Lecture 8 B cells Flashcards
(20 cards)
Why is the humoral immune response important?
Many bacteria and most intracellular pathogens multiply and spread through the extracellular fluids. Both of these are prevented/controlled by the humoral response. Antibodies produced by B cells. Antigens and helper T cells trigger the activation and differentiation of B cells into antibody secreting plasma cells. Helper T cells can also control isotype switching and have a role in initiating somatic hypermutation of V region genes.
What are the three functions of antibodies?
Neutralization- antibody prevents bacterial adherence. Opsonization- antibody promotes phagocytosis. Complement activation- Antibody activates complement, which enhances opsonization and lyses some bacteria.
What is the role of the B cell receptor in B cell activation?
The surface Ig that serves as the B cell antigen receptor has 2 roles in B cell activation. 1. Like the TCR it transmits signals directly to the cells interior after it binds antigen and this determines the behavior of the B cell.
2. It delivers antigen to intracellular sites where it is degraded and returned to the B cell surface as peptides bound to MHC class II.
How is the humoral response initiated?
- When B cells present the MHC class II: antigen complexes interact with helper T cells specific for that antigen. Antigens that require specific helper T cells to induce antibody responses called: thymus dependent or TD antigens. 2. Many microbrial constituents can induce antibody production in the absence of helper T cells e.g., bacterial polysaccharides. These are thymus independent or T1 antigens.
What effector molecules of armed helper T cells activate B cells?
Recognition of peptide: MHC class II complexes on B cells triggers armed helper T cell to synthesise effector molecules that synergise in activating the B cell. CD40 ligand binds to CD40 on B cells. CD40L and IL4,5 and 6 drive clonal expansion that preceded antibody production. After several rounds of proliferation, B cells can further differentiate into antibody secreting plasma cells.
How do TD antigens induce a response?
B cell received first signal from antigen-bound BCR. Armed helper T cells are recruited by antigen presented on B cell. Second signal required from armed CD4 Th2 cells e.g., IL-4, CD40L.
How do TI antigens induce a response?
Activate B cells through recognition of common microbial recognition of common microbrial constituent or by crosslinking BCRs. The antigen can provide both signals.
What are the effects of CD40 binding?
Binding of the CD40 by the CD40 ligand drives resting B cells into the cell cycle. This interaction is essential for B cell responses to TD antigens. Also increases expression of B7 molecules on the B cell that sustain T cell growth and differentiation. This enhances B cell-T cell interaction.
What is linked recognition?
T cell priming occurs when these recognise with their TCR the pathogen-antigens presented by dendritic cells or macrophages. B cells recognise antigens with their BCR and subsequently process and present them on their surface as MHC II: peptides. B cells are bound and thus activated by T cells that recognise the same antigen. However, one antigen (pathogen) may have numerous epitopes. Therefore, the BCR bound epitope and the MHC II presented epitopes must not be identical. Although the antigens recognised by the B and T cells are linked they do not have to recognise identical epitopes.
What is a use of the linked recognition concept?
Helps to ensure self-tolerance as auto immune response requires the simultaneous presence of a self-reactive T cell as well as a self-reactive B cell. Useful vaccine design. E.g., against Haemophilus influenzae type b, which causes meningitis. Adults mount very efficient thymus-independent responses to these polysaccharide antigens, children do not. H. influenzae polysaccharide is linked chemically to tetanus toxoid, a foreign protein against which children are routinely vaccinated and thus have tt-specific Th2 cells.
How are B cells used in vaccine production?
B cell binds bacterial polysaccharide epitope linked to tetanus toxoid protein. Antigen is internalized and processed. Peptides from protein component are presented to the T cell. Activated B cell produces antibody against polysaccharide antigen on the surface of the bacterium.
How are encounters between antigen specific B cell and helper T cell achieved?
Frequency of naive lymphocytes specific for any given antigen is between 1 in 10,000 and 1 in 1,000,000. The chance of an encounter of two lymphocytes that recognize the same antigen is between 1 in 10^8 and 1 in 10^12. Achieving an encounter between a T and a B cell is facilitated by T and B lymphocytes in secondary lymphoid organs e.g., spleen, lymph nodes.
How does B cell and T helper cell interaction occur?
Occurs via an APC in specific regions of the lymphoid organs e.g., T cell zones of the spleen. B cell interaction with an armed helper T cell activates both types of lymphocytes to produce a primary focus of clonal expansion. This is the first phase of the primary B cell response.
What are the steps to the first phase of the primary B cell response?
Antigen binding B cells are trapped in the T cell zone of the spleen. If there are no specific antigens to the B cell it will continue circulating. Antigen-binding B cells interact with armed helper T cells and begin to divide. Antigen-binding B and T cells migrate to the T zone-red pulp border where they proliferate to form a primary focus and form plasmablasts. After several days the plasmablasts stop dividing and either die or differentiate into plasma cells. Plasma cells secrete massive amounts of antibody but no longer respond to the T helper cells.
What is the second phase of the primary B cell immune response?
Some of the proliferating B and T cells migrate into a primary lymphoid follicle (specialised area of the lymph node) where they continue to proliferate and form a Germinal Centre. These are sites of intense B cell proliferation. B cells divide every 6-8 hours.
How is the germline centre different from the primary centre?
GCs do not result in prompt antibody secretion. They allow a more effective later immune response in case of chronic infection or re-infection. B cells undergo important modifications in the GCs. Somatic mutations, affinity maturation and isotype switching take place there.
What are the steps to the primary foci formation?
B cells develop in the bone marrow. Mature B cells travel to the lymph node via the bloodstream and leave via the efferent lymph. B cells that encounter antigen at the T cell/B cell border become activated. They form primary foci in the medullary cords. Some cells then migrate to the primary focille forming a germinal center. Plasma cells migrate to the medullary cords or leave via the efferent lymphatics. Plasma cells migrate to the bone marrow.
What happens to GC B cells with low affinity surface immunoglobin?
BCR is not cross linked and B cells cannot present Ag to T cell. Apoptosis
What happens to GC B cell with high affinity surface immunoglobin?
T cell helper and BCR cross linking sustain B cell proliferation and maturation. Memory B cells and plasma cells.
What happens when GC plasma cells migrate to the bone marrow?
A subset of them survive for years and is the source of the long lasting high affinity antibodies. Other GC B cells become memory cells. They were once stimulated by antigen and their genome is therefore fully rearranged. They divide very slowly and express surface immunoglobulin but do not secrete antibodies. They continue to circulate through the same secondary lymphoid organs as the naive B cells. After re-exposure to an antigen-matched armed effector T cell, they can resume proliferation and antibody secretion.
