Cancer Immunology I Flashcards
What are the phases of adaptive immunity?
The recognition phase where antigen is processed by antigen presenting cells and presented complexed with MHC to lymphocytes
The activation pahse where the selected lymphocytes synthesize new proteins, proliferate and differentiate maturing into effector or memory cells
The effector phase where the activated lymphocytes perform their function leading to elimination of the antigen
Homeostasis is then restored with the immune system returning to its basal state and most of the activated progeny dying via apoptosis
What is the role of immune surveillance in cancer?
In 1960 Sir MacFarlane Burnet proposed that a primary role of the immune system was to survey fro and eliminate neoplastic cells
Cancer patients have antibodies or cytotoxic T cells which are specific to their tumour
Tumours have evolved escape mechanisms from the immune system
What are the different types of tumour antigens?
Tumour specific antigens (TSA) which are formed from mutation of cellular genes like Ras uations, rearranged ABL-BCR products
Tumour associated antigens (TAA) which are normal cellular proteins which are either over expressed or aberrantly expressed in tumours
How do Innate natural killer cells respond to tumours?
These kill both virally infected cells and tumour cells through the release of perforin
How do tumouricidal macrophages respond to tumours?
In culture these will kill tumour cells through the release of lysozymes, reactive oxygen intermediates and TNF
How do cytotoxic T lymphocytes respond to tumours?
These have a tumour specific response and kill using perforin and FAS-induced apoptosis
How do antibodies respond to tumours?
These can kill tumour cells in culture in the presence of either complement or accessory cells
How can cancer cells be recognised and killed by NK cells?
NK cells kill cells that cannot switch off its killing signal
Inhibition of this killing signal is mediated through recognition of self MHC antigens
Tumour cells may alter or down regulate the expression of these preventing them from engaging NK inhibitory receptors and are therefore killed by the NK cell
How can cytotoxic T cells recognize and kill tumour cells?
They recognize the tumour cell through the antigen receptor
Engagement of this receptor activates the killing signal
Granules are deposited on to the surface of the tumour cell
The lymphocyte can then detach and move to another tumour cell with each lymphocyte killing approximately 10 tumour cells
What is the main method of immune cell killing of tumour cells?
Perforin though granzymes and Fas-FasL is also used
What are the two different types of immunotherapy?
Active immunotherapy where the patients own immune system is stimulated to produce a response against the cancer
Adoptive immunotherapy where the immunologically active agent like antibodies is transferred to the patient
How are monoclonal antibodies produced?
A mouse is injected with the antigen you wish to generate an immune response towards
The clones which react with this antigen are then selected and mixed with myeloma cells in the presence of polyethylene glycol allowing the production of a cell line which produces antibodies specific for the desired antigen
