ACAAI Review Book Ch 6: Immunologic disorders Flashcards
1
Q
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
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)
2
Q
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
A
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
3
Q
see table 6-5 for etiologies of SCID
A
page 209
4
Q
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
A
D. IL-16
2, 4, 7, 9, 15, 21
γc (CD132), gene is IL2-RG
T-B+NK-
5
Q
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
A
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+
6
Q
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
A
D. RAG1/2
Omenn’s syndrome
Ta B- NK+
7
Q
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
A. ADA
T- B- NK-
AR
premature lymphoid progenitor cell death = defective nucelotide salvage pathway = accumulation of toxic metabolites = all negative phenotypes
8
Q
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
A
C. PNP
defective purine nucleotide metabolism
T- B+ NK+/-
9
Q
go back to tables 6-6 on page 211 through 226 and make PID questions based on ITE review
A
see picture comparing DHR testing pg 223
10
Q
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
A
B. HIV DNA by PCR
11
Q
What are the most immunogenic HIV molecules?
A. p24 and p17
B. 2 RNA strands
C. reverse transcriptase
D. gp120 and gp 40
A
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
12
Q
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
A
E. protease inhibitors - RITONAVIR
also imdiniavir, nelfinavir, lopinavir, atazanavir
13
Q
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
A
D. HLA-B*5701
challenge is CONTRAINDICATED w/ h/o HS reaction or positive HLA testing
14
Q
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
A
C. nuceloside or nucelotide reverse transcriptase inhibitors - ABACAVIR
challenge is CONTRAINDICATED w/ h/o HS reaction or positive HLA testing
15
Q
Eotaxin-3 is strongly implicated in the pathology of what EGID?
A
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
16
Q
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
A
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
17
Q
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
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
18
Q
Mastocytosis- see page 1225 in Middleton’s
A
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)
19
Q
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
A
B. stem cell factor
- constituitive activation of KIT tyrosine kinase signaling and aberrant expression of anti-apoptotic proteins (Bcl-XL an Bcl-2)
20
Q
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
A
C. check baseline tryptase
- screen for mastocytosis
21
Q
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
A
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
22
Q
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?
A
imatinib (gleevec)
see treatments pg 245
23
Q
how important or tick borne diseases? or leprosy? hepatitis? JIA?
A
tick borne diseases 245-248
leprosy 250-251
hepatitis 252-255
JIA 276-277
24
Q
MSMD pge 249
A
look up graphic for pathway
25
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!
26
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
27
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!)
28
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
29
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
30
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
31
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
32
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
33
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
34
ALPS see page 297. MC form?
ALPS-FAS, AD, ~70%
| - elevated a/b DNT cells >1.5% total lymphs
35
Graves disease mechanism?
antibodies to TSH receptor stimulates -> excess thyroid hormone
- HLA-DR3
- CTLA-4 alleles
36
Hashimoto's disease mechanism?
antibodies to TPO, TG, and TSH
- Hurthle cells
- also HLA-DR3 and CTLA-4
37
A child presenting with CMC of the mouth and nails, hypoparathyroidism, autoimmune adrenal insufficiency, ectodermal dystrophy, diabetes most likely has a defect in which of the following?
```
A. FOXP3
B. 21-hydroxylase
C. WAS gene
D. AIRE
E. STAT1
```
D. AIRE
APECED
-autoimmune polyendocrinopathy, candidiasis, ectodermal dysplasia
38
A male infant presents with rash that does not respond to typical therapies, diarrhea, and infections. He most likely has a defect in which of the following?
```
A. FOXP3
B. 21-hydroxylase
C. WAS gene
D. AIRE
E. STAT1
```
A. FOXP3
IPEX
- depletion of Tregs
- immune dysregulation, polyendocrinopathy, enteropathy, X-linked. TX: BMT
- villous atrophy, FTT, T1DM, AI cytopenias
- IPEX-like presentation a/w CD25 and STAT5B mutations
39
A patient presents with weakness, fatigue, anorexia, hyperpigmentation, myalgias. They most likely have a defect in which of the following?
