Bursa/Bone Marrow-Derived Cells (B Cells) Flashcards

1
Q

How many B cells are produced daily? (in humans since we don’t do animals in this fuck-tarded class)

A

a billion (1.0*10^9)

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2
Q

T or F?

B cell lymphopoiesis occurs throughout the lifetime of all animals.

A

FALSE because it’s not all animals (invertabrates don’t have B and T cells).

It is TRUE for mammals though…
Amount produced decreases with age, hence why old farts are eventually immuno-suppressed.

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3
Q

What percentage of recirculating lymphocytes do B cells constitute?

A

10%-25%

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4
Q

How long do mature B cells survive without encountering their antigen?

A

A few days or weeks [short-lived cells].

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5
Q

Which B-cells are long-lived cells?

A

Memory cells…. hence being a memory.

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6
Q

The B cell expresses up to ____________ BCRs.

A

500,000 BCRs

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7
Q

True or False. All the BCRs on a single B cell have the same constant region.

A

FALSE. THey have the same variable region.

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8
Q

What are the two roles of the BCR?

A

1) Delivery of activating signal

2) Triggering endocytosis leading to processing for presentation to T-cells

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9
Q

The molecules that transduce the activation signal from an activated BCR.

A

CD79 molecules.

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10
Q

The molecules required for the surface expression of IgM and IgD.

A

CD79 molecules.

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11
Q

True or False. The rearrangement of Ig heavy chain (IgH) gene must occur before that of the Ig light chain (IgL).

A

TRUE. If IgH fucks up the IgL will not take place.

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12
Q

What chromosome are IgH genes on?

A

Chromosome 14 –> 200 Vh; 30 Dh; 6 Jh; 9 Ch; (h means heavy)

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13
Q

What chromosome are the IgL KAPPA genes on?

A

Chromosome 2 –> 100 Vk; 5 Jk; 1 Ck; (k means Kappa)

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14
Q

Which light chain arrangement occurs first? If that does not work then what takes its place?

A

KAPPA comes first and if that doesn’t work LAMBDA.

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15
Q

What chromosome are the IgL LAMDA genes on?

A

Chromosome 22–> 100 Vl; 6Jl; 4Cl; (l means LAMBDA)

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16
Q

True or False. One B cell will react with more than one antigenic determinant and will produce multiple antibodies, one for each antigen.

A

FALSE. They interact with ONE antigen and produce antibodies ONLY FOR THAT ONE.

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17
Q

True or False. This is very important for your clinical practice later in life.

A

FALSE. This is all a crock of shit and a waste of time.

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18
Q

How many BCRs does an individual possess?

A

1*10^11 BCRs –> 100 billion

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19
Q

What three mechanisms account for BCR diversity?

A

1) Somatic recombination of multiple germline gene segments
2) Junctional diversity: Base deletion; P-nucleotide and N- nucleotide additions
N-nucleotides: TdT is expressed by PRO-Bcell ONLY DURING THE STAGE OF IgH rearrangement.
Therefore, only IgH shows N-region Diversity.
3) Combining of identical IgH chains with different IgL chains. (Kappa and Lambda)

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20
Q

Stromal cells interact direclty with __(1)_____ and ___(2)____, providing them with cell-bound __(3)______

A

1) PRO- bcells
2) PRE- Bcells
3) survival signals

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21
Q

Cytokine supporting B-cell development.

A

IL-7

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22
Q

PRO- Bcell expresses ____ and ____ signaling molecules

A

CD79 – Ig-alpha and Ig-beta

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23
Q

True or False. PRO-Bcell express RAG enzymes and TdT?

A

TRUE.

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24
Q

True of False. Pro-Bcell Igµ gene arrangment occurs?

A

TRUE. Dh to Jh rearrangement followed by Vh to DhJh rearragement.
–> Once the Vh to DhJh occurs its a PRE-Bcell

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25
Q

True or False. PRE-Bcell express RAG enzymes and TdT?

A

FALSE. TdT activity has stopped but RAG enzymes are still getting it on.

