Flashcards in Ch. 6 Immunologic Disorders: Primary Immunodeficiency Deck (24):
which causes of SCID lead to isolated CD8 T cell lymphopenia, but preserved CD4 T cells?
MHC class I deficiency (TAP1/TAP2 or tapasin); ZAP 70 (imp for CD8 signaling)
which causes of SCID lead to isolated CD4 T cell lymphopenia, but preserved CD8 T cells?
Bare lymphocyte syndrome (MHC II deficiency), Lck deficiency. Also think about HIV
There is an x-linked and AR SCID that have an identifical phenotype? What are they and why are they the same?
X-linked SCID=common gamma chain; AR SCID= JAK3 mutation; Jak3 is the signaling protein for the common gamma chain; T-B+NK-
what are the radiosensitive SCIDs?
artermis, cernunnos, ligase IV, Nijmegen breakage syndrome (also ATM which isn't SCID)
why are RAG1/RAG2 mutations not associated with radiosensitivity since they are DNA repair genes?
they are limited to immune cells, unlike artemis, cernunnos, ligase IV, etc
what is the mutated gene/protein in ataxia telangiectasia?
ATM, which is a PI3 kinase that is responsible for DNA ds breaks
what viral infection is fatal in XLP?
EBV-becomes fulminant and activates CTLs and macrophages which can lead to HLH
what is the mutation in XLP1? XLP2?
SH21A encodes SAP; XIAP in XLP-2
what is the mutation, inheritance and clinical presentation of Wiskott Aldrich?
WASp; inherited X-linked recessive; present with diarrhea/recurrent infections, FTT, eczema and thrombocytopenia; WAS is involved in intracellular trafficking; platelets are affected; NK cell can also be affected
what is AD Hyper IgE
mutation in STAT3; recurrent infections pyogengic and mucocutaneous (due to absent Th17); pneumatoceles; skeletal abnormalities, joint extensibility, fracture risk, retained primary teeth, abnormal facies, eczema and IgE>2000
what is AR hyper IgE
mutation in DOCK8; severe and difficult to treat viral infections; more prominent eos; no skeletal issues. Tyk2 is absent protein expression and is similar phenotype to DOCK8
severe enteroviral infections
think XLA; also ECHO viruses
what are some of the AR forms of agammaglobulinemia with essentially same phenotype as XLA?
surrogate light chain (V pre-B; lambda5); mu IgM heavy chain (constant) Iga, IgB, BLNK. of these IgM heavy chain is most common
what is kabuki syndrome
mutation in KMT2D (histone methylation?); clinically: hypogamm, cleft palate, abnormal facies and DD
what does reduced memory B cells (CD27) help you in management of CVID?
shown to be associated with certain NON-infectious complications (esp hematologic autoimmunity)
what is WHIM and the pathophysiology?
Warts, Hypogamm, infections and myelokathexis (retention of mature neutrophils in bone marrow which can lead to neutropenia). AD GOF mutation in CXCR4 which is important for bone marrow homing; ligand for CXCR4 is CXCL12 (expressed on leukocytes)
what are the mutations associated with Severe congenital neutropenia?
Hax-1 (Kostmann's)-AR; ELA-2 (elastase)- AD
LAD type I is a defect in what?
CD18; recall binds to variable alpha chains (CD11a=LFA1; CD11b=LFA2; CD11c p150,95) results in recurrent infections, delayed wound healing, impaired pus production, gingival issues, omphalitis or delayed cord release; detected by decreased CD18 on flow
LAD 2 is a defect in what? clinical phenotype?
mutation in FUCT1 (absence of fucosylation) -no Sialyl Lewis x (CD15a) that typically binds p-selectin; less severe infections; also associated with developmental delay, microcephaly, short stature and Bombay phenotype (unable to form blood group A, B or O)
LAD3 clinical phenotype
like LAD1 + bleeding diathesis; issue with inside out signaling
mutations in LYST; giant lysosomal granules in PMNs poor NK cytotoxicity; clinically have oculocutaneous albinism, recurrent infections, bleeding, neuro deficits; at risk for HLH
what are the 5 key infectious organisms to recall in CGD?
Staph, Burkholderia, Serratia, Nocardia and Aspergillus;
what are the enzymes defective in CGD?
PHOX (phagocytic NADPH oxidase system) >50% g91phox (x-linked); p47; p 67 and p22 (AR)