```
A. antibodies to TSH receptor
B. antibodies to 21-hydroxylase
C. antibodies to TPO, TG, and TSH
D. AIRE mutation
E. antibody to CYP21A2
```
B. antibodies to 21-hydroxylase
Addison's disease
- decreased production of steroid hormones (GCC, MCC, androgens)
- increased ACTH
- give exogenous ACTH -> serum cortisol doesnt rise
- antibody to CYP21A2 (enzyme needed to make cortisol) = primary adrenal failure (decreased aldosterone, increased renin)
40
The most common nephrotic syndrome in adults is associated with what abnormality?
A. only podocyte effacement
B. subepithelial immunoglobulin deposits , granular staining of IgG and C3 along the GBM
C. diffuse podocyte effacement with mesangial involvement and sclerosis
D. low C3 with circulating immune complexes (and ab-ag complexes deposited in glomeruli), cryoglobulins, RF, elevated IgG
E. mesangial IgA staining on IF. elevated serum IgA and complexes with IgA
F. deposition of IgA immune complexes in affected organs
G. immune complex deposition, complement activation, monoclonal IgM to glomerular proteins
H. antibodies to alpha-3 chain of type IV collagen, staining of IgG along GBM in a linear distribution, crecents
B. electron-dense subepithelial immunoglobulin deposits , granular staining of IgG and C3 along thickened GBM
MEMBRANOUS NEPHROPATHY
A. only podocyte effacement = MCD
C. diffuse podocyte effacement with mesangial involvement and sclerosis = FSGS
D. low C3 with circulating immune complexes (and ab-ag complexes deposited in glomeruli), cryoglobulins, RF, elevated IgG = PSGN (prior strep infxn + anti-ASO or DNAse B titers
41
The most common glomerulonephritis in the world is associated with what abnormality?
A. only podocyte effacement
B. subepithelial immunoglobulin deposits , granular staining of IgG and C3 along the GBM
C. diffuse podocyte effacement with mesangial involvement and sclerosis
D. low C3 with circulating immune complexes (and ab-ag complexes deposited in glomeruli), cryoglobulins, RF, elevated IgG
E. mesangial IgA staining on IF. elevated serum IgA and complexes with IgA
F. deposition of IgA immune complexes in affected organs
G. immune complex deposition, complement activation, monoclonal IgM to glomerular proteins
H. antibodies to alpha-3 chain of type IV collagen, staining of IgG along GBM in a linear distribution, crecents
E. mesangial IgA staining on IF. elevated serum IgA and complexes with IgA = IgA NEPHROPATHY = MC GN in world
F. deposition of IgA immune complexes in affected organs = HSP = male kids s/p URI, abdominal pain, arthralgias, hematuria, purpuric LE rash
G. immune complex deposition, complement activation, monoclonal IgM to glomerular proteins = MPGN
- 2/2 mixed cryoglobulinemia and HCV
H. antibodies to alpha-3 chain of type IV collagen, staining of IgG along GBM in a linear distribution, crecents = ANTI-GBM disease
- GOODPASTURE'S SYNDROME
- pulmonary-renal vasculitic syndrome
- young male smokers & 60-70yp women
- sometimes pANCA and cANCA positive
42
Atypical hemolytic uremic syndrome in children is associated with what lab abnormality?
Factor H autoantibody
43
A patient presents with flaccid bullae and crusting over the scalp, chest and intertriginous areas, that extend to uninvolved skin when pressure is applied. Exam of the mouth reveals oral ulcerations. What autoantibody and immunopathology characterizes this disease?
A. IgA epithelial surface, desmocollin-1: epidermal IgA
B. IgG epithelial surface, desmoglein-3: epidermal IgG/C3
C. type VII collagen: linear basement membrane zone IgG/C3, linear IgA/IgM
D. IgG BMZ, BP180, BP230: IgG/C3 BMZ
E. desmoglein-1: epidermal IgG/C3
F. endomysial IgA, transglutaminase IgA: granular BMZ IgA
B. IgG epithelial surface, desmoglein-3: epidermal IgG/C3
PEMPHIGUS VULGARIS
- DESMOsome
- EPIdermal
- see pic on pg 311
- "row of tombstones" basal keratinocytes are attached to BM but not to each other
- TX: prednisone
44
An elderly patient presents with tense bullae on an urticarial base in the flexural areas, which is extremely itchy to the patient. Exam of the mouth reveals oral ulcerations. What autoantibody and immunopathology characterizes this disease?
