L12: Humoral Immunity Flashcards Preview

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Flashcards in L12: Humoral Immunity Deck (56)

Where does B cell maturation occur?

Bone marrow


How do antibodies mediate humoral immunity?

Neutralization: antibody prevents bacterial adherance

Opsonization: antibody promotes phagocytosis

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


What region is antigen binding specificity of antibody determined by?

V region


What region is biological activity of antibody determined by?

C region


What chain is rearranged first in antibodies?

Heavy chain


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

Pre-B receptor signaling


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

Large pre-B cells

These cells have heavy chain rearranged already


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

Light chain rearrangements


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

One rearranged heavy chain and one rearranged light chain


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

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


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

Clonal expansion prior to light chain rearrangement


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

2/3 of rearrangements are unsuccessful
Leads to repeated rearrangments


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

Kappa light chains are rearranged first

If this doesn't work, lambda chain rearrangement commences


Where does deletion of self-reacting clones occur?

In the bone marrow


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

They are eliminated


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

They are made anergic


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

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


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

B cell matures and migrates to periphery


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

Leads to anergy


What is required for B cells to produce antibody?

B cell activation


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



What does B cell activation require?

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


What T cells can provide help to the B cell?

T cells recognizing any viral peptide


What occurs when B cell binds its target antigen?

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


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



Where do B cells meet up w/ their antigen?

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


Where do naive B cells enter primary lymphoid follicles from?

Lymph or blood


What does T cell help consist of?

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

T cell help activates the B cell to proliferate


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

1. Begin to differentiate into IgM-producing plasma cells
2. Move into germinal center


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

In the germinal center


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

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


Where does recognition and T cell help occur?

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


What is somatic hypermuation?

Last chance for increasing diversity of BCR


What mediates somatic hypermutation?

Activation-induced cytosine deaminase (AID)


What does AID do?

It introduces point mutations into the rearranged V-region genes

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


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

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


What is the goal of affinity maturation?

To produce B cells w/ high-affinity to antigen


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

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


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

The infection is recetn


What does not occur in primary focus?

Somatic hypermutation

Also almost never get class switching


What is class switching driven by?

Initiation of transcription at an upstream promoter


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



What regions of DNA transcript are involved in class switching?

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


Describe DNA rearrangement in class switching

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


When and where does class switching occur?

After B cell activation by T helper cells

Rarely in primary foci
Primarily in germinal center


What does class switching require?

AID and CD40-CD40L interaction


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

Pts lacking either AID or CD40L

Results in sever immune deficiency (Hyper-IgM syndrome)


What do neutralizing antibodies do?

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


What does opsonization and complement activation by antibodies do?

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


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

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


What are bad antibodies?

Cross-reacting antibodies



Describe a resting mast cell

Filled w/ granules containing inflammatory mediators, such as histamine

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


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

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


What is IgE an important defense against?



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

Through T-independent antigens


What are the 2 kinds of T independent antigens?

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