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HIID > L12: Humoral Immunity > Flashcards

L12: Humoral Immunity Flashcards

1
Q

Where does B cell maturation occur?

A

Bone marrow

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2
Q

How do antibodies mediate humoral immunity?

A

Neutralization: antibody prevents bacterial adherance

Opsonization: antibody promotes phagocytosis

Complement activation: antibody activates complement, which enhances opsonization and lyses some bacteria

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3
Q

What region is antigen binding specificity of antibody determined by?

A

V region

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4
Q

What region is biological activity of antibody determined by?

A

C region

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5
Q

What chain is rearranged first in antibodies?

A

Heavy chain

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6
Q

Once heavy chain rearrangement occurs, what precludes further V-DJ rearrangements?

A

Pre-B receptor signaling

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7
Q

What cells in B cell development undergo proliferation (cell division)?

A

Large pre-B cells

These cells have heavy chain rearranged already

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8
Q

What occurs after large pre-B cells undergo cell division?

A

Light chain rearrangements

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9
Q

How many rearranged heavy and light chains does each B cell express?

A

One rearranged heavy chain and one rearranged light chain

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10
Q

How does light chain rearrangement following cell proliferation lead to more diversity?

A

One B cell can proliferate into many different cells and each of these cells then undergoes their own light chain rearrangement

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11
Q

What allows for a given VDJ H chain rearrangement to be paired w/ multiple different light chains?

A

Clonal expansion prior to light chain rearrangement

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12
Q

How many rearrangements are unsuccessful? What does this lead to?

A

2/3 of rearrangements are unsuccessful

Leads to repeated rearrangments

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13
Q

What light chain is rearranged first? What leads to rearrangement of the other light chain?

A

Kappa light chains are rearranged first

If this doesn’t work, lambda chain rearrangement commences

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14
Q

Where does deletion of self-reacting clones occur?

A

In the bone marrow

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15
Q

What occurs if immature B cells are stimulated by cell surface self-antigens?

A

They are eliminated

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16
Q

What occurs if immature B cells are stimulated by soluble self-antigens?

A

They are made anergic

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17
Q

If a BCR is strongly cross linked by self-antigens, what occurs?

A

B cell development stops and light chain rearrangement commences

If the new BCR that is expressed does NOT interact w/ any of the self-proteins, the B cell can continue in maturation process

If the new BCR is still self-reactive, it undergoes apoptosis

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18
Q

If there is no reaction to self antigens in the bone marrow, what occurs?

A

B cell matures and migrates to periphery

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19
Q

What occurs if BCR is strongly cross-linked by self antigens in the periphery?

A

Leads to anergy

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20
Q

What is required for B cells to produce antibody?

A

B cell activation

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21
Q

Does B cell act as an antigen presenting cell or an antigen binding cell?

A

Both

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22
Q

What does B cell activation require?

A

BCR cross-linking by antigen binding and also T cell help

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23
Q

What T cells can provide help to the B cell?

A

T cells recognizing any viral peptide

24
Q

What occurs when B cell binds its target antigen?

A

Antigen bound to BCR provides a signals and is also internalized and degraded; then presents it as a peptide on it its MHC molecule

25
Q

What interaction is important for driving B cells into the cell cycle and promotes class switching and somatic hypermutation

A

CD40:CD40L

26
Q

Where do B cells meet up w/ their antigen?

A

In secondary lymphoid tissues (spleen, lymph nodes, tonsils, peyer’s patches

27
Q

Where do naive B cells enter primary lymphoid follicles from?

A

Lymph or blood

28
Q

What does T cell help consist of?

A

CD40:CD40L interaction as well as cytokines produced by activated T cell

T cell help activates the B cell to proliferate

29
Q

Activated B cells can go one of 2 ways. What are these?

A
  1. Begin to differentiate into IgM-producing plasma cells

2. Move into germinal center

30
Q

Where do B cells undergo affinity maturation by means of somatic hypermutation?

A

In the germinal center

31
Q

What do B cells that enter the periphery from the bone marrow express?

