Immunopathology II Flashcards
describe the direct pathway of transplant rejection
in the direct pathway, donor class I and class II MHC antigens on antigen-presenting cells in the graft are recognized by host CD8+ cytotoxic T cells and CD4+ helper T cells.
- CD4+ cells proliferate and produce cytokines (IFN-gamma) which induce tissue damage by a local inflammatory reaction
- CD8+ T cells responding to graft antigens differentiate into CTLs that kill graft cells
describe the indirect pathway of transplant rejection
in the indirect pathway, graft antigens are picked up, processed, and displayed by host APCs and activate CD4+ T cells which damage the graft by an inflammatory reaction and stimulate B lymphocytes to produce antibodies
describe the time of onset, the mechanism and morphology of hyperacute rejection
- time of onset: minutes to few hours
- mechanism: preformed antibodies bind to graft endothelium
- morphology: vascular thrombosis +/- necrosis
describe the time of onset, the mechanism and morphology of acute cellular rejection
acute cellular rejection
- time of onset: days to weeks, months to years
- mechanism: T cells injure graft by direct cytotoxicity and type IV HS
- morphology: interstitial infiltrate of lymphocytes with tubulitis +/- arteritis
describe the time of onset, the mechanism and morphology of acute humoral rejection
acute humoral
- time of onset: days to weeks, months to years
- mechanism: antidonor antibodies against graft antigens
- morphology: microcirculatory inflammation +/- arteritis/thrombosis
describe the time of onset, the mechanism and morphology of chronic rejection
chronic rejection
- time of onset: months to years (irreversible)
- mechanism: T cell cytokines stimulate vascular smooth muscle proliferation
- morphology: arteriosclerosis; ischemic injury; interstitial fibrosis
describe what is seen in the image
describe what is seen in the image
describe what is seen in the image
describe what is seen in the image
describe graft versus host disease
- donor tissue is immunocompetent
- donor T cells react to “foreign” antigens of host tissues
- recipient is immuno-depleted (whole body irradiation or chemotherapy)
- most commonly occurs following allogeneic bone marrow transplantation
- activation of donor CD4 and CD8 T cells
- type IV HS rxn
describe the acute vs. chronic form of graft versus host disease
describe central tolerance
- apoptosis of self-reactive lymphocyte clones during maturation
- T cells in thymus
- B cells in bone marrow
- some survive to become regulatory T cells
describe peripheral tolerance
- back-up mechanisms to neutralize self-reactive T cells that escape central neutralization
- anergy
- suppression by regulatory T cells
- activation-induced cell death
- antigen segregation
in SLE, there are antibodies against ___ components and ____
in SLE, there are antibodies against nuclear components and phospholipids
the basic mechanism of SLE is the loss of _____
the basic mechanism of SLE is the loss of self-tolerance
describe how SLE affects the skin
describe what is seen in the image
describe what is seen in the image
describe how SLE affects the kidney
describe what is seen in the image
SLE
focal proliferative glomerulonephritis with 2 focal necrotizing lesions at the 11 o clock and 2 o clock positions
describe what is seen in the image
SLE
diffuse proliferative glomerulonephritis; note the marked increase in cellularity throughout the glomerulus
describe the image
SLE
lupus nephritis showing a glomerulus with several “wire loop” lesions representing extensive subendothelial deposits of immune complexes (PAS stain)
describe how SLE affects the joints
- non-erosive synovitis
- no deformities
- neutrophils and fibrin in synovial fluid
describe how SLE affects the heart and blood vessels
- pericarditis, myocarditis
- Libman Sacks endocarditis
- necrotizing vasculitis of small arteries & arterioles
a sensitive but not specific test for SLE (or any autoimmune disorder) is for ____
a sensitive but not specific test for SLE (or any autoimmune disorder) is for antinuclear antibodies (ANA)
name the 2 main specific antibodies used for diagnosis of SLE
name 3 other one
- specific antibodies
- anti-double stranded DNA (ds-DNA)
- anti-Smith (Sm)
- other antibodies
- antiphospholipid
- antiplatelets
- antiRBCs
___ levels are decreased in active SLE disease
complement levels are decreased in active SLE disease
name the antibodies specific for SLE
anti-dsDNA
anti-Sm
name the antibodies specific for drug-induced SLE
antihistone
name the antibodies specific for systemic sclerosis (scleroderma)
Scl-70
name the antibodies specific for CREST
anticentromere
name the antibodies specific for Sjogren syndrome
SS-A
SS-B
name the antibodies specific for myopathies
Jo-1
describe the significance of antiphospholipid antibodies in SLE and name 2 major complications
- against proteins complexed to phospholipids
- can bind to Cardiolipin Ag of Treponema (syphillis) and cause a false positive
- causes procoagulant complications:
- recurrent thromboemboli
- recurrent abortions, focal cerebral ischemia
- anti-phospholipid antibody syndrome = when without SLE
describe drug-induced SLE (4 drugs)
which antibody is present in this condition?
- drugs
- procainamide = most common
- hydralazine
- isoniazid
- D-penicillamine
- renal and CNS involvement uncommon
- remits with withdrawal of drug
- high frequency of anti-histone antibodies
in systemic sclerosis, there is excessive ___ throughout the body and ___ is almost always involved
name the 2 basic forms of the systemic type
in systemic sclerosis, there is excessive fibrosis throughout the body and the skin is almost always involved
- 2 basic forms of systemic type:
- diffuse
- limited (CREST syndrome)
describe symptoms associated with systemic sclerosis (scleroderma)
- skin abnormalities distinctive
- Raynaud phenomenon
- difficulty swallowing
describe how systemic sclerosis (scleroderma) affects the GI tract
- GI tract
- muscular and mucosal atrophy and fibrosis
- loss of normal motility and absorption
____ aka ____ is highly specific for systemic sclerosis (scleroderma)
while
____ is highly specific for CREST
anti-topoisomerase I aka anti-SCL 70 aka antiis highly specific for systemic sclerosis (scleroderma)
while
anticentromere is highly specific for CREST
describe CREST syndrome and symptoms
- limited form of systemic sclerosis
- relatively mild, indolent course
- acronym:
- Calcinosis
- Raynaud phenomenon
- Esophageal dysmotility
- Sclerodactyly
- Telangiectasia
in Graves disease, immunoglobulins mimic ___ which results in ____
in Graves disease, immunoglobulins mimic TSH which results in hyperthyroidism
in autoimmune gastritis, there are autoantibodies against ____ which leads to a decrease in ___ and ____
in autoimmune gastritis, there are autoantibodies against gastric parietal cells which leads to a decrease in acid secretion and intrinsic factor secretion (necessary for B12 absorption → leads to pernicious anemia)
