Lecture 21: Cancer Immunology Flashcards
what cell types never enter G0 phase of cell cycle
skin & hair follicles
GI epithelium
bone marrow
male gametes
_______ regulate the normal progression of the cell cycle
Checkpoints
Cancer occurs when ______ accure in the DNA of cells. resulting in the progression of the cell cycle without regulation at checkpoints
Mutations
what are the 2 classes of genes in which mutations result in deregulation of the cell cycle
Tumor Suppressor Genes (the brakes)
(Proto) Oncogenes (accelerator)
what are tumor suppressor genes
genes that produce proteins that inhibit progression through the cell cycle
- includes SNA repair enzymes and signaling proteins that block the cell cycle
- most common causes of cancer
what type of mutations do tumor suppressor genes cause?
recessive mutations
- both copies of the gene have to be inactivated
what are (proto) oncogenes
genes that produce proteins that promote progression through the cell cycle
mutations cause constitutive activation of signaling proteins in growth pathways
driver mutation
what type of mutations do proto oncogenes cause
dominant
- only one copy of the gene has to be activated
- cancer viruses like FeLV cause these kinds of mutations
what are passenger mutations
mutations that don’t deregulate the cell cycle
- instead, they endow cancer cell w/ other physiological changes that give them growth advantages (ex: cells that can survive in hypoxic conditions)
- can be caused by continued exposure to carcinogens or radiation or arise spontaneously due to defective DNA repair enzymes
what are tumor antigens
DNA mutations in cancer cells produce proteins that the immune system might recognize as foreign
the accumulation of mutations progressively increases the _______ of cancer cells
Antigenicity
- more mutations = more likely to be flagged by the immune system
what are tumor-specific antigens (TSA’s) or mutation-associated neoantigens (MANA’s)
unique to tumor cells
result from mutations in the exons of any gene or incorporation of oncogenic viruses
normal proteins that are inappropriately expressed by tumors
Tumor-associated antigens
what causes tumor associated antigens to form
mutations in gene regulatory elements
antigen that may be an overexpression of a protein or an expression of an embryonic or other immune privileged protein
tumor-associated antigen
explain immune surveillance
the capacity of the immune system to recognize and destroy transformed cells before they grow into tumors and to kill tumors after they are formed
- involved innate and adaptive immune responses
how do antibodies promote tumor cell destruction?
- enhancing innate immunity
- serving as opsonins
- activating complement and ADCC
cells capable of destroying tumor cells in a non-MHC restricted fasion. Are the first line of defense against many tumors
Natural Killer cells
cells that are effective against tumors with reduced levels of class I MHC
NK cells
what cells are strongly activated by INF-y and kill tumors by secreting TNF and ROS
Macrophages
- process and present tumor antigens to T cells
what is the most important immune mechanism for fighting tumors
tumor-specific Cytotoxic T-cells
- directed against tumor antigens presented by class I MHC molecules
what are the mechanisms for tumor elimination?
- tumor antigens get picked up by dendritic cells at the tumor site
- Cytotoxic T cells are activated in secondary lymphatics
- tumor-specific CTLs migrate back to the site and kill the tumor cells
what makes NK cells also critical in the killing of tumor cells
they recognize when MHC class I expression decreases…. which occurs in immunosuppressive tumor environments
what is ADCC
Antibody dependent cell-mediated cytotoxicity
