Humoral Immunity Lecture (2)


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Humoral Immunity Lecture (2)

  1. 2. HUMORAL IMMUNITY <ul><li>Antibody mediated </li></ul><ul><li>Part of Specific immunity along with cell-mediated type </li></ul><ul><li>When Nonspecific immunity fails, tissue macrophages take up the organisms </li></ul><ul><li>specific immune responses activated </li></ul><ul><li>Antibody is synthesized </li></ul>
  2. 3. HUMORAL IMMUNITY <ul><li>Primary molecular component: antibody </li></ul><ul><li>Ab is made by B-cells and plasma cells in response to Ag challenge </li></ul><ul><li>Ab: protection vs rechallenge </li></ul><ul><li>block spread of agent in blood </li></ul><ul><li>facilitate elimination of infectious agent </li></ul><ul><li>Ab must also interact with host cells (macrophage, complement) </li></ul><ul><li>Ab also serve as B-cell receptors to stimulate plasma cell growth and produce more Abs </li></ul>
  3. 5. HUMORAL IMMUNITY <ul><li>General Properties of an Antigen: </li></ul><ul><li>Foreignness </li></ul><ul><li>Chemical composition </li></ul><ul><li>> CHONs are best immunogens, CHOs are </li></ul><ul><li>weak; Lipids and nucleic acids: poor </li></ul><ul><li>Molecular size </li></ul><ul><li>500-1000 Da= min size for immunogenicity </li></ul><ul><li><10,000 Da = weak immunogen </li></ul><ul><li>>10,000 Da = strong immunogen </li></ul>
  4. 6. HUMORAL IMMUNITY <ul><li>General Properties of an Antigen: </li></ul><ul><li>Chemical Complexity </li></ul><ul><li>Response to Ag may vary according to: </li></ul><ul><li>Genetic composition of the host </li></ul><ul><li>Method of administration and dose </li></ul>
  5. 8. HUMORAL IMMUNITY <ul><li>ADJUVANT: when mixed with Ag enhances duration and magnitude of the immune response by: </li></ul><ul><li>Prolonging retention of immunogen </li></ul><ul><li>Increasing effective size of immunogen </li></ul><ul><li>Stimulating local influx of macrophages and/or other immune cell types to the injection site. </li></ul><ul><li>Ex. Freund’s adjuvant, liposomes, bacterial cell wall components, molecular cages for Ag and polymeric surfactant, E.coli, cholera toxin </li></ul>
  6. 9. HUMORAL IMMUNITY <ul><li>Immunogen = substance capable of eliciting an immune response </li></ul><ul><li>Antigen = substance recognized by immune response </li></ul><ul><li>Epitope = Molecular structure recognized by immune response </li></ul><ul><li>Hapten = incomplete immunogen that cannot initiate response but that can be recognized by Ab </li></ul>
  7. 10. HUMORAL IMMUNITY <ul><li>Carrier = protein modified by hapten to elicit response </li></ul><ul><li>Adjuvant = substance that promotes immune response to an Ag </li></ul><ul><li>T-independent Ags = Ags with large repetitive structures (e.g., bacteria, flagellin, lipopolysaccharide, polysaccharide) </li></ul><ul><li>T-dependent Ags = Ags that must be presented to T and B cells for Ab production </li></ul>
  8. 12. HUMORAL IMMUNITY <ul><li>Immune Component: Fc Receptor </li></ul><ul><li>Interaction: macrophage (opsonization) </li></ul><ul><li>PMNs (opsonization) </li></ul><ul><li>T cells (activation) </li></ul><ul><li>NK cells, ADCC (killing) </li></ul><ul><li>Mast cells for IgE (allergic </li></ul><ul><li>reactions, anti-parasitic) </li></ul>
  9. 13. HUMORAL IMMUNITY <ul><li>Immune Component: Complement </li></ul><ul><li>Interaction: Complement system </li></ul><ul><li>Function: Opsonization </li></ul><ul><li>Killing (especially bacteria) </li></ul>
  10. 15. HUMORAL IMMUNITY <ul><li>Antimicrobial Action of Antibodies: </li></ul><ul><li>Opsonic; promote ingestion and killing by phagocytic cells </li></ul><ul><li>Neutralize (block attachment) toxins and viruses </li></ul><ul><li>Agglutinate bacteria; may aid in clearing </li></ul><ul><li>Render motile organisms nonmotile </li></ul>
  11. 16. HUMORAL IMMUNITY <ul><li>Antimicrobial Action of Antibodies: </li></ul><ul><li>5. Combine with Ags on the microbial surface, activate complement cascade, thus inducing an inflammatory response, bringing fresh phagocytes and serum Abs into the site </li></ul><ul><li>6. Combine with Ags on the microbial surface, activate complement cascade, anchor the membrane attack complex (C5b to C9) </li></ul>
  12. 19. HUMORAL IMMUNITY <ul><li>Immuneglobulins (Antibodies) </li></ul><ul><li>1. IgD </li></ul><ul><li>> exists primarily as membrane/surface IgD on B-cell, along with IgM they are the only isotypes expressed by the same cell </li></ul><ul><li>> no known biologic function </li></ul><ul><li>> less than 1% of serum Igs </li></ul><ul><li>> 185 kDa molecular mass </li></ul>