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26
Q

What does a PRE-B Cell receptor consist of?

A

IgM Heavy chain
Surrogate Light chain
Ig-alpha and Ig-ß molecules

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27
Q

Can a PRE-B cell continue to develop without PRE-BCRs?

A

No.

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28
Q

What does the surrogate light chain consist of?

A

Two invariant proteins:

VpreB & lambda-5

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29
Q

What 4 things does the PRE-BCR do?

A

1) survival and proliferation of pre-B cell
it signals that it’s good-to-go and prevents apoptosis

2) inhibition of Vh to DhJh rearrangment of the heavy chain allele
its says stop that, we’re moving on to bigger and better parts of development

3) terminations of the surrogate light chain transcription
again, it says we’re moving on and don’t need this crap anymore

4) initiation of light chain[kappa, then if not successful lambda] gene rearrangement
it says lets move the fuck on

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30
Q

When does a PRE-B Cell become an IMMATURE B cell?

A

Once its BCRs become IgM with heavy chain AND light chain (not surrogate light chain). It will shed any left over PRE-BCRs and become the IMMATURE B Cell.

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31
Q

What happens if a BCR expresses high affinity for self antigen in the bone marrow?

A

One of three things:

1) It dies by apoptosis
2) Becomes ANERGIC
3) Receptor editing

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32
Q

What is receptor editing?

A

When the BCR expresses too much affinity and instead of dying it tries to correct the mistake.
RAG enzymes are RE-activated and LIGHT chain is acted upon.

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33
Q

True or False. TCRs and BCRs undergo receptor editing?

A

FALSE MOTHER FUCKER! Only BCRs do.

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34
Q

Where do IMMATURE B cells go?

A

to the SPLEEN for further development

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35
Q

Where do B Cells mature?

A

in the SPLEEN!

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36
Q

What makes a MATURE B Cell so mature?

A

the expression of IgM and IgD on their cell surface

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37
Q

True or False. A MATURE B Cell is the same as NAIVE B Cell?

A

True…. bitch.

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38
Q

True or False. The IgM and IgD express the same antigen specificity?

A

TRUE. They use the same VDJ exon and have identical light chains.

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39
Q

What makes up the B cell coreceptor complex?

A

CR2 (CD21)
CD19
CD81

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40
Q

What complement component does CR2 bind?

A

C3d.

C3d is a product of C3b being cleaved by Factor I once Factor H binds to it.

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41
Q

How does C3d bind to a B cell?

A

C3d picks up/binds antigen then C3d binds to CR2 while the antigen binds to the BCR

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42
Q

What results from C3d binding to CR2?

A

Phosphorylation of CD19.

43
Q

What happens when CD19 is phosphorylated?

A

It augments the signal coming from the BCR making it MUCH easier for a BCR to become activated as well as increasing/enhancing the response (antibody production)

44
Q

How much lower antigen level is needed when the coreceptor is activated at the SAME TIME as the BCR?

A

100-1000 Fold less. BCR activation is much easier.

45
Q

Where do Helper T-cell/B-cell interactions take place?

A

at the junction of the cortext and paracortex

46
Q

Where do B-Cells go once they are activated?

A

They migrate back into the PRIMARY follicles.

47
Q

Antigen recognition by B cells does:

A

1) enhances expression of co-stimulators that increase the ability for the B-cell to activate Helper T-cell
2) express receptors for cytokines that T helpers put out
3) change chemokine Receptors so they can follow chemokines more efficiently (this allows them to go where they are needed)

48
Q

True or False. Once activated the B cell will continue to present multiple antigenic epitopes to multiple T-cells

A

FALSE. Once ACTIVATED the cell will be VERY specific and only produce antibodies specific to the epitope on the organism recognized by the BCR variable region

49
Q

True or False. CD40L is on the the APC.

A

FALSE. CD40L is on the T-cell.

CD40 is on APC.

50
Q

Net results of B cell activation by T-helper?

A

clonal expansion
isotype switching
affinity maturation
formation of plasma cells & memory cells

pretty much fuckin everything.

