Immunologic Disorders Flashcards
What is the major mediator of swelling in HAE?
bradykinin
What is the difference between HAE type I vs HAE type II?
HAE type I has low or absent C1 inhibitor
HAE type II has normal C1 inhibitor levels but no or low function
What medications can be used to treat acute attacks of HAE?
berinert - C1 inhibitor
ecallantide - Kallikrein inhibitor
icatibant - bradykinin receptor antagonist
What medication is approved for HAE prophylaxis?
Cinryze - C1 inhibitor
Which complement component is decreased in acquired but not hereditary angioedema?
C1q
Which medication for HAE attacks has a black box warning for anaphylaxis?
Ecallantide
What is the difference between type I and type II acquired angioedema?
Type I: paraneoplastic (B cell lymphoproliferative - MGUS)
Type II: autoimmune (anti-C1q antobody)
What is the most common cause of acute angioedema seen in ERs?
ACE inhibitor related
What is the most common form of SCID?
X-linked: common gamma chain deficiency
Which IL receptor use the common gamma chain?
IL2, 4, 7, 9, 15, 21 receptors
Which forms of SCID are NK-?
ADA deficiency, JAK3, IL-1RG, reticular dysgenesis
What is the lymphocyte phenotype for X-linked SCID?
T-B+NK-
What is the lymphocyte phenotype for JAK-3 deficient SCID?
T-B+NK-
What is the lymphocyte phenotype for IL7R-alpha SCID?
T-B+NK+
What is the lymphocyte phenotype for RAG1/2 SCID?
T-B-NK+
What is the lymphocyte phenotype for ADA deficient SCID?
T-B-NK-
What is the lymphocyte phenotype for reticular dysgenesis form of SCID?
T-B-NK-
What is the lymphocyte phenotype for artemis deficient SCID?
T-B-NK+
Which radiosensitive form of SCID has absence of Hassal’s corpuscles?
Nijmegen breakage syndrome
Which forms of SCID can be missed on newborn screen?
bare lymphocyte syndrome, ZAP70, MHC class I deficiency (TAP 1/2 mutation), ADA deficiency
Which immunodeficiency has elevated alpha fetal protein, IgA deficiency, and radiosensitivity?
Ataxia-telangiectasia
Defects in which gene causes chronic mucocutaneous candidiasis?
AIRE gene
Which immunodeficiency is characterized by absent germinal centers?
CD40 or CD40L deficiency
Which immunodeficiency is due to inability to activate NFκB?
NEMO - NF-kappa B Essential Modulator”
Which immunodeficiency is characterized by EBV infection?
XLP - can’t eliminate EBV -> prolonged antigen presentation + hyperactivation
Which immunodeficiency has thrombocytopenia and decreased platelet size?
Wiskott-Aldrich syndrome
Some selective IgA deficiency is associated with what mutation?
TACI
X-linked agammaglobulinemia is due to a mutation in what?
Bruton’s tyrosine kinase (BTK) - B cells arrest at pre-B cell stage
Which infections are typical of XLA?
enteroviral encephalitis
What mutation causes APECED and what is the most common endocrinopathy seen in the disease?
AIRE; hypoparathyroidism
What mutation causes IPEX and what cell is affected by the disease?
FOXP3 and Tregs
What disease is characterized by CVID and a thymoma?
Good’s syndrome
Which enzymes are defective in hyper-IgM syndrome, causing lymphoid hyperplasia and adenopathy?
AID and UNG
What are the differences between HIGM1/3 and HIGM2/4?
HIGM1/3 are combined immunodeficiencies with severe infections and absent LN due to lack of CD40/CD40L interactions; HIGM2/4 are antibody deficiencies with lymphoid hyperplasia and adenopathy - defect is in B cell class switching
What is the molecular defect in WHIM syndrome?
CXCR4 activating defect
CD18 deficiency leads to what immunodeficiency?
LAD-1
LAD-2 is due to mutation in what?
Lialyl-Lewisx (CD15a)
What is the molecular defect in CGD?
PHOX (phagocytic NADPH oxydase system)
How are IRAK4 and MyD88 deficiency diagnosed?
decreased PBMC cytokine production when stimulated with TLR agonists
How do you distinguish between complement deficiency and complement consumption?
CH50 and AH50
A low CH50 but normal AH50 would be indicative of what?
early complement deficiency (classical pathway)
A low AH50 would indicate a defect in which components?
Factor B, D and properdin
DAF (decay-accelerating factor) and CD59 deficiency are associateed with which disease?
Paroxysmal nocturnal hemoglobinuria
HIV gp120 binds to which cell surface proteins?
CXCR4, CCR5, CD4
Coreceptor binding of HIV to a target cell causes a conformational change in which viral protein, allowing for fusion?
gp41
Which enzyme converts HIV ssRNA to dsDNA?
reverse transcriptase
Which enzyme inserts HIV DNA into the host DNA?
integrase
At what point is HIV infection considered AIDS?
when CD4 count drops below 200 or pt develops AIDS defining condition
What test is used to confirm HIV and what does it detect?
Western Blot; detects anti-p24, anti-gp41,
anti-gp160/gp120
When would you use HIV DNA by PCR as a detection method?
detect during acute viral syndrome before antibody has been produced
What gene should be screened for before starting a patient on abacavir?
HLA-B*5701
What is immune reconstitution inflammatory syndrome?
clinical deterioration after starting HAART for HIV attributed to reactivation of immune response causing cytokine storm - rapid rise in CD4 counts
What is rheumatoid factor?
IgM against Fc portion of IgG
What autoantibodies are associated with Sjogren’s syndrome?
Ro/SS-A; La/SS-B
What autoantibodies are associated with CREST syndrome?
anticentromere
What autoantibodies are associated with polymyositis and dermatomyositis?
