Transcript Primary Immune Deficiencies

Immune deficiency
Diseases (2)
Immune Deficiency Disorders
Immunodeficiencies can be divided into primary
immunodeficiency disorders, and secondary
immunodeficiency states,
1- Primary immunodeficiency;
are inherited defects affecting immune system
development,
2- Secondary immunodeficiency;
as complication of other diseases.
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Immune Deficiency Disorders
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Clinically;
Patients with immune deficiency present with increased
susceptibility to infections as well as to certain forms of
cancer.
The type of infections in a given patient depends largely
on the component of the immune system that is affected.
Patients with defects in Ig, complement, or phagocytic
cells typically suffer from recurrent infections with
pyogenic bacteria, whereas those with defects in cellmediated immunity are prone to infections caused by
viruses, fungi, and intracellular micro-organisms.
Immune Deficiency Disorders
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Primary Immune Deficiencies:
Primary immune deficiency states are fortunately rare.
Most primary immune deficiencies come to attention
early in life (between 6 months and 2 years of age),
usually because the affected infants are susceptible to
recurrent infections.
Most primary immune deficiency diseases are
genetically determined and affect either;
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Adaptive immunity (i.e., humoral or cellular) or
Innate host defense mechanisms, including complement
proteins and cells such as phagocytes and NK cells.
Immune Deficiency Disorders
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Defects in adaptive immunity are often subclassified on
the basis of the primary component involved (i.e., B cells
or T cells, or both); however, because of the interactions
between T and B lymphocytes, these distinctions are not
clear-cut.
For instance T-cell defects frequently lead to impaired
antibody synthesis, and hence isolated deficiencies of T
cells may be indistinguishable from combined
deficiencies of T and B cells.
Secondary Immunodeficiency
Disorders
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:Immune
deficiencies secondary to other diseases or
therapies are much more common than the primary
(inherited) disorders.
Secondary immune deficiencies may be encountered
in patients with:
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Infection (HIV)
Malnutrition,
Aging,
Immunosuppression, as in cancer, and renal disease
Autoimmunity,
Chemotherapy.
However, the most common cases of immune deficiency are
therapy-induced suppression of the bone marrow and of
lymphocyte function.
Acquired Immunodeficiency Syndrome
(AIDS)
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AIDS is a disease caused by the retrovirus human
immunodeficiency virus (HIV)
It is characterized by profound immunosuppression
leading to opportunistic infections, secondary
neoplasms, and neurologic manifestations
AIDS
Risk Groups
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Five groups of adults are at risk for developing AIDS:
Homosexual or bisexual men
Intravenous drug abusers
Haemophiliacs
Recipients of blood and blood components
Heterosexual contacts of members of other high-risk
groups.
In Children:
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from vertical transmission from the mother to fetus
hemophiliacs and others who received blood or blood products
before 1985
AIDS
Routes of Transmission
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Sexual Transmission
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virus is present in the semen, or in vaginal &
cervical cells of infected person both extracellular
& within the lymphocytes.
 Virus enters the recipient's body through abrasions
in the mucosa
Parenteral Transmission; blood transfusion or
drug abusers.
 Mother-to-Infant Transmission
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AIDS
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immunosuppression,
primarily affecting cellmediated immunity, is the
hallmark of AIDS
AIDS
Pathogenesis
There are two major targets for HIV infection:
1-The immune system :
HIV infects CD4+ T cells leading to their loss as well as an
impairment in the function of surviving cells .
 Macrophages & dendritic cells are also targets of HIV
infection.
 B lymphocytes are secondary affected by dysfunctioning T
helper cells.
2- The central nervous system :
Macrophages & microglia (monocyte & macrophage
derived) in the brain are infected with HIV
Neurons are not infected by HIV
Exact mechanism of brain damage is unknown,
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Natural History of HIV Infection
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The clinical course of HIV infection can best be understood in terms of an
interplay between HIV and the immune system. Three phases reflecting the
dynamics of virus-host interaction can be recognized: (1) an early acute
phase, (2) a middle chronic phase, and (3) a final crisis phase:
(1) An early, acute phase;
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Clinically associated with a self-limited acute illness
that develops in 50 to 70% of infected adults
The symptoms are non-specific and include sore
throat, myalgia, fever, rash +/- aseptic meningitis
They develop 3 to 6 weeks after infection and resolve
spontaneously 2 to 4 weeks later
Natural History of HIV Infection
2) A middle, chronic phase;
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There is continuous HIV replication, predominantly
within the macrophages & T-lymphocytes, which
may last for several years
Patients are either asymptomatic or develop persistent
generalized lymphadenopathy
Many patients have minor opportunistic infections
Natural History of HIV Infection
(3) A final, crisis phase;
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The CD4+ cell count is reduced below 500 cells/µl
After a variable period, serious opportunistic
infections, secondary neoplasms and/or neurologic
manifestations develop
(AIDS-defining conditions = the patient is said to
have developed full-blown AIDS= where CD+4 cell
count becomes less than 200/ml)
Phases of HIV Infection
© 2005 Elsevier
Natural History of HIV Infection
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The HIV patients are classified into three groups
according to CD4+ cell count:
(1) Patients with counts >500 cells/µL who are
generally asymptomatic
(2) Patients with counts between 200 & 500 cells/µL
who have early symptoms
(3) Patients with counts <200 cells/µL who have
severe immunosuppression (AID’s patient).
Opportunistic infections
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Opportunistic infections have accounted for
approximately 80% of deaths in patients with
AIDS. Their spectrum is constantly changing,
and their incidence is decreasing markedly as a
result of more effective highly active
antiretroviral therapy.
PROTOZOAL (toxoplasmosis)
FUNGAL INFECTIONS (candida)
BACTERIAL INFECTIONS (mycobacteria)
VIRAL INFECTIONS (cytomegalovirus)
Neoplasms
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Kaposi sarcoma: A vascular tumor that is otherwise rare in
the United States.
 Non-Hodgkin lymphoma :
They involve the nodes as well as extranodal sites such as liver,
gastrointestinal tract, and bone marrow.
They are primarily high-grade diffuse B-cell neoplasms
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Primary lymphoma of brain.
Invasive cancer of uterine cervix:
This is attributable to a high prevalence of human papillomavirus
infection in patients with AIDS whose immune systems are
compromised.
CNS Involvement
40% to 60% of patients have clinically
evident neurologic dysfunction.
 In addition to opportunistic infections and
neoplasms .
 And progressive encephalopathy clinically
designated the AIDS-dementia complex
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