Immunosurveillance

Question 1

Which cells are important for the defence against tumors?

Answer 1

• Cytotoxic T cells/ Th1 cells for activation
• Nk cells
• Special Ab’s
• Dendritic cells

Question 2

What triggers the activation of NK-cells?

Answer 2

Absence of MHCI (or other ligand presented by it) and precense of DAMPS

Question 2

How can Nk cells kill a cancerous cell?

Answer 2

• Direct cytolysis through perforn0granzyme
• TRAIL
  -ADCC (kiss of death) –> Ab depended cell mediated cytotoxicity
• Noticed a lot of stress markers (DAMP)

Question 3

Is phagocytosis of tumorcells important for the activation of the adaptive- or innate immune system?

Answer 3

Addaptive immunesystem

Question 4

What are the steps of phagocytosis?

Answer 4

Tumorcell Ag is present in DC for ex., and will get surrounded with plasma membrane. An enclosed vesicle is formed: phagosome/endosome. Phagosome fuses with lysosome: phagolysosome. This will get degraded

Question 5

Where are MHCII present in?

Answer 5

In Antigen Presenting Cells (APC’s)
APC’s: Monocytes, Macrophages, Dendritic Cells and Bcells

Question 6

What do MHCII present?

Answer 6

Extracellular peptide (phagocytosed)

Question 7

Where are MCHI present in?

Answer 7

All cells with a nucleus (Not on RBC)

Question 8

What do MHCI present?

Answer 8

Intracellular peptide

Question 9

Which 3 signals do CD4+ T cells need to get activated?

Answer 9

1: present Ag to Naive T cell (TCR (T cell) + MHCII/Peptide (DC)
2: Upregulation of co-stimulatoire molecules CD80 and CD86 (DC) and CD28 (Tcell)
3: Upregulation cytokines (CD); Th1: IL12 and IFNy

Question 10

Which cells are CD4+ cells?

Answer 10

Tcells:
- Th1: helps DC’s to stimulate an effective CD8+ T cell response + production of IFNy
- Tfh: helps B cells to produce Ab’s

Question 11

Which cells are CD8+ cells?

Answer 11

Tcells:
- Cytotoxic T cells (Cytotoxic Lymphocytes CTL). They kill infected cells (perforin, granzyme), they trigger apoptosis by secreting TNFa, FastL (ligand) and they secrete cytokines INFy and TNFa

Question 12

What Tcell helps with the activation of CTL cells?

Answer 12

Th1

Question 13

Name all the secundary organs where T cells get activated

Answer 13

• Lymph node (if tumor is in tissue)
• Spleen (if tumor is found in blood)
  -MALT

Question 14

In which cell is cross presentation of MHCI and MHCII present?

Answer 14

Dendritic Cells

Question 15

Which 2 mechanisms of killing is present?

Answer 15

1. Extrinsic pathway (receptor binding)
2. Intrinsic pathway (cytokine)

Question 16

How many signals do CD8+ Tcells need in order to kill tumor cell?

Answer 16

1 signal (MHCI/peptide) is enough for a Tcell to kill a tumor cell

Question 17

What is the immune surveillance hypothesis?

Answer 17

Elimination phase: when tumor arise in tissue, a number of immune cells can recognize and eliminate them

Equilibrium phase: variant tumor cells arise that are more resistant to being killed. Overtime a variety of different tumor variants develop

Escape phase: eventually, one variant may escape the killing mechanism, or recruit regulatory cells to protect it, and so spread unchallenged

Question 18

Why is EEE possible? So why can tumors escape the immune system

Answer 18

• Selection of poor immunogenic variants
• Subversion of the IS
• Low immunogenicity
• Tumor Ag is tolerated
• Tumor may loose/mutate the tumor Ag what is recognized by the IS
• Tumor induces immune suppression
• Physical barrier for IS

Question 19

Can tumors get recognized by specific Ag’s?

Answer 19

Yes these are tumor antigens

Question 20

What are tumor-induced immune suppression?

Answer 20

• Immunosuppressive cytokines secreted by tumor: TGFbeta, IL10
• Attraction or induction of Treg
• Expression of PD-L1 on tumor: binds to inhibitory receptor PD-1 on Tcells
• Expression of IDO