week 2- immunology Flashcards
• Who gets AI dzs? Causes?
o 5-10% of pop
o F:M 5:1
o Genetics, Environmental factors (chem, germ theory?)
o Bacteria & viruses influence immune system regulation
• What are AI dzs?
o Immune responses against “self” Ags
o Circulating auto-Abs or cell-mediated immunity
o → inflammation, deposition of immune complexes → organ damage
o Can affect any organ/system in body
• What are some organ-specific and non-OS AI dzs? Other examples?
o Specific: Hashimoto;s, Graves, Addison’s, Atrophic gastritis, Type 1 DM, MS
o Non: SLE, RA, Scleroderma, Dermatomyositis, Mixed connective tissue disease (MCTD), Sjögren’s
o Other: uveitis, pemphigus, goodpasture’s, UC, AIHA, rheumatic fever, hepatitis, oophoritis
• What are organ-specific AI tests?
o Compared to systemic AI tests: ↓ false (+) rate; Relatively disease/organ specific
o Endocrine: adrenal, Islet cell, insulin, thyroid peroxidase
o Heme: Coomb’s, Anti-plt, Anti-PL
o GI: tTG, Endomysial, Gliadin, HLA-DQ2/DQ8
o Neuro: AchR, Ganglioside
• What are the systemic AI serology tests?
o Compared to organ-specific tests: ↑ confusion w clinical utility, ↑ false (+) rate, No organ specificity; often dx inaccurate, need clinical correlation
o Arthritis: Rheumatoid factor, Cyclic Citrullinated Peptide, HLA-B27
o Vasculitis: Antineutrophil cytoplasmic (ANCA), Proteinase 3, Myeloperoxidase, Cryoglobulins
o CT dz: Antinuclear antibody (ANA), DNA/Chromatin/Histone, SSA/SSB, Sm/RNP, Centromere/Sci70, tRNA synthetases
• What is RA?
o ~1% pop; F:M ~ 3:1; any age usu 30-50;
o Joint erosions → deformity and disability
o Extra-articular: pulmonary, cutaneous, cardiac, ocular
o Ssx: Classic: insidious, symmetrical, distal polyarthritis
o Common variants: Acute onset, Polymyalgia-like, Palindromic rheumatism, monoarthritis
• What are the Abs in RA?
o RF
o Anti-Cyclic Citrullinated Peptide (CCP)
• What is RF?
o Ab (mc IgM) against constant region of IgG
o Low activity common in normal population
o common in many inflammatory conditions in small amounts (nonspecific): infx, neoplasm, other CT dz
o High titer is ~60% sens, ~80% spec for RA
• What is Anti-Cyclic Citrullinated Peptide (CCP)?
o 53-68% sens, ~95% spec for erosive, inflammatory arthritis
o Assoc w deforming dz in RA and poorer functional outcomes
• How is RA dx?
o 2010 ACR/EULAR classification criteria o Joint sxs 1-5 pts o Serology 1-3 pts o Sx duration 1 pt o Acute phase reactants 1 pt o > /= 6 = definite RA o
• What is spondyloarthropathy?
o up to 5% pop; M > F ~ 1.5-2.1x; peak 20-30
o 4 classical syndromes: Ankylosing spondylitis, Psoriatic arthritis, Enteropathic (IBD related) arthritis, Reactive arthritis (Reiter’s syndrome)
o Risk factors: FHx, HLA-B27 positivity
o Ssx: Inflam back pain (sarcoiliitis), Periarticular inflammation or bone marrow edema
o extra-articular: Psoriasis, IBD, Uveitis, Enthesitis or dactylitis
• Who has HLA-B27?
o In general pop: NA Caucasians 5-10%, Europeans 5-20%
o in Spondyloarthritis pts: AS, ReA 80-90%, Enteropathic 40-50%, PsA 20-40%
• what are the types of SpA?
o Axial: back pain, 3 mos, sacroilitis on xray OR HLA-B27, at least 1 other sx
o Peripheral: arthritis, enthesitis, or dactylitis w/o back pain, plus other sxs
• What are CT dzs?
