13a - Cell Mediated (T cell) Immunity - Partridge

Question 1

BRIEFLY describe the antigen independent T cell differentiation

Answer 1

in thymus, T cells acquire their T cell receptors. undergo thymic selection. Naive T cells expressing TCR + CD4/8 enter the 2ndry lymphoid tissue

Question 2

BRIEFLY describe the antigen dependent T cell differentiation

Answer 2

in 2ndry lymphoid tissue, T cells presented with foreign peptide in the context of self MHC allowing them to differentiate into effector T helper cells/ cytotoxic T cells/T regs
- secrete cytokines or directly kill infected host cells

Question 3

Describe the activation of adaptive immunity in the 2ndry lymphoid tissue

Answer 3

PRRs/TLRs recognise invading antigen. signals the lymph node to drain from infected tissues.
DCs/macrophages that have taken up the antigen can migrate to T cells to allow them to differentiate

Question 4

How is an effector T cell/memory T cell activated?

ie primed T cells

Answer 4

recognition of self MHC + peptide and the co-receptor

- TCR + CD3 + CD4/8 selfMHC + peptide (SIGNAL 1)

Question 5

How are naive T cells activated and how is this different?

Why are these extra steps necessary?

Answer 5

SIGNAL 1 is not enough to activate naive T cell. do not want to inappropriately activate them.
SIGNAL 1 as normal
then requires an additional SIGNAL 2 = interaction with a co-stimulatory molecule

Question 6

What happens to naive T cells in the absence of Signal 2?

Answer 6

naive T cells that have been stimulated by Signal 1 and NOT by Signal become unresponsive/tolerised

Question 7

Name the types of cells that express this co-stimulatory molecule, where are they mostly found?

Answer 7

macrophages, DCs and B cells

- DCs (probs most important in stimulating naive T cells) are most abundant in 2ndry lymphoid tissue

Question 8

Give an example of a co-stimulatory molecule

Answer 8

B7 expressed by B cells, DCs, macrophages
interacts w/ CD28 receptor on T cells which induces the expression of IL2 and IL2R
(both Ig gene superfamily members)
- IL2 acts on T H cells in an autocrine fashion. stimulates T cell growth and differentiation
- IL2 also activates cytotoxic T cells

Question 9

What is signal 3?

Answer 9

other cytokines direct T cell differentiation into different subsets of T effector cells (type of APC dictates the types of cytokines made)

Question 10

Give an overall summary of the functions of CD4 T helper cells and CD8 Cytotoxic T cells

Answer 10

CD4;

• secrete cytokines to stimulate monocytes, macrophages, Cytotoxic T cells
• activate B cells and promotes differentiation through class switching and somatic hypermutation

CD8;

• directly kill infected host cells
• down regulate immune responses

Question 11

How do T helper cells differ?

Answer 11

different subsets of TH cells differ in the cytokines they produce and therefore their role in immune responses

Question 12

how are different subsets of TH cells produced?

Answer 12

naive CD4+ T cells stimulated to differentiate into subsets by specific cytokines presented by for eg DCs and other innate cells. depending on the type of pathogen

Question 13

Summarise the hygiene hypothesis

Answer 13

insufficient exposure to certain types of infection eg dirt can shift the TH1/TH2 balance towards TH2.
more prone to allergy this way?
BUT see -ve correlation between helminth infections and allergy. assume that because we have IgE produced in response to parasite we should also get allergic response, this is not true

Question 14

Summarise the counter regulation hypothesis and give its alternative name

Answer 14

‘old friends’ hypothesis

• infection with macroorganisms or microbes plays a key role in establishing immunoregulation
• human immune system and ‘old friends’ co-evovled
• early infection with microbes allows immunoregulators to develop. producing IL-10/TGF-B (by TREGs) therefore downregulating TH1/TH2
• allowing for protection against allergy
• because less exposure nowadays, may also play a role in autoimmune diseases that are TH1/TH17 driven because cannot down regulate their responses

Question 15

What are the 2 main roles of Cytotoxic T cells?

Answer 15

• directly kill infected host cells

- controlling immune responses

Question 16

How does a CTC kill a target cell?

Answer 16

• specifically binds to infected target cell
  either
  1) produces perforin to create pores in membrane. releases proteases (granzymes) to enter in target cell….
  2) clustering of the Fas ligand death receptor through interactions with the Fas ligand on the CTC…

… both of these cause the activation of the caspase cascade. induces apoptosis.
killing is specific and clean in terms of all the a-optic products are kept contained and can be engulfed by macrophages

Question 17

How does a CTC kill a target cell?

Draw a diagram as well

Answer 17

• specifically binds to infected target cell
  either
  1) produces perforin to create pores in membrane. releases proteases (granzymes) to enter in target cell….
  2) clustering of the Fas ligand death receptor through interactions with the Fas ligand on the CTC…

… both of these cause the activation of the caspase cascade. induces apoptosis.
killing is specific and clean in terms of all the a-optic products are kept contained and can be engulfed by macrophages

Question 18

Once antigen eliminated/cleared ____% of activated and effector cells die

Answer 18

99

Question 19

what are the 2 mechanisms of down regulation?

Answer 19

TREGs and CTCs

Question 20

Give 2 examples of down regulation including diagrams

Answer 20

CTLA-4 expression;

• immune checkpoints expressed on lymphocytes
• activated T cells express the immune checkpoint CTLA-4
• binds B7 on APCs at higher avidity than CD28 therefore preventing T cell. activation. inhibitory signal can be delivered to the cell and it is switched off

Lymphocyte receptors with ITIM motifs;

• eg FcyIIb on B lymphocytes
• PD-1 expressed on B/T lymphocytes which interact w/ PD ligand
• PD-1 has ITIM motif therefore when it binds ligand, the ITIM becomes P

Question 21

How is it thought that drugs that target immune checkpoints may be used as anti cancer drugs?

Answer 21

cancers suppress the immune system by expressing these immune checkpoints. drugs that target these eg CTLA-4 targeting may be used to kill cancer cells