DON’T TOUCH THE POISON IVY! Fantastic Voyage Revisited: a conversation about the immune system, allergic hypersensitivity, and selected immunological issues OUTLINE OF ACTIVITY An overview of the immune system and vaccination stories (45 min) followed by a 15 minute break. Hypersensitivity (Bee stings and Poison Ivy), Anaphylaxis and stories (45 min) followed by a 15 minute break. Selected immune disorders [Hepatitis B, Type I Diabetes, HIV/AIDS, & one Zoonotic Example] (45 min) followed by discussion 15 minutes. *Constant questioning would be appreciated, let’s make this a conversation rather than a lecture! LET’S BEGIN THE FANTASTIC VOYAGE WHY DO WE NEED AN IMMUNE SYSTEM? BACTERIA, VIRUSES, FUNGI, PARASITES & NEOPLASTIC CELLS THINGS TO REMEMBER ON THE JOURNEY! Recognition Specificity Regulation Memory SO WHAT MAKES UP AN IMMUNE SYSTEM WHOA! ANTIGEN PRESENTATION AND T-CELL HELP & MEMORY HUMMORAL IMMUNITY B-CELL ACTIVATION ANTIBODY STRUCTURE KILLING OF MICROBES BY ANTIBODY CELLULAR IMMUNITY KILLING OF MICROBES BY CELLULAR IMMUNITY VACCINATION VACCINATION RATIONALE Vaccine Development Observations of natural immunity Identification of immunological targets Formulation and manufacturing Clinical trials, safety, efficacy Marketing Expected Outcome Elimination of clinical infection Eradication of disease All in the presence of evolving organisms, politics, opinions, legal challenges, and markets HOLD THAT THOUGHT! WE WILL BEGIN TO ITCH IN THE NEXT HALF HOUR. IGE-DEPENDENT IMMUNE RESPONSES & ALLERGIC DISEASE ACTIVATION OF TH2 CELLS AND PRODUCTION OF IGE Nature of Allergens WHAT HAPPENS UPON EXPOSURE TO ALLERGEN (ANTIGEN) MAST CELLS, BASOPHILS, & EOSINOPHILS MAST CELL & BASOPHIL MEDIATORS Biogenic amines Granule enzymes Proteoglycans Cytokines Lipid mediators Prostaglandin D2 Leukotrienes EOSINOPHIL MEDIATORS Granule proteins that are toxic to parasitic organisms and may injure normal tissue. Major basic protein Eosinophil cationic protein Eosinophil peroxidase Lipid mediators THE IMMEDIATE REACTION The wheal and flare reaction THE LATE-PHASE REACTION IGE MEDIATED ALLERGIC DISEASES Systemic Anaphylaxis ANAPHYLAXIS Vasodilation, fall in blood pressure (shock) Smooth muscle constriction of upper and lower airways, laryngeal edema, hypermotility of the gut, outpouring of mucous in the gut and respiratory tract, hives in the skin (respiratory distress) Epinephrine (adrenalin) reverses bronchoconstriction, vasodilation and increases cardiac output Antihistamines may also be beneficial OTHER IGE MEDIATED ALLERGIC DISEASES Bronchial Asthma Allergic Rhinitis Food allergies Urticaria and Eczema IMMUNOTHERAPY Desensitization (allergy shots) Shift from IgE to IgG Specific T cell tolerance Th2 to Th1 SO WHAT IS THE VALUE OF IGE & MAST CELLS? Protection against parasites Mast cells play an important protective role as part of innate immune response to bacterial infections Slower bleeding time in atopics, sudden cardiac arrest less common As a result of heightened response, protection against arthropod vectored diseases (my speculation) Just an unfortunate consequence of otherwise protective responses. The price we have to pay? Or have some organisms through evolution co-opted hypersensitivity to there own benefit (toxins)? CUTANEOUS “DELAYED” T-CELL MEDIATED HYPERSENSITIVITY Poison Ivy/Poison Oak Contact allergens Urushiol ALLERGIC DISEASE IN CATTLE: PSOROPTIC SCABIES (COWS ITCH TOO!!) YES!! ADDITIONAL IMMUNOLOGICAL TOPICS Autoimmune disease, > 30 diseases or syndromes Transplantation immunology Neuroimmunology Reproductive immunology Tumor immunology AUTOIMMUNE HEPATITIS Infection of the liver with the hepatitis B virus (HBV, serum hepatitis) 350 million people affected worldwide Little cytopathology caused by the virus Liver damage can be massive and devastating When serious damage occurs, it is the immune system that causes most, if not all, of the damage Both CD4 and CD8 cells are activated and a delayed-hypersensitivity reaction ensues. AUTOIMMUNITY: DIABETES (TYPE I) INSULIN DEPENDENT Age of onset 11 to 12 years Chronic autoimmune disease destroying the insulin + producing βcells in the pancreas (CD4 TH1, Cytokine TNF and IL-1, and potentially anti-insulin antibodies) No gender bias Strong genetic component (HLA-DR3, DR4) Possible onset with environmental “triggers” Viral infection, an example Serotype B Coxsackie virus Tandem repeats within the insulin promoter (genetic) T cells the major destructive agent with antigen being glutamic acid decarboxylase (GAD). Insulin itself also appears to be a target. Epidemiology data suggest that repeated infection protects from diabetes. Possible reason for increase incidence in developed countries. New Therapies: inducing immunological tolerance, generating or giving regulatory T cells to patients. A VIRAL DISEASE AFFECTING THE IMMUNE SYSTEM: HIV/AIDS First reported in 1981, opportunistic infections, Pneumocystis carinii, oral candidiasis, tuberculosis, and Kaposi’s sarcoma The human immunodeficiency virus (HIV) was identified in 1983 as a retrovirus. The coat proteins mutate at an extraordinarily high rate. Infects and causes a gradual loss of CD4 helper T cells Drug treatment is of 4 categories: nucleoside analogs, reverse transcriptase inhibitors, protease inhibitors and fusion inhibitors. HIV HIV has a surface coat protein gp 120 that specifically recognizes and binds to the CD4 molecule found on CD4 T cells Following binding the gp 120 molecule twists and reveals a second binding molecule gp 41 that binds a second coreceptor of the CD4 cell surface, called fusin. With both binding events the virus can enter the cell. Therapy Drug Cocktails – enfuvirtide blocks gp 41/fusin Vaccine is available for SIV and FIV, and observe cases of natural effective immunity. DNA based vaccine/CD8 preferential stimulation Molecular Medicine (gene therapy) antisense with target of suppression of fusin Selective expression of thymidine kinase and treatment with acyclovir ZOONOTIC IMMUNE DISORDER: CATTLE GRUB, HYPODERMA LINEATUM IMMUNE DISORDERS Human Case of Cattle Grub Infestation THE END BUT STAY TUNED .