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:DiabetesCancerViral 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

Iatrogenicdrugs immunosuppressive therapychemotherapy 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 weeksresembles influenza or

mononucleosissore throat, muscle aches, fever,

swollen glands, rash, headache or meningitis

•Seroconversion occurs 3 – 17 weeks after infection – HIV proteins can be detected in the bloodSeropositive patients have anti-HIV Ab’s circulatingFollowing 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 pneumoniaToxoplasmosis gondiiMycobacterium avium intracellulareMycobacterium 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