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  1. 1. Antibody
  2. 2. <ul><li>Antibody or immunoglobulin : </li></ul><ul><li>defined as glycoprotein produced from B cell against Antigen </li></ul><ul><li>They could be: </li></ul><ul><li>Carried on the surface of B cell where they act as Receptor for specific Antigen </li></ul><ul><li>Free Antibody in the blood and lymph. </li></ul><ul><li>When B cell and Antigen bind this cause B cells to develop into Antibody Forming Cell(AFC) or Plasma Cell which secretes large amount of Antibody. </li></ul>
  3. 3. <ul><li>GENERAL FUNCTIONS OF IMMUNOGLOBULINS </li></ul><ul><li>A. Antigen binding </li></ul><ul><li>Immunoglobulin's bind specifically to one or a few closely related antigens. Each immunoglobulin actually binds to a specific antigenic determinant. Antigen binding by antibodies is the primary function of antibodies and can result in protection of the host </li></ul><ul><li>B. Effector Functions </li></ul><ul><li>Frequently the binding of an antibody to an antigen has no direct biological effect. Rather, the significant biological effects are a consequence of secondary &quot;effector functions&quot; of antibodies. Such effector functions include </li></ul><ul><li>1)Fixation of complement - This results in lysis of cells and release of biologically active molecules </li></ul><ul><li>2) . Binding to various cell types - Phagocytic cells, lymphocytes, platelets, mast cells, and basophils have receptors that bind immunoglobulins. This binding can activate the cells to perform some function. Some immunoglobulins also bind to receptors on placental trophoblasts, which results in transfer of the immunoglobulin across the placenta. As a result, the transferred maternal antibodies provide immunity to the fetus and newborn </li></ul>
  4. 4. <ul><li>Basic Structure : </li></ul><ul><li>The immunoglobulin consist of a unit made of 4 chain model , it’s based on 2 type of polypeptide chain. </li></ul><ul><li>The light (smaller) chain has MWT of 25 k dalton </li></ul><ul><li>And is common to all classes. </li></ul><ul><li>The Heavy (larger) chain has MWT of 50-70 k dalton and it is structurally distinct for each class or subclass. </li></ul><ul><li>The hinge Region </li></ul><ul><li>The Light-Heavy chains are linked by Disulphide bond </li></ul>
  5. 5. <ul><li>All Light chain have One Variable One Constant Region. </li></ul><ul><li>The light chain have been shown to exist in 2 Forms called lambda (λ) and kappa (κ) </li></ul><ul><li>These are ISOTYPES being present in all individual </li></ul><ul><li>Light chain consist of 2 distinct Region: </li></ul><ul><li>C Terminal: is Constant (CL) Region </li></ul><ul><li>N Terminal : is Variable (VL)Region </li></ul>
  6. 6. <ul><li>The Class and Subclass of immunoglobulin are determined by it’s HEAVY chain. </li></ul><ul><li>There are 5 Classes of Immunoglobulin: </li></ul><ul><li>IgG, IgM, IgD, IgA and igE. </li></ul>
  7. 7. <ul><li>IgG has a typical Antibody structure: </li></ul><ul><li>It has 2 intrAchain disulphide bonds in Light chain (One in the Variable Region and One in the Constant Region) </li></ul><ul><li>There are 4 disulphide bonds in Heavy chain which is twice the length of the light </li></ul><ul><li>Each disulphide bond encloses a peptide loop of 67-70 Amino Acid Residue those represents a DOMAIN. </li></ul><ul><li>In both Heavy and Light chain, the first of these Domains corresponds to the Variable region </li></ul>
  8. 8. <ul><li>In Heavy chain of IgG, IgA and IgD there are 3 further Domain which make Constant part of the chain (CH1,CH2,CH3) </li></ul><ul><li>In Heavy chain of IgM, IgE chain have additional Domain immediately after CH1 </li></ul>
  9. 9. <ul><li>IgG have 4 subclasses differ Only slightly in there Amino Acid sequence ,most of the difference are clustered in the Hinge Region and give rise to differing patterns of InteRchain disulphide Bond between the 4 peptide </li></ul><ul><li>The most striking structural difference is the Elongated Hinge Region of igG3 which accounts for it’s Higher MWT and possibility for some of its enhanced activity </li></ul>
