Diseases of the Immune System IV Flashcards
cellular rejection
T cell response to transplant
CD8 and CD4
direct pathway of cellular rejection
T cells recognize antigens on donor MHC on APCs in graft
CD4 and CD8 response
**acute rejection
indirect pathway of cellular rejection
T cells recognize antigens of donor on own APCs
CD8 response not generated
-bc these CTLs recognize graft antigens presented by hosts APCs
**chronic rejection
humoral rejection
B cell response to transplant
hyperacute humoral rejection
preformed antidonor antibodies present in recipient
-ex/ multiparous women against paternal antigens from fetus
or blood transfusions
acute humoral rejection
exposure to antigens of donor graft stimulate antibody production
often attack vessels first - vasculitis
hyperacute rejection
within minutes or hours
in kidney - glomeruli have thrombi occlusion and fibrinoid necrosis
acute rejection
within days
in kidneys - vasculitis (humoral) and interstitial mononuclear infiltrate (cellular)
acute cellular rejection
CD4 and CD8
kidney - mononuclear cells in capillaries, glomeruli, tubules
endothelitis
respond well to immunosupressive therapy (cyclosporine)
acute humoral rejection
kidney - mainly damage to vessels
-proliferation of smooth muscles
deposition of C4d (from classical complement pathway)
chronic rejection
kidney - progressive renal failure with rise in creatinine over period of 4-6 months
dense obliterative intimal fibrosis in cortical arteries
increasing graft survival
unless identical twins - immunosuppressive therapy necessary
cyclosporine azathioprine steroids monoclonal anti-T-cell antibodies rapamycin mycophenolate mofetil
also, attempt to prevent costimulatory signals
-interrupt B7 CD28 interaction
cyclosporine
blocks NFAT
-no IL-2 production
transplantation of hematopoietic cells
from bone marrow
problems:
graft-versus host disease
immunodeficiency
graft-versus host disease
immune competent cells transplanted to immune crippled recipient
-transferred cells recognize host antigens
often with bone marrow transplant
depleting T cells in donor bone marrow can help to eliminate disease
acute GVH
within days or weeks
-involve immune system, skin epithelia, liver, intestines
rash, jaundice, bloody diarrhe
chronic GVH
cutaneous injury
fibrosis of dermis (may resemble scleroderma)
liver problems - jaundice
esophageal strictures
graft-versus-leukemia effect
T cells in bone marrow transplant control leukemic cells
primary immunodeficiency
genetic
most manifest in infancy
- 6 months to 2 years
- with recurrent infection
secondary immunodeficiency
due to infection, cancer, malnutrition, therapy, etc.
X-linked agammaglobulinemia
failure of B cell precursors to develop to mature B cells
heavy change rearranged first
-induce light chain rearrangement
mutation in Btk - no light chain rearrangement
seen mostly in males - around 6 months of age
-infections - haemophilis influenza, streptococcus pneumoniae, traphylococcus auresu
also susceptible to viral infections
Btk
mutated in X-linked agammaglobulinemia
-no light chain formation in B cells
clinical features of X-linked agammaglobulinemia
B cells decreased
-serum antibodies are all decreased
-pre-B cells in normal numbers
underdeveloped germinal centers
absent plasma cells
T cell responses normal
Tx of x-linked agammaglobulinemia
immunoglobulin replacement therapy
-allows most to reach adulthood