Lecture 18 - Tumor Immunology and Immunotherapy Flashcards
What are the two methods in which the immune system can respond to pathogens/abhorrent cells.
1 - Humoral immunity
2 - Cellular immunity
Describe both the humoral and cellular antibody response of the immune system.
Antibodies molecules are a humoral immune response and are capable of binding/recognizing certain antigens.
Antibody-bound cells are then destroyed via Macrophages - WBCs natural killer cells
The cellular immune response are the cytotoxic T-lymphocytes (CTLs) that bind and destroy targeted cells.
What is an adaptive immune response? How does it happen?
An adaptive immune response is when the immune system responds to a previously encountered pathogen.
Here, a sample of the antigen is taken up and recognized by a dendritic cell. The productive interactions between APC and helper T cells then leads to antibody production via the MHC class II and T-cell receptor.
The antigen antibody interactions attract complement proteins that open channels in the antigen presenting cell. MHC class I then displays a portion of all recently synthesized proteins on the target cell.
Killer T cells recognize MHC I and target the antigen displaying cell for destruction.
How to T cells kill? 2 step process.
1 - Perforin punches holes through plasma membrane of target cell (Granzymes enter cell)
2 - T cell introduces FasL ligand to the extracellular Fas receptors stimulating the extrinsic apoptosis pathway.
What is immune tolerance? What are regulatory T cells used for?
Immune tolerance is the fact that the immune system must be able to differentiate between self vs. non-self.
Regulatory T cells, T-reg’s, block cytotoxic T cells before they can eat healthy components in the environment.
What is immunosurveillance?
What are TSTAs, TATAs?
What happens if normal cells express the same antigens as the cancer cells?
The immune system, like a totalitarian state, monitors tissues for the presence of tumors.
Tumor cells can have specific antigens
Tumor specific transplantation antigens (TSTAs or TSAs)
Tumor associated transplantation antigens
(TATAs or TAAs)
***Melanomas often have high TATA expression & autoimmune response ensues
If the normal cells express the same antigens as the cancer cells then the immune system will attack the healthy normal cells.
Why are nude mice to awesome in cancer research?
What is IFN-y?
Nude mice lack thymus and the ability to properly train their T-cells (immunocompromised). However, they still retain some natural killer cells (NK).
Mice lacking interferon-y (IFN-y) are more susceptible to tumorigenesis. IFN-y is released by NK cells and attracts other immune macrophages. It leads to increased MHC-1 production in cells.
Macrophages, are they for or against cancer?
Macrophages can have both a pro-tumor and anti-tumor effect depending on the signal that is released. The signal determines which kind of macrophage is released.
How can the body detect cancerous cells a.k.a neoplastic tissues?
The body can distinguish between normal and cancer cells through antigens, MHC I and II complexes, etc…
Unusually shaped antigens such as p53, RAS, etc…
Overexpression of a single antigen (HER 1/2)
Abnormal location and timing of embryonic precursors.
How can cancer cells avoid the immune system?
List 3 ways.
1 - Cancer cells can reduce their expression of MHC-1 preventing T cells from recognizing them. However… NK cells will still attack cells with low MHC-1 expression.
2 - Cancers can block the FasL pathway avoiding destruction (extrinsic apoptosis initiation avoidance)
3 - Cancer cells can launch counter-attacks on lymphocytes by altering the function of T-regs to inhibit T-regs AND Tcs.
