LFS 319: Pathophysiology Immunity
Acquired Immune Deficiency Syndrome
(AIDS)
1. Structure of the virus:
Fig. 5.24, page 115
Cells that have CD4 receptors include:
o T4 cells
o Monocyte/macrophage cells
o Monocyte line cells which include:
Langerhans cells (in loose connective tissue
supporting GI and GU mucosa)
Dendritic cells (in lymph nodes)
Some B cells
Glial cells in brain
Chromaffin cells in duodenum, colon and rectum
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LFS 319: Pathophysiology Immunity
2. How does the virus enter the host cell?
Binding requires two types of receptors:
o CD4 receptor
o Chemokine co-receptor
R5: Displayed on the surface of all cells with
which HIV can merge.
R4: Restricted to CD4 + T-cell linage
The virus cannot empty its contents into the host cell unless it
binds to both receptors.
Q. Explain why some persons appear to have a very slow
progression to AIDS with HIV-1 infections, and some show an
apparent resistance to HIV infections?
3. HIV-1 strains:
R5 strain: Produced first & binds to cells of the monocyte
cell line.
R4 strain: produced later & attacks T4 cell line.
Link this to delay in immune system paralysis.
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LFS 319: Pathophysiology Immunity
4. Replication of HIV-1 (Fig. 5.25):
1. Viral gp120 binds to CD4 and R5 co-receptor (early in the
infection) or R4 co-receptor on Helper T cell (later in the
infection).
2. Viral contents gain access to the host cell (RNA, reverse
transcriptase, gp24)
3. Reverse transcriptase is used to transcribe RNA into
DNA.
4. Viral DNA is incorporated into the host cell DNA with
the help of gp24 (provirus).
5. Provirus remains there until cell division is triggered.
6. Provirus elements are replicated, producing thousands of
HIV RNA copies and other virion components.
7. The virion, studded with gp120 molecules is shed from
the host cell.
8. Host cell dies.
9. The virion goes on to infect other CD4 cells.
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LFS 319: Pathophysiology Immunity
5. Pathogenesis of AIDS
There are 3 phases in the course of AIDS development:
1. Acute phase
2. Chronic phase
3. Crisis phase
Acute phase
Infection with HIV is followed in 4-11 days by influenza-
like symptoms
Sore throat, muscle aches, fever, swollen glands,
and rash.
Nervous system manifestations: range from headache to
meningitis.
Seroconversion
3-17 weeks after infection HIV blood tests positive for viral
proteins (gp120 & p24).
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LFS 319: Pathophysiology Immunity
Chronic phase
This stage can last for years
Some people are asymptomatic for much of this time
Many experience chronic lymphadenopathy
During this period, HIV continues to replicate
HIV-infected T cells are mainly concentrated in lymph
nodes
There is a gradual drop in T4 cell count in the blood
(normal count is 800/mm3)
Number of HIV-infected T4 cells
(from 1 in 100,000 to 1 in 1000 in full-blown AIDS)
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LFS 319: Pathophysiology Immunity
Crisis phase
When T4 cell count drops below 200/mm3
A. ARC (AIDS-Related Complex):
Long-lasting fever (3 months or longer)
Persistent night sweats
Weight loss & diarrhea
There is a profound breakdown in TH-cell mediated
immunity
T4 cell counts are reduced significantly
Persistence of viral and fungal infections of the skin and
mucous membranes, including:
Thrush
Herpes simplex
Infection of the vagina by Candida albicans
Oral hairy leukoplakia
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LFS 319: Pathophysiology Immunity
B. AIDS:
AIDS is diagnosed when a person positive for HIV develops
any of a variety of infections or neoplasms that are highly
unusual in people with normal immune function.
1. Infections:
a. Pneumocystis carinii Pneumonia
i. Appears in 50% of AIDS victims
ii. Is the most common life-threatening opportunistic
infection in AIDS
b. Toxoplasmosis gondii infects the brain seizures and coma
c. Cryptococcus meningitis, damage to liver, bone, skin and
other tissues.
d. Cytomegalovirus pneumonia, encephalitis, blindness,
and inflammation of the GI tract
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LFS 319: Pathophysiology Immunity
2. Neoplasms:
a. Kaposi’s sarcoma (KS)
i. A skin cancer causing dark, large, irregular spots
ii. Develops in 15-25% of HIV-positive individuals
iii. More common among HIV-positive homosexual men
iv. May develop while the person is otherwise relatively
healthy
v. Develops in HIV infection because the function of
antitumor natural killer (NK) cells is impaired.
Remember!
The current, widely accepted view is that there is an
unavoidable continuum progressing from HIV infection to
ARC and then to AIDS.
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LFS 319: Pathophysiology Immunity
6. HIV and the Nervous System:
CNS manifestations start appearing with or following the
period of seroconversion and acute HIV infection.
At this point they include headache and aseptic meningitis.
70-90% of people dying with AIDS or ARC show brain and
spinal cord pathology at autopsy.
The most common primary CNS syndrome associated with
HIV in adults is chronic HIV encephalopathy. Symptoms
include:
o Difficulty concentrating and slowing of verbal and
motor responses
o Increase incidence of withdrawal, personality changes,
clumsiness, mutism, seizures, partial paralysis,
psychosis, incontinence, eventual confinement to bed,
and relative unresponsiveness.
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LFS 319: Pathophysiology Immunity
7. Impact of HIV Infection on Helper T Cells
Early replication of HIV is focused in the monocyte-
macrophage cell line minimal impact on immune system
Infection shifts to T4 cells
T4 count
B cells proliferation Lack of stimulation of
monocyte-macrophages &
neurtophils
Antigen-specific APCs Phagocytosis
antibodies
Impaired antigen presentation
ADCC function
& NK function
Complement fixation, impaired
inflammatory response & less effective Impaired antitumor function
phagocytosis
Increased rate and severity of infections
and tumor growth
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LFS 319: Pathophysiology Immunity
8. Transmission of HIV
HIV has been demonstrated in the saliva, tears, urine,
CSF, serum, TH cells, and macrophages of infected
people.
Semen and vaginal secretions are particularly rich in HIV
and infected lymphocytes.
Casual contact (shaking hands, eating together, and living
in close association) is not likely to cause infection.
What activities carry a high risk of transmission?
o Sexual activity (75%)
o Direct injection of infected lymphocytes or HIV
Intravenous drug users who share contaminated
needles, syringes or other drug paraphernalia.
Transfusion of infected blood or blood products.
Why screening tests have a slight false-negative rate?
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LFS 319: Pathophysiology Immunity
Infectivity:
Anyone who is infected is producing HIV particles
Increases with the number of HIV particles and number of
infected CD4 cells produced and passed. Therefore:
o Infectivity is very high in the acute phase when virions
are being produced at high rates.
o Infectivity declines during chronic HIV infection.
o Infectivity increases again as the HIV infection
progresses into AIDS.
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LFS 319: Pathophysiology Immunity
9. Health Care Workers & Risk of HIV infection
At maximum risk are nurses and doctors who work exclusively
with AIDS patients.
Sources of risk include:
Accidental inoculation of contaminated blood or tissue
by needle, wire, bone, or scalpel puncture, or exposure
of blood to the delicate membranes of the eye.
Bites by infected persons have not been shown to
transmit HIV.
Contact with body fluids other than blood.
Prinking with a needle may lead to HIV infection in
about 0.3% of cases.
Cardiac surgeons, assistants, and scrub nurses (0.5% per
year or greater).
Surgeons working with saws and drills (dentists and
orthopedic surgeons).
As the number of AIDS cases increases, it becomes clear that
health care workers MUST take routine precautions with all
patients.
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