Flashcards in L12: Humoral Immunity Deck (56)
Where does B cell maturation occur?
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?
What region is biological activity of antibody determined by?
What chain is rearranged first in antibodies?
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?
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?
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