Immunopathology I-II Flashcards
(20 cards)
(OBJ) List five stimulations that can lead to mast cell degranulation.
IgE-mediated mechanisms: asthma, hay fever, insect bites/stings, drug allergies, hives, food allergies (some)
Also: Anaphylatoxins, Neuropeptides, some drugs, physical stimuli (heat, cold, vibration), Interleukins
(OBJ) Explain how IgE leads to mast cell activation.
Antigen reappears, passes through mucosa -> binds IgE on mast cells -> cross-linking of IgE on surface of mast cells -> degranulation -> release of primary and secondary mediators
(OBJ) Name the preformed (3) and synthesized (3) mediators produced by an activated mast cell.
Immediate phase: release of PREFORMED mediators; vasodilation/leakage, smooth muscle contraction, glandular secretion
- -Histamine
- -Proteases: can digest BM, activate complement (promote inflammation and tissue damage)
- -Chemotactic factors for eosinophils and neutrophils -> eosinophils make MBProtein, damage epithelium
Delayed phase (>2 hours, can be sustained for days): synthesis of other soluble mediators; inflammatory tissue infiltration and injury, mucosal damage, remodeling
- -Leukotrienes B4, C4, D4
- -PGD2
- -PAF
(OBJ) Explain the basic mechanism active in type II hypersensitivity reactions. [Also, list four characteristics of these types of reactions]
Antibody (IgG, IgM) causes cell or tissue damage
–Lead to lysis/phagocytosis, complement damage, or alter function of cell surface molecules/receptors
Four characteristics:
- Antibodies that are able to fix complement circulate
- Abs localize to Ag on the cell surface or on some other tissue constituent
- Site of damage defined by location Ab binds
- Often causes severe disease and tissue injury
(OBJ) Explain the difference between acute and delayed transfusion reactions. [Also, give an example consequence of a transfusion reaction]
Ex. hemolysis: Abs coat RBCs, making them susceptible to phagocytosis in spleen/liver or fixing of complement to generate MAC
ACUTE: preexisting Abs at a high titer (normally ABO) -> rapid intravascular hemolysis
DELAYED: 1-2 weeks post-transfusion -> low/rising titer Ab -> slow extravascular hemolysis
(OBJ) Name the 4 Streptococcal antigens that cross react with human tissues in producing the phenomena of rheumatic fever.
From group A beta hemolytic streptococcus
Hyaluronidase -> cartilage -> arthritis
M protein -> heart muscle -> myocarditis
Group A carbohydrate -> heart valves -> endocarditis
Cell walls -> basal ganglia -> chorea
All -> immune complexes -> glomerulonephritis, vasculitis
(OBJ) Explain the mechanism and distinctions between thyrotoxicosis (Grave’s disease) and myasthenia gravis.
Grave’s disease: Abs bind to TSH receptor -> massive overproduction of thyroid hormone
–Ab HAS natural ligand activity
Myasthenia gravis: Abs bind to ACh receptor -> blockage of ACh receptors -> weakness
–Ab BLOCKS natural ligand activity
(OBJ) Explain the etiology and pathogenic mechanism of erythroblastosis fetalis. (4)
AKA severe hemolytic disease of the newborn
- F & M Rh mismatched: Mother Rh-, Father Rh+ -> baby Rh+
- Mother generates IgG Abs against Rh+ -> can cross placenta
- Upon second Rh+ pregnancy, Abs attack baby’s RBCs -> lysis
- Baby attempts to make tons of RBCs -> intrauterine death -> swollen, edematous baby
(OBJ) Describe the immunological phenomena causing type III hypersensitivity reactions. (7)
Due to deposition of Ag-Ab complexes – tissue damage determined by WHERE Ag-Ab complexes are deposited
- Sensitization of the immune system -> Ab production
- Continuous or repeated Ag exposure
- Ag-Ab complexes are formed
- Deposition in tissue, aided by size, hemodynamic/structural factors, IgE mediated increased vascular permeability
- Complement cascade activation -> C3a, C3b, C5, MAC
- Attraction/activation of NEUTROPHILS and MOs
- -NEUTROPHILS do most of the damage - Focal acute inflammation -> tissue destruction
(OBJ) List four diseases that are type III hypersensitivity diseases.
