Immunology Step 1 Flashcards
What are the X-linked immunodeficiencies?
SCID, Hyper-IgM syndrome, Wiskott-Aldrich syndrome, Chronic granulomatous disease, X-linked (Bruton) gammaglobulinemia
Thymic aplasia (DiGeorge)
3rd & 4th pharyngeal puches fail to develop
No thymus -> No mature T cells
No parathyroids -> hypocalcemia -> positive Chvostek and Trousseau signs
Recurrent viral, fungal, and protozoal infections
congenital defects in heart/great vessels (ToF, trunks arteriosus)
22q11 deletion
Chronic mucocutaneous candidiasis
T cell dysfunction vs. C albicans
Treatment: ketoconazole
IL-12 Receptor Deficiency
mycobacterial and fungal infections
Decreased Th1 response. Autosomal recessive
decreased IFN-gamma
Bruton agammaglobulinemia
X-linked (boys)
B cell deficiency -> defective tyrosine kinase gene -> low levels of all immunoglobulins
recurrent bacterial infections after 3-6 months
Selective Immunoglobulin Deficiencies
IgA deficiency is most common Most appear healthy Sinus and lung infections Associated with atopy, asthma Possible anaphylaxis to blood transfusions and blood products
SCID (Severe Combined Immunodeficiency)
Defect in early stem cell differentiation
Can be caused by at least seven different gene defects:
- Adenosine deaminase deficiency
Last defense is NK cells
Presentation triad
- Severe recurrent infections
- chronic mucocutaneous candidiasis
- fatal or recurrent RSV, VZV, HSV, measles, flu,
parainfluenza
- Pneumocystis jirovecii pneumonia (PCP)
- Chronic diarrhea
- Failure to thrive
No thymic shadow on newborn CXR
Ataxia-telangiectasia
IgA deficiency and T cell deficiency -> sinus and lung infections
Cerebellar ataxia and poor smooth pursuit of moving target with eyes
Telangiectasia of face (after 5 years of age)
Radiation sensitivity (try to avoid X-rays)
Increased risk: lymphoma and acute leukemias
Elevated AFP (after 8 months of age)
Average age of death: 25 years
Wiscott-Aldrich syndrome
WAITER WA - Wiskott-Aldrich I - Immunodeficiency T - Thrombocytopenia and purpura E - Eczema R - Recurrent pyogenic infections X-linked No IgM vs bacterial capsular polysaccharides Low IgM, high IgA
Hyper-IgM syndrome
Increased IgM; other Ab isotopes decreased
The two most important variants include:
- AR -> no CD40 on B cells
- X-linked -> no CD40L on helper T cells (most common)
Chronic Granulomatous Disease (CGD)
X-linked inheritance (65-70%)
Lack of NADPH oxidase -> phagocytes cannot destroy catalase-positive microbes
Especially susceptible to S. aureus and Aspergillus infections
Treatment
- Prophylactic TMP-SMX and itraconazole
- IFN-gamma also helpful
Chediak-Higashi Syndrome
Defective LYST gene (lysosomal transport)
Defective phagocyte lysosomes -> giant cytoplasmic granules in PMNs are diagnostic
Presentation triad:
- partial albinism
- recurrent respiratory tract and skin infections
- neurologic disorders
Hyper-IgE syndrome (Job syndrome)
Mutation in the gene for STAT3 signaling protein leading to:
- impaired differentiation of Th17 cells
- impaired recruitment of neutrophils
High levels of IgE and eosinophils
Presentation triad
- Eczema
- Recurrent cold S. aureus abscesses (think of biblical Job with boils)
- Coarse facial features: broad nose, prominent forehead (“frontal bossing”), deep-set eyes, and “doughy” skin
Also common to have retained primary teeth resulting in two rows of teeth
Leukocyte adhesion deficiency syndrome
Abnormal interns -> inability of phagocytes to exit circulation
Delayed separation of umbilical cord
Anti-TSH receptor Abs
Graves Dz
