cancer immunology

innate immunity cells

NK, macrophages, dendritic cells, neutrophils, eosinophils, basophils

how does cancer suppress the immune system? secreting TGF-B cells stimulating Treg cells secreting IL-10 all of the above

all of the above

herceptin

anti-HER2, breat cancer

keytruda

anti-PD-1 -- approved against non-small-cell lung cancer (NSCL)

avastin

anti-VEGF -- DEC angiogenesis

M1 macrophages

anti-tumor cells that release reactive oxygen species and cytotoxins towards cancer cells can recruit other immune cells by releasing certain cytokines

acquired immunity

antigen specific and adaptive THINK: what is the threat and how can we recognize it?

how do cancer cells use PD-L1 to weaken cytotoxic response?

bind of PD-L1 to PD-1 activates SHP-2 phosphatase --> inactivates P13K pathways w/in T cell and DEC its own survival mechanisms

keytruda

block PD-1 checkpoint

Yervoy

blocks CTLA4 checkpoint

epstien-barr virus

burkitt's lymphoma

indirect exhaustion

cancer cells DEC antigen expression / masking with CAR itself

human papillomavirus

cervical cancer

dendritic cells -- antigen presenting cell (APC)

communication expert of immune system; identify pathogen at source and keep antigens for reference

cytotoxic T cell (CD8+)

cytotoxic --> bind target cells displaying (Ag+MHCI) complex --> destroy TCR recognizes (Ag+MHCI)

CD8+ cells

cytotoxic! assassins that respond to antigens displayed by MHC1 carrying cells --> seek out target --> destroy it head-on via FAS activation, perforin, granzyme B

CAR T cell exhaustion types

direct, indirect, self-imposed

immunoediting

disguise themselves as healthy cells via remove TATAs and TSTAs and MHC

many tumor cells and viral-infected cells ____ have MHCI

do not --> trying to evade T-cell response

macrophages

engulf pathogens and aid initial immune response (antigen presentation and inflammation); go from monocytes --> macrophages

helper T cell (CD4+)

enhances B cells, CD8+ t cells, macrophages, NK cells TCR recognizes (Ag+MCHII)

oncolytic viruses

ex. T-VEC oncolytic virus deviated from herpes for melanoma; infect cancer cells (no mechanism to eliminate virus) --> lyse cancer cells --> releases viral and antigens for identification of immune system

provenge

first FDA approved vaccine against metastatic prostate cancer; patient APCs removed, activated with tumor antigens (pap and GM-CSF), then reinjected

antigen presentation

foreign protein is phgocytosed --> enters cell --> proteases cleave the foreign protein --> preserve Ag peptides --> cleaved peptides are loaded onto MHCI and MHCII on cell surface

plasma cells

front-line defenders release antibodies into the bloodstream, making pathogens their place

CD4+ cells

helpers! support cells that respond to antigens displayed by MHC-2 carrying cells and assist B cells, NKs, and macrophages in their duties

how do cancer cells compensate for down-regulating MHC1 after stress response?

inhibit stressor production or secreting them as decoy

memory cells

keep knowledge of antigens for future infections

cell expresses MHC I and MHC II --> kill or no kill?

kill

cell expresses only MHC II --> kill or no kill?

kill

what do Treg NORMALLY help to prevent?

prevent autoimmune responses, but cancer turns them against the entire immune system

how do cancer cells use CTLA-4 to counteract B7 ligand and CD28 receptor?

priming action inhibited by binding of B7 to CTLA-4 --> keeps T cells in their inactive state --> CTLA-4 normally used for immune regulation and DEC activity post-infection, but cancer cells exploit --> avoid destruction

activation of M2 can lead to ...

production of growth factors, angiogenesis, immunosuppression, invasion and metastasis

natural killer cells

rapidly attack pathogens while keeping self-cells safe (self-cells are deactivated via presentation of MHC1 and lack of stress molecules)

direct exhaustion

secretory of inhibitory molecules, Treg activation, and/or INC PD-L1

T cells require 2 signals to be fully activated

signal 1: TCR on T cell binds (Ag + MHCI or II) signal 2: B7 (APC) binds CD28 (T cell)

what does releasing Il-10 and TGF-B cell do?

