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MICROBIOLOGY- ALCAMO
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  1. MICROBIOLOGY- ALCAMO LECTURE: IMMUNE DISORDERS

  2. IMMUNE DISORDERS • Faulty immune system can either: • Over-react or • Under-react

  3. Introduction – Hay Fever • Hay fever – not dangerous, but causes great discomfort and inconvenience • 1870’s – British scientist Charles Blackley found that pollen grains could: • When placed in the eyes of some people, cause swelling • When rubbed into a skin scratch produce a local reaction

  4. Introduction Hay Fever • Now a known disorder of the immune system • About 35 million Americans suffer from hay fever • Thousands more are allergic to foods, cosmetics, leather or metals, and pets • Approximately 40-50 million people in the U.S. have some type of allergy

  5. Introduction – Hay Fever • The common denominator among allergies is hypersensitivity • Hypersensitivity stems from the activity of the immune system and involves both • Antibody mediated immunity • Cellular aspects of immunity • Currently intense research is going on to find ways to alleviate allergy symptoms

  6. Hypersensitivity • Multi-step phenomenon requiring: • Initial exposure to an antigen • Dormant stage when person is sensitized • Reaction to a second exposure to antigen • Reaction can be: • Immediate – response by antibodies within minutes • Delayed - cell mediated response over 2-3 days

  7. Hypersensitivity • Early 1970’s Gell and Coombs further classified Hypersensitivities • Immediate Hypersensitivity • 1. Type I Anaphylactic Hypersensitivity • 2. Type II Cytotoxic Hypersensitivity • 3. Type III Immune Complex Hypersensitivity • Delayed Hypersensitivity • 4. Type IV Cellular Hypersensitivity

  8. TYPE 1 ANAPHYLACTIC HYPERSENSITIVITY • Begins with entry of antigenic substance (allergens – bee venom, serum proteins, drugs, etc) • Sensitizing Dose – smallest dose of an allergen that sensitizes a person to cause a reaction (can be as low as 0.001 mg) • Immune system responds and B-lymphocytes produce IgE

  9. TYPE 1 ANAPHYLACTIC HYPERSENSITIVITY • IgE enters circulation and attaches to thousands of: • Mast cells (connective tissue cells with granules) • Basophils (white blood cells with granules) • Granules are released, flow into extracellular fluids and emit mediators: • Histamine • Serotonin

  10. TYPE 1 ANAPHYLACTIC HYPERSENSITIVITY • Mediators – principal activity is to contract smooth muscles in the body - Anaphylaxis • This constricts veins and capillaries and forces fluid out into the tissues • The skin becomes swollen around the eyes, wrists and ankles – called edema • This is accompanied by a hive-like rash and burning and itching of the skin as nerves are excited

  11. TYPE 1 ANAPHYLACTIC HYPERSENSITIVITY • Contractions also occur in the gastrointestinal tract (causes sharp cramps) and bronchial muscles (causes shortness of breath) • Person inhales rapidly, but can’t exhale to get rid of CO2 • Death can occur within 10-15 minutes due to asphyxiation

  12. WHOLE BODY INVOLVEDGet medical help fast!!!!!

  13. Medical Help • Adrenalin – stabilizes basophils and mast cells, opens air passages and constricts capillaries • Muscle relaxer – opens air passages, stops cramping • Antihistamine – competes with histamine for active sites on smooth muscle cells and inhibits histamine’s actions • If all else fails - tracheostomy

  14. TYPE 1 ANAPHYLACTIC HYPERSENSITIVITY • Desensitization – therapy used to reduce the possibility of anaphylaxis • Short-term - can inject tiny but increasing amounts of allergen over a period of hours to induce a gradual reduction of granules rather than a later massive degranulation • Long-term - can give a series of injections of allergen over a few weeks and the exposure causes immune system to produce IgG which can neutralize sensitized cells.

