immunopathy Flashcards
1
Q
Type I
A
- immediate hypersensitivity the injury is caused by TH2 cells, IgE antibodies, and mast cells and other leukocytes
2
Q
type II
A
- Antibody-mediated disorders, secreted IgG and IgM antibodies injure cells by promoting their phagocytosis or lysis and injure tissues by inducing inflammation
3
Q
type III
A
- immune complex-mediated disorders, IgG and IgM antibodies bind antigens usually in the circulation, and the antigen-antibody complexes deposit in tissues and induce inflammation
- Ex: systemic lupus erythematosus = nuclear antigens
4
Q
type IV
A
- in cell-mediated immune disorders, sensitized T lymphocytes (TH1 and TH17 cells and CTLs) are the cause of the tissue injury
- Ex: Rheumatoid arthritis = inflammation mediated by Th17 cytokines
5
Q
autograft
A
- tissue grafted from one bodily site to another on the same individual
6
Q
isograft
A
- tissue grafted between identical twins
7
Q
allograft
A
- tissue grafted from one individual to a genetically different individual of same species
- from cadaver or living donors
8
Q
Xenograft (heterologous)
A
- tissue grafted between species; rare, pig heart valves are an example
9
Q
describe KIDNEY: Cell-mediated cytotoxicity
A
- Type IV hypersensitivity rxn
- cell-mediated, occurs because the donors’ graft elicits a CTL reaction to destroy the graft;
- -> donor APC stimulates the recipient’s CTLs
10
Q
describe KIDNEY: delayed type hypersensitivity
A
- Type IV hypersensitivity rxn
- delayed-type, TH cells secrete cytokines, which results in inflammatory mediator release and tissue damage;
- -> recipient APCs take up Ag from the graft
11
Q
describe KIDNEY: humoral mechanisms
A
- Target graft vasculature
- -> Ab bind to HLA molecules in graft endothelium, activate complement –> acute inflammation or vasculitis resembling type II hypersensitivity reaction
- -> Ag-Ab complexes form in circulation or in situ (type III), fix complement –> necrotizing, immune complex vasculitis
12
Q
describe KIDNEY: hyperacute rejection
A
- recipient sensitized by prior transplant, multiple transfusions or pregnancies
- preformed Ab react against Ag in allograft endothelium –> local immune complex formation (III), complement activation, vasculitis with fibrinoid necrosis, thrombosis, ischemia
- immediate or within minutes to hours
- avoided by cross-matching recipient serum with donor lymphocytes to determine presence of cytotoxic Ab to donor MHC Class I and II antigens
13
Q
describe KIDNEY: acute rejection
A
- progresses rapidly once initiated
- mediated by cellular, humoral or combined/overlapping mechanisms
- occurs days-months post transplant or after withdrawal of immunosuppressive therapy
- LOTS OF INFLAMMATION!!
- Destroys epithelial cells and vessels
14
Q
KIDNEY: acute cellular rejection
A
- Cytotoxic (CD8+) lymphocytes infiltrate tubular & vascular basement membranes –> tubular damage, endothelitis
- Helper T-cells (CD4+) produce cytokines –> extensive interstitial inflammation
- typical morphology: lymphocytic infiltrates and tubular necrosis
15
Q
KIDNEY: acute humoral rejection
A
- anti-graft Ab deposit in graft vasculature
- morphologic patterns:
- -> necrotizing vasculitis
- -> intimal thickening due to accumulation of fibroblasts, foamy macrophages, myocytes
16
Q
KIDNEY: Chronic rejection
A
- occurs months to years after transplantation possibly from repeated humoral or cellular insult
- possible mechanisms:
- -> humoral injury = proliferative vascular lesions
- -> cellular injury = cytokine induced proliferation of vascular smooth muscle and production of COLLAGEN in ECM
- Morphology: vascular changes, interstitial FIBROSIS, tubular atrophy, chronic inflammation
17
Q
Liver transplantation
A
- Tx for progressive, advanced liver disease with organ failure; most common indication is Hepatitis C
- second most common solid organ transplanted
- Size, ABO grouping important, lesser requirement for immunosuppression than other solid organs
18
Q
Acute Liver Rejection
A
- cellular reaction occurs within 3 months following transplantation
- mixed inflammatory cell infiltrates with eosinophils
- infiltrate of lymphocytes, plasma cells, macrophages expanding portal tract causing damage to bile ducts
- Triad of features
- -> portal tract inflammation
- -> bile duct epithelial damage
- -> endothelitis of portal vein and hepatic artery branches
19
Q
Chronic liver rejection
A
- progressive disappearance of bile ducts due to direct immunologic destruction or loss of blood supply
- More Jaundice (AST and ALT are up)
- obliterative arteritis from proliferation of intimal layer –> ischemic changes
- End result = portal and hepatic fibrosis
20
Q
Heart transplantation
A
- treatment for advanced, irreversible myocardial disease with intractable congestive heart failure (cardiomyopathy)
- classic cellular rejection with interstitial and perivascular T cell infiltrates –> myocyte necrosis that histologically resembles myocarditis
- major complication: diffuse intimal proliferation –> coronary artery disease
21
Q
acute cardiac rejection
A
- endomyocardial biopsy showing lymphocytes surrounding and destroying myocytes
22
Q
chronic cardiac rejection
A
- coronary artery showing intimal proliferation with chronic inflammation
- transplantation associated arteriopathy
23
Q
cyclosporine
A
- blocks nuclear factor of activated T cells (NFAT), a transcription factor necessary for IL-2 stimulation of T cells
24
Q
steroids
A
- supress macrophage activity and inflammation
25
Q
azathioprine
A
- inhibits DNA synthesis
26
Q
Graft v host disease
A
- cell mediated reaction: donor T cells recognize the Host HLA antigens as foreign and mount a Type IV (DTH or CTL) reaction against graft elements and tissues
- immunocompetent graft cells destroy immunocompromised recipient cells
27
Q
Acute GVHD
A
- Occurs days-weeks post engraftment
- mechanisms: donor cytotoxic T cells or cytokines from helper T-cells destroy epithelial cells
- leads to:
- -> skin changes = rash, exfoliation
- -> GIT changes = ulcerative gastroenteritis
- -> hepatic changes = bile duct necrosis
- profound immunosuppression –> susceptibility to infection
28
Q
Chronic GVHD
A
- follows resolution of acute GVHD but may evolve insidiously without apparent acute phase
- develops from autoreactive T cells derived from donor stem cells that cannot be clonally deleted due to minimal immune function of recipient
- morphology mimics systemic sclerosis with generalized fibrosis
29
Q
transplantation of hematopoietic cells
A
- Treatment for hematologic disorders, non-hematologic malignancies, immunodeficiencies
- Stem cells harvested from donor bone marrow or from peripheral blood following simulation by hematopoietic growth factors
- Complications = graft versus host disease, infection, immunodeficiency
