11 - Adapt 5: B Cell Flashcards

1
Q

What parts of B & T cell development is similar

A
  • rearrangement of gene segments
  • screening processes to avoid self reactivity
  • production of subsets with discrete function
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2
Q

B & T cell development differences - location

A

T cells start in bone marrow then move to thymus for positive & negative selection

B cells start in bone marrow then go through negative selection in bone marrow

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3
Q

Differences between B & T cells - screening processes

A

T cells - positive & negative
B cells - negative

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4
Q

B and T cell development differences - eventual outcomes of antigen receptor stimulation

A

T cells require presentation & differentiate into helper or killer subset
Most B cells require T cell help for activation and secrete antibodies

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5
Q

How many Ig receptors does each B cell have

A

A single type

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6
Q

Once the B cell binds to antigen, what happens

A

Each cell will create a clone of cells bearing the same Ag receptor as the original

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7
Q

Once the B cell undergoes antigen-dependent proliferation, what happens?

A

It differentiates into memory cells or plasma cells which have massive ER & Golgi on diagrams

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8
Q

Plasma B cells produce what

A

Antibodies

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9
Q

2 B cell responses are elicited by distinct Ag types that are

A

T dependent (TD) responses & T independent (TI) responses

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10
Q

T dependent responses depend on

A

Help from helper T cells

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11
Q

T dependent responses are usually generated upon recognition of

A

Protein antigen

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12
Q

T independent responses are generated upon exposure to

A

Multitalented/polymerized Ag

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13
Q

TI-1 Ag binds to

A

B cells through PRRs

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14
Q

TI-2 Ag binds through

A

Cross-link/clustering of large numbers of B cell receptors (BCR)

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15
Q

T dependent B cell responses - B cells bind Ag via BCR which induces

A

Initial activation & proliferation events & proliferation induces formation of germinal centers in lymph nodes/spleen

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16
Q

T dependent responses - once germinal centers are formed, what happens to the Ag?

A

Some Ag is internalized and processed, then presented on cell surface by MHC class 2 molecules

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17
Q

TD B cell responses: interaction with helper T cells provides conditions for

A

Differentiation and memory cell production

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18
Q

How many signals do B cells get (TD response)

A

3

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19
Q

Signal 1 TD B cell response

A

Antigen binding onto B cell

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20
Q

Signal 2 - TD B cell responses

A

Antigen is presented on MHC 2 - T cell receptor sees it and CD4 ligand engages & drives signal back into B cells. T cell then undergoes proliferation & produces cytokines

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21
Q

Signal 3 TD cell response

A

Cytokines travel back into B cell

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22
Q

What causes clustering of B cell receptors upon Ag binding?

A

Ag binding causes oligomerization of Ag bound BCR molecules in the plane of the membrane

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23
Q

What is an integrin

A

Proteins that hold cells together maintained by cytoskeleton

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24
Q

In TD B cell responses, Ag receptor clustering induces

A

Internalization and Ag presentation

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25
Q

TD B cell responses - once signalling begins, BCR-Ag complexes are internalized and the internalized Ag proteins are proceses in the

A

Exogenous pathway

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26
Q

TD B cell response - Ag peptide fragments are presented

A

In MHC 2 molecules on the B cell surface to solicit T cell help

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27
Q

TD B cell response - Ag engagement upregulates

A

B cell CD40 (transmembrane protein) to facilitate B cell - T cell interaction. This part drives signal 2 & 3

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28
Q

After TD antigen activation, a conventional naive B cell turns into

A

Antigen activated GC precursor B cell

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29
Q

Antigen activated GC precursor B cells undergo proliferation and SHM which means

A

SHM = somatic hypermutation

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30
Q

What happens during SHM phase

A

Point mutations in areas of already recombined genes which increase affinity of B cell for antigen

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31
Q

What zone does proliferation and somatic hypermutation happen in

A

Dark zone of medullary cortex of spleen

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32
Q

after TD antigen activation, a conventional naive B cell migrates to

A

A germinal centre, usually medullary cortex of spleen

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33
Q

After proliferation & SHM, what process does the B cell go through

A

Selection

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34
Q

During the selection process what happens

A

T cell help - T cell binds to B cell & antigen presented on MHC2

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35
Q

What zone does selection happen in

A

Light zone

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36
Q

TD B cell response- after T cell binds to B cell, which always happens in light zone, what happens?