  15. Atopic Disease/Allergy • Also Type I Hypersensitivity, but in localized areas • Hay Fever: • immune stimulation by pollen antigens leads to IgE production • sensitization of mast cells in the eyes, nose and upper respiratory tract • Subsequent exposure causes the all too familiar sneezing, tearing and swollen mucous membranes

  16. Asthma • Asthma attacks are triggered by allergic reactions • Characterized by wheezing and stressed breathing • 15 million Americans suffer from asthma • Doctors usually prescribe bronchodilators and/or anti-inflammatory agents (steroids)

  17. Food Allergies • Characterized by symptoms in the gastrointestinal tract • Swollen lips • Abdominal cramps • Nausea and diarrhea • May develop urticaria – rash containing hives • Allergenic foods – chocolate, strawberries, oranges, cow’s milk and fish

  18. Why Me???? • Almost 20 % of Americans have some sort of allergy • Allergic individuals have 100 times the IgE level of normal individuals • Hypotheses: • IgA levels are greatly reduced in people with allergies. In normal people IgA may shield IgE lymphocytes from antigenic stimulation • Immune system feedback mechanisms are defective in allergic individuals (suppressor T-lymphocytes)

  19. Type II Cytotoxic Hypersensitivity • Cell-destroying reaction that occurs when IgG reacts with antigens on the surface of target cells • Transfusion reaction – mixing incompatible blood types • Human Blood Types: A, B, AB and O • Each type has antigens on the surface of RBC’s • If given the wrong blood type, a person’s antibodies will react with the antigens and agglutination (clumping) occurs

  20. Hemolytic or Rh Disease • 85-90% of Americans’ RBC’s have a surface antigen (Rh) and are Rh+ • If an Rh- woman marries an Rh+ man, there is a 75% chance the baby will be Rh+ • A first pregnancy will stimulate the production of Rh+ antibodies in the woman • In any subsequent pregnancies, the woman’s body will see the baby’s blood as foreign and destroy its blood cells • Treatment – injection of Rh antibodies within 72 hours of birth will remove Rh antigens from blood

  21. Autoimmune Diseases – Fighting Yourself • Thrombocytopenia – antibodies produced against thrombocytes • Leads to impaired blood clotting and hemorrhages on skin and mouth

  22. Goodpasture’s Syndrome • Antibodies combine with antigens in the kidneys and lungs • Can cause kidney and lung failure

  23. Myasthenia Gravis • Antibodies generated against muscle fiber membranes • Reduces nerve impulse transfer and results in loss of muscle activity, weakness, fatigue

  24. Graves’ Disease • Antibodies unite with receptors on the surface of thyroid gland cells causing increased secretion of thyroxine • This results in goiter and rise in metabolic rate

  25. TYPE III Immune Complex Hypersensitivity • When antibodies combine with antigens and form aggregates that accumulate in blood vessels or on tissue surfaces • Phagocytes are attracted to site and enzymes are released that cause tissue damage • Gradual development – usually not life threatening • Serum sickness – IgG produced against serum proteins – can cause kidney damage

  26. TYPE III Immune Complex Hypersensitivity • Systemic lupus erythematosus: • as old white blood cells are • disintegrating, B-lymphocytes produce IgG • Immune complexes accumulate in the skin and body organs • Causes butterfly rash and lesions in the heart, kidney and blood vessels

  27. Rheumatoid Arthritis • Immune complexes form in the joints causing inflammation - debilitating • Chronic disease – may have periods with no pain, but then it returns

  28. TYPE IV Cellular Hypersensitivity • T-cells involved • Delayed Reaction – maximal effect not seen until 24-72 hours has elapsed • Characterized by: • Induration - a thickening and drying of the skin tissue • Erythema – surrounding zone of redness

  29. TYPE IV Cellular Hypersensitivity • There is a localized reaction with lumps, hives or blisters • Contact dermatitis can develop after exposure to many different allergens (clothing, jewelry, cosmetics, fur) • For example: Poison ivy oil on leaves is an allergen

  30. IMMUNE DEFICIENCIES • Bruton’s Agammaglobulinemia: • Congenital disease • B-lymphocytes fail to develop in the bone marrow • No antibodies are made • Can’t fight infectious disease

  31. IMMUNE DEFICIENCIES • DiGeorge’s Syndrome: • Congenital disease • T-lymphocytes don’t develop because of failure in thymus gland • Cellular immunity is defective • Susceptible to fungal and protozoal diseases

  32. IMMUNE DEFICIENCIES • Severe Combined Immunodeficiency (SCID) • Congenital disease • Defects in both antibody and cellular immunity • All immune function is suppressed • David – longest surviving victim • Lived in a sterile, plastic bubble at Baylor College of Medicine for 12 years • Received a bone marrow transplant from his sister but died of blood cancer

  33. http://www.bbc.co.uk/news/health-11451810

  34. Acquired Immune Deficiency (AIDS) • Viral disease • Cellular immunity severely depressed • Antibody-mediated immunity also altered • Have very few T—cells • Ratio of T-cells is reversed: • Normal 2 Helper T-cells:1 Suppressor T-cell • AIDS 1 Helper T-cell:2 Suppressor T-cells