Immuno: Tumor And Tissue Transplantation Flashcards
(42 cards)
Immunosurveillance
-Recognition and elimination of tumor cells by immune system
-occurs on a regular basis to protect against cancer
Immunosurvelience is apart of a 3 phase tumor establishment process:
- Elimination (immunosurvelience)
- Equilibrium
- Escape
Elimination phase of tumor establishment :
Immune cells recognize and kill potential tumor cells
Equilibrium phase of tumor establishment :
Tumor cells undergo changes/mutations aiding in their survival
Escape phase of tumor establishment
Tumor accumulates t o sufficient mutations to evade immune system and grow unimpeded and becomes clinically detectable
2 ways that tumor cells are attacked by immune cells:
- Cell mediated immunity
- Antibodies made to tumor cell antigens
Cell-mediated immunity to eliminate tumor cells:
-TH1 dependent CD8 cells
-TH1 dependent macrophage activation
-cytotoxic mediators (TNF alpha)
-NK cells (ADCC, lysis)
Antibodies alone are _____________ for tumor cells undergo changes killing
Insufficient
Antibodies contribute to antitumor response by:
-Ab Opsonization that causes phagocytosis of tumor cells
-Ab induced ADCC causes killing of tumor cells by NK
T-cells, B-cells, and Ab can recognize 2 things:
-tumor specific antigens (TSA)
-tumor associated antigens (TAA)
TSA:
Antigen on tumor cells not expressed on normal, healthy cells
TAA:
Antigen on certain tumor cells also present on some types of normal cells (at lower levels or earlier stages)
TSAs/TAAs may be (2 things):
-cell surface Ag recognized by Ab
OR
-peptides from cell surface tumor Ag presented by MHC to T cells
TSAs and TAAs can be derived from:
-mutant cellular proteins acquired in oncogenesis
-abnormally expressed fetal antigens
-over-expressed proteins normally on cells at lower levels
3 ways that tumor cells evade immune responses:
- Down-regulation of cell surface molecules, resulting in low immunodeficiency
- Induction of peripheral tolerance
- Creation of physical barrier to immune system
What causes down regulation of cell surface molecules (3 things):
-loss of MHC I or MHC II expression
-loss of co-stimulator expression on tumor cells surface
-Ab-induced down-regulation of cell surface antigens by antigenetic modulation
3 ways of inducing peripheral tolerance:
-macrophage or Bcell APCs presenting tumor Ag to T cells in absence of co-stimulation induce anergy
-tumor secretes regulatory cytokines to inhibit T cells
-T regulatory cells recruited into tumor bed and draining lymph nodes are activated
Creating a physical barrier to the immune system leads to an…
immuno-priveledged site
How do tumors avoid recognition via low immunogenicity?
-No peptide or MHC ligand
-no adhesion molecules
-no co-stimulators molecules
How do tumor cells avoid recognition via treating as self antigen?
Tumor antigens are taken up and presented by APCs in absence of co-stimulation so T cells don’t get activated
How tumors avoid recognition via antigenic modulation
The tumor cell can Induce endocytosis and degradation of the antigen
How can tumor cell avoid recognition via tumor-induced immune suppression?
-TGF and IL-10 secreted by tumor cells and inhibit T cells directly
-Induction of regulatory T cells by tumors
How can tumor cell avoid recognition via tumor induced privileged site?
Factors secreted by tumor cells create a physical barrier to the immune system
How m-Ab recognize tumor-specific antibody and eliminate tumor cell (3 ways) :
-tumor specific antibody
-tumor specific antibody fragments conjugated to toxin
-tumor specific antibody conjugated to radio-nucleotide
