Cancer and the immune system Lecture 19

Question 1

What is the immune system

Answer 1

to fight disease, vital for life
First lines of defence are: Skin, saliva, stomach acid, mucous, tears, sweat
Majorty of lymphocytes contained in lymphatic system that runs throughout the body.

Question 2

Describe B cells

Answer 2

B cells made and mature in the bone marrow
ONce a B cell recognises its specific antigen, it will start to mature and differentiate into a plasma cell which will release antibodies into circulation.

Question 3

Describe T cells

Answer 3

T cells go to thymus where they will mature and enter circulation
Recognise small fragments of antigen that are presented on the surface of the cell in context of MHC molecules
Antigens are recognised by MCH class I. CD8 t cells are expressed within the cell then they are processed and presented on the surface of the same cell.
CD4 cells recognise antigen through MHC class II molecules.
The diversity in T cell recprotrs are due to VDJ recombination
T cells are quality controlled in the thymus during development

Question 4

Link of immune system with cancer

Answer 4

The immune system must normally be able to suppress the growth of tumours otherwise they would occur with much greater frequency than they do.
Must be a mechanism where damaged cells can be detected by immune system.
The tumour immunosurveillance hypothesis = small accumulation of tumour cells can develop and because of their possession of new antigenic potentialities they can provoke an immune reaction and regression of the tumour with no clinical hint of its existence.

Question 5

What is the evidence that the immune system recognises cancer?

Answer 5

1. Immunodeficiency leads to increased risk of cancer
2. Immunosuppressive medication required for graft rejection can enable reactivation of oncogenic viruses. Long term immunosuppression also increases non-virus associated cancer risk
3. Immune activation by infection can lead to regression of cancer
4. Increased number of immune cells in tumours can improve survival

Question 6

How do cancer avoid immune recognition?

Answer 6

1. Immunosuppressive cytokines secreted that prevent T cells from working. eg TGFbeta and IL-10 are heavily immunosuppressive. Treg and monocyte derived suppressor cells secrete these cytokines
2. Down regulation of MHC
   - Loss of components in processing pathways
   - Loss of MHC molecules - can’t recognise the cancer
3. Exploiting T cell checkpoints
   - Cancer cells can express the ligand that prevents T cell activation

Question 7

How can the immune system put pressure on the tumour

Answer 7

The immune system can pressure the tumour to evolve and mutate more to keep alive. The tumour could also create an invasion mechanism

Question 8

What future possible treatments for cancer involve immunotherapy?

Answer 8

1. Reawakening naturally occuring anti-tumour cells
2. Boosting numbers of anti-tumour T cells
3. Genetically engineer T -cells to recognise cancer (CAR-T therapy)