Transplant immunology Flashcards
What is the primary reason for morbidity and mortality in transplants?
The immune response
In a graft, if the MHC molecule doesn’t match, what will happen?
The T cells will recognize the graft as foreign and reject it
CD4+ T cells recognize what?
Antigen + MHC II
CD8+ T cells recognize what?
Antigen + MHC I
What do T cells need to do during education in order to not die?
The need to bind a self peptide and MHC with low avidity
What do T cells need to be activated other than binding something with high avidity?
Costimulatory molecules
Can alloantigen recognition be both direct and indirect?
Yes
What happens due to a hyperacute rejection?
IgM activates the complement cascade, cells die and the blood supply to the graft is clogged and the graft dies
In an acute reaction, what other reaction is also present?
The hyperacute reaction
What is the hyperacute reaction due to?
preexisting alloreactive antibodies. Antibodies then activate the complement cascade
What happens in an acute reaction?
CD8+ T cells are activated and they lyse host target cells. B cells are activated which produce antibodies and the hyperacute response occurs as well
What ultimately causes the rejection of a graft?
the loss of vascular supply to the tissue
What happens in a chronic graft rejection?
Alloreactive T cells produce cytokines that activate parenchymal macrophages. The inflammation can induce growth factor production which induces intimal thickening, thereby closing off the vascular supply
What is the best way to prevent graft rejection?
Prevention- so autologous or syngeneic transplants
What is the purpose of a bone marrow transplant?
Treatment for hematological disease- cancer, immunodeficiency etc. and to restore the immune system destroyed by radiation and chemotherapy
What is a potential major problem with a bone marrow transplant (other than what has already been talked about?)
The graft could target the host… basically it’s a new immune system attacking the alien host
Even though the primary physiological role of the immune system is to protect the organism from infectious microbes, can the immune system look for transformed cells and destroy them?
Yes
Some cancers can down-regulate the expression of MHC I, why is this important for the immune system?
Well, NK cells have 2 receptors- and inhibitory domain and an activating domain. The default for NK cells (no signal) means it’s activated. The inhibitory receptor is MHCI, so viruses and cancers that downregulate MHCI will actually serve to activate NK cells and then they die
T/F the function of macrophages depends upon the cytokine microenvironment, or those cytokines that surround the macrophages?
True
M1 macrophages do what?
M2 macrophages do what?
M1- can suppress tumors and kill tumor cells
M2- help repair wounds- cell proliferation/growth factors- so these can enhance tumors
What do cytotoxic T cells do?
They recognize antigen specific cells, bind to them and degranulate, inducing apoptosis- can occur with cancer cells
T cells are activated where?
In the lymph nodes
Most T cells in circulation are activated or dormant?
dormant
What is cross priming?
It is where an APC engulfs an infected host cell and expresses the microbe or tumor antigen.
CD4+ T cells are important to killing cancer why?
Because they produce cytokines that lead to M1 macrophage activation
Why are B cells important in cancer and killing cells?
There is something called antibody dependent cellular cytotoxicity- if antibodies are attached to a cancer cell, the NK cell can degranulate and kill it
How can the immune system lead to the development of cancer?
Cytokines can lead to increased cell proliferation (hyperplasia)
Hyperplasia can lead to dysplasia (abnormal cell development)
Free radicals can be formed and damage nucleic acids
