Immune Deficiencies Flashcards
X-linked Bruton Agammaglobulinemia
Defect: Defect in BTK, a tyrosine kinase gene - no B cell maturation. X linked recessive. Increased in boys.
Presentation: Recurrent bacterial and enteroviral infections after 6 months due to decreased maternal IgG
Findings: Normal CD19+ B cell count, decreased pro-B, decreased Ig of all classes. Absent/scanty lymph nodes and tonsils.
How to remember: BRUTES TIE up their BOYS who don’t even get Bs in school and leave them there for 6 MONTHS until they are LIMP (no lymph nodes) and NON-TONED (no tonsils).
Selective IgA deficiency
Defect: Unknown. Most common primary immunodeficiency
Presentation: Asymptomatic, can see airway and GI infections, autoimmune disease, atopy, anaphylaxis to IgA containing products
Findings: IgA < 7, with normal IgG, IgM levels
CVID
Defect: Defect in B cell differentiation. Many causes.
Presentation: Can be acquired in 20s-30s, risk of autoimmune disease, bronchiectasis, lymphoma, sinopulmonary infections.
Findings: decreased plasma cells, decreased immunoglobulins.
Thymic aplasia / DiGeorge
22q11 Deletion. Failure to develop 3rd and 4th pharyngeal pouches: absent thymus and parathyroids.
Presentation: Tetany / hypocalcemia, recurrent viral/fungal infections (T cell deficiency), cotruncal abnormalities (tetrolagy of fallot, truncus)
Findings: Decreased T cells, decreased PTH, decreased Ca2+, absent thymic shadow on CXR. 22q11 deletion detected by FISH.
(Also remember CAP - Cleft ectoderm, Arch mesoderm, Pouch endoderm). Remember Pouch mnemonic: Eat Tons of Inferior Parmesan and Thyme for Supper –> Ear, Tonsils, Inferior Parathyroids + Thymus, Superior parathyroids for 1st - 4th pouches.
IL-12 Receptor Deficiency
Defect: Decreased TH1 response, autosomal recessive.
Presentation: Disseminated mycobacterial and fungal infections, may present after BCG administration
Findings: Decreased IFN-gamma
How to remember: IL-12 induces differentiation of T cells into Th1 cells and also activations NK cells. 12 –> digits 1 and 2 –> Th1, and 2 * 6 (for NK cells) = 12.
Also remember: I got TB 12 days after I was vaccinated by my interfering (interferon) mother.
Autosomal dominant hyper-IgE syndrome (Job Syndrome)
Defect: Deficiency of Th17 cells due to STAT3 mutation –> impaired recruitment of neutrophils to infection sites.
Presentation: FATED Coarse Facies Abscesses (cold, noninflamed, staphylococcal) Teeth (retained primaries) IgE Dermatologic problems (eczema)
Findings: Increased IgE, decreased IFN-gamma
Remember: StEve Jobs likes Statistics and is Hyper and was FATED to be great even at the young age of 17.
Chronic mucocutaneous candidiasis
Defect: T cell dysfunction. Many causes.
Presentation: Noninvasive Candida albicans infection of skina nd mucous membranes.
Findings: Absent in vitro T cell proliferation in response to Candida antigens. Absent cutaneous reaction to Candida antigens.
Remember: Candida test tests for T cell related problems.
SCID
Defect:
- IL-2R gamma chain (most common, 60%, X-linked)
- ADA (autosomal recessive)
Presentation: Failure to thrive, chronic diarrhea, thrush. Recurrent viral, bacterial, fungal, and protozoal infections. Treat with bone marrow transplantation, no concern for rejection.
Findings: Decreased T cell receptor excision circles (TRECs) - small circles of DNA created in T cells during their passage through the thymus as they rearrange their TCR genes.
Absence of thymic shadow (CXR), germinal centers, (lymph node biopsy), and T cells (flow cytometry)
Remember: Similar presentation to HIV.
You SKID on your IL-TIRE (2R)
ADA - AUDOSOMAL
Ataxia-telangiectasia
Defect: Defects in the ATM gene –> DNA double strand breaks –> Cell cycle arrest
Triad: Cerebellar defects, spider angiomas, IgA deficiency
Findings: Increased AFP, Decreased IgA, IgG, IgE, lymphopenia, cerebellar atrophy.
Remember: A tax at the ATM.
It’s in the name, ataxia and telangiectasia.
Hyper IgM Syndrome
Defect: Most commonly due to defective CD40L on Th cells - class switching defect. X linked recessive.
Presentation: Severe pyogenic infections early in life. Opportunistic infection with Pneumocystis, Cryptosporidium, CMV.
Findings: Increased IgM, Decreased everything else.
Remember: When mom was, like, 40 she got really hyper and started switching all her classes; she was female (X-linked).
Wiskott-Aldrich syndrome
Defect: Mutation in WAS gene - X-linked recessive. T cells unable to reorganize actin cytoskeleton. Increased risk of autoimmune disease and malignancy.
Findings: Decreased to normal IgG, IgM. Increased IgE, IgA. Fewer and smaller platelets.
Remember: WATER TAX - T cells, actin, X-linked
Wiskott-Aldrich, Thrombocytopenic purpura, Eczema, Recurrent infections.
Leukocyte adhesion deficiency type 1
Defect: Defect in LFA-1 integrin (CD18) protein on phagocytes, impaired migration and chemotaxis, autosomal recessive.
Findings: Recurrent bacterial skin and mucosal infections, absent pus formation, impaired wound healing, delayed separation of the umbilical cord > 30 days.
Findings: increased neutrophils, absence of neutrophils at infection sites.
Remember: E- and P-selection, rolling, then integrins. 18 –> think goggles allowing you to swim into the endothelium, and then you swim over a HUMP.
HUMP - healing impaired, umbilicus separation delayed, mucosal infections, pus formation impaired
Chediak-Higashi syndrome
Defect in lysosomal trafficking regulator gene (LYST), microtubule dysfunction in phagosome-lysozome fusion, autosomal recessive.
REcurrent pyogenic infections by staph and strep, partial albinism, peripheral neuropathy, progressive neurodegeneration, infiltrative lymphohistiocytosis.
Giant granules in neutrophils and platelets. Pancytopenia, Mild coagulation defects.
Remember: After being stuck in traffic (lysosomal trafficking), the staph ate the white cheddar cheese and their brains degenerated.
Chronic granulomatous disease
Defect in NADPH oxidase –> decreased ROS (eg superoxide) and absent respiratory burst in neutrophils. X linked recessive.
Catalase positive susceptibility .
Findings: Abnormal dihydrorhodamine - flow cytometry test. Nitroblue tetrazolium dye reduction test is negative (test out of favor).
Remember: The Cat Aspirated Pseudofed, Listerine but Survived to Eat Candy and other Staph.
