Flashcards in Immune Deficiencies Deck (50)
What are the B cell disorders?
X-Linked (Bruton) agammaglobulinemia, Selective IgA deficiency, Common Variable immunodeficiency
What is the defect in X-linked agammaglobulinemia?
Defect in BTK, a tyrosine kinase gene (no B cell maturation). x-linked, therefore greater incidence in boys
What is the clinical presentation of X-linked agammaglobulinemia?
Recurrent bacterial and enteroviral infections after 6 months (due to decreased maternal IgG)
What are the findings in X-linked agammaglobulinemia?
Normal CD19+ B cell count, Decreased pro-B, decreased Ig of all classes. Absent/scanty lymph nodes and tonsils
Selective IgA deficiency defect?
Unknown. most common immunodeficiency
What is the presentation of IgA deficiency/
Majority Asymptomatic. Can cause Airway and Gi infections, Autoimmune disease, Atopy, Anaphylaxis to IgA containing products
Findings in selective IgA deficiency
What is the defect in common variable immunodeficiency
Defect in B-cell differentiation. Many causes
What is the presentation of common variable immunodeficiency?
Can be acquired in 20s or 30s; increased risk of autoimmune disease, brochiectasis, lymphoma, sinopulmonary infetions. Multiple joint pain, fatigue, weight loss
what are the findinds of common variable immunodeficiency?
decrease plasma cells, decrease immunoglobulins
What are the (4) T cell disorders?
1) Thymic aplasia (DiGeorge syndrome) 2) IL-12 receptor deficiency 3) Autosomal dominant hyper-IgE syndrome (Job Syndrome) 4) Chronic mucocutaneous candidiasis
Thymic aplasia (DiGeorge Syndrome) defect?
22q11 deletion; failure to develop 3rd and 4th pharyngeal pouches - absent thymus and parathyroids
Thymic aplasia (DiGeorge) presentation?
Tetany (hypocalcemia), recurrent viral/fungal infections (T-cell deficiency), coonotruncal abnormalities (i.e. tetralogy of Fallot, truncus arteriosus)
Thymic aplasia (DiGeorge) Findings
Decreased T cells, Decreased PTH, Decreased Ca++, Absent thymic shadow on CXR. 22q11 deletion by FISH.
IL-12 receptor deficiency
decreased Th1 response. Autosomal recessive
IL-12 receptor deficiency presentation
Disseminated mycobacterial and fungal infections; may present after administration of BCG vaccine.
IL-12 receptor deficiency findings
Autosomal dominant hyper-IgE syndrome (JOB syndrome) Defect?
Deficiency of Th17 cells due to STAT3 mutation - impaired recruitment of neutrophils to sites of infection
what is the clinical presentation in hyper-IgE syndrome (Job)
FATED: coarse Facies, cold (noninflamed) staphylococcal Abscesses, retained primary Teeth, increased IgE, dermatologic problems (eczema).
Autosomal dominant hyper-IgE syndrome (Job Syndrome)
increased IgE, decreased IFN-gamma
Chronic mucocutaneous candidiasis defect?
T-cell dysfunction. many causes
presentation of chronic mucocutaneous candidiasis?
noninvasive candidia albican infections of skin and mucous membranes
chronic mucocutaneous candidiasis presentation
absent in vitro T-cell proliferation in response to candida antigens. absent cutaneous reaction to candida antigens
What are the B & T cell disorders?
SCID, Ataxia-telangiectasia, Hyper-IgM syndrome, Wiskott-Aldrich Syndrome
What is the defect in SCID?
Several types including defective IL-2R gamma chain (most common, X-linked), adenosine deaminase deficiency (autosomal recessive
What is the presentation of SCID?
Failure to thrive, chronic diarrhea, thrush. Recurrent viral, bacterial, fungal, and protozoal infections.
What is the treatment of SCID?
Bone marrow transplant (no concern for rejection)
What are the findings in SCID?
Decreased T cell receptor excision circles (TRECS). Absence of thymic shadow (CXR), germinal centers (lymph node biopsy), and T cells (flow cytometry). Absence of tonsils. absence of T and B cells.
What is the defect in Ataxia Telangiectasia?
Defects in ATM gene - DNA double strand breaks - cell cycle arrest
What is the clinical presentation in Ataxia Telangiectasia?
Triad: cerebellar defects (Atazia), spider Angiomas (telangiectasia), IgA deficiency
What are the findings in Ataxia Telangiectasia?
Increased AFP, decreased IgA, IgG, IgE. Lymphopenia, cerebellar atrophy
What is the defect in Hyper-IgM syndrome
Most commonly due to defective CD40L on Th cells = class switching defect
What is the inheritance of Hyper-IgM syndrome?
What is the presentation of Hyper-IgM syndrome?
Severe pyogenic infections early in life; opportunistic infection with Pneumocystis, Cryptosporidium, CMV
What are the findings of Hyper-IgM syndrome?
Increased IgM. Decreased IgG, IgA, IgE
What is the defect in Wiskott-Aldrix Syndrome?
Mutation in WAS gene (X-linked recessive); T cells unable to reorganize actin cytoskeleton.
What is the presentation of Wiskott-Aldrich Syndrome?
WATER: Wiskott-Aldrich: Thrombocytopenia purpura, Eczema, Recurrent infections. Increased Risk of autoimmune disease and malignancy
What are the findings in Wiskott-Aldrich Syndrome?
Decreased to normal IgG, IgM. Increased IgE, IgA. Fewer and smaller platelets
What are the immune diseases with phagocyte dysfunction?
Leukocyte adhesion deficiency (type I), Chediak-Higashi syndrome, Chronic granulomatous disease
What defect is seen in Leukocyte adhesion deficiency (type I)?
Defect in LFA-1 integrin (CD18) protein on phagocytes; impaired migration and chemotaxis; autosomal recessive
What is the presentation of Leukocyte adhesion deficiency?
Recurrent bacterial skin and mucosal infections, absent pus formation, impaired wound healing, delayed umbilical cord seperation (
What are the findings in leukocyte adhesion deficiency?
1) increased neutrophils 2) absent of neutrophils at infection sites
What is the defect in Chediak Higashi syndrome?
Defect in lysosomal trafficking regulator gene (LYST). Microtubule dysfunction in phagosome-lysosome fusion
What is the presentation in Chediak Higashi syndrome?
Recurrent pyogenic infection by staph and strep, partial albinism, peripheral neuropathy, progressive neurodegeneration, infiltrative lymphohistiocytosis.
What are the findings in Chediak Higashi syndrome?
giant granules in neutrophils and platelets. Pancytopenia. Mild coagulation defects.
What is the defect in Chronic Granulomatoux Disease?
Defect in NADPH oxidase which leads to decrease in ROS (superoxide) and absent respiratory burst in neutrophils
What is the inheritance of Chronic Granulomatoux disease?
What is the inheritance of Chediak Higashi Syndrome?
What is the presentation of CGD?
Increased susceptibility to catalase + organisms (PLACESS): Pseudomonas, Listeria, Aspergillus, Candida, E. Coli, S. Aures. Serratia