  10. 10. <ul><li>IgG properties : </li></ul><ul><li>The predominant immunoglobulin in blood and lymph </li></ul><ul><li>It is the most Concentrated </li></ul><ul><li>It has Heave chain Gamma, and two of Kaba or Lamda Light chain </li></ul><ul><li>MWT of IgG= 150k dalton except for IgG3 that have MWT= 175k dalton </li></ul><ul><li>90-95% homology between the 4 subclasses </li></ul><ul><li>Half life of IgG=23 days except for IgG3=7-8 days </li></ul><ul><li>It can cross the placenta </li></ul><ul><li>It represent 70-75% of the total immunoglobulin </li></ul>
  11. 11. <ul><li>IgM: </li></ul><ul><li>The First immunoglobulin to be produced </li></ul><ul><li>It is called Macromolecules or Large molecule because of it’s large MWT=970 k Dalton </li></ul><ul><li>It is Pentameric </li></ul><ul><li>It has Extra Domain </li></ul><ul><li>It doesn’t have Hinge Region but it has J chain </li></ul><ul><li>Half life = 10 days </li></ul><ul><li>It represent 10% of the immunoglobulin </li></ul>
  12. 12. <ul><li>IgA: </li></ul><ul><li>It has Alpha Heavy chain </li></ul><ul><li>It is the major immunoglobulin found in the body fluid like Tears, Saliva, Respiratory mucosa, Vaginal secretion and gastric secretion </li></ul><ul><li>MWT=165K Dalton for Monomeric </li></ul><ul><li>It is secreted from Plasma cell as Monomeric but it exist in the fluids as Dimeric which is called Secretary IgA (s-IgA) with MWT=585 k Dalton </li></ul>
  13. 13. <ul><li>IgA Continue.. </li></ul><ul><li>S piece is a part of the epithelia cell, the IgA took it during its penetration of the cell membrane and it’s MWT=55K Dalton </li></ul><ul><li>There are 2 subclasses of IgA (IgA1, IgA2) </li></ul><ul><li>IgA1 represent 93% of total IgA </li></ul><ul><li>IgA2 represent 7% of total IgA </li></ul><ul><li>IgA represent (15-20)% of total immunoglobulin </li></ul><ul><li>Half life= 6 days </li></ul>
  14. 14. <ul><li>IgD: </li></ul><ul><li>Accounts for less than 1% of the total plasma immunoglobulin. </li></ul><ul><li>It is the Major component of the Surface Membrane of a many B cell. </li></ul><ul><li>Half life= 3days </li></ul><ul><li>MWT=180-184 k dalton </li></ul>
  15. 15. <ul><li>IgE: </li></ul><ul><li>Found in the surface membrane of Basophile and mast cell in all individuals </li></ul><ul><li>MWT=190-200 K Dalton </li></ul><ul><li>It has EXTRA Domain </li></ul><ul><li>It does not have Hinge Region but it has J chain </li></ul><ul><li>Half life= 2 days </li></ul>
  16. 16. <ul><li>Immunoglobulin show Isotypic , Allotypic and Idiotypic Variation </li></ul><ul><li>Isotypic Variation: </li></ul><ul><li>The gene for isotypic variants are present in all healthy member of a species. </li></ul><ul><li>For example genes for α1, α2, δ1, δ2, δ3, δ4, ε, γ, and μ lambda (λ) and kappa (κ) chains are all present in the human genome and therfore are isotypic . </li></ul>
  17. 17. <ul><li>Allotypic Variation: </li></ul><ul><li>This refer to genetic variation between individual within a species involving different alleles at a given locus. </li></ul><ul><li>Allotype occur mostly as variant in Heavy chain Constant region. </li></ul><ul><li>Idiotypic Variation: </li></ul><ul><li>Variation in the Variable Domain particularly in the Highly variable segment known as HyperVariable Region </li></ul>
  18. 18. <ul><li>These determine the binding specificity of Antigen binding site </li></ul><ul><li>Idiotypic are usually specific of individual B cell clone (Privet Idiotype) but are sometimes shared between different B cell clones (Public, cross reacting or Recurrent Idiotype) </li></ul><ul><li>HyperVariable segment in Antigen binding site allow Antibody to bind to a range of Antigen </li></ul><ul><li>HyperVariable segment: they are within the Variable region of both Heavy and Light chain they are short polypeptide segment show Exceptional Variability </li></ul>
  19. 19. Terms <ul><li>Antigen: is a molecule that stimulates an immune response. The word originated from the notion that they can stimulate anti body gen eration. We now know that the immune system does not only consist of antibodies. The modern definition encompasses all substances that can be recognized by the adaptive immune system. </li></ul>