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Immunology > B-cell Mediated Immunity > Flashcards

B-cell Mediated Immunity Flashcards

1
Q

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

A

The production of antibodies

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2
Q

How are acquired B cell responses retained?

A

In the form of memory cells that typically provide long-lasting immunity to infection

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3
Q

What is the first signal of B cell activation? How is it communicated to the nucleus?

A
  • Crosslinking of the BCR by binding of the Ig component of that BCR with its cognate antigen
  • Sufficient signaling will not occur unless multiple copies of the BCR are crosslinked with antigen
  • The signal transduction unit of the BCR is known as the Ig-alpha/Ig-beta complex. Once this signal has been transmitted to the nucleus, the B cell has now received its first signal of activation.
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4
Q

What is CR2?

A
  • CR2 is the B cell co-receptor, and has affinity for complement component C3b
  • When it binds to C3b, additional signals are transmitted as part of the 1st signal of activation
  • If an antigen recognized by a B cell has been opsonized by labeling with C3b, it’s a good sign the antigen is not a self-determinant and is likely to be pathogen-derived
  • Indicates to the immune system that an immune response is needed to clear an infection

NOTE: T helper cell signaling is also needed in most cases to activate the B cell

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5
Q

What are CD81 and CD19?

A
  • CD81 and CD19 are surface markers of B cells that are also part of the BCR complex
  • CD19 is an imp. component of the signaling apparatus of the BCR b/c it amplifies signals that are transmitted via the Igα/Igβ complex
  • The function of CD81 has not been clearly established
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6
Q

Describe the process of T-independent B cell activation. Is this sufficient to fully activate the B cell?

A
  • Some non-protein antigens (TI-1 antigens, or mitogens) can also activate B cells in the absence of T cell help
  • The antigen cross-links multiple BCRs on the surface of the cell, and another determinant of the antigen binds to an unlabeled receptor on the cell surface, the PRR - PRRs are receptors that recognize structures common to large numbers of bacteria (PAMPs)
  • Example: LPS receptor that binds to bacterial LPS, found on all G- bacteria - The combination of BCR and PRR engagement is only sufficient to partially activate the B cell

NOTE: B cells activated by T-independent antigens do not initiate germinal center reactions, and they do not result in immunological memory (no memory cells are generated). However, if these types of antigens are supplied in high enough concentrations (much higher than would ever be seen naturally in a host), they can activate B cells in a non-specific fashion (almost all IgM, with minimal IgG too)

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7
Q

What are T-independent type-2 antigens?

A
  • TI-2 antigens can cause B cell activation by heavily crosslinking BCRs on the surface of the B cell
  • Typically highly repetitive structures that have many copies of the ANTIGENIC DETERMINANT recognized by a B cell - Example: a cell wall polysaccharide
  • Subset of B cells (B1 B cells) that have a restricted BCR repertoire that account for most of this type of immune response
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8
Q

What would the AB response look like in the case of the lack of cognate T cells or the absence of a thymus?

A

No antibody response made in response to a T-dependent antigen, but because no T cell help is required for antibody responses against T-independent antigen, both TI-1 and TI-2 antigens will elicit a response

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9
Q

What does the AB response look like in infants?

A

Infants can produce effector T cells, so they can make antibody responses to T-dependent antigens. Infants can also make antibodies in response to TI-1 antigens. However, because the B1 B cell population is not formed until about 5 years of age, infants cannot respond to I-2 antigens

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10
Q

What types of B-cell antigens activate T cells?

A

This only occurs in response to T-dependent antigens because T cells can only recognize protein determinants

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11
Q

Which B-cell antigens induce immunological memory?

A

Only T-dependent antigens can elicit memory B cells (not TI-1 or TI-2)

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12
Q

Which B-cell antigens can activate B cells in an antigen-independent fashion?

A

This only occurs in the case of mitogens (TI-1 antigens)

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13
Q

Which B-cell antigens require repeated epitopes?

A

This is only true of TI-2 antigens

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14
Q

What happens in a germinal center reaction?

A
  • Germinal centers form in lymphoid follicles in B cell zone of secondary lymphoid tissues
  • The reaction is formed by the daughter cells of rapidly dividing B cells (all derived from a single B cell that was activated) and T cells (all descendent from the helper T cell that supplied the secondary activation stimuli to that B cell)
  • B cells: somatic hypermutation (which results in affinity maturation) and isotype switching (driven by the cytokines produced by helper T cells)
  • Positively selected, high-affinity isotype-switched B cells differentiate into plasma or memory cells
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15
Q

What happens to a naive B cell after it receives its first activation signal and is in the secondary lymphoid tissue?

A
  • B cell receives its first activation signal, binds to its cognate antigen, and moves into the T cell zone of the secondary lymphoid tissue
  • In the T cell zone, the B cell interacts with many T cells
  • If an effector CD4 T cell recognizes its cognate determinant bound to an MHC class II molecule on the B cell, it will supply the second signal of activation
  • The B cell and T cell will then begin to proliferate rapidly, forming a PRIMARY FOCUS in the T cell zone.

NOTE: either a Th1 or Th2 cell can supply the second signal of activation to any B cell.

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16
Q

How does 2nd activation of B cells lead to the formation of a germinal center?

A
  • As the B and T cell proliferate, some of the B cells will differentiate into plasma cells (and will produce IgM antibodies because they have not yet class switched)
  • At least one pair of the daughter B and T cells will eventually migrate into the lymphoid follicle of the B cell zone and continue proliferating, becoming a germinal center
17
Q

Where are helper T cells found in a germinal center rxn?

A

Around the periphery

18
Q

What are centroblasts? Centrocytes?

A
  • CENTROBLASTS are large B-cell precursors in the early stage of development. These cells are rapidly dividing and are beginning to undergo somatic hypermutation
  • As they develop and become smaller (now called CENTROCYTES) they move into an area that is filled with follicular dendritic cells
19
Q

How are follicular dendritic cells distinct from other dendritic cells? What is their role in the germinal center?

A
  • FDCs do not present peptide antigens to naïve T cells
  • Instead, they express a high density of Fc receptors and complement receptors on their surface (long dendrites with high SA for trapping)
  • They use these receptors to trap immune complexes (antigens that have been bound by C3b, antibody, or both) on their surface
  • The developing centrocytes compete for binding to immune complexes trapped on the FDC
  • Those with the highest affinity for antigen receive survival signals from the FDCs, process the antigen and present it to effector CD4 T cells that produce cytokines that drive isotype switching in the developing B cell
20
Q

What happens to B cells (centrocytes) that cannot compete effectively for binding to antigen trapped on FDCs? What is this process called?

A
  • They will not receive survival signals and will become anergic and die
    1. B cells bearing receptors that received somatic mutations that resulted in lower or similar affinity for the antigen will typically die, while those bearing receptors that received mutations that increased the affinity of the BCR for antigen will be positively selected to continue developing = AFFINITY MATURATION
21
Q

What are the 4 important steps of B-cell germinal center reactions?

A
  1. B and helper T cell proliferation
  2. Somatic hypermutation and affinity maturation
  3. Isotype switching (driven by the helper T cell cytokine array)
  4. Bcell differentiation into plasma cells and memory cells

Immunology (7 decks)

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