51
Q

Interleukins that contribute to B cell proliferation.

A

IL-2
IL-4
IL-5
and many more but he doesn’t mention them in this bullet point since he’s a jackass.

52
Q

TRUE or FALSE? IL-6 is important in Bcell development?

A

TRUE. VERY important. but i won’t tell you why on this slide.

53
Q

What does IL-6 do during B cell development?

A

Key role in differentiation of progeny B cells into ANTIBODY-SECRETING PLASMA CELLS.

54
Q

Name the cytokines that are involved in antibody differentation.

A

IL-2,4,5,6
IFN-gamma
TGF-ß

55
Q

What is the effector portion of an immunoglobulin (antibody)?

A

Fc region. Heavy chain C region to be exact

56
Q

What is isotype switching.

A

Heavy chain switching such that antigenic specificity is conserved but the effector function changes.

57
Q

True or False. Isotype switching is a random process in which the body gets lucky and produces the antibody it needs.

A

If you couldn’t tell by the wording of the question, its FALSE.
Isotype switching is regulated by cytokines.

58
Q

True or False. Initially most daughter B-cells express IgA BCRs

A

False. they start with IgM

59
Q

True or False. The average on the coming Immuno exam will be 100%.

A

False. Only when pigs shit daisies and Oprah admits she’s white.

60
Q

What page should you look at to see all the isotypes.

A

Page 99.

61
Q

The cytokine(s) for causing an Activated B cell to proliferate.

A

IL-2
IL-4
IL-5

62
Q

The cytokine(s) for causing a Proliferating B Cell to differentiate to IgG isotype.

A

IFN-gamma

63
Q

The cytokine(s) for causing a Proliferating B Cell to differentiate to IgA isotype.

A

TGF-ß

64
Q

The cytokine(s) for causing a Proliferating B Cell to differentiate to IgE isotype.

A

IL-4

65
Q

The cytokine(s) for causing a Proliferating B Cell to differentiate to IgM isotype.

A

IL-2
IL-4
IL-5
So no change in cytokine signaling from an activated B-cell to proliferating B-cell will result in IgM antibodies.

66
Q

Affinity Maturation

A

the process that results in an increase in the affinity of specific antibody for its antigen and is the result of somatic mutations of the previously rearranged Ig V(D)J genes, followed by selective survival of the B cells producing antibodies with the HIGHEST AFFINITY.

In short, molecular method of choosing the smartest antibodies.

67
Q

True or False. BCRs can isotype switch to IgD because they are very important antibodies.

A

False. They can neither switch to them nor are IgDs important antibodies.

68
Q

Does affiinity maturation take place in the Cell-Mediated immune response?

A

False. Only in the Humoral response.
This should make sense since antibodies are what make up the humoral response.
The cell-mediated response occurs with intracellular shit.

69
Q

What is imperative for release of cytokines that regulate somatic mutations with regards to BCRs?

A

CD40 (apc/B-cell) and CD40L (t-cell)

70
Q

What selects for high-affinity B cells?

A

Follicular Dendritic Cells

71
Q

True or False. FDCs are of bone marrow origin that are found in the lymph noes, spleen and MALT.

A

FALSE. they are not of bone marrow origin. However, where the fuck do they come from? If you know this please do share.

72
Q

True or False. FDCs are nonphagocytic cells and DO NOT present antigens to helper T-cells.

A

TRUE.

73
Q

How do NONDIVIDING B cells (meaning they are daughter cells that are the result of division from proliferation) in the germinal center survive programmed cell death?

A

by binding antigen. this is a perfect example of the BCR saving the B-cell from apoptosis.

74
Q

The net result of the selection process for antibody producing B cells.

A

Memory B cells with high antigen specificity.

Plasma cells with higher affinity for antigen than before the selection process.

75
Q

The source of antigens for the developing, differentiating, isotype switching B-cells

A

FDCs in the germinal centers

76
Q

Definition of plasma cells.

