Immunology Flashcards
What are the major alloantigens?
HLA, MHC and ABO
What is hyperacute rejection?
- An immediate reaction
- caused by pre-existing antibodies against donor antigens
Which alloantigen is most commonly an issue for hyperacute reactions?
ABO antigens, sometimes HLA
What is the pathophysiological reaction that occurs during a hyperacute rejection?
complement activation, endothelial damage, inflammation, thrombosis
What kind of reaction is an acute rejection?
- the host immune system becomes sensitized against donor antigens (HLA)
- occurs in almost all transplants
What kind of cells are activated during an acute rejection?
CD4+/CD8+ T cells and macromages
What kind of pathophysiological reaction occurs during an acute rejection?
Endothelialtitis
parenchymal cell damage
interstitial inflammation
What are the characteristics of chronic rejection?
Host immune response against the vasculature of the donor organ occurring more than 1 year after transplantation
What kind of cells are involved in chronic rejection?
CD4+ T cells
Macrophages/inflammatory cells
What is the pathophysiological response to chronic rejection?
Chronic DTH reaction in the smooth muscle wall, smooth muscle cell proliferation (thickening), vessel occlusion
Which part of a chimeric antibody are human and which are mouse/foreign?
Only the variable regions of the heavy and light are mouse, the rest is human antibody
What part of a humanized antibody are human and which are mouse/foreign?
The only AA from the mouse are in the CDR regions of the heavy and light chain, the rest are human.
What type of hypersensitivity reaction is serum sickness?
Type III
Where can we find CD25?
IN the alpha chain of the IL-2 receptor
What is the function of IL-2?
Growth factor for activated T cells
acts in an autocrine fashion to induce T cell proliferation
What is the inhibitory interaction of corticosteroids?
They directly inhibit activated glucocorticoid receptors and activated transcription factors- NF-kB & AP-1 which regulate gene expression of inflammatory molecules
What is the T cell activation pathway?
MHC binds TCR–> Increased [Ca+2}i binds calcineurin phosphatase–> dephosphorylates/activates NFAT–> NFAT enters the nucleus as a TF and induces IL-2 synthesis–>IL-2 Is synthesized and released to bind to the T cell and induce proliferation
What are 2 immunophilins?
cyclophylin
FKBP
What is the role of cyclophylin?
It is a petideal proleoisomerase which inhibits the CIS/trans isomerization of proline
What drug can cyclophylin bind too?
Cyclosporine
What is the function of calcineurin?
To dephosphorylate NFAT
What is the function of NFAT?
to translocate to the nucleus and stimulate IL-2 synthesis
What is the function of mTOR?
It is a protein kinase that increases the cell cycle progression of T cells, so increases growth and proliferation
What is the role of IMPDH?
It is the rate limiting enzyme in the de novo synthesis of guanine nucleotides–> converts IMP to XMP