stimulates Treg

which cancer type is associated with a virus? burkitt's lymphoma liver cancer cervical cancer stomach cancer

stomach cancer

stomach cancer is associated with a _____ called ____ and causes ____ which create cancer which create cancer after many iterations of injury and reconstruction of the stomach

stomach cancer is associated with a bacteria called H.Pylori and causes ulcers which create cancer after many iterations of injury and reconstruction of the stomach

What INC a patient's chance at 5-yr survival?

the more tumor-infiltrating lymphocytes (TILs) a patient has

which cells suppress MHC 1 expression?

viral-infected cells and tumor cells to evade t cell activation

acquired immunity cells

B cells, T cells, and their variations

after primary response ____ recall certain antigens for the ____ response if you get infected again

B cells; secondary

chimeric antigen receptor T cells

CAR-T cells genetically modified to better target cancer

self-imposed exhaustion

CAR-Ts competing with endogenous T cells for tumor antigen binding

which cells can be destroyed by HIV?

CD4+

what cells can't detect MHC1 if it is removed?

CD8+ and MHC1 can't detect therefore no immune response

what types of cells express MHC 1

all healthy and normal cells

what does Treg do after cancer recruits it?

DEC activity of CD8+ and CD4+ cells --> protecting cancer cells therefore INC [Treg] --> lower chances of survival

don't kill me, i'll kill you

INC IAPs and DEC FAS activity to prevent apoptosis from occurring --> release FAS ligand (soluble or in vesicles) to trigger apoptosis in immune cells --> to debuff lymphocytes and kill them they will release inhibitory cytokines IL-10 and TGF-B --> stimulates Treg

patients suffering from AIDS/autoimmune conditions are more susceptible to their associated cancers. which is the most common arising cancer for these individuals? what virus is it associated with?

Kaposi's sarcoma -- associated with herpesvirus

tumor cells tend to down-regulate ...

MHC 1, which are overlooked in favor of pro-mitotic, anti-apoptotic up-regulation --> leaves them vulnerable to NKC attacks and MICA (after stress response)

why does every cell present MHC I?

MHC I integral for T cell activation and for NK cells

inhibitory ligand

MHC class I --> NK cell wont kill normal, healthy cells express MHC I

activatory ligand

MHC class II presence of BOTH MHC I and MHC II --> activatory overrides inhibitory --> NK kills stressed cells express MHC II

which cells are part of the innate immune system? Macrophages Dendritic cells B cells T cells

Macrophages Dendritic cells

T cell immune checkpoint: PD-L1

PD-1 receptor on T cell interaction with PD-L1 receptor on tumor cell

what do pericytes help improve?

Pericytes improve survival and completion of survival of endothelial cells (EC)

T cell task

T cell receives intel from APCs in the form of tumor-specific antigens --> T cells seek out tumor cells and destroy them --> cellular remains harvested by other immune cells for antigen collection --> checkpoint one

MHC 1 expression is critical to the activation of which cell?

T cells

how does CAR-T cell therapy work?

T cells from patient modified via Lentivirus --> express antibody fragments (scFv) and T cell activation domains (CD3zeta) --> does NOT need MHCs to bind to bind to cancer cells --> takes immunoedited cells off guard

T cell immune checkpoint: CLTA-4

T cells must bind APCs by both MHCs and B7 ligand (detected by Ts CD28 receptor) to continue

M2 macrophages

TAMs -- pro-tumor cells that have been transformed by tumor cells to act in their favor, releasing hallmark-stimulating cytokines

because of the viruses that may be associated with certain cancers, is the immune system better prepared for it?

Yes, because the immune system is already on high alert from the pathogen presence

hepatitis B virus

liver cancer

inhibitory ligand for NK cells?

mhc 1

activatory ligand for NK cells? will nk cells kill?

mhc 2, yes

will NK cells kill cells with MHC 1? why?

no bc MHC 1 is an inhibitory ligand

cell expresses only MHC I --> kill or no kill?

no kill

innate immunity

not antigen specific but responds immediately to infection, inflammation, cellular damage THNK: is this a threat or not?

Rituxan

one of first antibodies developed - non hogkins lymphoma

B cells

originate in Bone marrow -- responsible for humoral (blood soluble) immunity

T cells

originate in Thymus gland -- responsible for cellular (binding) immunity

immunotherapy promotes _____ immunity

passive immunotherapy