A

Terminally differentiated B cells

77
Q

TRUE or FALSE. Plasma Cells are long-lived memory cells that live up to 150 years.

A

Erroneous on all accounts. FALSE. Memory cells are different. Plasma cells are Short-lived.
3-6 days
And apparently some migrate to Bone Marrow and can survive for years, but only if they’re in the Bone Marrow.

78
Q

True or False. Plasma cells are larger than naive B cells.

A

TRUE. B and T cells are small white blood cells.

79
Q

What does the plasma cell nucleus look like?

A

a Spoke-wheel

80
Q

How many plasma cells are found in circulation?

A

0.1% that’s a very small amount

81
Q

Where are most plasma cells found?

A

Extrafollicular sites in peripheral lymphoid organs and at inflammatory sites.
Red pulp in spleen
Medulla in lymph nodes
Lamina propria of MALT (respiratory and intestinal)
Sinusoids of bone marrow

82
Q

How many antibodies per second can a plasma cell make?

A

2000/second

83
Q

What do plasma cells lack that allow them to secrete immunoglobulins?

A

Transmembrane proteins. once they are moved to the membrane, instead of sticking around as BCRs in B-cells, they float away into the ECF.

84
Q

True or False. the Specificity is the exact same in secreted antibodies as it is to membrane BCRs.

A

TRUE. BCRs are essentially membrane bound antibodies.

85
Q

What the fuck is a Russell Body?

A

the accumulation of antibodies within a plasma cell.

86
Q

Define myeloma.

A

Plasma cell tumor.

87
Q

Why do we care about myelomas? (aside from the potential harm they can cause)

A

Monoclonal antibodies. Myelomas live forever and produce the SAME antibody forever. This has profound impact on providing antibodies for immunodeficient animals. The proteins they produce are called M-proteins.

88
Q

What is Ligh-Chain Diesease?

A

a Myeloma which makes only light-chains. Light chains are TOXIC to renal tubular cells and cause RENAL FAILURE.

89
Q

What is a Bence Jones protein?

A

proteins that precipitate (solidify) at 50˚-60˚C and redissolve at 90˚-100˚C…. weird right?

90
Q

True or False. Memory B cells are larger than its parent B-cell.

A

FALSE. they are the EXACT same size.

91
Q

What protein protects the B-cell from apoptosis?

A

Bcl-2 protein

92
Q

Where’s a good place to see the difference between Naive and Memory B cells?

A

Pg. 103

93
Q

What can provoke immunoglobulin production in the absence of T-cells?

A

T-independent antigens.

94
Q

What are some T-independent antigens?

A

Polysaccharides
Glycolipids
Nucleic Acids

95
Q

Why can T-independent antigens be just that, helper T-cell independent?

A

They are multivalent (possessing many of the same epitopes) allowing cross-linking of BCRs at one time.

96
Q

What is the response to T-ind antigens?

A

Mainly IgM antibodies of low affinity.

97
Q

Where’s a good place to see the difference between T-dependent and T-independent antigens?

A

pg. 103

98
Q

Clonal Selection Theory

A

Lymphoid stem cells differentiate randomly to produce clones

Antigen binding triggers the to proliferate

Specificity of antibodies is IDENTICAL to its RECEPTOR (that recognized the antigen in the first place)

Lymphocytes with receptors for Self-Peptides are deleted

99
Q

What is a lymphocyte mitogen?

A

an agent acpable of inducing cell division in high percentage of T or B cells.
it can activate both BCRs and TCRs as well as many clones of T or B cells irrespecitve of their antigen specificity
POLYCLONAL ACTIVATORS

100
Q

Sugar binding mitogens

A

Lectins

101
Q

B cell mitogens

A

LPS and Protein A

102
Q

T cell mitogens

A
PHA (phytohemagglutinin) red kidney bean
Concanavalin A (Con A, Jack bean)
103
Q

T-cell AND B-cell

A

Pokeweed (PWM if you needed an abbreviation)

104
Q

Where’s a great place to see the differences between T-cells and B-cells?

A

Pg. 105