o SLE, sjogren’s, scleroderma, poly/dermatomyositis
o =collagen vascular, AI dzs
o difficult to dx: nonspecific sxs, tend to overlap
o histo: inflam damage CT and blood vessels, fibrinoid material deposition
• what is ANA?
o Often used as a screen for CT and AI dzs
o (+) in 5-20% of healthy ppl
o Pre-test probability is important
o Titers
• Who is ANA (+)?
o Seen in AI thyroid and hepatic dz
o Mb (+) in sick people (non-rheumatic) and healthy people
o mb (+) in healthy relatives of ppl w SLE
o (+): drug-induced lupus, SLE, scleroderma, sjogren’s, MCTD, poly/dermatomyositis, RA, systemic vasculitis
• Who tested for ANA? Interfering factors?
o only w a consistent clinical suspicion of rheumatic dz
o Not a good screening test for pts w vague symptoms
o Interfere: OPCs, procainamide, thiazide diuretics
• How is ANA tested?
o ANA, mb anti-cytoplasmic; immunofluorescence common, against human tumor lines (HEp-2)
o Past: react with rodent cells, some false (-), “ANA-neg Lupus”
o Test: serum dilutes, dropped onto HEp-s slides (dots), Incubated, washed, 2nd Ab,IF scope (inherent variability bw techs)
o Results: +/-, titer, pattern of staining
• What are ANA test results based on titer?
o /= 1:320 = (+), need further workup (only 5% healthy ppl)
o Prevalence of SLE is 40-50 in 100,000 (but 5,000 will have + ANA)
o Each lab can change these cutoffs based on their patient population
• What are ANA results based on pattern of staining? Assoc dzs?
o Homogenous (non-specific): diffuse SLE, drug-induced SLE, RA; suggests aDNA, aHistone, aDNP (deoxyriboneucleoprotein)
o Outline: SLE, others; suggests anti-DNA Abs
o Speckled: non-specific; SSA (Ro) & SSB (La) (Sjogren & SLE), Smith (SLE), RNP (MCTD, SLE, Sjogren, scleroderma)
o Nuclear: scleroderma (anti-Scl-70), polymyositis, some SLE
o Centromere: CREST
o Cytoplasmic: poly/dermatomyositis (anti-Jo-1)
• What are the auto-Abs that correlate with CT dzs?
o SLE: dsDNA, SM o RA: RF, RA33 o Sjogren’s: Ro(SS-A), La(SS-B) o Systemic Sclerosis: Scl-70, centromere o Poly/Dermatomyositis: Jo-1 o MCTD: U1-RNP o Wegener’s Granulomatosus: c-ANCA
• What is SLE?
o AI multisystem dz, 1 in 2,000; F:M 9:1 (1 in 700); peak 15-25
o immune complex deposition
o photosensitive skin eruptions, serositis, pneumonitis, myocarditis, nephritis, CNS involvement
o dx: at least 4/11: ANA, arthritis, discoid rash, heme do, immune do, malar rash, neuro do, oral ulcers, photosensitivity, renal do, serositis
• what drugs are implicated in drug-induced Lupus?
o Carbamazepine, chlorpromazine, ethosuximide, hydralazine, isoniazid, methyldopa,
o minocycline, penicillamine, phenytoin, procainamide, quinidine, sulfasalazine
• what is sjogren syndrome?
o 1% pop, 10-15% RA pts; F:M 9:1; 40-60
o 33-44x ↑risk of lymphoma.
o Ssx: pain, abd pn, fatigue, jt pn, brain fog, dry mucus membranes/skin/eyes/mouth, tooth decay
o May affect skin, external genitalia, GI tract, kidneys, lungs
o Minor salivary gland bx: lymphocyte infiltration.
o Parotid x more sensitive and specific
o Assoc w Sjogren Syndrome A (RO-SS-A) in 60% and Sjogren Syndrome B (LA-SS-B) in 30%
• What are dx criteria for sjogren?
o Dry eyes ( > 3mos), sensation of sand, or use of tear substitutes > 3x/d
o Dry mouth (>3mos), recurrent or persistent swollen salivary glands, or frequent drinking of liquids to aid in swallowing dry food
o Schirmer-I test ( 4
o > 50 mononuclear cells/4mm2 glandular tissue
o Abn salivary scintigraphy or parotid sialography or unstimulated salivary flow
• Epidemiology of scleroderma? Types?