A. IgA epithelial surface, desmocollin-1: epidermal IgA
B. IgG epithelial surface, desmoglein-3: epidermal IgG/C3
C. type VII collagen: linear basement membrane zone IgG/C3, linear IgA/IgM
D. IgG BMZ, BP180, BP230: IgG/C3 BMZ
E. desmoglein-1: epidermal IgG/C3
F. endomysial IgA, transglutaminase IgA: granular BMZ IgA
D. IgG BMZ, BP180, BP230: IgG/C3 BMZ
BULLOUS PEMPHIGOID
- SUBepidermal
BP180- BPAG2
BP230- BPAG1
HEMIdesmosome
- TX: more topical (high potency CS, clobetasol)
45
An elderly patient presents with bullae over areas of trauma. Exam of the mouth reveals oral ulcerations. What autoantibody and immunopathology characterizes this disease?
A. endomysial IgA, transglutaminase IgA: granular BMZ IgA
B. desmoglein-1: epidermal IgG/C3
C. type VII collagen: linear basement membrane zone IgG/C3, linear IgA/IgM
D. IgG BMZ, BP180, BP230: IgG/C3 BMZ
E. IgG epithelial surface, desmoglein-3: epidermal IgG/C3
F. IgA epithelial surface, desmocollin-1: epidermal IgA
C. type VII collagen: linear basement membrane zone IgG/C3, linear IgA/IgM
EPIDERMOLYSIS BULLOSA ACQUISITA
- TX: colchicine or dapsone + steroids
46
A patient presents with flaccid bullae and crusting over the scalp, chest and intertriginous areas, that extend to uninvolved skin when pressure is applied. Exam of the mouth does not reveal oral ulcerations. What autoantibody and immunopathology characterizes this disease?
A. endomysial IgA, transglutaminase IgA: granular BMZ IgA
B. desmoglein-1: epidermal IgG/C3
C. type VII collagen: linear basement membrane zone IgG/C3, linear IgA/IgM
D. IgG BMZ, BP180, BP230: IgG/C3 BMZ
E. IgG epithelial surface, desmoglein-3: epidermal IgG/C3
F. IgA epithelial surface, desmocollin-1: epidermal IgA
B. desmoglein-1: epidermal IgG/C3
PEMPHIGUS FOLIACEOUS
(bullous impetigo a/w staph exfoliative toxin which is a serine protease that also attacks desmoglein-1 causing blisters in the stratum corneum)
47
A patient presents with flaccid bullae that extend to uninvolved skin when pressure is applied. Exam of the mouth does not reveal oral ulcerations. What autoantibody and immunopathology characterizes this disease?
A. endomysial IgA, transglutaminase IgA: granular BMZ IgA
B. desmoglein-1: epidermal IgG/C3
C. type VII collagen: linear basement membrane zone IgG/C3, linear IgA/IgM
D. IgG BMZ, BP180, BP230: IgG/C3 BMZ
E. IgG epithelial surface, desmoglein-3: epidermal IgG/C3
F. IgA epithelial surface, desmocollin-1: epidermal IgA
F. IgA epithelial surface, desmocollin-1: epidermal IgA
IgA PEMPHIGUS
48
A patient presents with rash consistent of small grouped vesicles over the lower extremities, buttocks, and extensor surfaces that are extremely itchy to the patient. They also have some stomach discomfort. What autoantibody and immunopathology characterizes this disease?
