Hypersensitivities, Autoimmune & Immunocompromised Disorders

Hypersensitivities, Autoimmune and Immunocompromised Disordersv    HypersensitivityØ     Classified I-IV by:§       Source of antigen: Environmental, acquired, etc§       Time sequence:       Immediate vs. delayed§       Basic immunologic mechanism causing the injury·       Histamine release, etc.Ø     Causes§       Foods:        Chocolate, eggs, wheat, milk, nuts, seafood (iodine), strawberries§       Medications:                        Antibiotics (Major Offender)§       Dyes in diagnostic tests:       Iodine/Barium §       Animals/pets§       Venoms                              Bees, hornets, wasps, spiders§       Inhalants:                            Allergies, Pollens, dust, cigarette smoke, pollutants    §       Serums: from animals:         Horse serum used in antitoxins§       Contactants:                       Tape, cosmetics§       Intrinsic:                             Bacteria: (G-) →shockv    Types of Hypersensitivity ReactionsØ     Type I- IgE mediated§       Exposure to antigen §       Bind with Mast cells—severe inflammation§       Histamine release—↑ permeability  §       Autonomic nervous system—Controls BP & constriction  §       Genetic predisposition—atopic §       Life threatening—anaphylaxis only§       Desensitization—allergy shotsØ     Type II- Tissue Specific§       Involves tissues and organs§       Antigen reacts with antibody on cell wall§       Antigen-antibody complexes form§       Destruction by:·       Activation of complement cascade resulting in cytolysis·       Enhanced phagocytosis·       Cytoxic T-cell interaction: b/c it thinks it will fight·       Malfunction of cell: if it doesn’t die§       Transfusion Reaction—within 15 minutes. ·       Symptoms:¨     Chills, N/V, Fever, Low back pain from kidneys!       ¨     Hypotension, Tachycardia    ¨     Shock, Anxiety                    ¨     Hyperkalemia         Ø     Type III§       2^ndary to antigen-antibody complexes§       Complexes deposited in tissues/blood vessels/joints→ tissue damage §       Local or systemic§       Immediate or delayed§       Common sites: kidneys, skin, joints§       Examples: SLE, RAØ     Type IV- T-Cell mediated!§       Delayed Hypersensitivity: Start S&S in 24 hrs, but can be months/years.§       T-cells – toxin killing mechanism·       Attack and destroy cells/multiply ·       Recruit phagocytic cellsØ     Example: tissue graft rejection, tuberculin reaction, allergic reactions—delayed and topical. Ex: Poison Ivy.  Usually localized. v    Autoimmune DisordersØ     SystemicØ     Tissue specificØ     Genetic susceptibilityØ     Environmental factors Ø     Systemic Lupus Erythematosus (SLE)§       Chronic§       Inflammatory§       Deposition of immune complexes: Type III Hypersensitivity §       Etiology·       Genetic: Women age 18-40, Blacks, and twins ·       Environmental·       Autoantibodies: against own tissues ·       Anti-nuclear antibodies (ANA)·       Anti-DNA antibodies·       Affect blood cells§       Clinical manifestations·       Facial rash—butterfly rash.  ·       Renal problems—inflammation damages kidneys ·       Arthritis·       Presence of ANA·       Hematological disorders: ↓ WBC/RBC & platelets.§       Diagnosis·       History: Occupation, exposures as child·       PE·       Serum analysis: Anti-DNA antibody most specific §       Treatment:  All treat symptoms b/c no cure!·       NSAIDS—                                Pain & inflammation ·       Antimalarial medication—         Plaquenil ·       Corticosteroids—                     Anti-inflammatory ·       Immunosuppresive Medsv    Host-Verses-Graft RejectionØ     Pathophysiology§       HLA antigens§       Type IV reaction                 T-cells!§       Hyperacute rejection—      Immediate §       Acute rejection—               days→months.  Antibodies against HLA antigen§       Chronic rejection—            months→years. Weak Type 4 reactionv    Graft-Versus-Host Disease:   Graft is rejecting YOU!