Anti-Jo-1, Anti-PL-7
What is Felty’s syndrome?
triad of RA, neutropenia and splenomegaly
What autoantibodies are more specific for RA than rheumatoid factor?
anti-CCP or ACPA
How does polymyositis differ clinically from myasthenia gravis?
in polymyositis symptoms involve proximal muscles; sensation and reflexes are preserved
Patient with proximal muscle weakness has biopsy showing basophilic rimmed vacuoles and filamentous inclusions. What is the Dx?
inclusion body myositis
What is CREST syndrome?
calcinosis, Raynaud’s, Esophageal dysmotility, sclerodactyly, telangiectasias
What autoantibodies are associated with scleroderma?
anticardiolipin
Which form of solid organ rejection occurs while the patient is on the operating table?
hyperacute
Which form of solid organ rejection occurs within 2-5 days?
accelerated
Which form of solid organ rejection occurs from 7 days to 3 months after transplant?
acute
Which form of solid organ rejection occurs months to years after transplant?
chronic
Which transplant tissues do not require HLA matching?
cornea, bone, joint tissue and hematopoetic stem cells
In stem cell transplant, how are the donor’s cells identified as stem cells?
CD34+
Which cytokines are important in graft vs. host disease?
IL-10, TNFα, IFNγ
What cells are involved in acute GVH disease and not chronic?
CD45RO+ T cells
What autoantibodies are associated with Graves’ disease?
Anti-TSH receptor Ab - stimulate thyroid gland
What genetic variants are associated with Graves’ disease?
HLA-DR3 (whites); CTLA-4
What is the function of AIRE and where does it function?
in thymic medulary epithelial cells - expression of antigens found elsewhere in the body - guides negative selection
What disease is associated with AIRE mutations?
autoimmune polyendocrine syndrome-1 (APECED)
Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is due to a mutation in what?
FOXP3 - absent Tregs
Mutations in which genes lead to autoimmune lymphoproliferative syndrome (ALPS)?
Fas; Fas ligand; Caspase-10
What autoantibodies are associated with Addison’s disease?
21-hydroxylase - used in adrenal cortex
What autoantibodies are associated with Type I DM?
anti-glutamic acid dehydrogenase (anti-GAD65) Ab
Membranous nephropathy has granular staining of what on the GBM?
IgG and C3
How long after infection does post-streptococcal glomerulonephritis occur?
10-14 days
7 y/o boy presents with abdominal pain, hematuria, and purpuric rash. Bx shows IgA immune complexes. What is the Dx?
Henoch-Schonlein Purpura
What autoantibodies are associated with pemphigus?
Desmoglein-1&3 Ab
What autoantibodies are associated with epidermolysis bullosa acquisita?
Type VII collagen Ab
What autoantibodies are associated with pemphigoid?
BP antigen Ab
Which has flaccid bullae and positive Nikolsky’s sign - pemphigus or pemphigoid?
pemphigus
Which has tense bullae and pruritis - pemphigus or pemphigoid?
pemphigoid
How can you distinguish episcleritis from scleritis?
drop of epi clears episcleritis but not scleritis
Which HLA class is associated with Celiac disease?
HLA DQ2
What are the most common foods to cause reactions in EoE?
milk, egg, wheat, soy
Which gene mutation is strongly associated with Crohn’s disease?
NOD
Myasthenia Gravis is associated with what autoantibody and what CT finding?
acetylcholine receptor; thymoma
What mutation in HES predicts good response to imatinib?
FIP1L1 fusion gene
What are the three subtypes of myeloproliferative HES?
myeloproliferative with FIP1L1; myeloproliferative with negative FIP1L1; chronic eosinophilic leukemia
Which type of HES has no response to imatinib?
lymphocytic
What infection is associated with Burkitt’s lymphoma?
EBV
MALT lymphoma is associated with what infection?
h. pylori
What serum markers are often elevated in granulomatous disease?
ACE, 1,25-vit. D
What is the difference in cellularity of BAL between sarcoidosis and hypersensitivity pneumonitis?
CD4/CD8 count is elevated in sarcoid, decreased in HP
What autoantibodies are associated with Wegener’s granulomatosis?
c-ANCA, anti-PR3
What is the most common form of amyloidosis and what is the pathophysiology?
primary amyoidosis; deposition of Ig light chains
What is the signature histiological finding in amyloidosis?
congo red and apple green birefringence
16 y/o girl with hearing loss, recurrent fevers, urticaria and joint pain every 3 weeks triggered by cold temps. Labs show proteinuria and amyloid deposits on Bx. What is the Dx?
Muckle-Wells syndrome
What is required for mas cell survival and is the ligand for c-KIT?
stem cell factor
What gene mutation can be found in systemic mastocytosis?
c-KIT
What disease is due to loss of phosphatidyl-insoitol-glycerol linkage proteins and presents with hepatic vein thrombosis?
Paroxysmal nocturnal hemoclobinuria
How does heparin induced thrombocytopenia occur and how does it present?
IgG to platelet FcIIa triggers platelet activation and consumption; presents with thrombosis and thrombocytopenia 5-14 days after starting unfractionated heparin.
Which autoantibodies are mainly associated with SLE?
Anti-dsDNA; Anti-Smith; anti-U1-RNP
Which neonatal receptor allows the transfer of maternal IgG across the placenta?
FcRn receptor
What is characterized by recurrent pregnancy loss, prolonged bleeding tie, hypercoagulability and false positive VDRL test?
Antiphospholipid Syndrome
What test can be performed for TB if skin testing is indeterminate?
interferon gamma release assay (IGRA)
Which cytokine is essential in granuloma formation?
TNFα
Detection of what indicates an acute Hep B infection?
IgM to core antigen
