Immunology Flashcards
ALPS dx
Lymphoproliferation, cytopenias, LN/splenomegaly
Required
- >6mo nonmalignant/inf LN or splenomeg
- elevated DNT cells
Accessory
- defective lymphocyte apoptosis
- somatic/germline mutation FAS, FASLG, CASP10
- elevated plasma sFASL or IL-10 or B12 or IL-18
- IHC findings
- autoimm cytopenias and elevated IgG
- FHx
ALPS Evans Syndrome - epi, tx
50% of ALPS have Evans
steroid + IVIG
pulse MP –> pred maintenance
+- MMF or sirolimus
1o Immunodeficiency red flags
4 AOM/y
FHx
FTT
fungal inf
2 pneumonia
2 sinus infection/y
2 mo IV atb
2 deep seated inf
recurrent deep skin inf
IV atb
components of innate and adaptive immunity
Innate
- physical barriers, complement, cytokines, fever, mucous
- neutrophils
- macrophage
- NK
- eosinophil
Adaptive
- T CD8 cytotoxic
- T CD4 helper
- B
immunodefic workup
quantitative: CBC, B/T subsets, Ig, complement
Qualitative:
- T: mitogen stimulation, TCR beta repertoire
- B: Ig, CD40L (class switching), vaccine titre
Other
- CXR (thymus)
- TREC (SCID)
neonatal Ig physiologic nadir
IgG 2-6mo
IgA/M increase from birth
SCID definition and screening
low/absent fxnl T cells (CD3 <300/uL)
+- nonfxnl B cells
absent TREC (T cell repertoire excision circles) on NBS
SCID presentation
thrush, severe viral, opportunistic, live vaccine infection
FTT
chronic diarrhea
rash
lack of thymus
T-B-NK- SICD types
ADA
Adenylate kinase 2
T-B-NK+ SCID types
RAG1 and RAG2
DCLRE1C (artemis)
DNA ligase IV
T-B+NK-
X linked SCID
JAK3
T-B+NK+ SCID
IL-7 receptor alpha (CD127)
T cell Ag receptor complex
CD45
ADA SCID type
T-B-NK-
Artemis (DCLRE1C) SCID
T-B-NK+
X linked SCID type
T-B+NK-
Omenn Syndrome
edema, fluid overload, inflammation, LN, rash
SCID supportive mgt
proph: Septra, fluc, IVIG
viral PCR surveillance
no BF until Mom CMV neg
protective isolation
SW
irradiated blood products
SCID HSCT
ASAP, ideally <3mo
MSD goal
MSD - no conditioning
haplo - no conditioning, T cell depletion
MUD - condition
SCID gene therapy
Bu conditioning
trial for ADA w lentiviral vector: OS 100%, immune reconstitution 96%
XLA mutation and pathophys
BTK (bruton tyrosine kinase) mutation -> pre-B cell arrest -> no Ab
XLA presentation
present at 6mo after maternal IgG nadir with
- recurrent bacterial infections
- chronic enteroviral meningoencephalitis
- vaccine associated paralytic poliomyelitis
XLA malig risk
lymphoproliferative malig
gastric, colorectal adenocarcinoma
SCC lung
XLA ix
flow low/absent CD19
absent Ig
neg vaccine titres
absent tonsil/adenoid/lymph tissue
BTK mutation testing
XLA tx
IVIG
+- atb proph
HSCT if refractory
WAS triad and genetics
eczema
microthrombocytopenia
immunodeficiency
- combined T/B
- high IgA/E
- lack of carbohydrate vaccine response
WASP gene (Xp11)
- flow cytometry
WAS malig risk
NHL
other EBV-driven B L+L
10-20% risk
WAS tx
HSCT - best <5yo w MSD
XLP genetics, presentation, tx
XLP1 = SH2D1A mutation
XLP2 = BIRC4 mutation
HLH post EBV inf
fatal infectious EBV
aplastic anemia
pulm lymphoid granulomatosis
hypogamm
HSCT
- outcomes 80%, but 50% if active HLH
CVID pathophys, presentation, dx, tx
humoral defect due to lack of plasma cell differentiation
sinopulmonary
chronic enteroviral meningoencephalitis
lymphoprolif
autoimmunity
flow low CD19
poor vaccine response
IVIG
AT features, genetics, malig risk
progressive cerebellar ataxia
oculocutaneous telangiectasia
immunodeficiency (sinopulm)
aut rec ATM mutation
lifetime malig risk 30-40%
L+L (T cell, DLBCL)
carcinoma: breast, gastric, thyroid, liver
Chediak Higashi presentation, inheritance, immune issue, dx
partial oculocutaneous albinism
frequent bacterial infections
progressive neuro dysfunction
mild-mod neutropenia
aut rec CHS1 mutation
profound NK/T cell, monocyte, lymphocyte dysfxn
giant lysosomal granules in blood/BM
giant lysosomal granules suggests
Chediak Higashi
Hyper IgE features, genetics
sinopulmonary
eczema
retained primary teeth
coarse facial features
STAT3 defic (aut dom)
DOCK8 defic (aut rec)
1 immunodeficiency
selective IgA deficiency
hyperIgM pathophys and tx
X linked CD40L deficiency -> no class switching -> no IgA/G
IVIG, Septra
HSCT