o 4-12 new cases/million/yr o F>M 3-4x o 20s-40s o Localized: morphea, linear o Systemic: limited cutaneous, diffuse cutaneous, systemic sclerosis sine
• What are dx criteria for scleroderma?
o 1: scleromatous skin changes proximal to MCP jts
o 2/3: sclerodactyly, digital pitting scars, bi-basilar pulmonary fibrosis on CXR
o Sclerodactyly: abd buildup of fibrous tissue in skin → tightens → fingers curl, ↓ mobility
• Ssx of scleroderma:
o Presentation: Raynaud’s; edema fingers and hands; skin thickening
o visceral manifestations: GI tract, lung, heart, kidneys, thyroid
o arthralgias and muscle weakness often
• what dzs is anti-centromere AB found in?
o in 90% of CREST syndrome (variant of scleroderma)
o Diffuse Scleroderma (skin and viscera): Excessive fibrosis and collagen deposition throughout body: skin , CV, kidney, GI
• What is CREST?
o C (calcinosis): calcium deposits in skin o R (Raynauds phenomenon): spasm of blood vessels dt cold/stress o E (esophageal dysmotility): acid reflux, ↓ motility o S (sclerodactyly): thick, tight skin of fingers, hands o T (telangiectasia): dilation of capillaries, red marks on skin surface
• What is poly/dermatomyositis?
o Proximal muscle weakness and nonsuppurative inflam of skeletal muscle
o Deltoid, biceps, pectoralis, frontalis, quadriceps, tibialis anterior
o 5 cases/million/yr
o F:M 2:1
o 40-60, pediatric variant 5-15
• How is poly/dermatomyositis dx?
o Dx idefinitive w all 4, 3 probable, 2 possible
o Rash accompanies these in dermatomyositis
o Proximal muscle weakness
o Elevated serum creatine kinase
o Myopathic changes on electromyography
o Muscle biopsy with evidence of lymphocytic inflammation
• When should you screen with Ab serologies?
o Never
o Most pts don’t have AI rheumatologic dzs
o Serologies have frequent false (+)
o Hx and PE firs to narrow ddx
• Some helpful hints on when to use AI Ab serology?
o a-CCP is a useful confirmatory test w polyarthritis thought to be RA
o To dx CT dos, check American College of Rheumatology criteria (mostly H&P items), not just ANA
o The unusual serologies (anti-U1 snRNP, anti-Ro, etc) are best used to clinch a likely dx
• What are the immunology tests for infx dzs?
o Anti-streptolysin O
o HIV
o TB screening
• What is ASO titer?
o Group A B-strep produce enzyme Streptolysin O (lyses RBCs)
o Immune system produces a-SO Abs
o Ab titer rises ~1 wk after infx, peaks 3-5 wks, remains ↑ for 6-12 mos
o Normal:
• When would you check ASO titer? What dzs are ASO ↑ in?
o Determine whether prior strep pharyngitis has caused post-strep dz (1-4 wks, hypersensitivity rxs)
o NOT to dx acute strep pharyngitis
o Rheumatic Fever 90%: post-resp tract infx; inflame heart (pancarditis), jts, vessels, subQ tissue; dt cross reactivity of anti-M protein Ab w heart tissue; mb reactivated by recurrent strep infx (nephritis doesn’t)
o Acute Glomerulonephritis 50% (PSGN): post-skin (MC) or resp infx; dt Ag-Ab complexzes on glomerular basement membrane; ssx: edema, HTN, hematuria, proteinuria
o Strep pyoderma 30-40%
• What are the various HIV tests?
o Dx (Ab/Ag testing): Enzyme Immunoassays (EIAs); Rapid tests; Western blot (WB)
o Early dx: p24
o Initiation and monitor tx: CD, Viral Load
• What are the old vs new indications for HIV screening (CDC, 2006)?
o Old: IV drugs, prego, MSM, F w recurrent vag candida, blood recipient from sero (+) donor
o New: all pts seeking primary care in health center should be screened for HIV and STIs
• What are the HIV screening tests?
