Immuno facts Flashcards
Type I interferons - induction and effects.
- dsRNA induces expression of IFN-alpha and beta.
- IFN-alpha and beta act through JAK/STAT to induce PKR and RNaseL.
- Used to treat hep B, hep C, condyloma accuminata, and hairy cell leukemia
- RNaseL degrades all RNA within the cell.
- PKR phosphorylates ELF2, which prevents transcription initiation.
Type II interferons - induction and effects.
- IFN-gamma is secreted by T-cells, NK-cells, and macrophages in response to antigens and mitogens.
- Promotes TH1 differentiation.
- Promotes MHC class II expression. Activates macrophages.
Lupus antibodies?
Lupus criteria?
Antibodies:
- ANA (sensitive but not specific)
- anti-dsDNA and anti-Smith (specific)
- anti-histone (drug-induced): HIP: INH, procainamide, hydralazine
Criteria: SOAP BRAIN MD. Need 4.
- Serositis
- Oral ulcers
- Arthritis
- Photosensitivity
- Blood changes (penias)
- Renal - wire loop lesions, nephrotic syndrome
- ANA
- Immunologic changes
- Neurologic changes (seizures, psychosis)
- Malar rash
- Discoid rash
Scleroderma antibodies?
CREST?
Systemic sclerosis: anti-scl-70 - anti-DNA topoisomerase I
CREST: anti-centromere
- Calcinosis
- Raynaud phenomenon
- Esophageal dysmotility
- Sclerodactyly
- Telangiectasias
Capsule vaccines? What must they have to generate IgG?
Pneumococcus, HiB, N. Meningitidis
Must be conjugated to a protein; T-cells cannot recognize polysaccharide-only antigens
Live attenuated vaccines?
Induces mainly Th1 cell-mediated response.
- Measles, mumps, rubella
- Varicella
- Polio (sabin - not used)
- Yellow fever
Inactivated or killed vaccines?
Induces mainly Th2 IgG antibody response.
- Cholera
- Hepatitis A
- Polio (Salk - currently used)
- Rabies
Toxoid vaccines
- Diphtheria
- Tetanus
- Botulinum
Allergic reactions: Immediate hypersensitivity vs Antibody-dependent cell-mediated cytotoxicity
- Immediate hypersensitivity
- Atopic type I hypersensitivity reaction
- IgE binds allergen
- IgE crosslinks receptors on mast cells and basophils, which release histamine, bradykinin, heparin, elastase & arylsulfatase, leukotrienes
- Antibody-dependent cell-mediated cytotoxicity
- Parasite binds IgE
- IgE crosslinks receptors on eosinophils, which release major basic protein and histaminase
- Or, tumor cell binds IgG (eg rituximab, trastuzumab, alemtuzumab, etc)
- crosslinks CD16 Fc-receptors on NK cells, resulting in IFN-gamma release and cell kill.
Histologic correlates of
- Hyperacute rejection
- Acute rejection
- Chronic rejection
- Hyperacute: vascular fibrinoid necrosis, neutrophil infiltration. Secondary to complement activation from preformed antibody reaction against HLA.
- Acute: dense interstitial lymphocytic infiltrate. Cytotoxic T-cell damage, CD4+ and CD8+ present.
- Chronic: fibrosis and vascular obliteration. Caused by antibody-mediated intimal injury and smooth muscle proliferation.
Describe the mechanism and receptors for neutrophil
margination, rolling, adhesion & crawling, transmigration
- Margination
- hemoconcentration and decreased shear stress, vascular leakage
- Rolling
- Neutrophil: Sialyl-Lewis X, PSGL1, L-selectin
- Endothelium: E-selectin and P-selectin (weibel-palade). Induced by cytokines.
- Activation
- Increased chemokine concentration leads neutrophils to express Mac-1 and LFA-1 (CD18 beta 2)
- Tight adhesion and crawling
- Neutrophil: Mac-1 and LFA-1; VLA-4
- Endothelium: ICAM; VCAM
- Transmigration: PECAM
Infection with PCP or Candida is a sign of what kind of immunodeficiency?
Encapsulated organisms? E.g. recurrent ear infx from H. influenzae, S. pneumoniae, Moraxella
Cell-mediated (T-cell defect).
Humoral immunodeficiency (B-cell defect).
What does the Candida skin test measure?
Cell-mediated immunity:
Macrophages, CD4+ T-cells, CD8+ T-cells, NK cells
Type II hypersensitivity. How mediated? How tested? Difficult Examples?
Type II: soluble antibodies against tissue.
Damage is mediated by complement activation (classical pathway: C1->C4,2->C3 convertase)
Test via indirect or direct (for HA) coombs.
- Rheumatic fever (vs PSGN)
- Goodpasture’s (!)
- Bullous pemphigoid, pemphigus vulgaris
Macrophage surface marker?
CD14
Type IV hypersensitivity (5)
T-cell mediated. Delayed. Mechanism of acute rejection.
MS
GBS
GVHD
PPD
contact dermatitis (eg urushiol, nickel)
Macrophage cell surface proteins involved in signaling
- CD14 - mediates LPS and LTA uptake
- CD40 - receptor for secondary activation signal (CD40L from TH1); B-cells have this also.
- B7 - costim for T-cells (receptor is CD28)
- MHC II (and MHC I)
Compare and contrast MHC I and MHC II loading
What are the HLA associated-diseases?
- Components
- MHC I: alpha chains, beta-2 microglobulin. Held together by peptide-loading complex (TAP, tapasin, et al)
- MHC II: alpha and beta chains. Held together by invariant chain / CLIP.
- Loading
- MHC I: loaded in ER
- MHC II: loaded in acidified endosome.
- Where expressed
- MHC I: all nucleated cells (not on RBCs)
- MHC II: professional APCs.
- HLA-associated diseases:
- HLA-A3: hemochromatosis
- HLA-B27: Ulcerative colitis-associated: Psoriasis, Ankylosing spondylitis, IBD, Reiter’s
- HLA-DR2: MS, hay fever, SLE, Goodpasture’s
- HLA-DR3: DMI, Graves’
- HLA-DR4: RA, DMI
- HLA-DR5: Pernicious anemia, Hashimoto’s
Unique marker for NK cells?
CD56. Also have CD16 which is an Fc receptor.
Complement deficiencies:
C1 esterase?
C3?
C5-9?
- C1-esterase: hereditary angioedema
- C3 deficiency: recurrent bacterial infections
- C5-9 deficiency: recurrent Neisseria
B-cell deficiency: which parasite and bacterial infections?
Parasite: Giardia (no IgA)
Bacteria: encapsulated
Agranulocytosis: which organisms are you vulnerable to?
Staph, Burkholderia, Serratia, Nocardia
Candida, Aspergillus
How does common variable immunodeficiency present?
Isolated decrease in plasma cells and immunoglobulin. Normal # of B cells.
Type III hypersensitivity reactions. Presentation vs type II? How tested for? Examples?
Immune complexes with antigen deposit in tissue. Systemic and vasculitic sx vs Type II localized dmg.
Test via immunofluorescence to look for complexes.
- SLE
- Polyarteritis Nodosa
- PSGN
- Serum sickness - abx derived from animals
- Arthus reaction (follows tetanus vaccine)
