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IMMUNITY

IMMUNITY. LANGE CHAPTER 59,60,61 SAMUEL AGUAZIM. ANTIBODY. Antibodies are globulin proteins ( immunoglobulins )that react specifically with the antigen that stimulated their production.

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IMMUNITY

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  1. IMMUNITY LANGE CHAPTER 59,60,61 SAMUEL AGUAZIM

  2. ANTIBODY • Antibodies are globulin proteins (immunoglobulins)that react specifically with the antigen that stimulated their production. • They make up about 20% of the protein in blood plasma. Blood contains three types of globulins, alpha, beta, and gamma, based on their electrophoretic migration rate. • produced by B cells

  3. Monoclonal antibodies • Polyclonal: heterogeneous representation of immunoglobulin's( several different clones of plasma cells) • Monoclonal: homogenous representation of immunoglobulin's( arise from a single clone of cell) • Single specificity antibodies formed by fusing a mouse B cell with a cancer cell.(hybridomas) • used in diagnosis of disease, identification of microbes and therapy

  4. FUNCTION OF ANTIBODY • The most important functions of antibodies are to neutralize toxins and viruses, to opsonize microbes so they are more easily phagocytosed, to activate complement, and to prevent the attachment of microbes to mucosal surfaces.

  5. IMMUNOGLOBULIN STRUCTURE • They are tetrapeptide ( 4 chains) • Two heavy and two light chain • Held together by Disulphide bond • L and H chains are subdivided into variable and constant regions. • Variable Regions: Two sections at the end of Y’s arms. Contain the antigen binding sites (Fab). Identical on the same antibody, but vary from one antibody to another. • Constant Regions: Stem of monomer and lower parts of Y arms. • Fc region: Stem of monomer only. Important because they can bind to complement or cells.

  6. IMMUNOGLOBULIN STRUCTURE • The variable regions of both L and H chains have three extremely variable (hypervariable) amino acid sequences at the amino-terminal end that form the antigen-binding site . • Only 5-10 amino acids in each hypervariable region form the antigen-binding site. • Antigen-antibody binding involves electrostatic and van der Waals' forces and hydrogen and hydrophobic bonds rather than covalent bonds. The remarkable specificity of antibodies is due to these hypervariable regions

  7. IMMUNOGLOBULIN STRUCTURE • If an antibody molecule is treated with a proteolytic enzyme such as papain, peptide bonds in the "hinge“ region are broken, producing two identical Fabfragments,which carry the antigen-binding sites, and one Fc fragment, which is involved in placental transfer, complement fixation, attachment site for various cells,and other biologic activities

  8. MORE BASIC CONCEPTS • Fab: fragment ab • Fc: fragment crystallize • Monomer: 1 ab molecule • Dimeric: 2 ab monomer held by J-chains(joining component) we say it is multimeric • Pentameric: group of ab molecules in which 5 monomers are held by J-chain • Valency: group of ab can binding to how many group of ag • Affinity: the tightening and strength of ag binding site • Avidity: looking at all the affinity together.

  9. IMMUNOGLOBULIN CLASSES • Why antibody are divided primary into 5 classes? • Plasma produces 5 classes of heavy chains and 2 classes of light chain. • Light chains are kappa and lamda( shows similar characteristics) • Heavy chains types are • Alpha( IgA) • Mu(IgM) • Gamma(IgG) • Delta(IgD) • Epsilon(IgE)

  10. IgM • IgM is the main immunoglobulin produced early in the primary response. • It is present as a monomer on the surface of virtually all B cells, where it functions as an antigen-binding receptor • Present in serum(pentameric) not present in interstitial fluid or other body fluid • Meaning high avidity. • first Ig to be made by the fetus • first Ig to be made by a virgin B cells • good complement fixing Ig; • good agglutinating Ig;

  11. Class switching

  12. IgD • This immunoglobulin has no known antibody function but may function as an antigen receptor; it is present on the surface of many B lymphocytes. • It is present in small amounts in serum

  13. IgE • Bind to mast cells and basophils • Very small traces in blood • IgE is medically important for two reasons: • (1) it mediates immediate (anaphylactic) hypersensitivity • (2) it participates in host defenses against certain parasites, eg, helminths (worms) infections, such as Strongyloides, • Trichinella, Ascaris, and the hookworms • Binds on parasite ag and also have receptors for eosinophils which release major basic protein that destroys parasite • Mast cells have receptor for Fc portion of IgE • Allergy activates the receptors and activate mast cells several mediators are released by the cells and immediate (anaphylactic) hypersensitivity reactions occur

  14. IgG • 2 light chains and 2 heavy chains held by disulfide bond • It is divalent • It has 4 subclasses • Most abundant Ig • Secondary response(defense against bacteria and virus) • Crosses placenta • Activates complement • IgG is the immunoglobulin that opsonizes. It can opsonize

  15. IgA • 2nd mc abundant • Structure: Dimer • Percentage serum antibodies: 10-15% • Location: Secretions (tears, saliva, intestine, milk), blood and lymph. • Half-life in serum: 6 days • Complement Fixation: No • Placental Transfer: No • Known Functions: Localized protection of mucosal surfaces. Provides immunity to infant digestive tract.

  16. Important function of immunoglobulins

  17. Another way to classify antibody

  18. Humoral & Cellular immunity I. Humoral (Antibody-Mediated) Immunity • Involves production of antibodies against foreign antigens. • Antibodies are produced by a subset of lymphocytes called B cells. • B cells that are stimulated will actively secrete antibodies and are called plasma cells. • Antibodies are found in extracellular fluids (blood plasma, lymph, mucus, etc.) and the surface of B cells. • Defense against bacteria, bacterial toxins, and viruses that circulate freely in body fluids, beforethey enter cells. • Also cause certain reactions against transplanted tissue.

  19. Antibodies are Produced by B Lymphocytes

  20. Primary and Secondary response • Primary response – after first exposure to an Ag immune system produces IgM and a gradual increase in Ab titer • Secondary response –after second contact with the same Ag, immune system produces a more rapid, stronger response due to memory cells

  21. Humoral & Cellular immunity II. Cell Mediated Immunity • Involves specialized set of lymphocytes called T cells that recognize foreign antigens on the surface of cells, organisms, or tissues: • Helper T cells • Cytotoxic T cells • T cells regulate proliferation and activity of other cells of the immune system: B cells, macrophages, neutrophils, etc. • Defense against: • Bacteria and viruses that are inside host cells and are inaccessible to antibodies. • Fungi, protozoa, and helminths • Cancer cells • Transplanted tissue

  22. Cell Mediated Immunity is Carried Out by T Lymphocytes

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