A. endomysial IgA, transglutaminase IgA: granular BMZ IgA
B. desmoglein-1: epidermal IgG/C3
C. type VII collagen: linear basement membrane zone IgG/C3, linear IgA/IgM
D. IgG BMZ, BP180, BP230: IgG/C3 BMZ
E. IgG epithelial surface, desmoglein-3: epidermal IgG/C3
F. IgA epithelial surface, desmocollin-1: epidermal IgA
A. endomysial IgA, transglutaminase IgA: granular BMZ IgA
DERMATITIS HERPETIFORMIS
- celiac dz a/w HLADQ2
- eliminate gluten
49
how important are immunologic neuropathies?
see table 6-50 and 6-51 pages 321-323
50
A child presents for recurrent fevers that occur at variable frequency and last 1-3 days. She sometimes reports associated rash, leg pain, abdominal pain, and chest pain. Her mother thinks her brother may have had a similar problem when they were kids. What is the best treatment?
```
A. steroids
B. NSAIDS
C. IL-1 blockade
D. colchicine
E. TNF-inhibitor
```
D. colchicine
FMF
MEFV gene (codes for pyrin)
colchicine prevents amyloidosis (SEffx: GI upset)
51
What is the most severe of the diseases associated with mutations in CIAS1 that presents with fever, urticarial rash, amyloidosis, conjunctivitis, arthralgias, sensorineural hearing loss, bony overgrowth and CNS findings with developmental delay and leptomeningeal inflammation?
A. familial cold-induced autoinflammatory syndrome
B. tumor necrosis factor receptor-associated periodic syndrome
C. Muckle-Wells syndrome
D. mevalonate kinase deficiency
E. chronic infantile neurological cutaneous and articular/neonatal onset multisystem inflammatory disease
E. chronic infantile neurological cutaneous and articular/neonatal onset multisystem inflammatory disease
CINCA/NOMID
- AD
- TX: IL-1 blockade
on a spectrum with MWS and FCAS
(amyloidosis on pg 330)
52
An infant is noted to have an urticarial rash in the delivery room and recurrent fevers in the first 6 months of life. He also seems to had frequent eye redness and sometimes refuses to walk or cries when he tries to walk. This disease is most likely associated mutations in which of the following?
```
A. MEVK
B. MVK
C. CIAS1
D. PLCy2
E. TNFRSF1A
```
C. CIAS1
FCAS
familial cold-induced autoinflammatory syndrome
- NEGATIVE ICE cube test
POSITIVE evaporative cooling test
generalized cold exposure. hives w/in 2 hrs can last 12 hrs. AD.
neutrophilic infiltration is observed without evidence of mast cell degranulation
53
An adult patient presents with recurrent febrile episodes lasting weeks at a time, with associated muscle pains, swelling around the eyes, redness of the eyes, headache, and a rash that seems to come and go starting in the extremities and moving to the trunk. This disease is most likely associated mutations in which of the following?
```
A. MEVK
B. MVK
C. CIAS1
D. PLCy2
E. TNFRSF1A
```
E. TNFRSF1A
TRAPS
- AD mutation in TNF-receptor
- TX: NSAIDS, steroids during attacks.
etanercept.
54
A 12 month old child presents with recurrent fevers that last 3-7 days. His mom states that this has happened after each time he has received vaccinations. He also has symptoms of swollen lymph nodes, ulcers in his mouth, red macules and urticarial lesions, and joint pain and swelling. This disease is most likely associated mutations in which of the following?
```
A. MEVK
B. MVK
C. CIAS1
D. PLCy2
E. TNFRSF1A
```
B. MVK
HIDS
mevalonate kinase deficiency
TX: steroids & IL-1 blockade
55
A 3 yo child presents with fever that lasts days at a time and occurs every 3-8 weeks. Associated symptoms include swollen tonsils and neck lymph nodes, apthous stomatitis, and negative infectious cultures. He is completely well between episodes with normal growth and development. What is the most likely diagnosis?
