Chapter 6: Secondary Lymphoid Tissue: B and T Lymphocyte Activation Flashcards
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The costimulatory molecules B7-1 (CD80) and B7-2 (CD86) on APCs bind to what cell marker on the mature, naive T cell?
CD28 which in on switch
Later in an immune response, B7 will preferentially bind to what receptor, effectively turning off the T-cell response
CTLA-4 or PD-1
What are some CTLA-4 agonist drugs?
Abatacept
Belatacept
Clinical use of abatacept?
rheumatoid arthritis
Clinical use of Belatacept?
renal transplants
Antagonists of CTLA-4?
ipilimumab
Clinical use of ipilimumab?
melanoma and in clinical trials for several other types of cancer
How does IL-2 release affect T helper cells and CD8 T cells? How are they expressed by each of these types of cells?
They help both types proliferate
They both have IL-2 receptors but helper T lymphocytes produce large amounts of IL-2
What are superantigens?
viral and bacterial proteins that cross-link variable β domain of T cell receptor to an α chain of class II MHC molecule outside of the normal peptide binding groove
cross-linking activates cell and induces T cell activation and proliferation in the absence of antigen-specific recognition of peptides in the MHC class II groove
What are the 3 major classes of helper T cells that arise from the same precursors Th0 cells?
- Th1
- Th2
- Th17
Draw out the subsets of helper T cells, their pathways, functions and cytokines produced.
Subsetsof T Helper Cells
Which type of T cells do T regs inhibit?
Th1 cell function
What are the markers that are found on Tregs?
CD25 and transcription factor FoxP3
What inflammation inhibiting cytokines do Tregs secrete?
IL-10 and TGF-B
Which cells produce is strong response to tuberculoid leprosy?
Th1 cells
Major symptoms of tuberculoid leprosy?
- intracellular pathogen with granuloma formation
- Some damage to skin and peripheral nerves, but the disease progresses slowly, if at all, and the patient survives
What type of cells produce a strong response when a patient has lepromatous leprosy?
Th2 response is turned on, and cell mediated response is depressed
Symptoms of lepromatous leprosy?
- diffuse acid fast staining throughout tissue
- much more severe presentation than tuberculoid
- ab production not protective
What are the 2 categories of ag that B lymphocytes encounter?
Thymus- independent (TI)
Thymus- dependent (TD)
Describe TI ag activated B lymphocytes.
Certain B lymphocytes can be activated by macromolecules such as lipids, polysaccharides, and lipopolysaccharides without having to interact with other T lymphocytes
Describe immune response upon B lymphocyte activation by TI ag as opposed to TD ag.
immune response is generally weaker than the response to TD antigens,
resulting primarily in the
secretion of IgM ab and the absence of immunologic memory
Describe TD ag.
Response to these molecules requires direct contact of the B cells with helper T cells are influenced by cytokines secreted by these cells
What are the 2 waves with which B lymphocytes activated by TD antigens are released?
Primary wave of activated B lymphocytes is comprised of strictly IgM secreting plasma cells which leave secondary lymphoid tissue shortly after activation.
Second wave: remains within follicles of secondary lympoid tissue undergoing clonal expansion and producing the germinal center.
What are 3 major events the B cells undergo in the germinal center?
affinity maturation
isotype switching
decision to become plasma cell or memory cell
Somatic hypermutation.
during periods of intense proliferation in germinal centers; there are random mutations in the coding of the variable domain region
(these slightly altered idiotypes have increased affinity for antigen
Affinity maturation.
when there are clones of B cells in germinal centers with more affinity for the antigen
Avidity increases when?
When binding site of Ig increase
