Immunodeficiencies HIV/AIDS

1. Immunodeficiencies HIV/AIDS

2. 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

3. 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

4. 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

5. 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

6. Routine treatment • No live vaccines • Be aware breaks in skin for routine blood tests can cause septicemia • At risk for Graft-versus-Host disease

7. Acquired Immunodeficiencies Nutritional deficiencies Iatrogenic drugs immunosuppressive therapy chemotherapy and radiation Trauma – esp. burns Stress

8. 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

9. Transmission • Sexual transmission • Contaminated needles – sharing • Blood products • Transplacental or nursing

10. 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

11. 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

12. 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

13. Health care workers are at risk • Nurses • Clinical lab techs • Most HIV + workers infected off duty • TAKE PRECAUTIONS !!!

14. 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

15. 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.

18. 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)

19. 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)

20. 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

21. 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)

22. 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.

23. 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

24. 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

25. 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

27. AIDS Related Diseases • Fungal: • Candidiasis • Cryptococcus • Viral: • Herpes simplex • Herpes zoster • Cytomegalovirus

28. Opportunistic infections Pneumocystis carinii pneumonia Toxoplasmosis gondii Mycobacterium avium intracellulare Mycobacterium tuberculosis

29. Treatment • Expensive: $1,200 -1,500 / month if healthy • Cocktail of 3 different meds

30. 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

33. Difficulties with Vaccines • HIV is antigenically variable • Antibodies are not protective • Can be transmitted by cell to cell contact • Animal models are protected species

34. Other problems • Viral DNA incorporated into host cell DNA • Virus mutates as the virus replicates