A

IgM and IgD (same rearranged V region, different C region)

32
Q

Where does recognition and T cell help occur?

A

At the boundary b/w the T and B cell areas of the lymph node

33
Q

What is somatic hypermuation?

A

Last chance for increasing diversity of BCR

34
Q

What mediates somatic hypermutation?

A

Activation-induced cytosine deaminase (AID)

35
Q

What does AID do?

A

It introduces point mutations into the rearranged V-region genes

Most of these mutations decreased ability of the B cell clone to bind antigen

36
Q

What occurs w/ clones w/ new point mutations through somatic hypermutation?

A

They re-encounter antigen in the germinal center

Those B cells w/ decreased affinity die

B cells w/ strong affinity for antigen obtain the T cell help needed to sustaion proliferation and differentiation into the antibody producing plasma cell

37
Q

What is the goal of affinity maturation?

A

To produce B cells w/ high-affinity to antigen

38
Q

Do all antigen activated B cells that have received T cell help move into the germinal center?

A

No; some form a primary focus where they do not undergo somatic hypermutation and mostly produce IgM

39
Q

If a patient has primarily IgM antibodies to a specific pathogen, what does that mean?

A

The infection is recetn

40
Q

What does not occur in primary focus?

A

Somatic hypermutation

Also almost never get class switching

41
Q

What is class switching driven by?

A

Initiation of transcription at an upstream promoter

42
Q

What determines the choice of promoter in initiation of transcription in class switching?

A

Cytokines

43
Q

What regions of DNA transcript are involved in class switching?

A

Switch regions present upstream of each of the potential constant region loci

44
Q

Describe DNA rearrangement in class switching

A

Transcription through the switch region is initiated by activation of the upstream promoter → AID and other enzymes introduce nicks into template enzyme → repair enzymes act to initiate double-strand break repair → the 2 switch regions are joined, excising intervening DNA sequences → the selected constant region is now adjacent to the VDJ region

45
Q

When and where does class switching occur?

A

After B cell activation by T helper cells

Rarely in primary foci
Primarily in germinal center

46
Q

What does class switching require?

A

AID and CD40-CD40L interaction

47
Q

What pts are unable to undergo class switching? What does this result in?

A

Pts lacking either AID or CD40L

Results in sever immune deficiency (Hyper-IgM syndrome)

48
Q

What do neutralizing antibodies do?

A

Block entry of extracellular pathogens (prevents them from getting internalized into cells)

49
Q

What does opsonization and complement activation by antibodies do?

A

Antibodies bound to bacteria (opsonization) allow binding to Fc receptors on macrophages and neutrophils

Activation of complement by antibody binding allows components bound to the bacterial surface to bind complement receptors on macrophages and neutrophils

50
Q

What does antibody binding antigen on the surface of target cells cause?

A

NK cells protect against intracellular pathogens

Antibodies binding to foreign antigens on the cell surface are recognized by Fc receptors on NK cells

FcrR cross-linking signals the NK cell to kill

51
Q

What are bad antibodies?

A

Cross-reacting antibodies

IgE

52
Q

Describe a resting mast cell

A

Filled w/ granules containing inflammatory mediators, such as histamine

Have surface receptors for the Fc portion of IgE (have receptor-bound antibodies)

53
Q

What occurs when antigen binds to the IgE on mast cells?

A

Antigen binding cross links these receptor-bound antibodies → mast cells degranulate

54
Q

What is IgE an important defense against?

A

Parasites

55
Q

How can there be (a little) antibody production w/o T cell help?

A

Through T-independent antigens

56
Q

What are the 2 kinds of T independent antigens?

A
  1. T-independent-1 antigens are TLR ligands like LPS, and cause polyclonal B cell stimulation leading to a non-specific antibody response by plasma cells
  2. T-independent-2 antigens have a repetitive structure and can activate antigen-specific, mature B cells in the absence of T-cell help by cross-linking

These antibodies are low affinity, but important at the early stages of a bacterial infection

HIID (27 decks)

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