T Cells II Flashcards
Describe how Tfh cells help B cells get activated by antigen and switch immunoglobulin class
Soon after the arrival of antigen-presenting DC in the lymph node, some activated Th cells can be seen migrating into the follicles of the cortex, where B cells are abundant. These are referred to as follicular helpers, and their role is to help B cells that have recognized antigen become activated and differentiate into antibody-secreting plasma cells. Tfh secrete a variety of cytokines, and by direct contact they stimulate the B cells to switch from secreting IgM, to IgG, IgA, or IgE. They tend to be heterogeneous; the Tfh in the gut, for example, switch B cells preferentially to IgA; those in spleen switch B cells to IgG.
(B cell binds the epitope that the B cells receptor is specific for –> bound molecule is endocytosed and broken down in endocytic vesicle –> peptide fragments bind to MHC Class II moleciles brought in by other vesicles that fuse with the endosome and MHC-peptide complex moves to surface –> B cell displays antigen + Class II MHC –> correct Tfh comes along and sees its epitope + Class II MHC on B cell –> binds and focuses surface interactions and helper lymphokines on B cell. )
Define mitogen.
protein that stimulates T cell division
Suggest uses for T or B cell mitogens in the clinical laboratory.
Lectins have affinity for certain sugars- usually ones that the organism they come from doesn’t itself have. They may function as primitive “immune” molecules, gumming up the surfaces of foreign invaders. Some of them bind to and stimulate T and B cells, and they are thus very useful in the research and clinical labs. For example, phytohemagglutinin, PHA, a bean lectin, stimulates all T cells to divide because it binds to CD3, fooling the cell into thinking it has bound antigen. Because it stimulates T cell mitosis it is called a mitogen. Pokeweed mitogen (PWM) stimulates both T and B cells (nonspecifically) to divide. The usefulness of these agents is considerable. For example, to see a person’s karyotype (metaphase chromosome picture) you need dividing cells. Take some blood leukocytes, add PHA, and in three days or so you have all the lovely metaphase mitotic figures you could want. Or if you want to see if someone’s T cells can divide normally, or make IL-4, but you don’t know what antigens she’s immune to, just add some PHA to her blood cells; it will stimulate all helpers and CTL without regard to their antigen specificity.
Distinguish between the effects of a mitogen and an antigen, when added to normal blood lymphocytes
a. Antigens are specific, mitogens are nonspecific
b. Mitogen: doesn’t actually bind to antigen-binding site on T cell, like an antigen does. What it does bind to is the CD3 domain that controls signal transduction from the antigen-binding chains. This is like bypassing the light switch in your house- the lights are going to always stay on because there’s no longer a mechanism for turning them off.
Compare and contrast the antigen receptors of T and B cells: B cells
Bind antigen directly with surface antibodies. Because T cells see antigen only when it is complexed with cell-surface MHC molecules, T cells focus their attention on cell surfaces, and do not interact with free antigen; that is a job for the B cell and its antibodies
Compare and contrast the antigen receptors of T and B cells: T cells
T-cell receptor for antigen (TCR) is made up of 2 chains, alpha and beta, and each has a common and variable portion. The T cell makes the receptor out of V, (D) and J regions recombined (just like B cells) and (like antibodies) each chain has 2 CDRs (complementarity-determining regions). This is taking place in the thymus. Both alpha and beta chains have trans-membrane domains (unlike surface Ig where ONLY the heavy chain is trans-membrane domain).
Compare and contrast the antigen receptors of T and B cells: Careful control of the T cell with antigen receptors
On the TCR is a complex of molecules called CD3. When T cell binds correct antigen + MHC with its TCR, the actual signal that turns the T cell on is transmitted by CD3. 2. When a Th0 binds to antigen-presenting cell, APC gives T cell boost by secreting IL-12. Needs these signals to be activated.
Discuss the structures recognized by T cell receptors and antigen recognition by helper T cells. Explain the special role of dendritic cells in this process.
Antigen enters the body –> infects locally and causes innate response –> breakdown products are ingested by dendritic cell –> within DC endosome, proteins are broken down to peptides via lysosome —> the endosomal peptides then fuse with vesicles containing Class II MHC molecules embedded in their membrane (facing IN) –> some of the peptide associates with the MHC molecule –> endosome goes to cell surface and fuses with plasma membrane and MHC + antigenic peptide are exposed to outside world the appropriate T cell (HELPER T’s) recognizes both the MHC + antigen and is turned on.
Discuss the structures recognized by T cell receptors and antigen recognition by cytotoxic T cells. Explain the special role of dendritic cells in this process.
Protein in made within the cell –> chopped up into peptides –> fuses with vesicles containing Class I MHC molecules embedded in their membrane –> some of the peptide associates with MHC molecules –> fuses with plasma membrane and MHC + peptide are exposed to outside world –> appropriate T cell (CYTOTOXIC) recognizes both the MHC + antigen and is turned on.
Discuss what is meant by “MHC-restriction”.
PART 1: T cells are restricted in their recognition of antigen, to antigen on the surface of cells (target cells) genetically identical to themselves. T cells do not “see” antigen alone, but nly antigen presented to them on the surface of a genetically identical cell. T cell and antigen-presenting cell must come from individuals who share alleles at the Major Histocompatability Complex (MHC)—codes for surface glycoproteins. Basically, T cells are MHC-restricted and my T cells won’t work in another person.
PART 2: Two classes of MHC molecules, MHC Class I and MHC Class II. All nucleated cells have MHC Class I on their surfaces. Class II products are only on dendritic cells, macrophages and B cells (the cells involved with presenting antigenic peptides to T helper cells). Antigen is endocytosed and presented by dendritic cells via Class II MHC to the T cell. Proteins synthesized within a cell are presented via Class I MHC (Most are normal, but some can be viral, bacterial, etc).
Describe the role of T cells in ridding the body of a viral infection
a. CTL cells will “see” an infected/foreign cell (because MHC Class I will have it bound) and then will activate the target cell to commit suicide because it has a Fas CD95L Ligand (binds to Fas CD95 receptor on target cell) OR secretes lytic granules that trigger apoptosis.
b. HELPER cells will “see” antigen presented on a dendritic cell, B cell or macrophage via MHC Class II. They will activate the immune response and divide
Describe the characteristics of T-independent antigens.
Most antigens require T cell help to achieve a reasonable antibody response, but some don’t. These are T-independent antigens are usually have the same epitope repeated over and over (rare in proteins, but common in carbohydrates, ie: Streptococcus pneumoniae). Carbohydrate chain binds to the B cell antibodies –> cell is activated and begins to divide –> The response to T-independent antigens is almost all IgM (T cells needed to switch from IgM to IgG, IgA or IgE). So, if a person is very deficient in T cells, they still have make antibody to carbohydrates. With protein antigen—NO IgM and NO IgG is made without T cell help.
Outline an experiment that shows that an antibody response can be “T-dependent”.
T-dependent response require T cell help to achieve a reasonable antibody response. To test this, we could expose cells to antigens and see what antibodies are produced.
