Unit 1 Nature of the Immune System
Part 7 Immunodeficiency Diseases
Terry Kotrla, MS, MT(ASCP)BB
Introduction
 The body’s immune cells attack and kill what they see as
foreign invaders, usually bacteria, viruses, and fungi.
 Any defect in the immune system decreases a person's ability
to fight infections.
 A person with an immunodeficiency disorder may get more
frequent infections, heal more slowly, and have a higher
incidence of some cancers.
Immunodeficiency Disorder
 Immunodeficiency (or immune deficiency) is a state
in which the immune system's ability to fight infectious
disease is compromised or entirely absent.
 Immunodeficiency disorders are a group of disorders in
which part of the immune system is missing or defective.
 Causes the body's ability to fight infections to be impaired.
 Person with an immunodeficiency disorder will have
frequent infections that are generally more severe and last
longer than usual.
Immunodeficiency Disorder
 Defects can occur in any component of the immune system
or in more than one component (combined
immunodeficiency).
 Different immunodeficiency diseases involve different
components of the immune system.
 The defects can be:
 Inherited
 present at birth (congenital)
 acquired
Immune Deficiency
 Any of the following parts of the immune system may be
affected:
 Humoral (adaptive) immunity – B cells
 Cellular immunity – T cells (remember there are 3 different
kinds!)
 Innate immunity – natural body structures and functions.
 More than 120 different congenital forms of
immunodeficiency have been reported.
What Do I Need to Know?
 For each deficiency discussed you must know:
 The name of the disorder.
 What part of the immune system is affected.
 Brief description of the immune disorder.
Immune Deficiency Disease Classification
 Four Classification
 Humoral System Deficiencies (which cell will be affected?)
 Cellular Immunity Deficiencies (which cell will be affected?)
 Combined Deficiencies
 Acquired Deficiencies
Humoral Deficiencies
 Conditions which cause impairment of humoral immunity,
which can lead to immunodeficiency.
 Caused by failures of B cells, the plasma cells they
differentiate into, or the antibody secreted by the plasma
cells.
 Associated with increased vulnerability to infection, but can
be difficult to detect (or asymptomatic) in the absence of
infection.
Humoral Deficiencies
 Types we will discuss:
 Agammaglobulinemia
 X-Linked Bruton’s Agammaglobulinemia
 IgA Deficiency
 Common Variable Immunodeficiency
Agammaglobulinemias
 Genetic defects in B-cell maturation or mutation leading
to defective interaction between B- and T-cells.
 Many types of deficiencies involving deficiency in one or
more antibody classes.
 Infant values different than adult, may have transient
hypgammaglobulinemia.
X-Linked Bruton’s Agammaglobulinemia
 Genetic – X-linked affects males exclusively.
 Lack a specific type of B cell.
 Exhibit deficiency of immunoglobulins of ALL classes.
 Have NO plasma cells.
 T-cells present in normal numbers and function.
 Develop recurrent bacterial infections.
 Treat with gammaglobulin as needed.
 Diagnosed by serum protein electrophoresis and testing for
the CD19 positive B cells in peripheral blood.
IgA Deficiency
 Most common congenital immunodeficiency, 1:500.
 Varying expressions of the disease and most are
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asymptomatic.
Symptoms include respiratory and GI tract infections.
Individuals who are IgA deficient may develop anti-IgA and
may develop analphylactic shock during blood transfusion.
No real treatment.
Diagnosed by serum protein electrophoresis
Common Variable Immunodeficiency
 Have normal number of B cells but do not develop into
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plasma cells.
Production of one or more of the immunoglobulin types is
decreased and the antibody response to infections is
impaired.
Generally develops around the age of 10-20.
Symptoms vary, may have frequent infections, and some also
will experience anemia and rheumatoid arthritis.
Diagnosis of exclusion.
Treat with IV immunoglobulin.
Cellular Immunity Deficiencies
 Cell-mediated immunity is an immune response that does
not involve antibodies or complement but rather involves
 Activation of macrophages,
 natural killer cells (NK),
 antigen-specific cytotoxic T-lymphocytes, and
 the release of various cytokines in response to an antigen.
 Cellular immunity deficiencies primarily involve problems
with T-cells
DiGeorge Anomaly
 T lymphocyte deficiency that starts during fetal development and
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is the result of a deletion in a particular chromosome.
Children with DiGeorge syndrome either do not have a thymus
or have an underdeveloped thymus.