SYSTEMIC: serum sickness, SLE, drug reactions
–Serum sickness: horse IgG -> lots of Ag-Ab complexes 7 days later
LOCALIZED: arthus reaction, vasculitis, glomerulonephritis, arthritis, pneumonitis
- -Post-streptococcal glomerulonephritis: lumpy-bumpy pattern of immune complex deposition in glomerulus
- -Vasculitis: immune complex deposition in small/medium arteries -> occlusion of lumen; necrosis of wall, tons of neutrophils outside of vessel
- —Often associated with drug reactions
(OBJ) Discuss the role of complement in hypersensitivity diseases.
Ag-Ab complexes -> complement activation
- Chemotactic factors -> neutrophil/Mo recruitment -> activation of phagocytes -> release of lysosomal enzymes -> necrosis
- Anaphylatoxin generation -> release of vasoactive amines -> vasodilation and edema
- Direct lysis by MAC complex
(OBJ) Explain the basic mechanism underlying type IV hypersensitivity.
Attack of antigen-specific, sensitized T cells accompanied by MOs
–T cells, APCs, MOs essential
(OBJ) Give three examples of type IV hypersensitivity disorders.
- Delayed-type hypersensitivity - CD4+ and MO mediated
- -Ex: the tuberculin reaction, granuloma formation - T cell mediated cytotoxicity - CD8+ mediated response to tumor, viruses, and allogenic cells
- Rejection of a transplanted organ - both CD4+ and CD8+, B cells and Abs may be involved
(OBJ) Explain the underlying mechanisms of hyperacute, acute and chronic allograft rejection.
HYPERACUTE: moments to 48 hours
- -Involves preformed Abs
- -Ag-Ab reaction at endothelium
- -Results in rapid thrombosis of vessels
ACUTE: weeks to months
- -Acute cellular: involves sensitized CD4/CD8 cells; lymphocyte/MO infiltrates
- -Acute humoral: involves anti-graft Abs -> vasculitis, thrombosis, endothelial proliferation
CHRONIC: months to years
- -Very slow cell-mediate DTH reaction gradually eats away at organ and turns it into scar tissue
- -Chronic vasculitis, intimal fibrosis, obliteration of lumen, organ ischemia, interstitial Mo cell infiltrates, organ atrophy
Distinguish the four types of hypersensitivity reactions.
I (anaphylactic/atopic): mediated by IgE and the products of mast cells, eosinophils, and basophils
II (cytotoxic): mediated by direct Ab binding to cells or tissue components
III (immune complex): mediated by deposition of Ag-Ab complexes and activation of complement and neutrophils
IV (delayed-type): mediated by T cells and MOs
Distinguish direct and indirect pathways of antigen presentation from a graft.
Direct: APC in the graft (from donor) presents its own Ags
Indirect: recipient’s APC presents donor Ags
Briefly, explain how mast cells are primed with IgE.
Antigen -> DC -> Th2 cell stimulated -> helps B cell, which is bound to antigen -> plasma cell -> IgE -> FcRe on mast cells
Describe Goodpasture’s Disease.
Goodpasture’s disease: Type II HS - antibody attaches to type IV collagen in BM of kidney and lung
List 5 histological features of rheumatic fever.
- -Vegetations are STERILE (have NO bacteria in them)
- -Thickening, shortening, fusing of chordae tendinae
- -“Fish-mouth” deformity of aortic valve - leaflets fuse
- -Aschoff bodies (giant cells, 4-6 nuclei)
- -Anitschkow monocyte (insignificant, chromatin looks like a caterpillar)
(OBJ) Describe the cause of graft versus host disease.
Occurs post bone marrow transplantation
Lymphocytes from donor bone marrow start attacking you
Acute (up to 100 days): destruction of epithelium of skin, liver, GI tract; mild inflammation
Chronic (more than 100 days): widespread damage in multiple tissues, marked inflammation
