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Clinical Immunology When the Immune System Causes Disease
Clinical Immunology When the Immune System Causes Disease
Clinical Immunology When the Immune System Causes Disease
Clinical Immunology When the Immune System Causes Disease
Clinical Immunology When the Immune System Causes Disease
Clinical Immunology When the Immune System Causes Disease
Clinical Immunology When the Immune System Causes Disease
Clinical Immunology When the Immune System Causes Disease
Clinical Immunology When the Immune System Causes Disease
Clinical Immunology When the Immune System Causes Disease
Clinical Immunology When the Immune System Causes Disease
Clinical Immunology When the Immune System Causes Disease
Clinical Immunology When the Immune System Causes Disease
Clinical Immunology When the Immune System Causes Disease
Clinical Immunology When the Immune System Causes Disease
Clinical Immunology When the Immune System Causes Disease
Clinical Immunology When the Immune System Causes Disease
Clinical Immunology When the Immune System Causes Disease
Clinical Immunology When the Immune System Causes Disease
Clinical Immunology When the Immune System Causes Disease
Clinical Immunology When the Immune System Causes Disease
Clinical Immunology When the Immune System Causes Disease
Clinical Immunology When the Immune System Causes Disease
Clinical Immunology When the Immune System Causes Disease
Clinical Immunology When the Immune System Causes Disease
Clinical Immunology When the Immune System Causes Disease
Clinical Immunology When the Immune System Causes Disease
Clinical Immunology When the Immune System Causes Disease
Clinical Immunology When the Immune System Causes Disease
Clinical Immunology When the Immune System Causes Disease
Clinical Immunology When the Immune System Causes Disease
Clinical Immunology When the Immune System Causes Disease
Clinical Immunology When the Immune System Causes Disease
Clinical Immunology When the Immune System Causes Disease
Clinical Immunology When the Immune System Causes Disease
Clinical Immunology When the Immune System Causes Disease
Clinical Immunology When the Immune System Causes Disease
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Clinical Immunology When the Immune System Causes Disease

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  • 1. Clinical Immunology When the Immune System Causes Disease or Doesn’t Work
  • 2. Immune Deficiencies and Hypersensitivities
  • 3. Allergies and Autoimmunity <ul><li>Allergies are IgE immune responses to harmless antigens </li></ul><ul><li>The immune response causes the disease = hypersensitivity </li></ul><ul><li>Other hypersensitivities are caused by IgG or by Th1 or Tc activities </li></ul><ul><li>Autoimmune reactions occur against self antigens </li></ul>
  • 4. Hypersensitivities
  • 5. Type I Hypersensitivity: Allergy <ul><li>Immediate hypersensitivity </li></ul><ul><li>Reaction in ~ 30 minutes </li></ul><ul><li>Inflammation </li></ul><ul><li>Symptoms depend on where allergen enters </li></ul>
  • 6. Common Allergens <ul><li>Pollens </li></ul><ul><li>Cat dander </li></ul><ul><li>Dust mite feces </li></ul><ul><li>Food antigens </li></ul>
  • 7. Type I (Immediate) Hypersensitivity
  • 8. Effects of Allergic Mediators
  • 9. <ul><li>Systemic anaphylaxis : inflammation throughout circulation  death </li></ul>
  • 10. IgE Effector Function <ul><li>Eosinophils bind an IgE-coated schistosome larva via Fc  receptors </li></ul>
  • 11. Hygiene Hypothesis <ul><li>Asthma rates are increasing in the US </li></ul><ul><li>Children in day care have lower asthma rates than children kept at home </li></ul><ul><li>People from areas with high helminth infections have low allergy rates </li></ul><ul><ul><li>When those people move to the US, their allergy rates increase </li></ul></ul>
