Microbiology and Immunology

WORLD OF MICROBIOLOGY AND IMMUNOLOGY Rh and Rh incompatibility

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copy is made, the DNA inserts itself into the T cell’s DNA.

The inserted DNA then begins to produce large numbers of

viral RNA that are identical to the infecting virus’s RNA. This

new RNA is then transcribed into the proteins that make up the

infecting retrovirus. In effect, the T cell is transformed into a

factory that produces more retroviruses. Because reverse tran-

scriptase enzyme is unique to retroviruses, drugs that inhibit

the action of this enzyme are used to treat retroviral infection,

such as HIV. Reverse transcriptase is vital for retrovirus repli-

cation, but not for human cell replication. Therefore, modern

reverse transcriptase inhibitor drugs are specific for retro-

viruses. Often, reverse transcriptase inhibitors are used in

combination with other drugs to treat HIV infection.

Retroviruses are especially lethal to humans because

they cause a permanent change in the T cell’s DNA. Other

viruses merely commandeer their host cell’s cytoplasm and

chemical resources to make more viruses; unlike retroviruses,

they do not insert their DNA into the host cell’s DNA. Nor do

most viruses attack the body’s T cells. Most people’s cells,

therefore, can recover from an attack from a virus. Eventually,

the body’s immune system discovers the infection and neu-

tralizes the viruses that have been produced. Any cells that

contain viruses are not permanently changed by the viral

infection. Because retroviruses affect a permanent change

within important cells of the immune system, cellular recov-

ery from a retrovirus infection does not occur.

In 1980, researchers headed by Robert Gallo at the

National Cancer Institute discovered the first human retro-

virus. They found the virus within leukemic T cells of patients

with an aggressive form of T cell cancer. These patients were

from the southern United States, Japan, and the Caribbean.

Almost all patients with this form of cancer were found to

have antibodies (immune system proteins made in response to

an infection) to HTLV.

HIV is perhaps the most famous retrovirus. Discovered

independently by several researchers in 1983, HIV is now

known to be the causative agent of AIDS. People with AIDS

test positive for HIV antibodies, and the virus itself has been

isolated from people with the disease.

HIV attacks T cells by docking with the CD4 receptor

on its surface. Once inside the cell, HIV begins to transcribe

its RNA into DNA, and the DNA is inserted into the T cell’s

DNA. However, new HIV is not released from the T cell right

away. Instead, the virus stays latent within the cell, sometimes

for 10 years or more. For reasons that are not yet clear, at some

point the virus again becomes active within the T cell, and

HIV particles are made within the cell. The new HIV particles

bud out from the cell membrane and attack other T cells. Soon,

all of the T cells of the body are infected and die. This infec-

tion cycle explains why very few virus particles are found in

people with the HIV infection (those who do not yet have

AIDS); many particles are found in people who have fulmi-

nate AIDS.

No cure has yet been found for AIDS. Researchers are

still unsure about many aspects of HIV infection, and research

into the immune system is still a relatively new science.

Several anti-retroviral drugs, such as AZT, ddI, and ddC, have

been administered to people with AIDS. These drugs do not

cure HIV infection; but they usually postpone the develop-

ment of AIDS. AIDS is almost invariably fatal.

Simian immunodeficiencyvirus (SIV) is the primate

version of HIV. In fact, monkeys infected with SIV are used to

test AIDS drugs for humans. Rous sarcoma virus (RSV)

causes cancer in chickens and was the first retrovirus identi-

fied. Feline leukemia virus (FELV) causes feline leukemia in

cats and is characterized by symptoms similar to AIDS. Feline

leukemia is a serious disease that, like AIDS, is fatal. Unlike

AIDS, a vaccinehas been developed to prevent this disease.

See alsoAIDS, recent advances in research and treatment;

Immunogenetics; T cells or T lymphocytes; Viral genetics;

Viral vectors in gene therapy; Virus replication; Viruses and

responses to viral infection

REVERSE TRANSCRIPTION •seeTRANSCRIPTION

RRh and Rh incompatibilityH ANDRH INCOMPATIBILITY

Human red blood cells contain protein molecules (antigens) in

their cell membranes that determine the blood type of an indi-

vidual. There are several kinds of antigens present on human

red blood cells, as well as the Rh antigen. People with the Rh

antigen are distinguished with a blood type ending in a plus

(+); those without the Rh antigen have a minus (–) in their

blood type.

Rh disease occurs when an Rh-negative mother is

exposed to Rh-positive fetal blood and develops antibodies.

During pregnancy, and especially during labor and delivery,

some of the fetus’s Rh-positive red blood cells get into the

mother’s (Rh -) bloodstream. Higher passage of fetal cells is

observed in women who have undergone amniocentesis and

other invasive diagnostic procedures, and in women with pla-

cental anomalies. This triggering of the mother’s immune

response is referred to as sensitization, or isoimmunization. In

pregnancies occurring after exposure (usually not in the first

pregnancy), maternal antibodies may lyse (disintegrate) the

red blood cells of an Rh-positive fetus, leading to red blood

cell destruction and fetal anemia. In the case of Rh, the pre-

dominant maternal antibody belongs to the G type (igG)

which can freely cross the placenta and enter the fetal circula-

tion. The consequent anemia may be so profound that the fetus

may die in the uterus. Reacting to the anemia, the fetal bone

marrow may release immature red blood cells (erythroblasts)

into the fetal peripheral circulation, causing erythroblastosis

fetalis. After birth, affected newborns may develop ker-

nicterus. At any further pregnancy, the Rh incompatibility

mechanism tends to be accelerated.

Since 1968, there has been a treatment that can prevent

Rh disease. Without prophylaxis (preventative treatment),

about one in six Rh negative women who deliver a Rh positive

infant will develop anti-Rh antibodies from fetomaternal hem-

orrhage occurring either during pregnancy or at delivery. No

universal policy exists for postnatal prophylaxis. The standard

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