8.2 B Cell development and the functions of antibodies Flashcards

1
Q

Name 2 B cell genetic defects

A

XLA - X linked agammaglobinemia

Hyper IgM Syndrome

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2
Q

What happens in XLA?

A

mutations in BTK (bruton tyrosine kinase) gene, depleting B cells and hence there are no antibodies

more susceptible to bacterial infections

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3
Q

How is XLA treated?

A

IV Ig

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4
Q

What happens in Hyper IgM Syndrome?

A

mutations in CD40 ligand gene
70% X-linked
low levels of IgG, IgA, and IgE

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5
Q

How is Hyper IgM syndrome treated?

A

IV Ig

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6
Q

What are the 4 main stages of a B cell life cycle?

A

Proliferation
Screening
Activation
Differentiation

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7
Q

What happens in the proliferation phase of B cell life cycles?

A

B cell precursor rearranges immunoglobulin genes, generating receptors in the bone marrow

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8
Q

What happens in the screening phase of B cell like cycles?

A

immature B cell bound to the self cell-surface antigen is removed from the repertoire (negative selection)

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9
Q

What happens in the activation phase of B cell screening?

A

the mature B cells migrate to the peripheral lymphoid organs and are activated when bound to foreign antigen

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10
Q

How do H-chains undergo rearrangement?

A

D and J regions

then V rearrangement

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11
Q

How is the success of the H-chain rearrangement checked?

A

if it can be transiently expressed on the B cell surface in a non-functional manner, it is okey dokey

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12
Q

how is rearrangement of L-chains checked?

A

expressed as IgM on the B cell surface

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13
Q

What is the hallmark of a mature B cell?

A

co-expression of IgM and IgD

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14
Q

What are the 2 light chains to choose from?

A

kappa / lambda

the 2 kappa genes are used first and if this doesn’t work we then try lambda

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15
Q

What is the ratio of kappa to lambda light chains?

A

2-3 : 1

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16
Q

What does allelic exclusion ensure?

A

one B cell produces antibody of one specificity

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17
Q

How can we stop further recombination?

A

preventing Rag expression / function

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18
Q

What are the 2 ways we can prevent the survival of B cells recognizing self?

A

multivalent surface molecules

soluble self molecules

19
Q

What are the characteristics of T-independent antibody response?

A

IgM, some IgG

Low affinity Ab

20
Q

What are the characteristics of T-dependent antibody response?

A

IgM, IgG, IgA, IgE
high affinity Ab
memory
long-lived

21
Q

Where is IgM found?

A

Naive B cells

serum

22
Q

What does IgM do?

A

classical pathway of complement activation

23
Q

Where is IgD found?

A

Naive B cells

24
Q

Where is IgG (1-4) found?

A

memory B cells

serum

25
Q

What do IgG (1 + 3) do?

A

classical pathway of complement activation

placental transfer

26
Q

Where is IgE found?

A

mast cells

27
Q

What does IgE do?

A

high affinity binding to mast cells and basophils

28
Q

Where are IgA (1,2) found?

A

mucosa

serum

29
Q

What is the stucture of IgM?

A

pentamer linked by a J chain

30
Q

How many epitopes can IgM bind?

A

10

31
Q

What is the structure of IgA?

A

Dimer linked by a J chain

32
Q

How many epitopes can IgA bind?

A

4

33
Q

Where is IgA normally transported?

What is required for this?

A

epithelia

secretory components

34
Q

How can epitopes be structured?

A

linear

conformational

35
Q

Name 3 ways antibodies help eliminate pathogens

A

Neutralization
Opsonization
Complement activation

36
Q

What happens in neutralization?

A

bind to toxins

complex ingested by macrophage

37
Q

What is different about complement activation?

A

can enhance neutralisation and opsonisation

leads to direct lysis of bacteria

38
Q

What are FcgammaR?

A

allow antibody-coated antigens to be recognised by cells

there are lots of these, some result in activation and some in inhibition

39
Q

What is ADCC?

A

Antibody-dependent cellular toxicity

an antibody can bind to pathogenic antigens on host membranes

this causes host cell apoptosis

40
Q

What is required to kill a bacteria without LPS?

A

complement is enough!

41
Q

What is required to kill a bacteria with LPS?

A

complement + antibody

42
Q

What mechanism has staphylococcus developed to ward off host defence?

A

is able to interfere with every step of the complement cascade

43
Q

What are the 3 main functions of monoclonal antibodies?

A

neutralise / block targets
label cells for killing
activate / inhibit FcR