Immuno 9: B cell Mediated Immunity Flashcards

1
Q

What is the major contribution of B cells to the immune response?

A

Antibody production

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2
Q

Do antibodies have any toxic or destructive properties in-and-of themselves?

A

No. Abs serve as a bridge that encourages effector cells and molecules (phagocytes, NK cells, and complement proteins) to participate in the adaptive immune response.

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3
Q

__________ are retained in the form of memory cells that typically provide long-lasting immunity to re-infection.

A

Acquired B cell responses

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4
Q

Once a B cell has received its 2nd signal of activation from a ____ cell, the B cell ________ and _________, and the final effector cells that are produced are ________ cells and ________cells.

A

T cell; proliferates and differentiates; plasma cells (secrete antibodies) and memory cells (a clonally expanded pop. of daughter B cells that occupy secondary lymphoid tissues of the body for long periods of time)

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5
Q

The 1st signal of B cell activation is crosslinking of the B cell receptor by binding of the immunoglobulin component of that BCR with ________________.

A

Its cognate antigen

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6
Q

T/F: Sufficient signalling will occur with a single BCR cross-link to an antigen.

A

False. Sufficient signalling will not occur unless multiple copies of the BCR are cross-linked with antigen.

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7
Q

Another component of the B cell receptor is responsible for ________________________ so that the cell will know that the BCR has encountered its cognate antigenic determinant.

A

transmitting signals to the nucleus of the cell

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8
Q

The signal transduction unit of the BCR is known as the:

A

Ig-alpha/Ig-beta complex

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9
Q

List two more signalling pathways that can increase the intensity of the 1st activation signal that a B cell receives.

A

1) The B cell co-receptor, complement receptor 2, or CR2, has affinity for C3b. Upon binding C3b, additional signals are transmitted.
2) CD19 is a surface marker of B cells that is also part of the B cell receptor complex. CD19 amplifies the signals that are transmitted via the Iga/IgB complex.

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10
Q

Non-protein antigens can elicit a partial B cell activation even without the help of T cells. Explain how this occurs.

A

The antigen cross-links multiple BCRs on the surface of the B cell, in addition to another determinant of the antigen that binds to a PRR on the B cell surface (visualize one non-protein molecule binding to 3 receptors on a B cell surface). The combination of BCR and PRR engagement is sufficient to partially activate the B cell.

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11
Q

Do B cells that are activated by T-cell independent antigens initiate germinal center reaction and result in immunological memory?

A

No.

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12
Q

Briefly describe the two types of T-independent antigens.

A

1) T-independent 1 (TI-1) antigens. This type of TI antigen has PAMPs and can crosslink BCRs. Called mitogens.
2) T-independent 2 (TI-2) antigens can cause B cell activation by heavily crosslinking BCRs on the surface of the cell. Highly repetitive structures.

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13
Q

What are B1 B cells?

A

A subset of B cells that have a restricted BCR repertoire that accounts for most of the TI-2 type of immune responses.

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14
Q

A high concentration of mitogens (TI-1) will generate a poly or monoclonal Ab response?

A

polyclonal Abs released

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15
Q

A low concentration of mitogens (TI-1) will generate a poly or monoclonal Ab response?

A

monoclonal Abs released

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16
Q

TI-1 activation results in production of Abs that are almost all of the _______ isotype.

A

IgM. Some programmed class switching to IgG, but because no germinal center rxn, no other class switching will occur.

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17
Q

Will there be any immunological memory generated by TI-1 or TI-2 activation?

A

No. Remember, T cell activation is required for immunological memory generation.

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18
Q

In the absence of cognate T cells or in the absence of a thymus, will there be an antibody response made in response to a T DEPENDENT antigen?

A

No. But because no T cell help is required for Ab responses against T-INDEPENDENT antigens, both TI-1 and TI-2 antigens will elicit a response (although it will only contain IgM and possibly some IgG Abs).

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19
Q

Infants can respond to T-dependent antigens and TI-1 antigens, but are unable to generate a response to TI-2 antigens. Why is this?

A

The B1 B cell population is not formed until about 5 yrs of age, therefore infants cannot respond to TI-2 antigens.

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20
Q

Can TI-1 and TI-2 antigens activate a T cell?

A

No. Remember only peptides can activate a T cell (i.e. only T dependent antigens).

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21
Q

Capsular polysaccharides and flagellin are good examples of TI-2 antigens. Explain why.

A

They are both highly repetitive structures. Remember, TI-2 antigens are highly repetitive structures.

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22
Q

T/F: Germinal centers, formed in the lymphoid follicles within the B cell zone of secondary lymphoid tissues derive from a single B cell that was activated and T cells that are all descendent from the T cell that supplied the secondary activation signal to that B cell.

A

True

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23
Q

Somatic hypertmutation occurs where?

A

germinal center of secondary lymphoid tissue

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24
Q

What is the result of somatic hypermutation?

