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54 Cards in this Set

  • Front
  • Back
What are oncogene products?
mutated Ras, Bcr/Abl fusion proteins
What is a tumor suppressor gene product that gets mutated?
p53 protein
what self proteins are sometimes overexpressed in tumors?
tyrosinase, gp100, cancer/testis antigens
What are some oncogenic viruses and the protein products they produce?
HPV E6 and E7 proteins in cervical carcinoma and EBNA proteins in EBV induced lymphomas
What are the majority of tumor antigens?
endogenous cytosolic proteins displayed on MHC 1
All cells display peptides on MHC I. However tumor cells do often express what?
MHC II
For CD8 cells to proliferate what has to occur?
they can become activated by MHC I receptors but they also need the help of CD4 cells which are stimulated by MHC II presentation
What is cross priming?
also called cross presentation, it occurs when dendritic cells engulf to tumor cells or antigen and present them to CD8 and CD4 cells
In order for a CD8 cell to become activated by dendritic cells they need what receptors?
CD8 cells have CD28 which binds costimulator B7 on dendritic cells
CD8 cells have to do what in order to kill tumor cells?
differentiate with CD4 help
What are 3 ways tumors evade immune response?
1) do not express antigen (Antigen loss variant)
2) do not express MHC 1
3) produce a CD8 inhibitory ligand
Tumors that do not express MHC1 can still be killed via?
NK cells
What cytokine do tumors secrete that suppresses immune response?
TGF-beta
When treating B cell tumors with an antibody, what is the antibody directed against?
CD20
animals that are identical to one another are called what?
syngeneic
What does allogeneic mean?
animals of the same species that are not identical
What is xenogeneic?
animals of different species
antigens of allografts are that are the principal target of rejection are proteins encoded in what?
MHC
what is the MHC found in humans called/
HLA
How many MHC 1 alleles are there and what are they?
6, HLA-A, B, C one from each parent
There are at least 6 MHC II alleles what are they?
HLA-DQ, DR, DP one from each parent
All MHC molecules are targets of immune rejection, although 2 alleles are associated with the least immune response. What are they?
HLA-C and DP
What elicits one of the strongest immune responses?
MHC antigens on another individuals cells
What recognizes MHC molecules?
TCRs on T cells
What is an example of an immunologic cross reaction?
allogeneic MHC molecules because they are recognized by recipient T cells and are also have bound foreign peptide to them (direct recognition)
What does negative selection in the thymus do?
eliminate T cells that strongly recognize self MHC
What is the difference between allgeneic grafts MHC recognition and that of an infected self cell in terms of T cell recognition and response?
Only a few MHC types on an infected cell will display foreign antigen, whereas all of the MHCs on a graft can be interpreted as foreign
What are non-MHC antigens on allogeneic grafts called?
minor histocompatibility antigens which are allelic forms of normal cellular proteins that happen to differ from donor to recipient
What are examples of minor histocompatibility complex reactions that occur in the body?
1) blood transfusions
2) bone marrow transplantation
recipient APCs can present alloantigens to recipient T cells. Can recipient T cells recognize and interact with donor APCs? What is the process called?
yes, direct recognition because it is a direct presentation of alloantigens
what is indirect recognition of alloantigens?
recipient dendritic cells display alloantigen to recipient T cells that induce the immune response. This is similar to cross presentation in tumor cells
What is different about the response generated between direct and indirect recognition of grafts?
in indirect the CTLs are specific for alloantigen displayed by self MHC molecules on host APCs and cannot recognize and kill cells in the graft
Is a delayed type hypersensivity with graft rejection seen with direct or indirect alloantigen presentation? why?
indirect because CTLs cannot directly kill donor cells, so CD4 cells move with other APCs to graft and slowly secrete cytokines that destroy the tissue
Is acute or chronic rejection mediated by direct or indirect recognition?
acute = direct
chronic = indirect
How is hyperacute graft rejection characterized? What is an example?
occurs within minutes via thrombosis of graft vessels and ischemia

blood donation
What is the cause of hyperacute graft rejection?
preformed antibodies to endothelial cells on grafts. Antibodies may include IgM for blood groups, or allogenic antibodies from past blood transfusion, pregnancy, or prior organ transplant
The antibodies in both acute and hyperacute rejection do what?
bind endothelium and activate complement and clotting systems
How is hyperacute rejection avoided?
cross matching the blood type
what reaction occurs with xenotransplantation?
hyperacute
When does acute rejection present?
within days or weeks and is the principal cause of early graft failure
What occurs in acute rejection?
mainly a T cell mediated reaction to alloantigens, although antibodies also contribute especially to the vascular damage
When does chronic rejection occur?
within months to years leading to a progressive loss of graft function
What occurs cellularly in chronic graft rejection?
fibrosis and gradual narrowing of graft blood vessels via T cells stimulating fibroblasts and vascular smooth muscle
What is the most clinically useful drug in blocking graft rejection?
cyclosporine because it blocks T cell phosphatase (calcineurin) needed to activate NFAT so cytokine production is inhibited
What is the problem with drugs other than cyclosporine?
they are nonspecific immunosuppressants
Why do the blood group antigens not elicit T cell responses?
because they are sugars
princeps, principis
earliest, first
leader, chief
What is the MOA of FK506? What else is it known as?
same as cyclosporine, blocks release of cytokines from T cells

Tacrolimus
What is the MOA of mycophenolate mofetil?
blocks lymphocyte proliferation by inhibiting guanine nucleotide synthesis... inhibits inosine monophosphate dehydrogenase which is particularly effective at destroying lymphocytes because they lack the alternative salvage pathway
what is the MOA of rapamycin?
blocks lymphocyte proliferation by inhibiting IL2
What is the MOA of corticosteriods?
reduce inflammation by blocking cytokine release from macrophages
WHat is the MONA of anti-CD3 monoclonal antibody?
Depletes T cells by binding CD3 and promoting phagocytosis or complement-mediated lysis (drug is muromonab)
What is the MOA of anti-IL2 receptor antibody?
inhibits T cell proliferation by blocking IL2 binding... drug is called daclizumab
What is the MOA of CTLA4-Ig?
inhibits T cell activation by blocking B7 costimulator binding to T cell CD28... drug is (abatacept)