A. familial cold-induced autoinflammatory syndrome
B. tumor necrosis factor receptor-associated periodic syndrome
C. Muckle-Wells syndrome
D. mevalonate kinase deficiency
E. periodic fever, apthous stomatitis, pharyngitis, adenitis
E. periodic fever, apthous stomatitis, pharyngitis, adenitis
PFAPA
TX: steroids & IL-1 blockade
ppx: collchicine, cimetidine, montelukast, tonsillectomy
see pages 325-329
DIRA = deficiency of IL-1R antagonist = uninhibited IL-1 activity = neonatal multifocal osteomyelitis + pustular rash TX: anakinra
PAPA = pyogenic sterile arthritis pyoderma gangrenosum and acne syndrome = CD2 binding protein 1 mutation = prolonged inflammasome activation = TX: IL-1 blockade
56
A patient presents with urticarial rash that occurs upon cold exposure. Unsure if he had it in the delivery room. He also seems to had frequent sinusitis, pneumonias, and rhinitis. This disease is most likely associated mutations in which of the following?
```
A. MEVK
B. MVK
C. CIAS1
D. PLCy2
E. TNFRSF1A
```
D. PLCy2
PLAID
PLCy2-associated antibody deficiency and immune dyregulation
+ antibody deficiency
- NEGATIVE ICE cube test
POSITIVE evaporative cooling test
TX: AH and IG
57
granulomatous diseases p334-337
markers: ACE, 1, 25(OH)2D3, osteopontin
refer back for sarcoidosis & beryllosis
Sarcoidosis:
- perilymphatic noncaseating granulomas
- intracellular and cytokine staining profiles Th1 (IFNy)-predominany cytokine pattern (CD4/CD8 ratio >4 - vs Hypersensitivity pneumonitis has decreased ratio w/ CD8 predominance)
- PFTs restrictive
-LOFGREN's syndrome = acute sarcoid p/w BL hilar LAD, erythema nodosum, and arthritis. self limited, tx NSAIDs
58
see table 6-58 page 240 for GVHD reactions
CF page 347
59
Young male child of Jewish descent presents with recurring fevers lasting 1-3 days, joint swelling and pain, and abdominal pain. The underlying gene defect in this disease causes a mutation in what protein?
```
A. IL1-B
B. TNFRSF1A
C. unknown
D. pyrin
E. mevalonate kinase
```
D. PYRIN - FMF
FMF- fever 1-3 days, serositis, arthritis, rash. high risk ethnic groups for FMF: Jewish, Armenian, Arab, Turkish, Italian. AR mutations in MEFV coding PYRIN. Renal amyloidosis as a complication. TX: colchicine.
60
An adolescent presents with recurrent episodes of fever with serositis, arthritis, MIGRATORY RASH and PERIORBITAL EDEMA lasting WEEKS! This has happened most of his lifetime. The underlying gene defect in this disease causes a mutation in which of the following?
```
A. IL1-B
B. TNFRSF1A
C. unknown
D. pyrin
E. mevalonate kinase
```
B. TNFRSF1A - TRAPS
The TNF Receptor Associated Periodic Syndrome.
AD mutations in TNFRSF1A, encodes the p55 TNF receptor.
TX: NSAIDs, steroids, Etanercept (TNF blocker)
(Anti-TNF monoclonal antibodies may exacerbate TRAPS)
61
A 3 yo presents with recurrent episodes of fever lasting 3-7 days, associated with diffuse maculopapular rash, prominent cervical LAD, apthous ulcers, abdominal pain, arthritis and arthralgias. This has occurred since infancy and seems to worsen when he gets childhood vaccines. The underlying gene defect in this disease causes a mutation in which of the following?
```
A. IL1-B
B. TNFRSF1A
C. unknown
D. CIAS1
E. mevalonate kinase
```
E. mevalonate kinase - HIDS
Most frequently seen among Dutch, Northern Europeans
• Some patients have fevers and MVK mutations but normal
IgD levels
• Serum IgD levels do not correlate with the acute attacks of HIDS
• MVK mutations may lead to decreased geranylgeranylation
and consequent increased IL IL-1β production
62
A 1 yo presents with recurrent episodes of fever, hives like skin rash, arthralgia, conjunctivitis, and headache/crying upon generalized exposure to cold. Rash comes on 2 hrs after cold exposure and lasts 12 hours. This started in infancy. The underlying gene defect in this disease causes a mutation in which of the following?
