Transcript Immunodeficiencies HIV/AIDS

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
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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
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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
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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
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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