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Transcript
Immunodeficiencies HIV/AIDS Immunodeficiencies • Due to impaired function of one or more components of the immune or inflammatory responses. • Problem may be with: – B cells – T cells – phagocytes – or complement Immunodeficiencies may be: •Congenital (primary) •Caused by a genetic abnormality •Acquired (secondary) – more common •Normal physiologic changes – aging •Severe malnutrition or selective deficiency •Caused by another illness: Diabetes Cancer Viral infection Main cause is disruption of lymphocyte function Stem cell defect : Prevent normal lymphocyte development and total failure of immune system Lymphoid organ dysfunction: prevents maturation of B or T cells or final maturation of B cells = lack of specific class of immunoglobulins Hallmark: Tendency to develop unusual or recurrent, severe infections. Deficiencies in T cells suggested by recurrent infections with viruses, fungi and yeast. Deficiencies in B cells suggested by recurrent infections with certain bacteria or viruses affected by humoral immunity Routine treatment • No live vaccines • Be aware breaks in skin for routine blood tests can cause septicemia • At risk for Graft-versus-Host disease Acquired Immunodeficiencies Nutritional deficiencies Iatrogenic drugs immunosuppressive therapy chemotherapy and radiation Trauma – esp. burns Stress HIV/AIDS • • • • • • • Human immunodeficiency virus Acquired immunodeficiency syndrome Two forms : HIV1 and HIV-2 High mortality rate Asymptomatic carriers Logarithmic increase in number of patients Medical community cannot control spread Transmission • • • • Sexual transmission Contaminated needles – sharing Blood products Transplacental or nursing History • Probably arose in central Africa before 1931 • Believed to be a monkey virus mutated to affect humans • Found Ab’s against HIV in serum samples taken in 1960’s • First cases reported 1980’s in male homosexuals • In 1995, the number 1 cause of death for ages 25 – 44 in U.S. • Heterosexual transmission is increasing in the U.S. and is the most common route of transmission outside of the U.S. • Greater than 50% of cases are women High Risk Individuals • • • • Homosexual/bisexual men I.V. drug abusers Recipients of blood products Female partners of bisexual men/ I.V. drug abusers • Children of infected mothers • Health care workers are at risk – Nurses – Clinical lab techs • Most HIV + workers infected off duty • TAKE PRECAUTIONS !!! Pathogenesis • Retrovirus – RNA plus reverse transcriptase, integrase and protease • Attachment: Binds to CD4 receptors (TH) and chemokine receptors gp 120 or gp 41 • Internalization – RNA enters the cell • Reverse transcriptase converts RNA →DNA • Integrase inserts viral DNA into Host DNA • Viral DNA is transcribed into mRNA • mRNA is translated into protein – polyprotein • Cleavage of polyprotein into usable proteins • Viruses are assembled • Host cell is killed as viruses are released • BUT helper T cells are replaced and viruses are killed, but CD4 cells decrease over time. Helper T cells • Coordinate the response of both B and T cells • Patients susceptible to infections and malignancies • Normally 600 - 1200 /mm3 • Category1: > 500 cells/ μL • Category 2: 200- 499 cells/ μL • Category 3: < 200 cells/ μL (AIDS) Clinical Manifestations • Category A: no symptoms or persistent generalized lymphadenopathy or symptoms of primary HIV infection • Category B: symptoms of immune deficiency not serious enough to be called AIDS • Category C: person has AIDS defining illness (chart 15-2) Clinical manifestations • Infection - serologically negative • In seven days followed by acute phase in 30-70 % of people lasts a few days - 2 weeks resembles influenza or mononucleosis sore throat, muscle aches, fever, swollen glands, rash, headache or meningitis •Seroconversion occurs 3 – 17 weeks after infection – HIV proteins can be detected in the blood Seropositive patients have anti-HIV Ab’s circulating Following infection through blood products, in general see anti-HIV Ab’s in 4-7 weeks Following infection through sexual exposure, it may take 6-14 months for detection of anti-HIV Ab’s (one case - years) Window period = time between infection, Ab detection: An infected person can infect others within 2 weeks of initial HIV exposure, at a time well before anti-HIV Ab’s can be detected. Average time from initial infection to AIDS is about 10 years, though this rate of development is lengthening with new treatments available. • Chronic phase – can last for years – Asymptomatic – Viral load decreases – Chronic lymphadenopathy – orofacial herpes zoster, oral candidiasis – B cells make antibodies, but are ineffective – Gradual drop in T4 cells – no symptoms until below 200/mm3 • Crisis phase – ARC – AIDS-related complex – CD4 count < 200 cells/ μL – Long lasting fever < 3 months – Malaise – Diarrhea – Weight loss and wasting syndrome – Multiple opportunistic infections – Persistent viral or fungal infections of the skin – Without therapy death in 2-3 years AIDS Related Diseases • AIDS: To be positive for AIDS requires positive lab test and clinical symptoms -Unusual infections or neoplasms • Kaposi’s sarcoma • Non-Hodgkins lymphoma • Wasting syndrome • AIDS dementia complex AIDS Related Diseases • Fungal: – Candidiasis – Cryptococcus • Viral: – Herpes simplex – Herpes zoster – Cytomegalovirus Opportunistic infections Pneumocystis carinii pneumonia Toxoplasmosis gondii Mycobacterium avium intracellulare Mycobacterium tuberculosis Treatment • Expensive: $1,200 -1,500 / month if healthy • Cocktail of 3 different meds Treatment • Restore immune function – Hasn’t been easy or successful: • Bone marrow transplant, immunomodulators, transfusions • Prevent viral replication – Reverse transcriptase inhibitors (AZT) – Protease inhibitors – Integrase inhibitiors – Maturation inhibitors – Fusion inhibitors - newest Difficulties with Vaccines • • • • HIV is antigenically variable Antibodies are not protective Can be transmitted by cell to cell contact Animal models are protected species Other problems • Viral DNA incorporated into host cell DNA • Virus mutates as the virus replicates