A

Differentiation & CSR

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37
Q

TD B cell response - what is differentiation

A

The B cell turning into either a plasmablast or memory B cell precursor cell

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38
Q

TD B cell response - what is CSR

A

Class Switch Recombination which allows for recombining of constant region of heavy chain & converts B cell receptor from IgM to IgA, IgG,,etc

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39
Q

TD B cell response - the type of Ig the receptor changes to depends on the

A

Constant region being replaced during CSR

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40
Q

TD B cell response - somatic hypermutation (SHM) affinity selection occurs within the

A

Germinal center

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41
Q

SHM produces individual point mutations in

A

Ig heavy and light-chain rearrangements

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42
Q

SHM - mutations increase over time and with repeated exposures which is followed by

A

Affinity selection result in increased affinity for Ag over time

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43
Q

Somatic hypermutation - mutational apparatus targets

A

Mutational hot spots are sequence motifs far more likely to be targeted. This prevents mutations in non-Ig areas

44
Q

Ag-induced selection of B cells with higher affinity - this means

A

B cells that can bind, process, and present more Ag to T cells for cytokine assistance survive - B cells are selected for survival of fittest

45
Q

Higher affinity B cells may actually steal Ag from

A

Lower-affinity B cells promoting their own survival signals (the girls are fighting 💅)

46
Q

Class switch recombination occurs within the germinal center after

A

Ag contact

47
Q

During CSR, recombination occurs between

A

Donor and acceptor switch regions which contain targeting sites for AID (an enzyme that induces CSR)

48
Q

Signals that cause CSR:

A

B cells must receive costimulatory signals from CD40 to engage in CSR

49
Q

What determines which Ig isotope is going to be produced?

A

Which cytokine signal from T cells is received

50
Q

Why does the type of Ig produced matter?

A

Clinical relevance! If you have a mucosal pathway, you need Ig that is on mucosal surface so IgA

51
Q

Are most newly generated B cells lost at the end of the primary immune response?

A

Yes

52
Q

After the Ag is cleared, are most of the effector signals required?

A

No

53
Q

What does B cell memory provide

A

A rapid/strong response to secondary infection & high affinity antibody right away

54
Q

IgM-bearing memory B cells generated prior to

A

Somatic hypermutation

55
Q

IgG-bearing memory cells have undergone SHM producing

A

Higher affinity antibody

56
Q

T-independent Ag stimulate antibody production without

A

Need for T cell help

57
Q

How do we know T independent B cell responses exist

A

Nude mice - have a Foxn1 mutation that results in no T cells but they still create antibodies

58
Q

TI-1 Ag - typically

A

Bacterial cell wall components, bind to innate immunity PRRs on B cells

59
Q

T1-2 Ag - typically responds to

A

Polymeric protein Ag and capsular polysaccharides, crosslink many more IgM BCRs

60
Q

There are 2 novel subclasses of B cells that mediate responses to T-independent Ag

A

B-1 B cells & marginal zone B cells

61
Q

B1-B cells are

A

CD5+, primarily in pleural cavities and are 5% of B cell popn in humans/mice, primarily produce IgM

62
Q

B1-B cells produce

A

“Natural” antibodies independent of T cell help that bind a broad spectrum of Ag with low affinity

(Natural means a more broad scale of antigens on surface)

63
Q

Marginal zone B cells must receive

A

Low level signals through BCR for survival

64
Q

Marginal zone B cells respond to

A

Blood borne Ag entering the immune system through the spleen

65
Q

Marginal zone B cells can renew themselves in

A

The periphery & differentiate from T2 B cells in the spleen

66
Q

Shutting down BCR signalling may be required to

A

Stop proliferation when it is no longer needed

67
Q

What shuts down unnecessary BCR signalling?

A

Negative signalling through CD22

68
Q

CD22 bears ITIMs, which do what

A

Act as a brake to the immune system, usually in B cell negative regulation

69
Q

Do ITIMs and ITAMs have the same function

A

No, they are enemies & have opposite functions. ITIMs act as an immune system inhibitor, whereas ITAMs are immune system activators

70
Q

Negative signalling through FcyRIIb (CD32) receptor inhibits

A

B cell activation. It possesses ITIMs similar to those in CD22

71
Q

FcyRIIb process simply explained (sorry i dont get it when its complicated)

A

Once antibody binds to FcyRIIb, that process tells B cells that there is already soluble antibody floating around, and more does not need to be produced

72
Q

Phosphatases are recruited to phosphorylated ITIMs, which

A

Strips phosphates from signalling molecules and inactivates ITIMs

73
Q

CD5 acts as a negative regulator of

A

B cell signalling

74
Q

CD5 is induced on B-2 B cells following

A

BCR-CD40 (this is signal 2) engagement

75
Q

Many CD5+ B cells secrete

A

IL-10

76
Q

B-10 cells act as negative regulators by

A

Secreting IL-10 which shuts down inflammatory responses by T cells and APCs. A small popn of splenic B cells responsible for this

77
Q

What mechanisms increase antibody response efficiency?