A

results in affinity maturation (could be higher or lower affinity)

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25
Q

Where does isotype switching occur?

A

germinal center of secondary lymphoid tissue

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26
Q

Isotype switching is driven by the ________ produced by the __________ cells.

A

cytokines; helper T cells

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27
Q

The positively selected high-affinity isotype switched B cells differentiate into either ______ or _______ cells.

A

plasma or memory cells

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28
Q

Where does the B cell receive its second activation signal by T cells?

A

In the T cell zone of the secondary lymphoid tissue

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29
Q

An effector CD4 T cell will recognize its cognate determinant bound to an _________ molecule on a B cell and then will supply the second signal of activation.

A

MHC class II molecule

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30
Q

Which cell, a Th1 or Th2 cell can supply the second signal of activation to any B cell?

A

Either

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31
Q

What are centroblasts?

A

Large B cell precursors that are at the early stage of development. Found in a germinal center. These cells are rapidly dividing and are beginning to undergo somatic hypermutation.

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32
Q

What are follicular dendritic cells?

A

They are different from the Dendritic cells we have already talked about. FDCs do not present peptide antigens to naive T cells. Instead, these cells express a high density of Fc receptors and complement receptors on their surface. They use these receptors to trap immune complexes (antigens that have been bound by C3b, Ab, or both) on their surface. The centrocytes compete for binding to immune complexes that are trapped on the FDCs. Those with highest affinity for the antigen will receive survival signals from the FDCs. Those that survive will process the antigen and present it to an effector CD4 T cell, that will produce cytokines that drive isotype switching in the developing B cell.

33
Q

Briefly summarize the events that occur during a germinal center reaction.

A

B and helper T cell proliferation (after 1st/2nd signals of activation)
somatic hypermutation and affinity maturation
Isotype switching (driven by the helper T cell cytokine array)
B cell differentiation into plasma and memory cells

34
Q

Describe the result to developing B cells during isotype switching of T cell signalling by IL-4.

A

Induces class switching to IgE. Also promotes switching to IgG isotypes that are weakly opsonizing.

35
Q

Describe the result to developing B cells during isotype switching of T cell signalling by IL-5.

A

Augments class switching to IgA (both subtypes)

36
Q

Describe the result to developing B cells during isotype switching of T cell signalling by IFN-gamma.

A

Promotes class switching to strongly opsonizing isotypes of IgG.

37
Q

Describe the result to developing B cells during isotype switching of T cell signalling by TFG-beta.

A

Induces class switching to weakly opsonizing subtypes of IgG.

38
Q

Th1 cytokines promote class switching to strongly or weakly opsonizing isotypes of IgGs, IgA and IgE?

A

Strongly opsonizing

39
Q

Th2 cytokines promote class switching to strongly or weakly opsonizing IgG subtypes?

A

Weakly opsonizing

40
Q

A resting B cell has surface immunoglobuin and MHC class II molecules for presenting antigen to naive or effector T cells. Does it secrete very much Ab?

A

No.

41
Q

A plasma cell, produces large quantities of Abs. Does it display surface immunoglobulins or MHC class II?

A

No. Plasma cells are terminally differentiated effector B cells that no longer have the ability or need to present antigens to T cells or to recognize cognate antigen.

42
Q

Distribution of Ab isotypes in the tissues:

___ is found in extravascular spaces; also found in the serum.

A

IgG

43
Q

Distribution of Ab isotypes in the tissues:

____ is found primarily in the blood.

A

IgM

44
Q

Distribution of Ab isotypes in the tissues:

____ is primarily found in mucosal secretions; also found in serum.

A

IgA

45
Q

Distribution of Ab isotypes in the tissues:
____ is primarily found bound to the high affinity FceRI receptor on mast cells in the skin and in the linings of the GALT and BALT (resp. tract).

A

IgE

46
Q

What is transcytosis?

A

The process where Abs are actively transported into secretions or into extravascular spaces.

47
Q

Multimeric Abs (IgA & IgM) bind to a receptor known as the __________ for transport across the epithelial layers that line the gut and respiratory tracts as well as into secretions such as saliva and breast milk.

A

Poly-Ig receptor

48
Q

T/F: transport of IgM across epithelium is very efficient.

A

False. IgM is huge, so it is very inefficient.

49
Q

_________ is responsible for active transport of IgG across vascular endothelium and into extravascular spaces and also for transporting IgG across the placental barrier into the fetal circulation during pregnancy.

A

Brambell receptor (FcRn)

50
Q

Describe passive immunization and what it is used to protect against.

A

The transfer of immunity to a non-immune person by injection of specific antibody, immune serum, or T cells. Used to protect against pathogens or toxins.

51
Q

Describe Natural passive immunity.

A

The transfer of Abs from a mother to her fetus via placental transfer of IgG (by FcRn), or transfer of IgA Abs from the mother to her child via breast milk.

