USMLE Step 1 Web Prep — Failures of the Immune System:
Immunodeficiency
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Types of Immunodeficiencies
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Phagocytic deficiencies
Complement deficiencies
B-cell deficiencies
T-cell deficiencies
Combined B-cell T-cell deficiencies
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Phagocytic deficiencies
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Chronic granulomatous disease (CGD)
Chediak-Higashi syndrome
Leukocyte adhesion deficiency (LAD)
Glucose-6-phosphate dehydrogenase (G6PD) deficiency
Myeloperoxidase deficiency
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Complement deficiencies
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C3 deficiency: Increased susceptibility to pyogenic infections
C5-C8 deficiency: Recurrent Neisseria infections
C1 inhibitor: Hereditary angioedema
C2 deficiency: Increased incidence of connective tissue disorders (eg. SLE)
C1, C4, or C2 deficiency: Opsonization not efficient (LAD)
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B-cell deficiencies : Bruton X-linked hypogammaglobulinemia
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First appears in childhood (>6 months)
Immunologic findings
i.
Low immunoglobulin – all classes
ii.
No circulating B cells (ie. surface immunoglobulin [sIg] positive)
iii.
Pre-B cells in the bone marrow
iv.
Normal cell-mediated immunity
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Primary defect: a block in maturation of the B cell due to a deficiency of a
tyrosine kinase
Treatment: monthly -globulin replacement, antibiotics for infection
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B-cell deficiencies : Transient hypogammaglobulinemia of infancy
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Delayed onset of normal IgG synthesis
Seen in the fifth to sixth month of life
Usually resolves by 16-30 months of age
Treatment: antibiotics and sometimes -globulin replacement
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B-cell deficiencies : Common variable (acquired)
hypogammaglobulinemia
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Immunoglobulin levels decrease with time
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First appears in late teens to early 20s
Associated with autoimmunity in the patient or in the family
A syndrome that is probably several different diseases
Low immunoglobulins – any class
B cells present in the peripheral blood
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B-cell deficiencies : Selective Ig deficiency (dysgammaglobulinemia)
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Several different diseases described
Selective IgA deficiency is the most common
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Repeated sinopulmonary infection, gastrointestinal disease
Many with IgA deficiency have no symptoms
If both IgA and IgG2 subclass deficiencies, more likely to have infections
Treatment: antibiotics, not Igs
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T-cell deficiencies : DiGeorge syndrome
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Failure of development of third and fourth pharyngeal pouches
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Hypoplastic thymus
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Hypoplastic parathyroid glands
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Clinical features
i.
Thymic aplasia
ii.
Recurrent viral and fungal infections
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Hypoparathyroidism – hypocalcemic tetany
iv.
Cardiac anomalies
v.
Facial anomalies (fish mouth and flat face)
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T-cell deficiencies: Chronic mucocutaneous candidiasis
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This group of patients has severe chronic skin and mucous membrane infections
with the fungal pathogen Candida albicans. Specific treatment in these cases is
antifungal drugs.
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Combined B-cell T-cell deficiencies: Adenosine deaminase (ADA)
deficiency
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This was the first human disease successfully treated with gene therapy.
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Combined B-cell T-cell deficiencies: Severe combined immunodeficiency
disease (SCID)
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SCID has many other X-linked and autosomal inheritance pattern problems.
Some of the causes of SCID are deficiencies in class I molecules, class II
molecules, T-cell receptors, cytokine receptors, and signal-transduction
molecules.
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Combined B-cell T-cell deficiencies: Wiskott-Aldrich syndrome
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Complex immune deficiency in which there is a triad of symptoms:
thrombocytopenia from birth, eczema, and immunodeficiency.
X-linked recessive disease.
Patients are prone to the development of malignant lymphomas.
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Combined B-cell T-cell deficiencies: Ataxia-telangiectasia (develops 1–2
years of age)
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Sinopulmonary infections
Autosomal recessive
Ataxia: uncoordinated muscle movements
Telangiectasia: dilation of small vessels; seen in sclera of eye
Immunodeficiency
i.
Selective IgA deficiency
ii.
Cell mediated defects – variable
iii.
Other immunoglobulin – variable
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Treatment: antibiotics
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In a Nutshell
Immune Deficiency
B cell
T cell
C3
C5–8
Phagocytes
Predominating Opportunist
Pyogenic bacteria
Viruses and fungi; also
mycobacteria
Pyogenic bacteria
Neisseria
Pyogenic bacteria