CMB2004/L07 Acquired Immune Response

Question 1

Why is immunological tolerance needed? (3)

Answer 1

Random generation of repertoire of BCR and TCR
Many self-reactive specificities produced
If no tolerance, autoreactivity would lead to serious pathology

Question 2

Random TCR (a/B) gene rearrangement leads to T cells expressing TCR that… (3)

Answer 2

Fail to recognise self-MHC (apoptosis)
Recognise self-MHC + peptide from Ag present in thymus (expanded by positive selection, eliminated by negative selection)
Recognise self-MHC + any other peptide not present in thymus (survive)

Question 3

Describe positive then negative selection of T cells. (3)

Answer 3

T cells with low affinity TCR eliminated during positive selection
T cells binding MHC too well eliminated by negative selection
Leaves population with TCRs with medium affinity for self-MHC

Question 4

Describe autoimmune regulator protein (AIRE).

Answer 4

Transcription factor
Role in tolerance induction
Allows expression of many tissue-specific Ag (TSA) in thymus (+ve/-ve selection of T cells recognising these Ag)

Question 5

Explain how selection of B cells is different to that of T cells.

Answer 5

B cells get a second chance to re-arrange self-reactive BCR (receptor editing via a new light chain)
Autoreactive B cells still negatively selected (in bone marrow)

Question 6

Describe B cell tolerance.

Answer 6

Random Ig gene rearrangement leads to autoreactive BCRs
Autoreactive B cells negatively selected in bone marrow OR
Rearrange another light chain (receptor editing)

Question 7

What is an anergic B cell?

Answer 7

B cells that bind self-antigen

Question 8

Describe B cell tolerance via anergy.

Answer 8

When immature B cell BCR encounters Ag in bone marrow that isn’t multivalent, downregulate BCR and leave bone marrow as unresponsive (anergic)

Question 9

Describe how T cells can become anergic.

Answer 9

Unstimulated macrophages do not deliver co-stimulatory signal to T cells recognising nonbacterial antigen
(Naive T cell receives signal 1 but no signal 2)
Naive T cell becomes anergic/unresponsive

Question 10

Describe immunological ignorance.

Answer 10

Many Ag not presented at sufficient levels to activate T cells

Question 11

Describe privileged sites.

Answer 11

Ag sequestered from immune system (suppressive cytokines also prevalent)

Question 12

Describe how B cell responses can be T cell-dependent.

Answer 12

If Ag-specific T cells are absent/tolerant, no help for B cells is available
No antibody response

Question 13

Describe the role of T(reg) (CD4+).

Answer 13

Suppresses immune response

Question 14

Describe the difference between n(atural)T(reg)) and iT(reg).

Answer 14

Arise in thymus from T cells with high affinity TCR for self Ag (nT(reg))
Induced in periphery (iT(reg))

Question 15

Which cytokines released by T(reg) inhibit self-reactive T cells? (2)

Answer 15

IL-10
TGF-B

Question 16

What other cell can secrete IL-10 to prevent autoimmunity?

Answer 16

B cells (B(reg/10))

Question 17

Give 3 reasons for regulation of immune response.

Answer 17

Ensure responses continue only for as long as needed
Minimalise collateral (tissue) damage
Ensure responses are qualitatively appropriate

Question 18

What is the function of CD4+ T(H)1 cells?

Answer 18

Activation of macrophages, NK cells, cytotoxic T cells
Secrete IFN-y, GMCSF, TNF-a
Express CD40L

Question 19

What is the function of CD4+ T(H)2 cells?

Answer 19

Promote responses mediated by eosinophils and mast cells
Role in antibody responses, especially IgE

Question 20

What is the function of CD4+ T(H)17 cells?

Answer 20

Promote responses against fungi by recruiting neutrophils early
Secrete IL-17

Question 21

What is the function of CD4+ T(FH) cells?

Answer 21

Found in GC to help B cells
Specialised T(H)

Question 22

How can CD4+ T(H)1 kill chronically infected macrophages? (3)

Answer 22

Fas ligand/Fas induced apoptosis
Released bacteria destroyed by healthy macrophage
Other cells can kill the pathogens

Question 23

Give 2 types of CD4+ T(reg) cells.

Answer 23

CD4+CD25+
Some CD8+ T cells have T(reg) activity

Question 24

What is the function of IL-10?

Answer 24

Inhibits APC function

Question 25

What is the type of T(H) response influenced by?

Answer 25

Cytokines present when T cells are activated (signal 3)

Question 26

Give the 3 key cytokines involved in naive T cell activation.

Answer 26

IL-12 and IFN-y induce T(H)1 responses
IL-4 induces T(H)2 responses

Question 27

Which cytokine triggers production of T(reg) cells?

Answer 27

TGF-B

Question 28

Which cytokine triggers production of T(FH) cells?

Answer 28

IL-6

Question 29

Which cytokines trigger production of T(H)17 cells?

Answer 29

TGF-B
IL-6

Question 30

Which cytokines trigger production of T(H)1 cells?

Answer 30

IL-2
IFN-y

Question 31

Which cytokines triggers production of T(H)2 cells?

Answer 31

IL-4

Question 32

Describe T(reg) inhibition of T(H)1 cells.

Answer 32

Activation of T(H)2 cells secrete IL-4
IL-4 inhibits proliferation of T(H)1 cells AND
Inhibit development of T(H)17 cells

Question 33

Describe T(reg) inhibition of T(H)2 cells.

Answer 33

Activation of T(H)1 secrete IFN-y
IFN-y inhibits proliferation of T(H)2 cells AND
Inhibits development of T(H)17 cells

Question 34

Why are polarised responses important? (2)

Answer 34

Ensures correct responses for different types of pathogens
Prevents allergy
Control of autoreactivity/pregnancy