Self, Non-Self Discrimination Flashcards Preview

MD1 Neuroscience > Self, Non-Self Discrimination > Flashcards

Flashcards in Self, Non-Self Discrimination Deck (56):
1

What is the site for central tolerance?

Thymus for T cells
Bone marrow for B cells

2

What is the site for peripheral tolerance?

Secondary lymphoid organs
Peripheral tissues

3

What are the mechanisms that induce tolerance?

Deletion
Anergy
Ignorance
Regulation

4

Which uncommitted progenitor gives rise to the development of B cells?

Common lymphoid progenitor (CLP)

5

Where do B cells develop?

Bone marrow
Also in neonatal spleen and liver

6

When does the generation of new B cells end?

Continues through life

7

What is the configuration of the BCR in a CLP?

In germline configuration

8

What happens in BCR development during the early pro-B cell stage?

DJ heavy chain rearrangement

9

How are genes chosen to make a BCR/TCR?

Enzymes come in and randomly chop DNA
Recombined via RAG

10

What happens in BCR development during the pre-B cell stage?

Heavy mu chain produced by combining V, D, and J segments

11

How many chances does a pre-B cell get to make a functional heavy mu chain?

2 because of 2 alleles

12

What happens to a pre-B cell that cannot make a functional heavy mu chain?

Die

13

How is a pre-B cell saved from death?

Heavy mu chain tested for functionality by pairing with surrogate chains > pre-BCR
Functional pre-BCR signalling engaged by dimerisation/oligomerisation - no Ag needed

14

What is the significance of pre-BCR testing?

Important checkpoint for transition of pro-B cell to pre-B cell

15

What enzyme is needed for pre-BCR signalling, and what disease occurs when this enzyme is not present?

Bruton's tyrosine kinase
Disease: Bruton's X-linked agammaglobulinaemia

16

How many chances does an immature B cell get to make a functional light chain?

4 because of 2 loci: kappa and lambda - on 2 alleles

17

Do BCRs on a B cell express both a kappa and lambda light chain?

No, only one type is used by a single B cell = isotypic exclusion

18

What is the transition between a small pre-B cell to an immature B cell?

Light chain and heavy chain forming IgM

19

What is the default response of lymphocytes during development?

To die - must be actively saved from apoptosis via signals

20

How does central tolerance of B cells work?

No self reaction in bone marrow > migrate to periphery > mature B cell
Multivalent self molecule binding > clonal deletion/receptor editing > apoptosis/generation of non-autoreactive mature B cell
Soluble self molecule binding (smaller signal) > migrates to periphery > anergic B cell
Low-affinity non-cross-linking self molecule binding > migrates to periphery > mature B cell (clonally ignorant)

21

Are there any self-reactive B cells in the periphery?

Yes, a little bit of self-reactivity goes through because of low signal or low affinity binding

22

Why is an anergic state of lymphocytes maintained in the periphery?

In case receptor strongly recognises foreign molecule

23

Is B cell central tolerance of equal stringency as T cell central tolerance?

No, B cell tolerance less stringent

24

By when does the thymus fully develop?

Fully developed by birth

25

When does the thymus start to involute?

During puberty

26

What effect does DiGeorge syndrome have on the thymus?

Thymic aplasia because 3rd and 4th pharyngeal arches don't develop properly

27

Does T cell development continue throughout life?

Yes, but it sharply drops during puberty when thymus starts to involute

28

What are the three main fates of thymocytes entering the thymus?

Alpha/beta T cells
Gamma/delta T cells
Invariant NKT cells

29

What are alpha/beta T cells?

Conventional T cells
Further differentiate into CD4 helper T cells and CD8 killer T cells

30

What are gamma/delta T cells?

Primarily located in epithelial and mucosal sites
Don't have CD4 and CD8
Don't undergo positive and negative selection
Produced earlier in embryonic development than conventional T cells

31

What happens to double negative (DN)1 thymocytes?

TCR genes still in germline configuration

32

What happens to DN2 thymocytes?

Become responsive to IL-2
Beta chain rearrangement starts

33

What happens to DN3/4 thymocytes?

Rearrangement of beta chain continues
Pre-TCR testing determines whether cell expresses CD4 and CD8

34

What happens to double positive (DP) thymocytes?

Rearrangement starts at alpha chain locus
Single beta chain can associate with many different alpha chains

35

How many times can a thymocyte try and make a functional beta chain?

2 times because of 2 alleles

36

What is positive selection?

Ensures thymocytes can recognise and bind to MHC
Determines whether or not cell will be CD4 or CD8

37

Which cells do thymocytes bind to in negative selection?

Professional antigen presenting cells expressing self-Ag

38

What is negative selection?

Thymocytes that recognise self-Ag strongly are deleted

39

What does death by neglect involve in the thymus?

Thymocytes bind too weakly to MHC so they die because of too weak a signal

40

What is the role of Tregs in peripheral tolerance?

Have intermediate self-reactivity
Suppress function of other T cells

41

What do Tregs express?

CD25
Foxp3

42

What do Tregs secrete?

IL-10
TGF-beta

43

What is the defect in immunodysregulation polyendocrinopathy X-linked syndrome (IPEX)?

Foxp3

44

What happens to mice who don't express Foxp3, and what does this illustrate?

Develop autoimmune diseases
Removing just one peripheral tolerance mechanism causes autoimmunity > peripheral tolerance important

45

What are the symptoms of Grave's disease?

Tachycardia
Loss of weight
Heat intolerance
Exophthalmos = abnormal protrusion of eyeballs
Sleep disturbances
Hot flushes
Agitated nervousness

46

How is Grave's disease mediated?

Autoimmune Abs produced against TSH receptor on thyroid gland > stimulates thyroid to produce hormone
Thyroid hormones shut down TSH production but have no effect on autoAb production > excessive thyroid production > hyperthyroidism

47

How is myasthenia gravis mediated?

Ab blocks Ach receptor at NMJ

48

What are the symptoms of myasthenia gravis?

Progressive weakness following diurnal pattern

49

Why does decreasing the amount of Ach activity at the NMJ have such profound effects?

Small minute changes in fine control muscles have large effects
Eg: levator palpebrae superioris > person can't keep eye open when looking up after a while

50

What is the treatment in severe cases of myasthenia gravis?

Can elute Abs from blood but it's not Ag specific
Danger of becoming vulnerable to other infections and diseases

51

What is multiple sclerosis (MS)?

Loss of myelin sheath through autoimmune process
Debilitates nerve conduction
Can affect any part of CNS > people present with variety of symptoms

52

Which immune cell is believed to be implicated in MS?

Th17 cells

53

What is one possible treatment in development for MS?

Trying to trap autoreactive T cells in periphery

54

What is molecular mimicry?

Pathogen derived Ags resemble self tissues

55

What are two examples of where molecular mimicry occurs?

Rheumatic feveer
Guillain-Barre syndrome

56

What are some possible environmental risk factors that cause tolerance failures?

Industrialisation
Small family sie
Affluent, urban homes
Stable intestinal microflora
High antibiotic use
Low/absent helminth burden
Good sanitation > low orofaecal burden

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