Transcript Immunodeficiencies HIV/AIDS

Immunodeficiencies
HIV/AIDS
Immunodeficiencies
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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
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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 (caused by physician,
hospital, etc)
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
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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
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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
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In 2008, CDC adjusted its estimate of
new HIV infections because of new
technology developed by the
agency. Before this time, CDC
estimated there were roughly 40,000
new HIV infections each year in the
United States.
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
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Today, more people than ever before
are living with HIV/AIDS. CDC
estimates that about 1.1 million
persons in the United States are living
with HIV or AIDS. An estimated 21%
of these persons do not know that
they are infected: not knowing puts
them and others at risk.
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Health care workers are at risk
– Nurses
– Clinical lab techs
Most HIV + workers infected off
duty
 TAKE PRECAUTIONS !!!
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HIV is a fragile virus. It cannot live for very
long outside the body. As a result, the virus
is not transmitted through day-to-day
activities such as shaking hands, hugging,
or a casual kiss. You cannot become
infected from a toilet seat, drinking
fountain, doorknob, dishes, drinking glasses,
food, or pets. You also cannot get HIV from
mosquitoes.
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HIV is primarily found in the blood, semen,
or vaginal fluid of an infected person. HIV is
transmitted in 3 main ways:
– Having sex (anal, vaginal, or oral) with someone
infected with HIV
– Sharing needles and syringes with someone
infected with HIV
– Being exposed (fetus or infant) to HIV before or
during birth or through breastfeeding
Pathogenesis
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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
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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
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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
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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
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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 antiHIV 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.
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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
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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
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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
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Fungal:
– Candidiasis
– Cryptococcus
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Viral:
– Herpes simplex
– Herpes zoster
– Cytomegalovirus
Opportunistic infections
Pneumocystis carinii pneumonia
Toxoplasmosis gondii
Mycobacterium avium
intracellulare
Mycobacterium tuberculosis
Treatment
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Expensive: $1,200 -1,500 / month if
healthy
Cocktail of 3 different meds
Treatment
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Restore immune function
– Hasn’t been easy or successful:
 Bone marrow transplant,
immunomodulators, transfusions
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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
(primates)
HIV virus exclusively infects and
causes disease in humans
Other problems
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Viral DNA incorporated into host cell
DNA
Virus mutates as the virus replicates