o ELISA: serum Abs to HIV 1 (mc) & HIV 2 (more in West Africa), develop 2-6 wks after sx onset (window period, could get false (-) → repeat)
o Saliva test/finger stick
o No longer requires submission of informed consent signed by physician and patient
o + screen repeated on same blood sample. If + again, do Western Blot or IFA to confirm
• What are HIV rapid tests?
o To screen (need 2nd test to confirm +)
o Qualitative assay to detect HIV Abs
o Most detect HIV 1 & 2
o Advantages: in-office results, no reschedule, no blood draw (finger stick or oral swab), can use whole blood
• What are the EIAs for HIV?
o Quantitative assay of HIV Abs
o Most detect HIV 1 & 2
o Ag coated in microwells → several incubation and wash steps
o HIV Ag/Ab rxn detected by color change (auto reader, optical density)
o Intensity of color reflects amount of Ab in serum
o Some assays can detect both HIV Ab & Ag (close window period)
o Easy to “add on” if other blood tests ordered; pt RTC for results, etc
• What are the western blot/ line immunoassays fro HIV?
o Mc supplemental test for confirmation, difficult cases
o Detects HIV Abs on cellulose strip: gp41, gp120, gp160, p17, p24, p31, p40, p51, p55 p66
o Issues: Multiple standards for performance and interpretation, Expensive, Limited commercial availability; high range intermediate results, complex
• What is HIV p24 Ag?
o Core protein of virus
o EIA detects p24 before Ab can be detected (~6 d), 2-3 wks after infx
o Used for: dx pediatric HIV-1 infx, Blood bank safety (high incidence countries)
o Issues: Level 4 complexity, Properly maintained equipment required
• What is the chronological typical sero profile in HIV infx?
o 1- p24 Ag (peak)
o 2- IgM Ab
o 3- AgG Ab
o 4- p24 Ag again
• What are CD4 T-lymphocytes used for w HIV?
o Determine clinical px o Assess criteria for ART o Monitor tx o Manual and automated methods o Issues: NOT a substitute HIV Ab test, Cannot be used to determine if HIV (+)
• What is Lymphocyte Immunophenotyping in HIV?
o Determines # CD4 and CD8 Lymphocytes and CD4/CD8 ratio
o Normal CD4 ct = 600-1500
o N CD8 = 300-1000
o Nl CD4/CD8 ~2:1 (
• What are methods to screen for TB in US?
o Mantoux tuberculin skin test (TST)
o Interferon Gamma Release Assay (IGRAs): QuantiFERON-TB Gold In-Tube (QFT-GIT)®, and T-Spot.TB®
o do not exclude LTBI or TB dz
o Decisions about medical/public health management should include other info/data, and not rely only on TST/IGRA results
• What are characteristics of TB dz (infectious)?
o ↑ active TB bacteria in body o May spread TB to others o Mb sick, cough, fever, weight loss o Usu (+) TB skin or blood test; mb (+) sputum smears and culture o Mb abn CXR o Needs tx for TB dz o May require respiratory isolation o A TB case
• What are characteristics of LTBI (infected)?
o ↓ TB bacteria in body, alive, but inactive
o Can’t spread to others
o Not sick, but may become sick if bacteria become active
o Usu (+) TB skin or blood test; (-) sputum and culture
o Usu normal CXR
o Consider tx for LTBI to prevent TB dz
o Doesn’t require respiratory isolation
o Not a TB case
• What is the mantoux TB skin test (tst)?
o Purified protein derivative (PPD), from tuberculin, injected 0.1 mL (5 TB units) bw skin layers in forearm w Mantoux technique
o Infx person’s immune cells recognize TB proteins in PPD, respond to site → wheal (6-10 mm)
o Follow universal precautions for infx control
o (+) 2-8 wks after infx
o ??Targeted skin testing should only be conducted among high-risk groups
• How is the tst interpreted?