  13. 20. HUMORAL IMMUNITY <ul><li>Immuneglobulins (Antibodies) </li></ul><ul><li>2. IgM </li></ul><ul><li>> first Ab produced versus Ag challenge </li></ul><ul><li>> can be produced in T-independent manner </li></ul><ul><li>> 5-10% of total Igs in the adult </li></ul><ul><li>> half life 5 days </li></ul><ul><li>> pentameric: 5 units joined by disulfide bonds and the J chain (900 kDa) </li></ul>
  14. 21. HUMORAL IMMUNITY <ul><li>Immuneglobulins (Antibodies) </li></ul><ul><li>2. IgM </li></ul><ul><li>> theoretically has 10 Ag binding sites; </li></ul><ul><li>> binds complement the best (1 pentamer activates the classic pathway) </li></ul><ul><li>> Monomeric IgM is with IgD on surface of B cells </li></ul><ul><li>> cannot go from blood to tissue because of size </li></ul>
  15. 22. HUMORAL IMMUNITY <ul><li>Immuneglobulins (Antibodies) </li></ul><ul><li>2. IgM </li></ul><ul><li>> immunity vs polysaccharide Ags (capsules) </li></ul><ul><li>> promotes phagocytosis and bacteriolysis through complement activation </li></ul><ul><li>> major component of rheumatoid factors </li></ul>
  16. 23. HUMORAL IMMUNITY <ul><li>Immuneglobulins (Antibodies) </li></ul><ul><li>3. IgG </li></ul><ul><li>> about 85% of all Igs in the adult </li></ul><ul><li>> half life of 23 days (longest) </li></ul><ul><li>> molecular mass of 184 kDa </li></ul><ul><li>> 2 L chains of 22,000 Da and 2 H chains of 55,000 Da each </li></ul><ul><li>> 4 subclasses: IgG 1-4, diff structure, relative concentration and function </li></ul>
  17. 24. HUMORAL IMMUNITY <ul><li>Immuneglobulins (Antibodies) </li></ul><ul><li>3. IgG </li></ul><ul><li>> production is T-cell dependent; can cross the placenta </li></ul><ul><li>> principal Ig in booster and anamnestic response </li></ul><ul><li>> high binding capacity for Ags, fixes complement, stimulates chemotaxis and acts as opsonin </li></ul>
  18. 26. Cross-reactive antibodies <ul><li>May react with more than 1 microorganism when they share similar Ag’ic determinants </li></ul><ul><li>Historically called Natural antibodies </li></ul><ul><li>Immune properties well documented in lab animals </li></ul><ul><li>Often directed against polysaccharides with similar structures across different species, genera and families </li></ul>
  19. 27. HUMORAL IMMUNITY <ul><li>Immuneglobulins (Antibodies) </li></ul><ul><li>4. IgA </li></ul><ul><li>> 5-15% of all Igs in the adult </li></ul><ul><li>> half life of 6 days </li></ul><ul><li>> molecular mass of 160 kDa, basic 4-chain monomer, but can occur as dimers, trimers or multimers thru the J chain </li></ul><ul><li>> Secretory Iga = appears in body secretions for local immunity </li></ul>
  20. 28. HUMORAL IMMUNITY <ul><li>Immuneglobulins (Antibodies) </li></ul><ul><li>4. IgA </li></ul><ul><li>> production requires T-cell help and mucosal stimulation by adjuvants like cholera toxin and attenuated salmonella </li></ul><ul><li>> binds to poly-Ig receptors on epithelial cells for transport across cells </li></ul><ul><li>> remains bound to IgA and cleaved to become Secretory Component once secretory IgA is secreted </li></ul>
  21. 29. HUMORAL IMMUNITY <ul><li>Immuneglobulins (Antibodies) </li></ul><ul><li>4. IgA </li></ul><ul><li>> about 2 gms of IgA/day secreted by adults </li></ul><ul><li>> appears in colostrum, intestinal and respiratory secretions, saliva, tears and other secretions </li></ul><ul><li>> IgA-deficient persons have more frequent respiratory tract infections </li></ul>
  22. 30. Pneumonia in IgA Deficiency
  23. 31. HUMORAL IMMUNITY <ul><li>Immuneglobulins (Antibodies) </li></ul><ul><li>5. IgE </li></ul><ul><li>> less than 1% of total serum Igs in adults </li></ul><ul><li>> half life of about 2.5 days </li></ul><ul><li>> most are bound to Fc receptors on mast cells and serve as receptors for allergens and parasite Ags </li></ul><ul><li>> once Ige is bound by Ag, mast cells release histamine, prostaglandin, platelet activating factors and cytokines </li></ul>
  24. 32. HUMORAL IMMUNITY <ul><li>Immuneglobulins (Antibodies) </li></ul><ul><li>5. IgE </li></ul><ul><li>> serve as protection versus parasitic infections </li></ul><ul><li>> responsible for the manifestations of anaphylactic (Type 1) hypersensitivity </li></ul>
  25. 33. Anaphylactic shock
  26. 34. THANK YOU