```
A. CIAS1
B. mevalonate kinase
C. unknown
D. IL1-B
E. TNFRSF1A
```
A. CIAS1
FCAS (familial cold autoinflammatory syndrome)
CAPS (CIAS1 Associated Periodic Fever Syndromes)
Not true urticaria: neutrophils , not mast cells
•AD
•Amyloidosis rare
63
A child presents with recurrent episodes of fever, hives like skin rash, limb pain, and is noted to have sensorineural hearing loss. This started in infancy. The underlying gene defect in this disease causes a mutation in which of the following?
```
A. CIAS1
B. mevalonate kinase
C. unknown
D. IL1-B
E. TNFRSF1A
```
A. CIAS1
Muckle Wells
- fever, urticarial like rash , arthritis, sensorineural deafness, amyloidosis
CAPS (CIAS1 Associated Periodic Fever Syndromes)
64
A child presents with recurrent episodes of fever, hives like skin rash, limb pain with bony overgrowth, CNS abnormalities, chronic meningitis, and developmental delay. This started in infancy. The underlying gene defect in this disease causes a mutation in which of the following?
```
A. IL1-B
B. mevalonate kinase
C. unknown
D. cryopyrin
E. TNFRSF1A
```
D. cryopyrin - NOMID
Neonatal Onset Multisystem Inflammatory Disease
Caused by dominant or de novo mutations in CIAS1/NLRP3 which encodes cryopyrin in the inflammasome, characterized by excessive IL 1ß production
65
A child presents with recurrent episodes of fever, periosteitis, skin pustulosis, and multifocal osteomyelitis. This started in infancy. The underlying gene defect in this disease causes a mutation in which of the following?
```
A. IL1-B
B. mevalonate kinase
C. IL1RN
D. cryopyrin
E. TNFRSF1A
```
C. IL1RN - DIRA
Deficiency of the IL 1 Receptor Antagonist
Mutations in IL1RN, IL1 Receptor Antagonist Gene
66
A child presents with recurrent episodes of fever, pyogenic arthritis, pyoderma gangrenosum, and acne. This started in infancy. The underlying gene defect in this disease causes a mutation in which of the following?
```
A. IL1-B
B. PSTPIP1
C. IL1RN
D. cryopyrin
E. TNFRSF1A
```
B. PSTPIP1 - PAPA syndrome
PAPA- Pyogenic Arthritis Pyoderma gangrenosum Acne
Caused by mutations in PSTPIP1
(interacts with pyrin to cause
increased IL 1 β activation)
• RX: steroids, TNF blockade,
IL 1 blockade
67
mutations in what cause SCN and CN?
ELA2 (ELANE mutations) neutrophil elastase
RECESSIVE
Kostmann’s syndrome
Mutations in HAX1
Leukemia in severe neutropenia
Mutations in GCSFR gene acquired
digital, oral, perineal infections, usually self
healing with recovery of counts, bacteremia
uncommon
• relatively low baseline PMN count with valleys of profound neutropenia, about every 3 4 weeks
68
- recurrent cutaneous, sino pulmonary infections
- Gram negative rods, staphylococci, streptococci
- mild neutropenia (intramedullary destruction)
- partial oculo cutaneous albinism
- mental retardation, neuropathy (late)
lymphoproliferative accelerated phase
likely disease and mutation?
Chediak- Higashi syndrome
Lyst (CHS1) mutation
giant granules; killing and chemotactic defects
Giant 1' primary granules
fused 2' granules
69
What bacteria are the most common causes of infection in CGD?
```
Catalase positive: SSABN
S. aureus
S. marsescens
Aspergillus
B. cepacia
Nocardia
(BCG, Salmonella)
```
```
the three that prove you are a consultant:
Chromobacterium violaceum (warm brackish water, e.g., Disney)
Francisella philomiragia (brackish water, e.g., Chesapeake)
Granulibacter bethesdensis (widespread but very hard to grow)
```
recurrent life life-threatening infections with catalase catalase-positive bacteria and fungi; tissue granuloma formation
– infections : lung, liver, lymph nodes, skin, bone
70
What are the X-linked genetic defects in CGD?
g91phox
>50% mutations
– carrier females are mosaic ( Lyonization
– 50% of offspring of carrier Mom will receive the gene
– X linked male: ALL daughters carriers, NO sons
71
What are the AR genetic defects in CGD?
p22, p47, p67
72
What are the cytosolic components of the NADPH oxidase system?
