B Cell Activation Flashcards

1
Q

What are anergic B cells

A

B cells that have downregulated their bcrs because they recognised soluble ag in bone marrow negative selection

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2
Q

What happens to naive B cells after recognising ag

A

Clonally expand, proliferate and differentiation into plasma cells releasing antibodies or memory cells

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3
Q

Where is ag looked for by B cells

A

In B cell area of lymph node

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4
Q

What are the major roles of antibodies

A

Naturalisation of toxins/pathogens by binding

Opsonisation direct and indirect via fc receptors

Complement activation then Mac

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5
Q

How does opsonisation work

A

Antibodies with attached pathogen easily bound to phagocytic cells via fc receptors recognising antibody fc domain

Also happens via c3b

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6
Q

How many signals needed to activate B cells to differentiate and proliferate in the lymph node

A

Atleast 2

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7
Q

Which bcr are they when they leave bone marrow

A

Igm or igd depending on alternative splicing
Already undergone nhej recombination of vdj
Attached to iga and igb

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8
Q

What is signal 1 and role of iga and igb in this

A

Binding of ag to bcr

Iga and igb itam domains get phosphorylated and this causes strong b signal

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9
Q

What attaches to ag to cause a stronger bcr signal 1

A

Complement molecules like c3d

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10
Q

What do complement molecules attached to ag for stronger signal 1 binding to (augment the signal)

A

Co receptors on B cells (CR2) which can bind eg c3d same time ag binds to bcr

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11
Q

What are the 2 types of ag

A

Thymus independent ti

Thymus dependant (need T cells)

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12
Q

When can ag provide both signals

A

If it binds to bcr and something else on B cell surface Eg TI 1 antigens

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13
Q

What other than bcr can TI1 ag bind to to form both signal

A

Bind to prr like TLR4 via their lps

Allows the proliferation and differentiation of B cells

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14
Q

How are TI 2 ag different to ti 1

A

TI 2 only recognised by bcr, but by MANY because of their repeated epitopes eg polysaccharides

Cross link many Bcrs at once

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15
Q

Which type of response is not developed in children under 5

A

Response to TI 2 cross linking antigens (can’t fight pathogens with these)

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16
Q

Is ti2 signal stronger than augmented signal 1 via cr2 bcr complexes

A

Yes

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17
Q

Why is recognition and signalling via ti2 longer

A

More ag is needed for cross linking bcr to produce signal 2

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18
Q

Why do TI ag not produce any other antibodies but igm and igd

A

No class switching occurs (need T cells)

19
Q

Explain thymus dependant antigen process to signal 2

A
Signal 1 is the ag binding to the bcr 
B cell takes it up via rme 
Processed in endocytic pathway 
Shown on MHC II to CD4 T cells 
T cells cause B cell signal 2, aswell as allow class switching
20
Q

What causes signal 2 to be received in B cells via TD antigen system

A

T cells activated can express cd40L binding to cd40 on B cells and release cytokines

Both cause signal 2

21
Q

How does B cell allow T cell activation for the T cell to then activate B cell via cytokines

A

B cell provides signal 1 and 2 via bcr and cd40 (co stimulatory)

22
Q

Why are td antigens better for B cell activation

A

Because ultimately leads to shm and class switching due to cytokine release of T cells

This causes higher affinity B cells and different types (Ti antigens only produce igm)

23
Q

Why do TD antigens need 2 parts

A

1 part needs to be recognised by bcr and the other (peptide part) needs to be recognised by tcr on MHC II

24
Q

How do conjugate vaccines work to deliver antibodies which class switch via TD antigens

A

TD antigens can be made by attaching proteins (for tcr recognition) to a polysaccharide ag (usually a ti 2). This produces a TD antigen response with T cells and therefore class switching

25
Q

Why are conjugate vaccines given to children under 5

A

Because they don’t respond to TI2 antigens like polysaccharides. By attaching a protein they can go through a TD response and release antibodies for the pathogen with ti 2 ag

26
Q

When cd40 on B cells bind cd40 L in TD antigen response what happens

A

Signal induced AID for somatic hypermutation

And also class switching

27
Q

Why are cytokines released from T cells important for B cells

A

Proliferation / B cell expansion

Also determine type of switching occurs from aid which was induced by cd40 signal

28
Q

What is b and T cell interaction in the lymph node called

A

B/t cell conjugates

29
Q

Where do B cells proliferate and undergo shm after b/t cell conjugates (due to cd40 and cytokines)

A

Germinal centre of B cell follicles in lymph nodes

30
Q

What are B cells which are undergoing proliferation, shm and isotype switching called

A

Centroblasts

31
Q

When centroblasts stop dividing what are they called

A

Centrocytes

32
Q

What is the importance of B cell shm in the germinal centre (aided by cd40 signalling)

A

Hope to find a better affinity bcr for the ag

33
Q

Which apc is present in germinal centre with ag presentation ready to be taken off the highest affinity cell to receive a survival signal

A

Follicular dendritic cells

34
Q

What does the highest affinity B cell which has taken ag off the fdc do next

A

Presents to tfh cells

35
Q

What cytokine causes tfh effector cell production

A

Il 6 (released by T cells aswell as apc in signal 3)

36
Q

Why is tfh favoured in germinal centre over other T cells

A

Ag is presented quicker to these cells to b cells for bcr checking

37
Q

What happens to outcompeted cells or cells which don’t efficiently bind ag with affinity to tfh

A

Apoptosis or goes back to germinal centre dark zone for further shm and proliferation

38
Q

What happens if successful with tfh cell presentation

A

They become plasma and release antibody or become memory cells

39
Q

Other than pick the best centrocyte what do tfh help

A

Release cytokines which cause specific class switches

40
Q

How do FDC have ag bound to them for presentation to centrocytes

A

Via their fc receptors and complement receptors

41
Q

What does CD40 signal prevent in B cells

A

Apoptosis.

Instead aid is induced and causes class switching and shm in germinal centre

42
Q

What would cd40L deficiency on T cells cause

A

Lack of class switching via cd40 interaction lack

Only igm produced

43
Q

How does cytokine specifically choose what class switch occurs via cd40 activated AID

A

Breaks dna close to the c region wanted

Eg il 4 breaks up to c e causing igE switch

44
Q

Can position of ag affect class switch

A

Yes Eg if ag was in mucosal area iga would be class switched to