Thymus directs the production of T-lymphocytes, these patients
have very low numbers of T-lymphocytes.
Susceptible to recurrent infections, particularly viral and fungal.
Usually have other abnormalities as well- low-set ears, a small
receding jawbone, and wide-spaced eyes.
In some cases, no treatment is required for DiGeorge syndrome
because T lymphocyte production improves, otherwise fetal
thymus transplant or bone marrow transplant.
Combined Deficiencies
 Combined immunodeficiencies (or combined immunity
deficiency) are immunodeficiency disorders that involve
multiple components of the immune system, including both
Humoral immunity and Cell-mediated immunity.
 Topics we will cover:
 Severe Combined Immunodeficiency
 Wiskott-Aldrich Syndrome
 Ataxia-Telangiectasia
Severe Combined Immunodeficiency
 AKA “Bubble Boy Syndrome”
 Results in impaired humoral and cellular immune responses.
 Caused by the defective development or function of BOTH
T- and B-cells.
 Usually recognized during the first year of life with infections
by nearly any type of organism.
 Tends to cause a fungal infection of the mouth (thrush),
diarrhea, failure to thrive, and serious infections.
 If not treated with a bone marrow transplant, a person with
SCID will generally die from infections before age two.
Wiskott-Aldrich syndrome
 Rare X-linked recessive disease characterized by eczema,
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thrombocytopenia, immune deficiency and bloody diarrhea
(secondary to the thrombocytopenia).
Abnormalities in both humoral and cellular immunity.
Usually have low levels of IgM, normal IgG and IgA, increased
IgE.
Platelets have short half life and are small – why will this affect
bleeding time?
T-cells affected, B-cells not.
Immune deficiency leaves the body vulnerable to infection, may be
serious infections such as pneumonia, meningitis, and sepsis.
Splenectomy can help with thrombocytopenia.
BMT or cord blood stem cell transplant.
Ataxia-Telangiectasia
 Rare, neurodegenerative, autosomal-recessive disease that
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affects many parts of the body and causes severe disability.
Ataxia refers to poor coordination and telangiectasia to small
dilated blood vessels, both are hallmarks of the disease.
Combined defect of cellular and humoral immunity.
Poor antibody response, IgG2, IgA and IgE low or absent.
Decreased T cells
Most individuals do not live long in to their 20's.
Only therapy is allogeneic BMT.
Defects of Neutrophil Function
 A defect in the life cycle of neutrophils can compromise host
defenses.
 Defects in neutrophil functions will lead to inflammation and
increased susceptibility to recurrent and severe bacterial and
fungal infections.
Defects of Neutrophil Function
 Chronic Granulomatus Disease
 Other Microbicidal Defects
 Leukocyte Adhesion Deficiency
Chronic Granulomatus Disease
 X-lined or autosomal recessive.
 Phagocytes (i.e., neutrophils, monocytes and macrophages)
are unable to kill bacteria and fungi.
 Require an enzyme to produce reactive oxygen to destroy
ingested bacteria, a process known as the oxidative burst.
 Recurrent suppurative infections which eventually are fatal in
childhood although 50% live to adulthood..
 Treatment: granulocyte transfusions, cytokines or BMT
Defects of Neutrophil Function
 Other microbicidal defects
 Neutrophil G6PD deficiency leads to condition similar to CGD.
 Myeloperoxidase deficiency – recurrent candidal infections
 Leukocyte Adhesion Deficiency
 CD18 deficiency leads to abnormal adhesion, motility,
aggregation, chemotaxis and endocytosis.
 Several molecular defects of leukocyte adhesion cause recurrent
life-threatening infections.
 Can cause delayed wound healing, chronic skin infections,
intestinal and respiratory tract infections and periodontitis.
Acquired Immunodeficiency
 Immune deficiency may be the result of external processes or diseases;
 The resultant state is called "secondary" or "acquired“
immunodeficiency.
 Common causes for secondary immunodeficiency are malnutrition,
aging and particular medications such as chemotherapy,
 Many specific diseases directly or indirectly impair the immune system
and include
 many types of cancer, particularly those of the bone marrow and blood cells
 certain chronic infections.
 acquired immunodeficiency syndrome (AIDS), caused by the human
immunodeficiency virus (HIV). HIV directly infects a small number of T
helper cells, and also impairs other immune system responses indirectly
The End Of Part 7