ACAAI Review Book Ch 6: Immunologic disorders Flashcards
All of the following gene defects are associated with diseases that confer sensitivity to ionizing radiation except:
A. ZAP70 B. Artemis C. Cernunnos D. Ligase IV E. NBS1
A. ZAP70
All T- B- NK+
- bird like facies and microcephaly in most (except Artemis, which uniquely affects Athebascan-speaking Navajo/Apaches)
- ## defect in recombinase DNA repair protein in most (except NBS1)
The following gene defects do not lead to a complete T-cell lymphopenia except:
A. TAP1/2 deficiency B. tapasin deficiency C. ZAP70 deficiency D. Adenylate kinase 2 E. MHC class II deficiency F. LCk deficiency G. HIV
D. Adenylate kinase 2- causes AR form of T-B-NK- SCID Reticular Dysgenesis - neutropenia, deafness, hematopoeitic defects
CD8 lymphopenia: A. TAP1/2 deficiency- MHC class I deficiency B. tapasin deficiency- MHC class I deficiency C. ZAP70 deficiency
CD4 lymphopenia:
E. MHC class II deficiency (bare lymphocyte syndrome)
F. LCk deficiency
G. HIV
see table 6-5 for etiologies of SCID
page 209
All of the following cytokine receptors signal through the common gamma chain γc except:
A. IL-21 B. IL-9 C. IL-7 D. IL-16 E. IL-2 F. IL-4
D. IL-16
2, 4, 7, 9, 15, 21
γc (CD132), gene is IL2-RG
T-B+NK-
A defect in all of the following genes leads to a T-B+NK+ SCID phenotype except?
A. IL7-Ra B. IL2-Ra C. CD45 D. JAK-3 E. CD3δεζ
D. JAK-3 T-B+NK- - signaling protein of γc so same phenotype
A. IL7-Ra (CD127)- specific only for T cell development, so B+NK+
B. IL2-Ra (CD25)
C. CD45 - tyrosine phosphatase involved only in TCR signaling, so B+NK+
D. JAK-3
E. CD3δεζ- CD3 subunits involved only in TCR signaling, so B+NK+
RAG1/2 involved VDR rearrangement of T and B cell Ag receptor formation -> T-B-NK+
An infant presenting with erythroderma, diarrhea, failure to thrive, HSM, alopecia, and recurrent infections is found to have an elevated IgE, ESR/CRP and eosinophilia. What is the most likely gene defect?
A. ADA B. IL2-Ra C. CD45 D. RAG1/2 E. IL2-RG F. JAK-3
D. RAG1/2
Omenn’s syndrome
Ta B- NK+
An infant presenting with skeletal abnormalities including bulbous enlargement of costocondroital junctions on CXR, abnormal iliac bone, deafness, infections likely has a defect in what gene?
A. ADA B. IL2-Ra C. PNP D. RAG1/2 E. IL2-RG F. AK2
A. ADA
T- B- NK-
AR
premature lymphoid progenitor cell death = defective nucelotide salvage pathway = accumulation of toxic metabolites = all negative phenotypes
An infant presenting with neurological impairment, autoimmune hemolytic anemia, and infections likely has a defect in what gene?
A. ADA B. IL2-Ra C. PNP D. RAG1/2 E. IL2-RG F. AK2
C. PNP
defective purine nucleotide metabolism
T- B+ NK+/-
go back to tables 6-6 on page 211 through 226 and make PID questions based on ITE review
see picture comparing DHR testing pg 223
What is the best test for an infant who has been exposed to HIV-1?
A. HIV RNA by PCR B. HIV DNA by PCR C. HIV p24 antigen D. ELISA or EIA E. Western blot
B. HIV DNA by PCR
What are the most immunogenic HIV molecules?
A. p24 and p17
B. 2 RNA strands
C. reverse transcriptase
D. gp120 and gp 40
D. gp120 and gp40
gp120 binds CD4 and either:
- CCR5 on monos/macros
- CXCR4 on T cells
HIV specific CTLs are the most effective adaptive immune response to infection
Which of the following classes of medications is a strong CYP3A4 and CYP2DG inhibitor that can increase inhaled and intranasal corticosteroid to systemic levels causing Cushing’s syndrome?
A. entry/fusion inhibitors
B. integrase inhibitors
C. nuceloside reverse transcriptase inhibitors
D. non- nuceloside reverse transcriptase inhibitors
E. protease inhibitors
E. protease inhibitors - RITONAVIR
also imdiniavir, nelfinavir, lopinavir, atazanavir
A patient who has HIV is being started on antiretroviral medications including the nuceloside or nucelotide reverse transcriptase inhibitor abacavir. What testing is indicated?
A. Western blot
B. HIV RNA PCR
C. HLA-DRQ
D. HLA-B*5701
D. HLA-B*5701
challenge is CONTRAINDICATED w/ h/o HS reaction or positive HLA testing
A patient who has HIV is being started on antiretroviral medications has positive HLA-B*5701 testing. Which of the following classes of medications contains a medicine which is contraindicated in this patient?