o Trained personnel must read in 48–72 hrs = delayed hypersensitivity rxn, indicates T-cell response to PPD Ag
o Palpate (feel) injection site to find raised area
o Measure diameter of induration across forearm; only measure induration, not redness
o Record size of induration in millimeters; record “0” if no induration found
o > 5 mm ind (+):HIV (+), Recent contacts of infectious TB, fibrotic changes on CXR consistent w prior TB, organ transplants or immunosuppressed
o > 10 ind (+): Recent travel to high-prevalence country, IV drugs, Residents and employees of high-risk congregate settings
o > 10 (+): Mycobacteriology lab personnel, conditions that ↑ risk for progressing to TB, 15 (+): no known risk factors for TB
• What are contraindications for tst?
o hx (+) PPD test (repeat testing may produce severe reaction → skin sloughing) o hx immunization with BCG (Bacille Calmett-Guerin) (anti-TB vaccine using avirulent M. bovis; will give + test)
• what are interferon gamma release assays for TB?
o Detect TB infx by measuring immune response in blood
o Cannot differentiate bw TB and LTBI; other tests needed
o mb used for surveillance/screening, or to find those who will benefit from tx
o do not boost subsequent test results; administered with one patient visit
• when should you do IGRAs?
o mb used in place of, usu not in addition to TST, unless high risk and TST (-) or unclear
o Preferred: ppl Who might not return for TST reading; received BCG vaccination
o Not: children
• what is a tumor marker?
o Tumor-specific, absent in healthy ppl, readily detected in body fluids (but not all markers fit this model)
o Produced directly by tumor or effect of tumor on healthy tissue, released directly into blood, detectable at small concentrations
o ↑ Concentration w tumor progression, highest levels w mets
o mb proteins, oncofetal Ags, hormones, metabolites, receptors, enzymes
• what is the application of tumor markers?
o Screening populations at risk, but not all are good screening tools
o Dx: Use results from markers, imaging, risk factors, sxs
o Px: Concentration of marker
o Detection of recurrence: Once tumor removed, elevations of marker can indicate regrowth
o Monitor response to tx: ↓ levels = tx works; ↑ may = need to change tx
• What is the alpha fetoprotein tumor marker?
o Abundant serum protein normally synthesized by fetal liver
o Re-expressed in certain types of tumors
o Normal 100)
• How is AFP used clinically?
o Dx, px, tx monitoring of hepatocellular carcinoma, 400 ng/ml (↓ w tx)
o Screening (High-risk; HBV or HCV pts)
o chronic hepatitis often >4000 w carcinoma
o not completely specific for HCC, also some ovarian CA, mediastinal GCTs
o also a tumor marker for non-seminomatous test CA (w B-hCG)
o mb ↑ in prego & benign liver dz
• What is the tumor marker human chorionic gonadotropin?
o normally secreted by trophoblasts in placenta during pregnancy
o ↑ w ovarian and testicular GCTs, gestational trophoblastic dz, mediastinal GCTs
o help dx and monitor tx
• What is the cancer antigen 125?
o Detect ovarian tumors at early stage, monitor tx without surgical restaging
o 50% of time, ↑ before mets
o Normal
• What is the carcinoembryonic antigen tumor marker?
o mc tumor marker for colorectal CA
o px, postsurgery surveillance, monitor chemo tx
o Normal
• what is the HER-2/NEU tumor marker?
o Encodes Epidermal Growth Factor Receptor (EGF-R)
o A proto-oncogene that is converted to oncogene by Mutation (esp point) or ↑ expression
o Marker for breast and ovarian CAs
o Test the cancer itself, not serum
o Now routinely measured in breast CA (IHC and FISH) to determine tx
o Breast CA (+) for HER-2/NEU is responsive to tx (Herceptin), 1/5 F
• What are the recommended tumor markers for specific types of CAs?
o HCC: AFP
o Ovarian: CA-125, BRCA1 (inherited)
o Breast: CA15-3, CEA, HER-2/NEU, E & P receptors, BRCA1/2 (inherited)
o Head of pancreas: CA 19-9, CEA
o Colorectal: CEA, 19-9
o Pheochromocytoma: vanillylmandelic acid (VMA) in urine
o Non-seminomatous testicular: AFP, B-hCG, CEA
o Vesticular mole & choriocarcinoma: B-hCG
o Prostate: PSA
• Are there any ideal tumor markers?
o None known
o So take good hx, PE
o Use mult markers
Also histo, US, bx to confirm
