLandVH. • Note that both VL and VH have threeextremely variable amino acid sequences called hypervariable regions. They are the antigen binding site. • Isotype (class): • The isotype of immunoglobulin molecule is determined by constant domains of heavy chains (CH1, CH2, CH3). • There are five classes of immunoglobulins (IgG, IgM, IgA, IgD, IgE). • Some classes have subclasses such as IgG and IgA. • Idiotype: • It means the antigen binding specificity of immunoglobulin molecule. It is determined by hypervariable regions of antibody molecule. Dr. Emad AbdElhameed Morad

  16. Hypervariable regions of immunoglobulin molecule Dr. Emad AbdElhameed Morad

  17. Fragments of immunoglobulin molecule: • Papain is a proteolytic enzyme that divide antibody molecule at the hinge region into three fragments. • Two antigen binding fragments (Fab). So each antibody molecule can bind two similar antigens. • Each Fab fragment is formed of complete light chain and VH and CH1 domains of heavy chain. • The third portion is called fragment crystallizable (Fc portion). • Fc portion is formed of CH2 and CH3 of the two heavy chains. Dr. Emad AbdElhameed Morad

  18. Fragments of immunoglobulin molecule Dr. Emad AbdElhameed Morad

  19. Classes of immunoglobulins: • IgG: • It is the major immunoglobulin in plasma (75% of total immunoglobulins). • It has the longest half life (23 days). • It has four subclasses (IgG1,2,3,4). • Functions are: • The major immunoglobulin in secondary immune response. • The only antibody that passes through the placenta because placenta has receptors for its Fc portion. • Antitoxin & neutralize viruses • Complement fixation through its Fc portion. • Opsonization of bacteria by coating them and attaching them to macrophages through its Fc portion. Dr. Emad AbdElhameed Morad

  20. Antibody dependent cellular cytotoxicity (ADCC) by coating virus infected cells and attaching them to the NK cells through its Fc portion. • It is class of antibodies formed against Rh antigens. Opsonization ADCC Virus infected cell Lysis of the infected cell Dr. Emad AbdElhameed Morad

  21. IgM: • It is the largest immunoglobulin molecule because it is a pentamer formed of five molecules joined together at their Fc portions by J chain. Dr. Emad AbdElhameed Morad

  22. Functions are: • The major antibody in the primary immune response. • The major agglutinating antibody. • Complement fixation. • Antigen receptor on the surface of B lymphocytes. (It is attached to the cell surface through Fc portion). • It is the class of antibodies formed against ABO antigens. • IgD: • It acts as antigen receptor on the surface of mature B lymphocytes. (It is attached to the cell surface through Fc portion). Dr. Emad AbdElhameed Morad

  23. IgA: • This class is found in both serum and mucosal surfaces. • IgA present in the serum is called serum IgA and it is found in the monomeric form. • IgA present at mucosal surfaces is called secretory IgA. It is found in the dimeric form (formed of two molecules linked together at Fc portion by J chain). • Secretory IgA has a secretory piece which protects it from degradation by IgA proteases produced by some bacteria as gonococci. • IgA has two subclasses IgA1 and IgA2. (IgA2 is more resistant to degradation by proteases so it is more important in local immunity). • The main function of secretory IgA is to provide local immunity at mucosal surfaces such as respiratory tract, GIT. Dr. Emad AbdElhameed Morad

  24. Secretory IgA Dr. Emad AbdElhameed Morad

  25. IgE: • It is present in a very low concentration in plasma. • It is elevated in plasma in two conditions: • Type І hypersensitivity such as bronchial asthma. IgE has the ability to bind to mast cell surface through its Fc portion (so, it is called cytotropic antibody). When it becomes attached to its specific antigen, the mast cell becomes degranulated with release of histamine. • IgE is the main antibody that provides immunity against parasites. Dr. Emad AbdElhameed Morad

  26. Thank You Dr. Emad AbdElhameed Morad

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