CMB2004/L07 Acquired Immune Response Flashcards

1
Q

Why is immunological tolerance needed? (3)

A

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

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2
Q

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

A

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)

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3
Q

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

A

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

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4
Q

Describe autoimmune regulator protein (AIRE).

A

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)

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5
Q

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

A

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)

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6
Q

Describe B cell tolerance.

A

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

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7
Q

What is an anergic B cell?

A

B cells that bind self-antigen

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8
Q

Describe B cell tolerance via anergy.

A

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

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9
Q

Describe how T cells can become anergic.

A

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

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10
Q

Describe immunological ignorance.

A

Many Ag not presented at sufficient levels to activate T cells

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11
Q

Describe privileged sites.

A

Ag sequestered from immune system (suppressive cytokines also prevalent)

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12
Q

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

A

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

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13
Q

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

A

Suppresses immune response

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14
Q

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

A

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

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15
Q

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

A

IL-10
TGF-B

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16
Q

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

A

B cells (B(reg/10))

17
Q

Give 3 reasons for regulation of immune response.

A

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

18
Q

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

A

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

19
Q

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

A

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

20
Q

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

A

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

21
Q

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

A

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

22
Q

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

A

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

23
Q

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

A

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

24
Q

What is the function of IL-10?

A

Inhibits APC function

25
What is the type of T(H) response influenced by?
Cytokines present when T cells are activated (signal 3)
26
Give the 3 key cytokines involved in naive T cell activation.
IL-12 and IFN-y induce T(H)1 responses IL-4 induces T(H)2 responses
27
Which cytokine triggers production of T(reg) cells?
TGF-B
28
Which cytokine triggers production of T(FH) cells?
IL-6
29
Which cytokines trigger production of T(H)17 cells?
TGF-B IL-6
30
Which cytokines trigger production of T(H)1 cells?
IL-12 IFN-y
31
Which cytokines triggers production of T(H)2 cells?
IL-4
32
Describe T(reg) inhibition of T(H)1 cells.
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
33
Describe T(reg) inhibition of T(H)2 cells.
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
34
Why are polarised responses important? (2)
Ensures correct responses for different types of pathogens Prevents allergy Control of autoreactivity/pregnancy