Combined B-Cell and T-Cell
Deficiencies
Combined B-cell and T-cell deficiencies include (a) severe combined immunodeficiency, (b) Wiskott–Aldrich syndrome, (c) ataxia telangiectasia, and (d) MHC class II deficiency.
Severe combined immunodeficiency (SCID) includes many syndromes
with severe deficiency of both humoral and cell-mediated immune responses. All
these are inherited diseases with a defect in the differentiation of early stem
cells. These are of two types: X-linked and autosomal.
X-linked SCID: The sex-linked SCID is
associated with adefect of the gene that codes for a polypeptide chain common
to several interleukin receptors (IL-2, IL-4, IL-7, IL-11, and IL-15). This
chain is involved in signaling of second messages, thus in its absence, T-cell
precursors fail to receive the signals necessary for their proliferation and
differentiation. There is T- and B-cell lymphopenia and decreased production of
IL-2. There is an absence of delayed-type hypersensitivity, cellular immunity,
and of normal antibody synthesis following immu-nogenic challenge.
Autosomal SCID: This is due to a mutation in
the geneencoding a tyrosine kinase called ZAP-70, which plays an important role
in signal transduction in T cells. Other SCID patients show mutations in other
genes, such as RAG-1 or RAG-2, that are essential to produce T-cell antigen
receptor and the IgM monomer on the B cell that acts as antigen carrier.
SCID is a disease of infancy, presenting with failure to thrive.
Affected individuals frequently die during the first 2 years of life.
Clinically, they may develop a measles-like rash, show hyperpigmentation, and
develop severe recurrent (especially pulmonary) infections. These patients have
heightened suscep-tibility to Pneumocystis
carinii, C. albicans, and other
pathogens. Even attenuated microorganisms, such as those used for
immu-nization, e.g., attenuated poliomyelitis viruses, may induce infection in
SCID patients. All these forms of SCID can be cor-rected with a bone marrow
graft from HLA-DR matched sib-lings. The graft is usually successful, but there
is a great risk for the development of graft-versus-host disease.
Graft-versus-host disease
(GVHD): It is a problem in SCIDpatients receiving unirradiated blood
transfusions. It can also develop after transfusion of any fresh blood
component contaminated with viable T lymphocytes. It is characterized by fever,
maculopapular rash involving the volar surfaces, diarrhea and protein-losing
enteropathy, Coombs’ positive hemolytic anemia, thrombocytopenia, and
splenomegaly. In full-blown cases, the outcome is generally poor, with death
occurring within 10–14 days from the onset of symptomatology. The reaction may
be prevented in the case of transfusion by using frozen or irradiated blood
products. Current attempts at eliminating all cells except stem cells from bone
marrow grafts appear promising.
Wiskott–Aldrich syndrome is an X-linked recessive immuno-deficiency
disease of infants. It is characterized by thrombo-cytopenia, eczema, and
increased IgA and IgE levels. There is decreased cell-mediated immunity. The
inability to mount an IgM response to capsular polysaccharide of bacteria is
the most important defect. IgA and IgE are increased, but IgM is dimin-ished,
although IgG serum concentrations are usually normal. By electron microscopy, T
cells appear to lack the markedly fimbriated surface of normal T cells. T cells
have abnormal sialophorin. The defect appears to be caused by the inability of
T cells to provide help to B cells. Bone marrow transplantation corrects the
deficiency.
It is an autosomal recessive disease caused by mutations in the
gene that encodes DNA repair enzyme. This condition is characterized by ataxia,
telangiectasia, and recurrent infections in babies by 2 years of age. IgA
deficiency and lymphopenia commonly occur.
It is an autosomal recessive disease failing to express MHC
molecules on the surface of antigen presenting cells, such as macrophages and B
cells. This results in a deficiency of CD4 T cells. The lack of these helper T
cells results in production of deficient antibodies.
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