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BC4022 AM > Lecture 1 > Flashcards

Lecture 1 Flashcards

1
Q

What is the purpose of immunosuppression?

A
  • Prevention of organ transplant rejection
  • Treatment of autoimmune diseases
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2
Q

What is autoimmunity?

A

An aberrant response to self-antigen (tolerance to self-antigen has broken down) - requires immunosuppressants to halt immune activation

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3
Q

Why are immunosuppressants used to prevent organ transplant rejection?

A

Because transplantation of a donor graft requires the recipient’s immune system to see the graft as ‘self’ (immunosuppressants used to prevent immune responses to the graft)

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4
Q

Autoimmunity can be classified into either __ or __ disease

A

organ-specific or systemic disease

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5
Q

Examples of systemic autoimmune diseases

A

RA, scleroderma, SLE

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6
Q

Examples of organ-specific autoimmune diseases

A

T1DM, Goodpasture syndrome, MS, Crohn’s disease, psoriasis, Grave’s disease

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7
Q

Psoriasis is caused by…

A

autoreactive T cells against skin-associated antigens

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8
Q

Rheumatoid arthritis is caused by…

A

autoreactive T cells and autoantibodies against antigens localised to joint synovium

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9
Q

Grave’s disease is caused by…

A

autoantibodies against TSH receptor

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10
Q

Hashimoto’s thyroiditis is caused by…

A

autoantibodies and autoreactive T cells against thyroid antigens

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11
Q

SLE is caused by…

A

autoantibodies and autoreactive T cells against DNA, chromatin, proteins and ubiquitous ribonucleoprotein antigens

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12
Q

Sjogren’s syndrome is caused by…

A

autoantibodies and autoreactive T cells against ribonucleoprotein antigens

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13
Q

Crohn’s disease is caused by…

A

autoreactive T cells against intestinal flora antigens

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14
Q

Multiple sclerosis is caused by…

A

autoreactive T cells against brain and spinal cord antigens

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15
Q

Type 1 diabetes is caused by…

A

autoreactive T cells against pancreatic islet cell antigens

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16
Q

What is central tolerance?

A

How the immune system learns to discriminate self from non-self (naive lymphocytes are essentially screened via positive and negative selection)

17
Q

What is peripheral tolerance?

A

Preventing over-reactivity of the immune system

18
Q

Heavy chains are composed of which regions?

A

V, D and J

19
Q

Light chains are composed of which regions?

A

V and J

20
Q

What causes junctional diversity?

A

Recombinational inaccuracies that cause differences in the amino acid sequence

21
Q

What is insertional diversity a result of?

A

Terminal deoxynucleotide transferase activity (this enzyme adds nucleotides randomly at V-D and D-J junctions)

22
Q

Decreased __ levels ensure allelic exclusion

A

RAG

23
Q

B cells are negatively selected if…

A

they have a high affinity for self-antigen, or do not have a functional BCR to recognise its specific Ag (central tolerance)

24
Q

Which TCR domain is nearest the cell membrane: constant or variable?

A

constant

25
Q

What happens to thymocytes that do not successfully rearrange their β chain genes?

A

They die by apoptosis as they can not express the receptor

26
Q

Successful synthesis of a rearranged β chain allows the production of a pre-T cell receptor that…

A

triggers cell proliferation and blocks further β chain gene rearrangement

27
Q

Positive selection of T cells

A

Rescue DP cells from apoptosis, mature into SP (CD4+ or CD8+) that must recognise self-MHC (depends on engagement of CD4 with MHC II, and CD8 with MHC I)

28
Q

What gives the TCR an intrinsic specificity for MHC molecules?

A

CDR1 & CDR2 loops of both α and β chains of TCR

29
Q

Positive selection of T cells is mediated by __

A

cortical thymic epithelial cells (cTECs)

30
Q

What transcription factor regulates negative selection of T cells?

A

AIRE (autoimmune regulatory element)

31
Q

What cells express AIRE?

A

medullary thymic epithelial cells (mTECs)

32
Q

What happens when AIRE is absent?

A

T cells reactive to tissue-specific antigens mature and leave the thymus

33
Q

Peripheral tolerance aims to eliminate autoreactive T cells. What is the exception?

A

Some self-reactive T cells that are CD4+ will escape the thymus following central tolerance - regulatory T cells (FoxP3+, CD25hi)

34
Q

How are Tregs important for peripheral tolerance and preventing autoimmunity?

A

Tregs are CD25+. CD25 is α chain of IL-2R. Tregs bind to any circulating IL-2, which prevents other T cells from utilising it and becoming autoreactive.

35
Q

Tregs compete with Teff cells for…

A

IL-2 and MHC

36
Q

Difference between natural Tregs and induced Tregs?

A

nTregs (from thymus) develop in response to stimulation by self-Ags
iTregs are driven by TGF-β

37
Q

‘Immunologically privileged’ sites

A

Brain, eye, testis, uterus

38
Q

What immunosuppressive cytokine is produced in these immunologically privileged sites?

A

TGF-β

BC4022 AM (8 decks)

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