40, 47, 67
73
What are the membrane components of the NADPH oxidase system?
22, 91
74
LAD1 is due to deficiency of what, causing absent what?
CD18
absent:
LFA1, Mac 1, P150,95
- recurrent necrotizing infections of skin,
perineum, pneumonia, gut
- infections with enteric GNR,
GPC
- baseline leukocytosis with further WBC response to infection
- rare, consanguinity common
75
LAD2 is due to deficiency of what, causing absent what?
CD15 a (Sialyl Lewis X)
Mediates binding to selectins = No fucose , No binding
76
characteristic features & infections in HIES?
STAT3
- recurrent sinopulmonary infections:
S. aureus
H.
influenzae
S. pneumo
- post infectious pulmonary cyst formation
- recurrent S. aureus skin abscesses
- characteristic facies , eczema, scoliosis, fractures
- very elevated IgE (>2000 IU), eosinophilia
77
what are the HIV coreceptors?
CCR5 & CXCR4
78
defect in WHIM syndrome
CXCR4
- neutropenia
- myelokathexis
- decreased B & T cell #s
- hypogam
79
Which of the following antiphospholipid antibodies is predominantly IgG & IgM isotypes that specifically target epitopes of the negatively charged phospholipid binding protein of cell membrane and prothrombin?
A. anticardiolipin (aCL) antibody
B. lupus anticoagulant (LA)
C. anti-beta2-glycoprotein (GP)
B. lupus anticoagulant (LA)
80
What is the expected result on DAT testing for warm vs cold AIHA?
positive:
IgG + C3 in WARM (IgG against Rh protein antigen)
C3 in cold (IgM against I polysaccharie antigen)
81
mechanism of pernicious anemia and low B12
Autoantibodies to parietal cell and intrinsic factor and H+ and K+ ATPase
82
What is the difference in treatment for these 2 patients with ocular diseases:
1) young, localized redness over conjunctiva that blanches with phenylephrine
2) older, femlale, rheumatologic pt, syphilis infxn, extremely painful, and redness of sclera does not blanch
1) episcleritis- self limiting, NSAIDs and weak topical steroids
2) scleritis- EMERGENCY! PO steroids, immunosuppressants, & NSAIDs (Type 3 HS, IC deposition)
83
All of the following are true about primary biliary cirrhosis except:
A. a/w HLA-A *0201 and HLA-DR8
B. CD4 and cD8 T cell mediated autoimmune attack on bile duct cells
C. anti-smooth muscle antibodies
D. Middle aged women
E. slow progressive interlobular destruction of bile ducts leading to pruritis, fatigue, RUQ pain
C. antiMITOCHONDRIAL antibodies (AMA)
PBC = AMA
84
All of the following are antibodies typical of type 1 autoimmune hepatitis except:
A. anti-SMA (F-actin)
B. anti-LKM1
C. ANA
D. pANCA
B. anti-LKM1 , and ALC-1= T2 AIH
85
a female patient with fatigue, pruritis, fever, ulcerative colitis, and cholangitis is found to have intra and extrahepatic bile duct strictures. the most likely antibodies to be found are:
A. anti-SMA (F-actin)
B. anti-LKM1
C. ANA
D. pANCA
A. anti-SMA (F-actin)
C. ANA
Primary sclerosing cholangitis (PSC = SMA & ANA)
increased risk of cholangiocarcinoma
86
Mutations of ATG16L1 mutation (a/w autophagy p320) and NOD2/CARD15 (also a/w Blau syndrome) is a/w what other disease?
Crohn's
87
What is the expected outcome of a mixed leukocyte reaction between recipient and donor leukocytes with matching MHCs?
no reaction- no proliferation - no visible radioactivity
