Immune Lecture 22 Study Notes
1. How can inflammation cause cancer?
-many chronic inflammatory diseases increase the risk
IBD = chronic inflammation of the GI tract can cause colon/rectal cancer (10% get
within the general population, 0.05% develop colon or rectal cancer
-reactive oxygen and nitrogen species can mutate DNA
2. What does ROS do?
-can generate many mutated DNA bases
-chemically altered forms of DNA created by superoxide or hydrogen peroxide
-DNA repair might fix them but sometimes it doesn’t
3. Discuss inflammation, infection and cancer.
-chronic infection can lead to cancer (helicobacter pylori = infection of the stomach)
will colonize the stomach and induce inflammation
this damage will lead to the cancer
-some viruses carry cancer-causing genes
oncovirus (enter infected cell and use gene to take over cell division)
epstein-barr virus, kaposi’s sarcoma virus, HPV
4. How much of cancer do infections cause?
-infections may cause up to 25% of all cancers
-vaccination against these viruses can prevent these cancers
5. What is HPV?
-human papilloma virus
-causes cervical cancer (5 most common in women)
-250 000 deaths per year
6. What are the different strains?
-HPV-16, 18, 6 and 11
-6/11 mostly cause warts, rarely cancer
-others cause cervical cancer
-HPV can also cause anal, vaginal, penile, head, neck and oral cancers
7. Discuss the HPV vaccines.
-guardacil protects against all forms
-cervarix protects against 16 and 18
-both consist of empty (no genome) virus-like particles containing HPV organs
8. How well does the vaccine work?
-farely new but so far in patients that have used it: majority are protected against
precancerous lesions s 9. What helps tumours to grow?
10.What purpose does tumor inflammation serve?
-drives angiogenesis to provide blood supply to the growing tumor
-creates a microenvironment which suppresses TH1 responses
11.Why is angiogenesis required for tumor growth?
-cells need oxygen and nutrients to grow
-when it stops growing the tumour will secrete VEGF which will cause new blood
vessels to form, penetrate the tumour and allow more O2 and nutrients to expand
-much larger and can metastasize
12.Why does tumor angiogenesis require immune cells?
-neutrophils lie within the blood vessels
-when they crawl out of them to go towards the tissue they create a channel
-producing angiogenic factors/growth factors and create new endothetlial cells
which will form the blood vessel
-this gives the tumour a new blood vessel
13.How do we stop blood vessels from being formed?
-experiment where Nu were killed using antibodies
-if new channels aren’t formed then VEGF can’t be secreted to stimulate the growth
of new blood vessels
14.What is a tumour associated macrophage?
-somehow activates an M2 (alternatively)
-they start producing anti inflammatory cytokines, pro-healing, angiogenic factors
and neutrophil attractors
-TFFbeta, IL-10, CXCL1/2/3/8, VEGF and VEGA
15.How do we get an M2?
-monocytes enter the tumour are exposed to M-CSF, IL4/10/13 which turn it into an
-from here, it will produce CXCL1/2/3/8 which will recruit neutrophils in order to
-VEGF/chemokines/cytokines produced to make angiogenesis occur
-VEGF/VEGA also produced by macropage to stimulate angiogensis
-M2 will release growth factors and tissue repair factors to stimulate tumour growth
-M2 will release IL10 and TGFbeta
-TGFbeta will cause T cells and DC to make TH2 or Treds while IL10 will stimulate
16.Can inflammation kill cancer?
-trying to tweak our immune system to be more tumor killing -kill tumour cells in high enough quantities: ROS, RNS, proteases, pore-forming
proteins and antibody-dependent cell cytotoxicity
17.Can our adaptive immune system fight cancer?
-experiments with mice:
mice with certain immune mutations have a higher incidence of cancer
gamma delta T-cells missing
RAG/STAT1 (making T cells) knockouts
perforin knockouts (released in granzymes)
-experiment with mice: give them irradiated tumour cells (killed; so they c