Immunodeficiency Disorders

Immunodeficiency disorders increase susceptibility to infection. They

may be second or primary; secondary is more common.
Primary immunodeficiencies are classified by the main component of
the immune system that is deficient, absent, or defective.
• B cells (or Ig)
• T cells
• Natural killer cells (very rare)
• Phagocytic cells
• Complement proteins ary or primary; secondary is more common.
• Secondary immunodeficiencies: Causes include systemic disorders (eg,
diabetes, undernutrition, HIV infection) and immunosuppressive
treatments. Secondary immunodeficiency also occurs among critically ill,
older, or hospitalized patients. Prolonged serious illness may impair
immune responses; impairment is often reversible if the underlying
illness resolves.
B-cell defects causing Ig and antibody deficiencies account for 50 to 60% of primary
immunodeficiencies. Serum Ig and antibody titers decrease, predisposing to
infections with encapsulated gram-positive bacteria. The most common B-cell
disorder is selective IgAdeficiency.
T-cell disorders account for about 5 to 10% of primary immunodeficiencies and
predispose to infection by viruses, Pneumocystis jirovecii, fungi, other
opportunistic organisms, and many common pathogens. T-cell disorders also cause
Ig deficiencies because the B- and T-cell immune systems are interdependent. The
most common T-cell disorders are DiGeorge syndrome, ZAP-70 deficiency, X-linked
lymphoproliferative syndrome, and chronic mucocutaneous candidiasis.
Combined B- and T-cell defects account for about 20% of primary
immunodeficiencies. The most important form is severe combined
immunodeficiency (SCID). In some forms of combined immunodeficiency (eg,
purine nucleoside phosphorylase deficiency), Ig levels are normal or elevated, but
because of inadequate T-cell function, antibody formation is impaired.
 Immunodeficiency should be suspected when recurrent infections are the
following:
• Severe
• Complicated
• In multiple locations
• Resistant to treatment
• Caused by unusual organisms
• CBC with manual differential
• Quantitative Ig measurements
• Antibody titers
• Skin testing for delayed hypersensitivity
• Prognosis Prognosis depends on the primary immunodeficiency disorder.
Most patients with an Ig or a complement deficiency have a good
prognosis with a near-normal life expectancy if they are diagnosed early,
are treated appropriately, and have no coexisting chronic disorders (eg,
pulmonary disorders such as bronchiectasis). Other immunodeficient
patients (eg, those with a phagocytic cell defect or combined
immunodeficiencies, such as Wiskott-Aldrich syndrome or ataxia-
telangiectasia) have a guarded prognosis; most require intensive and
frequent treatment.
Treatment:
• Vaccines and avoidance of exposure to infection
• Antibiotics and sometimes surgery
• Replacement of missing immune components
DiGeorge syndrome is thymic and parathyroid hypoplasia or aplasia leading to T-cell
immunodeficiency and hypoparathyroidism.
DiGeorge syndrome results from gene deletions in the DiGeorge chromosomal region at
22q11, mutations in genes at chromosome 10p13, and mutations in other unknown
genes, which cause dysembryogenesis of structures that develop from pharyngeal
pouches during the 8th wk of gestation. Most cases are sporadic; boys and girls are
equally affected. Di-George syndrome may be partial (some T-cell function exists) or
complete (T-cell function is absent)
Prognosis often depends on severity of the heart disorder.
Diagnosis:
• Immune function assessment
• Parathyroid function assessment
• Chromosome analysis

Treatment:
In partial DiGeorge syndrome, hypoparathyroidism is treated with Ca and
vitamin D supplementation; long-term survival is not affected. Complete
DiGeorge syndrome is fatal without treatment, which is transplantation of
cultured thymus tissue.
shows a moderately enlarged heart with
an egg-on-side configuration and
increased pulmonary vascularity. The
superior mediastinum is narrow because
of thymic hypoplasia. Note that the
anterior upper mediastinum is empty in
lateral view 
 Ataxia-Telangiectasia
Ataxia-telangiectasia results from a T-cell defect and causes progressive
cerebellar ataxia, oculocutaneous telangiectasias, and recurrent
sinopulmonary infections.
Diagnosis:
Clinical findings of cerebellar ataxia (particularly when telangiectasias are
present), low levels of IgA, and high levels of serumα1-fetoprotein suggest
the diagnosis. Diagnosis is confirmed by identifying mutations on both alleles
of the gene for ATM protein.
Treatment: Treatment with antibiotics or IV immune globulin may help, but
no treatment is effective for the CNS abnormalities. Thus, neurologic
deterioration progresses, causing death, usually by age 30.
Ocular telangiectasia for a patient with ataxia
telangiectasia patient.