Microbiology and Immunology

Immunodeficiency diseases, genetic causes WORLD OF MICROBIOLOGY AND IMMUNOLOGY

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foreign. Excesses in the latter constitute the autoimmune dis-

eases. Deficiencies in the body’s ability to recognize antigens

as foreign or a diminished capacity to respond to recognized

antigens constitute the immunodeficiencysyndromes.

There are many causes associated with immunodefi-

ciencies. Primary immunodeficiencies are inherited conditions

in which specific genes or genefamilies are corrupted by

mutationsor chromosome deletions. These syndromes are dis-

cussed elsewhere in this volume. Secondary immunodeficien-

cies are acquired conditions that may result from infections,

cancers, aging, exposure to drugs, chemicals or radiation, or a

variety of other disease processes.

Bacteria, viral, fungi, protozoa, and even parasitic infec-

tions can result in specific deficiencies of B cells, T cells,

macrophages, and granulocytes. The best characterized of the

infectious diseases is the acquired immunodeficiency syn-

drome (AIDS).

Infection by two viruses, HIV-1 and HIV-2, is associ-

ated with a wide range of responses in different people from

essentially asymptomatic to a full-blown AIDS in which cell-

mediated immunityis seriously compromised. HIV-1 and HIV-

2 are retrovirusesthat attack humans and compromise cellular

function. In contrast, the human T cell lymphotrophic viruses

(HTLV) tend to provoke lymphoid neoplasms and neurologic

disease. AIDS is most often associated with HIV-1 infection.

The chance of developing AIDS following infection with HIV-

1 is approximately one to two percent per year initially, and

increases to around five percent per year after the fifth year of

infection. Roughly, half of those infected with the virus will

develop AIDS within ten years. In between those who are

asymptomatic, and those with AIDS who are symptomatic

with conditions associated with AIDS.

In AIDS, cellular immunity mechanisms are disrupted.

Some immunologic cells are reduced in number and others,

such as natural killer cells, have reduced activity despite their

normal numbers. HIVinfects primarily T helper lymphocyte

cells and a variety of cells outside of the lymphoid system

such as macrophages, endothelial, and epithelial cells.

Because the T helper cells normally express a surface glyco-

protein called CD4, counts of CD4 cells are helpful in pre-

dicting immunologic depression in HIV-infected individuals.

The amount of viral RNAin circulation is also a helpful pre-

dictor of immunologic compromise. In addition to cell-medi-

ated immunity, antibodyresponses (humoral immunity) are

also muted in individuals with AIDS.

Initially, there is a period of several weeks to months

where the host remains HIV antibody negative and viral repli-

cation occurs rapidly. Some subjects develop an acute response

that appears like the flu or mononucleosis. Symptoms typically

include fever, malaise, joint pain, and swollen lymph nodes. As

the initial symptoms dissipate, patients enter an antibody posi-

tive phase without symptoms associated with AIDS. A variety

of relatively mild symptoms like thrush, diarrhea, fever, or

other viral infections may manifest along with a wide array of

partial anemias. Nerve function can become compromised

resulting in weakness, pain, or sensory loss. Eventually, life

threatening opportunistic infections resulting from decreased

immunologic function occur and may be accompanied by

wasting, dementia, meningitis, and encephalitis. Drug therapy

in the form of antiretroviral agents is directed toward inhibition

of proteases and reverse transcriptase enzymeswhich are crit-

ical for replication of the viruses.

Although not nearly as well known as AIDS, there are a

variety of other acquired immunodeficiencies. Infections other

than HIV can significantly alter the numbers and functions of

other cells within the immune system. While individually

these various infections may appear to be relatively uncom-

mon, depression in the numbers of platelets, T cells, B cells,

natural killer (NK) cells, and granulocytes can lead to

immunologic dysfunction. The manifestations of these various

conditions will depend on the specific cell population that is

involved and its normal function within the immune system. B

cell deficiencies tend to result in an increased susceptibility to

bacterial infections. Decreased natural killer cell activity can

result in the survival of tumor cells which would otherwise be

destroyed by the immune system.

Chemical and physical agents (such as radiation) also

can potentially depress various fractions of cells within the

immune system, and like the immunodeficiencies caused by

infectious agents, the manifestations of these agents will differ

depending on the cells which are influenced. Cancer

chemotherapeutic agents are often immunosuppressive.

Likewise, immune function often declines with age. T cell

populations (including the T helper cells) decline as the thy-

mus gland activity decreases. Frequently, B cell populations

proliferate at an accelerated rate in older people. Over produc-

tion of cells within the immune system such as leukemias,

lymphomas, and related disorders also may disturb immune

function by radically altering the distribution of white cells. A

number of other diverse disease processes can alter or com-

promise immune function. These include diabetes, liver dis-

ease, kidney disease, sickle cell anemia, Down syndrome, and

many of the autoimmune diseases.

See alsoAIDS, recent advances in research and treatment;

Autoimmunity and autoimmune diseases; Immunodeficiency

diseases, genetic causes

IMMUNODEFICIENCY DISEASES, GENETIC

CAUSESImmunodeficiency diseases, genetic causes

The complex workings of the immune systemrequires the

cooperation of various organs, tissues, cells and proteins and

thus, it can be compromised in a number of different ways.

People who have normal immune function at birth who later

acquire some form of immunodeficiencyare said to have sec-

ondary or acquired immunodeficiency diseases. Examples

would include AIDS, age-related immune depression, and

other immune deficiencies caused by infections, drug reac-

tions, radiation sickness, or cancer. Individuals who are born

with an intrinsically reduced capacity for immunologic

activity usually have some genetic alteration present at birth.

There are varieties of different genes involved, and they ren-

der people susceptible to infection by an assortment of dif-

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