Immune deficiencies Flashcards
Defect in BTK, a tyrosine kinase gene –> no B cell maturation. X-linked recessive
X-linked (Bruton) agammaglobulinemia
- Recurrent bacterial and enteroviral infections after 6 months (loss of maternal IgG); GIARDIA
X-linked (Bruton) agammaglobulinemia
- absent CD19+ B cells, decreased pro-B, decreased Ig of all classes; absent/scanty lymph nodes and tonsils
X-linked (Bruton) agammaglobulinemia
Most common primary immunodeficiency
Selective IgA deficiency
Anaphylaxis after transfusion
Selective IgA deficiency
5 As of selective IgA deficiency
- majority Asymptomatic
- Airway and GI infxns
- Autoimmune
- Atopy
- Anaphylaxis
Defect in B cell differentiation, many causes
Common variable immunodeficiency
Can be acquired in 20s-30s (!)l increased risk of autoimmune disease, bronchiectasis, lymphoma, sinopulmonary infections
Common variable immunodeficiency
lab findings in selective IgA deficiency
IgA < 7 mg.dL with normal IgG and IgM levels
lab findings in common variable immunodeficiency
decreased plasma cells and immunoglobulins
Bruton is due to a defect in what gene?
BTK, a tyrosine kinase, that contributes to B cell maturation
22q11 deletion; failure to develop 3rd and 4th pharyngeal pouches –> absent thymus and parathyroids
DiGeorge
- Tetany
- recurrent viral/fungal infections
- conotruncal abnormalities
DiGeorge
Why do people with DiGeorge get tetany?
Hypocalcemia (low PTH)
Why do people with DiGeorge get recurrent viral/fungal infections
T cell deficiency
What types of conotruncal abnormalities might you see in DiGeorge?
Tetralogy of Fallot,
Truncus arteriosus
Lab tests of DiGeorge
- Decreased T cells, PTH, and calcium
- Absent thymic shadow on CXR
- 22q11 deletion detected by FISH
What do lymph nodes lack in Bruton?
Germinal centers
Disseminated mycobacterial and fungal infections; may present after administration of BCG vaccines
IL-12 receptor deficiency
How is IL-12 receptor deficiency inherited?
autosomal recessive
What are the labs/pathophys of IL12 deficiency?
Decreased IL12 –> decreased Th1 –> decreased IFN-gamma
Deficiency of Th17 cells due to STAT3 mutation –> impaired recruitment of neutrophils to sites of infection
Hyper IgE (autosomal dominant)
Presentation of Hyper IgE (FATED)
coarse Facies cold (non inflamed) staph Abscesses retained primary Teeth increased igE Dermatologic problems (eczema)
Lab findings of hyper IgE
increased IgE and decreased IFN-gamma
T cell dysfunction; many causes
chronic mucocutaneous candidiasis
noninvasive candida albicans infections of skin and mucous membranes
chronic mucocutanous candidiasis
labs/findings of chronic mucocutaneous candidiasis
- absent in vitro T cell proliferation in response to Candida antigens
- Absent cutaneous reaction to Candida
Three B cell (only) disorders
- Bruton
- Selective IgA deficiency
- Common variable immunodeficiency
Four T cell (only) disorders
- DiGeorge
- IL-12 receptor deficiency
- Hyper IgE
- Chronic mucocutaneous candidiasis
Two types of SCID
- Defective IL-2R gamma chain (x-linked)
- adenosine deaminase deficiency (AR_
Failure to thrive ,chronic diarrhea, thrush. Recurrent viral, bacterial, fungal, and protozoal infections
SCID
tx SCID
bone marrow transplant (no concern for rejection)
Findings in SCID
- decreased TRECS (T cell receptor excision circles)
- absence of thymic shadow on CXR
- absence of germinal centers on lymph node biopsy
- absence of T cells on flow cytometry
Defects in ATM gene –> DNA double strand breaks –> cell cycle arrest
Ataxia-telangiectasia
Ataxia (cerebellar atrophy) + telangiectasias + infxns (lymphopenia)
Ataxia-telangiectasia
Findings in ataxia-telangiectasia
Increased AFP
Decreased IgA, IgG, and IgE
Lymphopenia, cerebellar atrophy
What causes hyper IgM?
Defective CD40L on Th cells = class switching defect
how is hyper IgM inherited
x-linked recessive
Severe pyogenic infections early in life; opportunistic infection with Pneumocystis, Cryptosporidium, CMV
Hyper IgM
findings in hyper IgM
increased IgM
decreased IgG, IgA, IgE
large tonsils and lymph nodes
where is the mutation in wiskott aldrich?
WAS
pathophys of wiskott aldrich
WAS mutation –> T cell sun able to reorganize actin cytoskeleton
Triad of wiskott-aldrich
Thrombocytopenia purpura, eczema, recurrent infxns
increased risk of what in wiskott aldrich?
autoimmune disease and malignancy
Labs in Wiskott Aldrich
Decreased to normal: IgG, IgM
Increased IgE and IgA
Fever and smaller platelets
Defect in LFA-1 integrin (CD18) protein on phagocytes; impaired migration and chemotaxis; autosomal recessive
leukocyte adhesion deficiency
recurrent bacterial skin and mucosal infections, absent pus formation, impaired wound healing, delayed separation of the umbilical cord (>30 days)
leukocyte adhesion deficiency
findings in leukocyte adhesion deficiency (type 1)
increased neutrophils, absence of neutrophils at infection sites
defect in lysosomal trafficking regulator gene (LYST); microtubule dysfunction in phagolysosome fusion; autosomal recessive
Chédiak-Hisgashi syndrome
- Recurrent pyogenic infections by staph and strep,
- partial albinism,
- peripheral neuropathy,
- progressive neurodegeneration,
- infiltrative lymphohistiocytosis
Chédiak-Higashi syndrome
Findings in Chédiak-Higashi
- Giant granules in neutrophils and platelets
- Pancytopenia
- Mild coagulation defects
Defect of NADPH oxidase –> decreased ROS (superoxide) and absent respiratory burst in neutrophils; x-linked recessive
Chronic granulomatous disease
increased susceptibility to catalase positive organisms
Chronic granulomatous disease
catalase positive organisms
PLACESS
- pseudomonas
- listeria
- aspergillus
- candida
- e coli
- staph aureus
- serratia
- abnormal dihydrorhodamine test (flow cytometry)
- nitroblue tetrazolium dye reduction is negative
CGD
