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40 terms

Primary Immune Deficiencies

Sources: First Aid, p.213-214 Ch. 5 Medium Robbins Lecture 5/9/11, Acute Inflammation (for phagocyte dysfunction) Lecture 5/20/11, Immunodeficiencies (Dr. El-Dahr)
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agammaglobulinemia (B-cell disorder)
Defect: Blocks B cell differentiation/maturation. X-linked recessive (more common in males). Defect in BTK, a tyrosine kinase gene.
agammaglobulinemia (B-cell disorder)
Presentation: Recurrent bacterial infection (haemophilus influenzae, staph, strep) after 6 months (↓IgG) after depletion of maternal Ig and subsequent opsonization defect. Tx: IV Ig
agammaglobulinemia (B-cell disorder)
Labs: Normal pro-B, normal T cells, ↓ maturation, ↓ B cells, ↓Igs of all classes
Common Variable Immunodeficiency (CVID) (B-cell disorder)
Defect: Defect in B-cell maturation; many causes
Common Variable Immunodeficiency (CVID) (B-cell disorder)
Presentation: Very similar to XLA, except for age of onset. Can be acquired in 20s-30s; males and females affected equally. ↑risk of autoimmune dx (hemolytic anemia, pernicious anemia, RA), lymphoma, gastric carcinoma. 20% develop Herpes simplex infect'n
Common Variable Immunodeficiency (CVID) (B-cell disorder)
Labs: Normal number of B cells; ↓plasma cells, ↓Ig, suggesting a block in antigen-stimulated B cell differentiation
Isolated IgA deficiency (B-cell disorder)
Defect: Defect in isotype switching → deficiency in IgA class switch. Molecular basis not understood. Most common primary immune deficiency (1/700).
Isolated IgA deficiency (B-cell disorder)
Presentation: recurrent sinus and lung infections, milk allergies and diarrhea, Anaphylaxis on exposure to blood products with IgA. May evolve to CVID.
Isolated IgA deficiency (B-cell disorder)
Labs: IgA deficiency most common. Failure to mature in plasma cell. ↓ secretory IgA. Normal or elevated levels of IgM and IgG.
hyper-IgM syndrome (B-cell disorder)
Defect: Defective CD40L on helper T cells = inability to class switch from IgM to IgG, IgA, IgE. X-linked in 70% cases.
hyper-IgM syndrome (B-cell disorder)
Presentation: Severe pyogenic infections early in life due to low levels of opsonizing IgG. Intracellular pneumocystis carinii infect'n, suggesting T-cell immunity deficiency.
hyper-IgM syndrome (B-cell disorder)
Labs: ↑ IgM; ↓↓ IgG, IgA, IgE
DiGeorge syndrome (T-cell disorder)
Defect: 22q11 deletion; failure to develop 3rd and 4th pharyngeal pouches
DiGeorge syndrome (T-cell disorder)
Presentation: Tetany (hypocalcemia), recurrent viral/fungal infections (T-cell deficiency), congenital heart and great vessel defects.
DiGeorge syndrome (T-cell disorder)
Labs: Thymus and parathyroid glands fail to develop→↓T-cells, ↓PTH, ↓Ca2+; absent thymic shadow on CXR
DiGeorge's syndrome (T cell disorder)
Tx: thymic transplant
Chronic mucocutaneous candidiasis (T-cell disorder)
Defect: T-cell dysfunction
Chronic mucocutaneous candidiasis (T-cell disorder)
Presentation: Candida albicans, infections of skin and mucous membranes, yeast infection, common cause of vaginitis. Associated w/ endocrinopathy such as diabetes, Addison's dx, hypoparathyrodism.
Interferon-gamma or IL-12/receptor deficiency (T-cell disorder)
Defect: ↓Th1 response. IL-12, IL-12R, and interferon-gamma are all involved in Th1 mediated activation of macrophages.
Interferon-gamma or IL-12/receptor deficiency (T-cell disorder)
Presentation: Intracellular bacterial infections (eg. mycobacterial)
Interferon-gamma or IL-12/receptor deficiency (T-cell disorder)
Labs: ↓IFN-gamma
SCID (Severe combined immunodeficiency) (B and T cell disorder)
Defect: Several types: X-linked SCID aka gamma chain deficiency (most common, defective receptors for IL-2/4/7/9/15), adenosine deaminase deficiency (unable to metabolize purine, autosomal recessive), failure to synthesize MHC-II antigens
SCID (Severe combined immunodeficiency) (B and T cell disorder)
Presentation: Recurrent bacterial (B cell), viral, fungal, and protozoal infections (T cell deficiency). Opportunistic infection by Candida, Pneumocystis, Pseudomonas, CMV, varicella. Tx: bone marrow transplant
SCID (Severe combined immunodeficiency) (B and T cell disorder)
Labs: ↓IL-2R=↓T-cell activation. ↑adenosine=toxic to B and T cells by inhibition of DNA synthesis.
X-linked SCID (aka gamma chain deficiency)
Most common SCID. T cell development blocked due to lack of function IL-2/4/7/9/15 receptors.
ADA and PNP Deficiency
Autosomal recessive SCID. ADA,PNP = "housekeeping enzymes," clean up waste products of purine metabolism. No T or B cells.
Autosomal SCID
Defect: recombination-activating genes, RAG1, RAG2, or DNA-PK prevent lymphcytes from copleting VDJ recombination.
Wiskott-Aldrich syndrome (B and T cell disorder)
Defect: X-linked recessive; progressive deletion of B and T cells
Wiskott-Aldrich syndrome (B and T cell disorder)
Presentation: Triad (TIE): Thrombocytopenic purpura, Infections, Eczema. Typically presents in infants in first few months w/ petechia and ottis media. Tx: bone marrow transplant
Wiskott-Aldrich syndrome (B and T cell disorder)
Labs: ↑IgE, IgA; ↓IgM
Leukocyte Adhesion Deficiency (phagocyte dysfunction)
Defects: Defect in LFA-1 integrin (CD18) on phagocytes
Leukocyte Adhesion Deficiency (phagocyte dysfunction)
Presentation: Recurrent bacterial infections of soft tissue, absent pus formation despite high WBC count in peripheral blood, delayed separation of umbilicus (>6wks)
Leukocyte Adhesion Deficiency (phagocyte dysfunction)
Labs: neutrophilia (↑neutrophils)
Chediak-Higashi syndrome (phagocyte dysfunction)
Defect: Autosomal recessive; defect in microtubule function with ↓ phagocytosis; endosomes do not fuse w/ lysosomes, so phagocytosed microbes are not digested.
Chediak-Higashi syndrome (phagocyte dysfunction)
Presentation: Recurrent pyogenic infections by staph and strep; partial albinism (melanin deficit), peripheral neuropathy
Chronic granulomatous disease (phagocyte dysfunction)
Defect: Lack of NADPH oxidase→↓ROS and absent respiratory burst in neutrophils.
Chronic granulomatous disease (phagocyte dysfunction)
Presentation: ↑susceptibility to catalase-positive organisms. IFN-gamma tx for Staph infection.
Chronic granulomatous disease (phagocyte dysfunction)
Labs: Negative Nitroblue tetrazolium dye reduction test
Complement deficiency, early component
Defect: C1, C2, C4 proteins. Lead to immune complex disease and autoimmunity.
Complement deficiency, late component
Defect: C5-C9. Leads to infections with Neisseria, especialy meningitides, so should always be suspected w/ recurrent meningitis.