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 (T H ) 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 /mm 3 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/mm 3

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