A

Somatic hypermutation, affinity selection, and class switching recombination

78
Q

Antibody responses can be generated with and without T cell assistance - true or false ?

A

TRUE !!!! It depends on antigen type and structure

79
Q

Antibody mediates the clearance and destruction of pathogen in a variety of ways - true or false?

A

True! Each Ab isotope has distinct properties and traits that enable it to do so. IgG, IgA, IgM, and IgE all mediate different effector functions

80
Q

Antibody-mediated effector functions

A

Neutralization, agglutination, opsinization, complement activation, and antibody-dependent cell-mediated cytotoxicity

81
Q

Neutralization

A

Protects against viral or bacteria infection or the damaging effects of toxins

82
Q

Agglutination

A

Enhances neutralization and more efficient clearance of pathogens from the body

83
Q

Opsonization

A

Promotes or enhances the engulfment of antigens by phagocytes

84
Q

Complement activation

A

Results in the generation of the membrane attack complex (MAC), creating pores in pathogen membranes and killing the microbe

85
Q

Antibody dependent Cell-mediated Cytotoxicity

A

Activates the killing activity of several types of cytotoxic cells eg natural killer cells

86
Q

What is the first Ab produced in an immune response?

A

IgM

87
Q

Effector functions of IgM

A

-Tends to be lower affinity
- very good at complement fixation leading to MAC complex and target lysis
- also good at forming dense Ab-pathogen complexes that are efficiently engulfed by macrophage

88
Q

IgM size

A

Pentavalent - 10 total Ag binding sites so lots of binding sites for Ag, bug clusters

89
Q

IgG ab functions

A

All variants bind to Fc receptors, which enhances phagocytosis by macrophages

90
Q

IgG has several subclasses, which means what

A

There’s a division of labour between subclasses, as each of them has a speciality when dealing with different types of pathogens (however, we don’t care what the specialities are for this class)

91
Q

IgA is typically found in

A

Major isotype found in secretions - mucus in gut, milk, tears, saliva etc

92
Q

IgA is effective in neutralizing

A

Toxins and pathogens but does NOT fix complement so does NOT drive inflammation

93
Q

IgA has a long half-life in secretions due to

A

Protease-resistant amino acid sequence in Fc region

94
Q

Effector functions in IgE

A

Best known for role in allergy and asthma, but may also play a role in protection against parasitic helminths and Protozoa

95
Q

IgE effects

A

Degranulation of eosinophils/basophils & release of molecules such as histamine to damage large pathogens

96
Q

Fc receptors mediate many

A

Effector functions of Ab

97
Q

Fc receptor signalling involves

A

Multiple FcRs need to be cross-linked to initiate a signal & signal may be positive (enhancing effector function) or negative (inhibiting effector function)

Outcome depends on whether receptor is associated with ITAM/ITIM

98
Q

FcyR

A

Most diverse group of FcRs, four families total & are main mediators of Ab functions in the body

99
Q

Most FcyR are activating receptors (3 activating, 1 inhibiting family). What are functions?

A

Will induce phagocytosis if expressed by macrophages
Will induce degranulation if expressed by cytotoxic cells

100
Q

FceR expressed by

A

Granulocytes - mast cells/basophils & eosinophils

101
Q

FceR triggers a signalling cascade that releases

A

Histamines, proteases, and other inflammatory mediators - most often associated with allergy symptoms

102
Q

FceR expressed by

A

Myeloid cells - monocytes/macrophages, granulocytes, dendritic cells

103
Q

FcaR contributes to pathogen destruction by

A

Triggering ADCC and phagocytosis & stimualates myeloid cells to release inflammatory cytokines and generate superoxide free radicals to help kill internalized pathogens

104
Q

FcuR & Fca/uR recently described. What are they expressed on?

A

FcuR- B, T, & NK cells - regulates cell activation

Fca/uR - B cells, macrophages, and follicular dendritic cells - binds IgM with high affinity (induces phagocytosis) and IgA with intermediate affinity

105
Q

PolyIgR - polymeric immunoglobulin receptor that is expressed by epithelial cells and initiates transport of

A

IgA and IgM from blood to lumen of multiple tracts (GI, Resp, and Repro).

Responsible for carrying Ab into tears and milk and populating gut mucosa with IgA to protect against ingested microbes and toxins