Immuno: Tumor And Tissue Transplantation Flashcards
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
Tumor specific antibody’s lead to binding of antibodies to the tumor cell which activates…
NK cells with Fc receptors (CD16) to kill tumor cells
Antibody fragment conjugated to the toxin binds to the tumor cells and leads to…
The conjugates being internalized and killing the cell
Antibody fragment conjugated to radionucleotide binds to the tumor cells surface and leads to…
Tumor cell and neighboring tumor cells being killed via radiation
Transplantation refers to…
The act of transferring cells, tissues, or organs (GRAFT) from one individual (DONOR) to another (RECIPIENT)
Autographs
Self-tissues transferred from one body site to another in the same individual
Syngenic/isograft:
Tissue transferred between genetically identical individuals
Allograft:
Tissue trasnferred between genetically different members of the same species
Xenograft:
Tissue transferred between different species
Graft vs. host disease:
-host is attacked by transplanted T cells
-if donor cells see the host as foreign the donor will attack the host
Host vs graft disease
-Transplanted tissue is rejected by host
-mature T cells in host recognize the graft as foreign
Lymphoma
primarily cancer of the lymph nodes that begins in lymphocytes
Leukemia
-Cancer that originates in blood forming tissue
-usually white blood cells in the bone marrow
Leukemia tend to proliferate as…
Single cells
Localized cancer therapy:
-surgical removal of cancerous organs or tissues
-application of ionizing radiation to known primary site and suspected metastatic sites
Systemic cancer therapy:
-chemotherapy is the administration of cytotoxic drugs
Which cytokines are associated with tumor-induced suppression of the immune response?
IL-10
Which cytokines are associated with tumor-induced suppression of the immune response?
IL-10
TNF is secreted by:
Macrophages
