Disorders in Immunity.


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Disorders in Immunity.

  1. 1. Foundations in Microbiology Chapter 17 PowerPoint to accompany Fifth Edition Talaro Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
  2. 2. Disorders in Immunity Chapter 17
  3. 3. Immunopathology <ul><li>Allergy, hypersensitivity – an exaggerated, misdirected expression of immune responses </li></ul><ul><li>Involves the same types of immune reactions as those at work in protective immunities. </li></ul><ul><li>Autoimmunity – abnormal responses to self Ag </li></ul><ul><li>Immunodeficiency – deficiency or loss of immunity </li></ul><ul><li>Cancer – results from a lack of surveillance </li></ul>
  4. 6. Type I Hypersensitivity <ul><li>Atopy – any chronic local allergy such as hay fever or asthma </li></ul><ul><li>Anaphylaxis – a systemic, often explosive reaction that involves airway obstruction and circulatory collapse </li></ul>
  5. 7. Mechanism of Type I <ul><li>sensitizing dose – on first contact with allergen, specific B cells form IgE which attaches to mast cells and basophils </li></ul><ul><li>provocative dose - subsequent exposure with the same allergen binds to the IgE-mast cell complex </li></ul><ul><li>degranulation releases mediators with physiological effects such as vasodilation and bronchoconstriction </li></ul><ul><li>symptoms are rash, itching, redness, increased mucous discharge, pain, swelling, and difficulty breathing </li></ul>
  6. 9. Role of Mast Cells & Basophils <ul><li>Mast cells are located in the connective tissue of virtually all organs; high conc. in lungs, skin, GI and genital tract </li></ul><ul><li>Basophils circulate in blood, migrate into tissues </li></ul><ul><li>each cell can bind 10,000-40,000 IgE </li></ul><ul><li>cytoplasmic granules contain physiologically active cytokines, histamine, etc </li></ul><ul><li>cells degranulate when stimulated by allergen </li></ul>
  7. 10. Chemical mediators
  8. 12. Systemic Anaphylaxis <ul><li>Sudden respiratory and circulatory disruption that can be fatal in a few minutes </li></ul><ul><li>Allergen and route are variable </li></ul><ul><li>Bee stings, antibiotics or serum injection </li></ul>
  9. 13. Strategies for circumventing allergic attacks
  10. 14. Blocking Ab
  11. 15. Type II Hypersensitivity <ul><li>Reactions that lyse foreign cells </li></ul><ul><li>Involve antibodies, complement, leading to lysis of foreign cells </li></ul><ul><li>Transfusion reactions </li></ul><ul><ul><li>ABO blood groups </li></ul></ul><ul><ul><li>Rh factor – hemolytic disease of the newborn </li></ul></ul>
  12. 20. Type III Hypersensitivity <ul><li>A large quantity of soluble foreign Ag stimulates Ab that produce small, soluble Ag-Ab complexes </li></ul><ul><li>Immune complexes become trapped in tissues & incite a damaging inflammatory response </li></ul><ul><ul><li>Arthus reaction – local reaction to series of injected Ag to same body site </li></ul></ul><ul><ul><li>Serum sickness – systemic disease resulting from repeated injections of foreign proteins </li></ul></ul>
  13. 22. Autoimmunity <ul><li>In certain type I & II hypersensitivities, the immune system has lost tolerance to self molecules and forms autoantibodies and sensitized T cells against them. </li></ul><ul><li>More common in females </li></ul><ul><li>Disruption of function can be systemic or organic specific </li></ul><ul><ul><li>Systemic lupus erythematosus </li></ul></ul><ul><ul><li>Rheumatoid arthritis </li></ul></ul><ul><ul><li>Endocrine autoimmunities </li></ul></ul><ul><ul><li>Myasthenia gravis </li></ul></ul><ul><ul><li>Multiple sclerosis </li></ul></ul>
  14. 27. Type IV Hypersensitivity <ul><li>Cell-mediated </li></ul><ul><li>A delayed response to Ag involving activation of and damage by T cells </li></ul><ul><li>Delayed allergic response – skin response to allergens – tuberculin skin test, contact dermititis from plants, metals, cosmetics </li></ul><ul><li>Graft rejection – reaction of cytotoxic T cells directed against foreign cells of a grafted tissue; involves recognition of foreign HLA </li></ul>
  15. 31. Immunodeficiency diseases <ul><li>Components of the immune response system are absent. Deficiencies involve B and T cells, phagocytes, and complement </li></ul><ul><ul><li>Primary immunodeficiency – genetically based congenital lack of B-cell and/or T cell activity </li></ul></ul><ul><ul><li>B cell defect – agammaglobulinemia – patient lacks antibodies </li></ul></ul><ul><ul><li>T cell defect – thymus is missing or abnormal </li></ul></ul><ul><ul><li>Severe combined immunodeficiency - both limbs of lymphocyte system are missing or defective; no adaptive immune response </li></ul></ul><ul><ul><li>Secondary (acquired) immune deficiency – due to damage after birth (infections, drugs, radiation) AIDS </li></ul></ul>
  16. 33. Cancer <ul><li>Overgrowth of abnormal tissue arises due to malfunction of immune surveillance </li></ul><ul><li>Tumors may be benign (nonspreading) or malignant (a cancer) that spreads from tissue of origin to other sites </li></ul><ul><li>Malignant tumors may be </li></ul><ul><ul><li>carcinomas originate from epithelial tissue </li></ul></ul><ul><ul><li>sarcomas originate from embryonic connective tissue </li></ul></ul><ul><li>Cancers occur in nearly every cell type </li></ul>
  17. 34. Characteristics of cancerous growths <ul><li>Disorganized behavior and independence from surrounding normal tissues </li></ul><ul><li>Permanent loss of cell differentiation </li></ul><ul><li>Expression of special markers on their surface </li></ul>
  18. 35. Interrelationship between genes and cancer <ul><li>Cancer cell often have damaged chromosomes </li></ul><ul><li>A specific alteration in a gene can lead to cancer </li></ul><ul><li>Predisposition for some cancers is inherited </li></ul><ul><li>Rates of cancer are highest in individuals who cannot repair damaged DNA </li></ul><ul><li>Mutagenic agents cause cancer </li></ul><ul><li>Cells contain genes that can be transformed to cancer-causing oncogenes </li></ul><ul><li>Tumor-supressor genes exist in the normal genome </li></ul>
  19. 36. Mechanism of Cancer <ul><li>Some type of gene alteration turns a normal gene (proto-oncogene) that regulates the onset of mitosis into an oncogene </li></ul><ul><li>The oncogene overrides normal mitotic controls and cause the cell to divide continuously </li></ul><ul><li>Tumor suppressor genes may be missing or inactivated </li></ul>
  20. 38. Role of viruses in cancer <ul><li>Some viruses carry oncogenes whose products cause transformation of host cells into cancer cells </li></ul><ul><li>Viral genome may be inserted into regulatory sites </li></ul><ul><li>Human papillomavirus cervical cancer </li></ul><ul><li>Epstein-Barr virus – Burkitt’s lymphoma </li></ul>
  21. 41. Function of immune system in cancer <ul><li>Cells with cancer-causing potential arise constantly in the body but the immune system normally discovers and destroys them </li></ul><ul><li>Cell-mediated immunity, T C , NK & macrophages, antibodies </li></ul><ul><li>Immune system fails in cancer </li></ul><ul><ul><li>may not be immunogenic enough </li></ul></ul><ul><ul><li>may retain self-markers and not be targeted </li></ul></ul><ul><li>Maybe a slight or transient failure allows cancer to develop </li></ul>