Ø     Pathophysiology§       Immunocompromised transplantation—common w/ bone marrow transplant§       GVHD development·       Functional cellular immune component—from T-cells·       Foreign antigens·       Immunocompromised recipient§       Acute§       Chronicv    ImmunodeficienciesØ     Congenital=inherited & often opportunistic §       Abnormalities in cell maturation§       Hypogammaglobulinemia—↓ antibodies in blood §       Severe combined immunodeficiencies (SCIDs)·       Cell mediated T-cells & antibody (plasma B-cells)§       Adenosine deaminase deficiency (ADA)·       Lacks enzyme so toxins buildup.  Causes lymphocytes to not mature properly §       Purine nucleoside phosphorylase deficiency (PNP)Ø     DeGeorge Syndrome§       T-Cell deficiency§       Defect on chromosome 22§       Clinical manifestations·       Facial disorders·       Low set and angulated ears·       Hypocalcemia·       Chronic infections§       Treatment·       Thymus transplant·       Bone marrow transplantØ     Selective Immunoglobulin A Deficiency§       Affects mature B cells·       Genetic·       Environmental§       Symptoms·       Asymptomatic·       URI’s·       Allergic manifestations§       Treatment·       NoneØ     Acquired§       Nutritional§       Iatrogenic§       Trauma§       Stressv    AIDSØ     HIV§       Retrovirus§       RNA§       Reverse transcriptase§       Double stranded DNA§       New genetic make-up§       Viremia§       Low HIV levels – 10 to 12 years (poss)·       Replicating at fast rate§       HIV looking for CD4 receptors·       Lymphocytes·       Monocytes/macrophages·       Astrocytes·       Oligodendrocytes §       T cells have more CD4 receptors·       Unfortunate: T- cells play a key role in the immune system’s ability to recognize and defend itself against pathogens·       Normal CD-4 level is 800 – 1200 cells/microliter·       Normal life span = 100 days; HIV = 2 days·       Destroys 1 billion CD4 T cells every day·       Healthy immune system = CD4 T at 500 cells/microliter·       CD4 T= 200-499 – immune problems·       CD4 T= < 200 – opportunistic infectionsØ     Transmission of HIV§       Blood§       Semen and Vaginal fluid§       Breast milk§       Saliva§       Tears§       Sweat§       InsectsØ     Variables for Transmission§       Duration & frequency of contact§       Volume of fluid§       Virulence & concentration of the organism§       Host immune statusØ     Primary Infection Phase§       High viral load§       Dramatic drop in CD4 cell counts§       Flu-like symptoms§       Window period§       Antibodies develop (usually can be detected in 4-12 weeks) Ø     Latency Phase: Initial§       Asymptomatic phase§       Vague symptoms§       CD4 T count > 500 cells/microliter§       High risk à even though no symptoms, can still transmit HIV to othersØ     Latency Phase: Intermediate§       Asymptomatic but virus is replicating§       May have recurrent infections of sinuses/respiratory tract, ^ fatigue§       CD4 T counts continue to fall – between 200-500§       Damage to lymphatic structures à loose ability to  contain destructive HIVØ     Latency Phase: Late§       Continued decrease of CD-4 Cells§       Occurrence of opportunistic infections·       Oropharyngeal candidal infection·       Shingles·       P. carinii pneumonia·       Oral/genital herpes·       Kaposi Sarcoma·       Oral hairy leukoplakiaØ     Overt AIDS Phase§       Diagnosis of AIDS (Acquired Immunodeficiency Syndrome)§       Immune system becomes severely compromised§       CDC Diagnostic criteria for AIDS= HIV positive§       At least one of: ·       CD4+ below 200/ul.·       Opportunistic infection·       Development of opportunistic cancer·       Wasting syndrome occurs (loss of 10% ideal body mass)·       Dementia Ø     Diagnosis§       HIV antibody test (ELISA)§       Western Blot Assay§       PCR§       OraSure test§       Ora Quick Rapid HIV-1 Antibody TestØ     Treatment§       NO CURE§       Anti-Retroviral medication= HAART§       Drugs§       Antibiotics§       Antifungals§       Vaccines§       Influenza§       Pneumonia