Primary Immunodeficiency Flashcards
(36 cards)
Top 6 antibody defiencies
- Agammaglobuinemia (x-linked and AR) 2. Hyper-IgM Syndrome 3. IgA deficiency 4. Common variable immunodeficiency 5. Specific antibody deficiency 6. Transient hypogammaglobulinemia of infancy
Agammaglobulinemias
Caused by defects in B-cell development. Germinal center formation in these patients is defective (underdevelopment of lymphoid tissues, lymph nodes, peyer’s patches, spleen, tonsils, adenoids)
Enzyme associated in lyonized boys/females with agamaglobulinemias?
B cell tyrosine kinase
Mode of inheritance for agammaglobulinemia?
85% x-linked
Role of BTK?
Associated with pre-B cell receptor and is required for transducing signals downstrream=Stimulate B-cell maturation
Characterisitics of X-linked agammaglbulinemia
Approximately half are due to positive family history. IgG is usually<100 mg/dl; B-cells<2% of lymphocytes (usually 0.05-0.3%), and NORMAL T-CELL FUNCTION AND NUMBER
Hyper-IgM Syndrome characteristics
Defects in B-cell isotype switching. Normal numbers of B-cells, but express elevated levels of IgM with low IgG, IgE, and IgA
Mutant proteins in Hyper-IgM syndrome
CD40, CD40L, IKK-gamma (NEMO), AID, UNG
IgA Deficiency Characteristics
Most common primary immunodeficiency (1:500 healthy blood donors); IgA<5-7 mg/dl; Usually asymptomatic (occasionally increased sinopulmonary infections, diarrhea, autoimmune disease
Common Variable Immunodeficiency characteristics
2nd most frequent PID in humans after IgA. Most prevalent PID. Recurrent infections (sinusitis most common followed by pneumonia, life threatening infections). Granulomatous disease, autoimmune disorders, splenomegaly, and certain malignancies (300x LYMPHOMA RISK), REDUCED SERUM IgG, IgA, and/or IgM, Abset or impaired specific antibody responses to previous infection or vaccination
Specific antibody deficiency
Recurrent sinopulmonary infections; Normal IgG, IgA, IgM; Normal B-cell number and Normal T-cell number and function; Impaired vaccine response (polysaccharide); Impaired antibody response to natural infection with encapsulated bacteria
Encapsulated organisms
Streptococcus pneumoniae and pyogenes; Staph aureus; Klebsiella; Haemophilus influenzae; Pseudomonas aeruginosa; Neisseria menigngitidis; Cryptococcus neoformans (Mycoplasma, bordetella pertussis, some e coli, streptococcus agalactiae, Yersinia Pestis (F1 envelope)
Transient Hypogammaglublinemia of infancy
Recurrent sinopulmonary infections, low IgG, NORMAL SPECIFIC ANTIBODIES, normal lymphocyte number and function, delay in maturation of T-cell help for antibody production, Onset of about 6 months of age, resolve by age 4
Types of SCID And Lymphocyte development deficiencies
- Adenosine deaminase deficiency (worst case)/PNP Deficiency 2. Gamma-c? Deficiency 3. DiGeorge syndrome 4. RAG Deficiency
Mode of inheritance Adenosine deaminase deficiency; step involved
autosomal; stem cell to pro-B cell AND stem cell to Pro-T-cell
Mode of inheritance PNP Deficiency; step involved
autosomal; stem cell to pro-B cell AND stem cell to Pro-T-cell
Mode of inheritance RAG deficiency; step involved
autosomal; Pro-B cell to Pre-B cell AND Pro-Tcell to Pre-T cell
Mode of inheritance with gamma c deficiency; step involved with gamma c and digeorge syndrome
X-linked; Stem cell to pro-t cell
Omenn syndrome characteristics
Hypomorphic mutations (most common in RAG genes); Low to normal number of T-cells but oligoclonal T-cell population; early onset (<3 months) of a diffuse exudative erythroderma; lymphadenopathy; hepatosplenomegaly; chronic persistent diarrhea; failure to thrive; elevated IgE and eosinophili (can be confused with normal baby eczema); “leaky SCID”
Digeorge syndrome characteristics
Defect in embryogenesis 3rd and 4th pharyngeal pouches. Most have deletion of chromosome 22q11.2. Dysmorphic faces (micrognathia, low set ears), hypocalcemia (lack of parathyroids, hypoplastic to aplastic thymus, congenital heart disease (aortic defects, VSD), presents in first few days of life. Affects both males and females
Diagnosing of digeorge syndrome
Diagnosed immediately by lateral chest x-ray (absence of thymic shadow)
Partial DiGeorge Syndrome
More frequent; thymic hypoplasia (normal corticomedullary differentiation, presence of Hassall’s corpuscles, normal thymic function); CD4 cells>400/mm3; T-cell function adequate, B-cell numbers and function normal, usually free of infections
Complete Digeorge Syndrome
Uncommon; thymic apalsia, CD4 cells<400mm3, B-cells numbers normal; antibody response decreased; susceptible to infections; susceptible to GVHD
Wiskott Aldrich Syndrome
Eczema; THROMBOCYTOPENIA WITH SMALL PLATELETS (look for low MPV); immunodeficiency; Inovlved with actin polymerization