A. entry/fusion inhibitors
B. integrase inhibitors
C. nuceloside or nucelotide reverse transcriptase inhibitors
D. non- nuceloside reverse transcriptase inhibitors
E. protease inhibitors
C. nuceloside or nucelotide reverse transcriptase inhibitors - ABACAVIR
challenge is CONTRAINDICATED w/ h/o HS reaction or positive HLA testing
Eotaxin-3 is strongly implicated in the pathology of what EGID?
EoE
- IL-5 required for eos infiltrate esophagus
- IL-13 induces eotaxin-3 expression
- also a/w TSLP SNP variants
review Parrish’s EoE lecture
A 45 year old male presents with HSM, cardiac arrythmia, and eosinophilia over 2500/mm3 on two occasions. B12 is elevated along with tryptase, but low hemoglobin and platelets. He is found to have PDGFRB and FGFR1 rearrangements. What is the next best step in management?
A. start abacavir B. start an anti-IL5 biologic therapy C. bone marrow biopsy D. start imatinib E. start systemic glucocorticoid therapy
D. start imatinib
Myeloproliferative HES:
- IMATINIB tyrosine kinase inhibitor is first line
- cardiac injury = add prednisone simultaneously
- also a/w JAK2 mutation
- deletion on 4q12 -> FIP1L1 -> PDGFRA fusion
A 50 year old female presents with erythroderma, pruritis, eczema, urticaria, and eosinophilia over 1700/mm3 on two occasions. IgG is elevated. she develops cough, abdominal pain, and spned time gardening outside barefoot. You are going to check troponins, chemistries, EKG and PFTs. What is the next best step in management?
A. rule out or empirically treat Strongyloides infection with Ivermectin B. start an anti-IL5 biologic therapy C. bone marrow biopsy D. start imatinib E. start systemic glucocorticoid therapy
A. rule out or empirically treat Strongyloides infection with Ivermectin
THEN!
E. start systemic glucocorticoid therapy
T cell lymphocytic HES:
- glucocorticoids are first line initial tx for non-myelo HES
Mastocytosis- see page 1225 in Middleton’s
see page 243 table 6-27 for classification table of SM
- activating mutations in ckit (KITD816V)
- constituitive activation of KIT tyrosine kinase signaling and aberrant expression of anti-apoptotic proteins (Bcl-XL an Bcl-2)
What is the ligand for c-KIT (CD117) required for mast cell survival?
A. KIT D816V B. stem cell factor C. CD25 D. BCL-XL E. BCL-2
B. stem cell factor
- constituitive activation of KIT tyrosine kinase signaling and aberrant expression of anti-apoptotic proteins (Bcl-XL an Bcl-2)
A patient presents with severe anaphylaxis after a hymenoptera sting. What is the next best step in management?
A. prescribe an epinephrine autoinjector B. check urine histamine C. check baseline tryptase D. skin test to venoms E. in vitro testing for venoms
C. check baseline tryptase
- screen for mastocytosis
All of the following are criteria for diagnosis of systemic mastocytosis except:
A. biopsy with multifocal dense infiltrates of MCs (≥15 MCs in aggregates)
B. focal dense mast cell infiltrates (>15 MCs/cluster) or diffuse mast cell infiltrates (>20 MC/hpf) on skin biopsy
C. c-KIT point mutation at codon 816 (D816V)
D. expression of CD2 and/or CD25 on CD117+ MCs
E. Baseline serum tryptase level >20 ng/mL
F. biopsy with >25% of all MCs having spindle-shaped or atypical morphology
B. focal dense mast cell infiltrates (>15 MCs/cluster) or diffuse mast cell infiltrates (>20 MC/hpf) on skin biopsy
- this is required (+ c-KIT D816V mutation) for CM dx
the others are required for SM dx:
1 major (A) + 1 minor (C-F)
or 3 minor
A patient presents with discrete yellow brown macular papular plaque like lesions that become urticarial and erythematous when you scratch them. Associated symptoms include flushing, abdominal pain, diarrhea, NV, bone pain, heart racing, fatigue, weight loss. If the patient is not found to have a mutation in D816V c-KIT, what management could be tried if his course became more aggressive?
imatinib (gleevec)
see treatments pg 245
how important or tick borne diseases? or leprosy? hepatitis? JIA?
tick borne diseases 245-248
leprosy 250-251
hepatitis 252-255
JIA 276-277
MSMD pge 249
look up graphic for pathway
All of the following are risk factors for systemic lupus erythematosus except:
A. HLA-DR2
B. early complement component deficiencies (C1, 2, 4)
C. FcyRII/III polymophisms
D. HLA-DR5
D. HLA-DR5
it is HLA-DR3!
All of the following are seen on renal biopsy immunofluorescence in a patient with proteinuria, hematuria, and casts due to systemic lupus erythematosus except:
A. IgG B. IgA C. IgM D. C3 E. C4 F. C1q
E. C4
“full house” on DIF
immune complex nephritis
Which of the following immunologic markers is more likely to be associated with sytemic drug-induced systemic lupus erythematosus?