52
Q

Which receptor transfers IgG from mother to fetus across the placental barrier?

A

Brambell Receptor (FcRn)

53
Q

Which receptor transfers IgA from mother to child across the epithelium of milk secreting glands of the breast?

A

Poly Ig Receptor

54
Q

Many toxins are produced in an inactive form. Where are they activated and begin to do harm to a host cell?

A

Once they have been taken up by the host cell, they are activated inside the host cell and begin to do damage there.

55
Q

Which Abs have neutralizing capacity and how do they neutralize toxins?

A

IgG and IgA. Abs w/ specificity for a toxin can bind to the toxin and sterically hinder the binding of the toxin to its cellular receptor. Thus, they are never taken up by cells and cannot do harm.

56
Q

How do some Abs inhibit viruses from harming host cells?

A

They bind to viral envelope receptor and inhibit the virus from binding to the host cell. Thus they never gain entry to the cell for replication and subsequent lysis.

57
Q

How do some Abs inhibit intracellular pathogens from doing harm to host cells?

A

They bind to the intracellular pathogen’s surface receptors and inhibit it from binding to host cells for uptake.

58
Q

Which Fc receptor has a binding strength many orders of magnitude higher than the other Fc receptors?

A

FceRI

59
Q

Which Fc receptor can bind to its Ab ligand when that antibody is not bound to its cognate antigen?

A

FceRI is the only Fc receptor type that has such high affinity for its Ab ligand that it binds to it regardless of whether it is bound to an antigen or not.

60
Q

________ (Fc receptor type) is important becaue of its role in antibody-dependent cell-mediated cytotoxicity (ADCC).

A

FcgRIII

61
Q

_____ (Fc receptor type) is important because of its role in the function of mast cells and eosinophils.

A

FceRI

62
Q

Explain why Abs are important to host defense against encapsulated bacteria.

A

Phagocytes to not recognize any surface elements of encapsulated bacteria and therefore do not know to eat them. Once encapsulated bacteria are coated with Abs, then phagocytes will recognize them as foreign substances, phagocytize an destroy them.

63
Q

A critical effector function of ____ cells is to recognize host cells that have been opsonized with IgG1 or IgG3 antibodies (due to presence of intracellular pathogen-derived proteins on cell surface) and to kill the host cells by initiating programmed cell death. This effector function is termed ADCC.

A

NK cells

64
Q

Mast cells do not produce antigen specific receptors. How do they bind to antigens and effect inflammatory mechanisms?

A

They bind with very high affinity to IgE an use the IgE as an antigen specific receptor. Once IgE on a mast cell becomes crosslinked by antigen binding, the mast cell degranulates (releases powerful mediators of inflammation and compounds that are toxic to worm parasites).

65
Q

With what Fc receptor do mast cells bind with such high affinity to IgE?

A

FceRI

66
Q

Eosinophils do not produce antigen specific receptors. How do they bind to antigens and effect inflammatory mechanisms?

A

Same as mast cells. They bind with very high affinity to IgE an use the IgE as an antigen specific receptor. Once IgE on a mast cell becomes crosslinked by antigen binding, the mast cell degranulates (releases compounds that are toxic to worm parasites).

67
Q

A monoclonal antibody has a single or multiple antibody specificities?

A

Single

68
Q

The term _______ refers to a cloned B cell line that has been fused with a tumor cell.

A

Hybridoma

69
Q

Why are hybridomas easier to culture than B cells?

A

B cells are high maintenance to culture and die if not fed regularly and taken on long walks. Hybridomas are low maintenance and grow rapidly, as they are essentially tumor cells that secrete monoclonal antibodies.

70
Q

T/F: A polyclonal Ab preparation is likely to include Abs of all isotypes (except IgD), and it will also contain Abs that have many specificities.

A

True

71
Q

Are polyclonal Abs targeting the same or different antigens?

A

The same antigen, just different epitopes on that specific antigen.

72
Q

Unlike the majority of drugs, mAbs must be administered how?

A

IV, SC or IM

73
Q

What is the injectate volume restriction for SC injections?

A

<2mL

74
Q

What is the injectate volume restriction for IM injections?

A

<5mL

75
Q

It is hypothesized that absorption of mAbs administered IM or SC occur via the ______ system.

A

Lymphatic system. Peak serum [C] may take up to 8 days to achieve.

76
Q

Cellular uptake of mAbs is by ________ and _______-mediated endocytosis.

A

pinocytosis; receptor-mediated endocytosis

77
Q

Rather than being modified structurally to yield water soluble and thus more readily eliminated metabolites, mAbs are degraded in _______ or ________ processes/

A

Lysosomal or cytosolic processes

78
Q

Have drug-drug interactions been observed in mAbs?

A

Not “hitherto”.

79
Q

Why are mAbs not “washed out” of our system in urine?

A

They are too big to pass through the glomerulus.