  • 12. Strategies for Avoiding Allergic Symptoms
  • 13. Allergy Shots <ul><li>Shots induce IgG formation; IgG binds all the allergen so it can’t reach IgE on mast cells </li></ul>
  • 14. Hypersensitivities
  • 15. Type II Hypersensitivity <ul><li>IgG/IgM antibodies bind RBC antigens </li></ul><ul><li>Complem e nt is activated, lyses RBC </li></ul><ul><li>ADCC: macrophages or NK cells bind antibody-coated RBC, kill them </li></ul>
  • 16. Hemolytic Disease of the Newborn
  • 17. Prevention of Hemolytic Disease of the Newborn
  • 18. Other Type II Hypersensitivities <ul><li>Medication allergies </li></ul><ul><li>Mismatched blood (transfusion rxn) </li></ul><ul><li>Rheumatic fever (Strep throat) </li></ul><ul><li>Autoimmune hemolytic anemia </li></ul>
  • 19. Hypersensitivities
  • 20. Immune Complex Disease
  • 21. Type III Hypersensitivities <ul><li>Serum sickness: horse anti-snake venom </li></ul><ul><li>Lyme arthritis </li></ul><ul><li>Systemic lupus erythematosis (SLE): autoimmune disease </li></ul>
  • 22. Hypersensitivities
  • 23. Type IV: T-Cell Mediated Poison Ivy
  • 24. Contact Dermatitis
  • 25. Type IV Hypersensitivities <ul><li>TB Skin test </li></ul><ul><li>Contact dermatitis to nickel </li></ul><ul><li>Chronic asthma </li></ul><ul><li>Autoimmune diabetes (Type I) </li></ul><ul><li>Transplant rejection </li></ul>
  • 26. Transplant Rejection Responses
  • 27. Transplant Rejection <ul><li>Organ grafts: Host T cells kill cells in graft with foreign MHC I and II </li></ul><ul><li>Bone Marrow Transplant: mature T cells in graft kill cells in host with foreign MHC I and II </li></ul>
  • 28. MHC Inheritance
  • 29. Transplant Rejection <ul><li>We each have ~6 different Class I and ~6 different Class II MHC proteins; each has many alleles </li></ul><ul><li>Best chance of sharing MHC alleles is between close blood relatives </li></ul><ul><li>No time for tissue typing in heart transplants; just do blood typing </li></ul>
  • 30. Anti-Rejection Drugs <ul><li>Block inflammation </li></ul><ul><ul><li>corticosteroids </li></ul></ul><ul><li>Block T cell activity </li></ul><ul><ul><li>Cyclosporine A </li></ul></ul><ul><ul><li>monoclonal antibodies </li></ul></ul>
  • 31. Autoimmunity <ul><li>Often triggered by an infection </li></ul><ul><li>Molecular mimicry : Immune response to a pathogen antigen generates antibodies and T cells that also bind self antigens </li></ul><ul><li>Linked to certain MHC alleles </li></ul>
  • 32. Autoimmune (Type I) Diabetes <ul><li>Virus infection (Coxsackie) </li></ul><ul><li>Anti-virus T cells recognize self peptides on islets </li></ul><ul><li>Islets destroyed --&gt; insulin dependence </li></ul>
  • 33. Role of MHC in Diabetes ©1999 by Elsevier Science Ltd/Garland Publishing From Immunobiology: The immune system in health and disease by Charles A. Janeway
  • 34. Immune Deficiencies <ul><li>Inborn </li></ul><ul><ul><li>usually a problem in cell development or mutation in gene for an essential protein </li></ul></ul><ul><li>Acquired </li></ul><ul><ul><li>usually due to microbe virulence factors </li></ul></ul>
  • 35. Immune Deficiencies <ul><li>Also deficiencies of innate immunity </li></ul>
  • 36. David the “Bubble Boy” <ul><li>SCID: no T or B cells </li></ul><ul><li>Kept alive in sterile environment </li></ul><ul><li>Died from cancer caused by EBV in bone marrow transplant from his sister </li></ul>
  • 37. What You Should Know <ul><li>Mechanisms of hypersensitivities </li></ul><ul><li>Normal function of IgE </li></ul><ul><li>Role of MHC in transplant rejection and autoimmunity </li></ul><ul><li>Molecular mimicry trigger for autoimmunity </li></ul><ul><li>SCID </li></ul>

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