A. ANA B. Anti ds-DNA C. Anti-Smith D. Anti-Ro (SS-A), Anti-La (SS-B) E. Antihistone F. Antiphospholipid
E. Antihistone >90%
- hydralazine, procainamide, isoniazid, methyldopa, quinidine
- Anti-Smith a/w ILD
- Antiphospholipid- blood clot and miscarriages
- Anti-Ro (SS-A), Anti-La (SS-B) more w/ Sjogren’s and NEONATAL lupus
- congenital heart block (Anti-Ro makes baby’s heart GO!)
A patient presents with erythema that is worse in the sun and scaly annular plaques. She denies arthralgias, myalgias, skin nodules, and no hepatomegaly on exam. She was started on a few new medications 1-2 moths ago, including hydrochlorothiazide, a calcium channel blocker, and ACE-inhibitor, and an oral antifungal. What is the most likely immunologic marker to be positive?
A. ANA B. Anti ds-DNA C. Anti-Smith D. Anti-Ro (SS-A), Anti-La (SS-B) E. Antihistone F. Antiphospholipid
D. Anti-Ro (SS-A), Anti-La (SS-B)
Cutaneous DILE!
Anti-Ro (SS-A), Anti-La (SS-B) more positive rather than antihistone Ab in systemic DILE
A 30 year old female presents with rash on her eyelids and face, difficulty getting up from a chair, weakness brushing her hair, rash over finger joints, photosesitivity. Muscle biopsy shows perifascicular atrophy due to microvascular damage. What is the most likely immunologic marker to be positive
A. Anti-Jo-1 and Anti-Mi-2 B. Anti ds-DNA C. Anti-Smith D. Anti-Ro (SS-A), Anti-La (SS-B) E. Antihistone F. Anti-Jo-1 and Anti-SRP
A. Anti-Jo-1 and Anti-Mi-2
DERMATOMYOSITIS
- Antibody-mediated complement attack
- Around muscle
- ANTIBODY = AROUND
POLYmyositis a/w Anti-Jo-1 and Anti-SRP
- cell mediated endomysial inflammatory infiltrate with primarily CD8 T cells
- w/in muscle - NECROSIS
- Complement = neCrosis
scleroderma- pg 284, Sjogren’s 281
lymphomas pg 285-288
Myelomas pg 289-292
Mulitple Myeloma mnemonic: Calcium increased Renal failure Anemia Bone lesions >3g/dl monoclonal paraprotein spike on SPEP, >10% BM involved
vs MGUS - <3g/dl, <10% BM involved
Type I and Type II/III cryoglobulinemias are each associated with which two of the following:
A. plasma cell dyscrasias B. hepatitis C infection C. hepatitis B infection D. multiple myeloma E. MGUS
cryoglobulinemias (reversible precipitation at low temperatures)
- Type I A. plasma cell dyscrasias D. multiple myeloma - MONOCLONAL. IgM>IgG or A - SX: hyperviscosity & thrombosis
- Type II/III (MC)
B. hepatitis C infection - 2 = MONOCLONAL
- 3 = POLYCLONAL
- RF is positive
- RF IgM complexes with fragmented crystallizable Fc portion of polyclonal IgG
- SX: joint involvement, renal IC dz, cutaneous vasculitis, peripheral neuropathy
pg 292-293, 331-333
Which of the following is the mechanism behind cold autoimmune hemolytic anemia?
A. polyclonal IgG against RBCs which attach to Fc receptors on macrophages in the spleen
B. anti-RBC IgG antibody against the P-antigen on RBC
C. loss of PIG-linkage proteins on surface of RBCs
D. IgM binds to I antigen
E. Rh disease
D. IgM binds to I antigen
- polysaccharide on all RBCs, binds @ temps <37C
A. polyclonal IgG against RBCs which attach to Fc receptors on macrophages in the spleen- WARM AIHA
B. anti-RBC IgG antibody against the P-antigen on RBC- paroxysmal cold hemoglobinuria
C. loss of PIG-linkage proteins on surface of RBCs- PNH
D. IgM binds to I antigen
E. Rh disease- HDNewborn
Patient presents with fever, anemia, thrombocytopenia, renal failure, and neurologic changes. Most like has what abnormality?
A. polyclonal IgG against RBCs which attach to Fc receptors on macrophages in the spleen
B. autoantibody against von WIllebrand factor-cleaving protease (ADAMTS13)
C. IgG or IgM antibody binds anionic phospholipid-protein complexes
D. IgG Fab binds drug-dependent antigent on platelet glycoproteins IIb/IIIa and Ib/IX
E. IgG inhibitory antibody to Factor VIII
B. autoantibody against von WIllebrand factor-cleaving protease (ADAMTS13)
TTP
FAT RN mnemonic for sx
C. IgG or IgM antibody binds anionic phospholipid-protein complexes =
LUPUS anticoagulant or Antiphospholipid antibody
D. IgG Fab binds drug-dependent antigent on platelet glycoproteins IIb/IIIa and Ib/IX
= Quinine induced thrombocytopenia
ALPS see page 297. MC form?
ALPS-FAS, AD, ~70%
- elevated a/b DNT cells >1.5% total lymphs
