T Cells Flashcards
Why is T cell maturation more complicated than B cell maturation?
it contains various T cell subsets that differ in receptor specificity and effector functions
How do T cell receptors differ from B cell receptors?
no light & heavy chain, no isotype switching, not secreted, do NOT have Fc portions, NO affinity maturation, antigen does not cross-link the receptors, bind to peptides, dual specific
What is the only function of T cell receptors?
T cell activation
What do T cell receptors associate with?
CD3 complex
What does the CD3 complex do?
signals events after the antigen-binding site has bound antigen, cell surface expression of T cell receptors
How do TCR genes compare to immunoglobulin genes?
the same, V, D, & J segments rearrange to from complete genes with tremendous diversity
What must T cell receptors recognize?
complex peptide & MHC, is specific for both (dual specificity)
Compare & contrast CD4 & CD8.
both are co-receptors for alpha:beta T cell receptors, CD8 binds MHC class I molecules, CD4 binds MHC class II
What do antigen-presenting cells do?
place of MHC:peptide expression, including dendritic cells, macrophages, and B cells; present costimulatory molecules
What are the of y:S T Cells about?
NOT MHC-restricted, do NOT undergo positive selection, part of mucosal immunity, “primitive” cytotoxic cells and secrete cytokines when activated
Where a:B T cells mature?
thymus, called thymocytes, cortex to corticomedullary junction to medulla
Where do T cell precursors enter the thymus?
cortex
What are stromal cells? what do they include?
resident cells in the thymus, epithelial cell, dendritic cells and macrophages
What are double negative cells? double positive cells? single positive cells?
T cell precursors that enter thymus (do not express receptor or co-receptor), once receptors are acquired, lose coreceptor (functional)
What happens if cells fail to express functional T cell receptors?
death
What is positive selection?
immature T cells with receptors are given positive signal to allow for proliferation, those that don’t die, mediated by cortical epithelial cells causing T cells to become MHC restricted
What is negative selection?
after positive selection, if T cell receptors bind well to self MHC & self antigens they could form autoimmune diseases so they are killed, mediated by dendritic cells and macrophages, is a form of deletion for immune self tolerance
What is antigen processing?
series of proteolytic events to generate antigenic peptides and occurs inside APCs
How are antigens outside APCs (exogenous antigens) cleaved?
proteases in endosomes and lysosomes, CD4 cells & class II molecules
How are endogenous antigens cleaved?
in the cytosol by proteasomes in ER with peptide transporter TAP, CD8 cells class I cells
Major Histocompatibility Complex (MHC) name in humans?
Human Leukocyte Antigens (HLA)
How many genes are expressed?
multiple MHC class I & class II
What does it mean that MHC classes are highly polymorphic?
different alleles are present for each gene, unrelated individuals express different MHC molecules
What does it mean that MHC classes are allogenic antigens?
they impact transplantation
Why is it important that polymorphism is present in MHC?
dictates what peptides mind MHC molecules and what antigens can be recognized by a:B T cells
Where are MHC class I expressed?
all nucleated cells, NOT RBCs
What is characteristic of B2microglobulin of MHC Class I?
it is NOT polymorphic and is the same for all MHC class I molecules
What is the peptide-binding cleft or groove?
where antigenic peptides bind
What expresses MHC Class II molecules?
“professional” antigen-presenting cells (macrophages, dendritic cells, B cells)
What is unique about MHC Class I peptide binding groove?
both chains are polymorphic, one molecule can bind an array of peptides
What are the 3 consequences of MHC restriction & polymorphism?
a:B T cells are required to interact physically with cells exposed to antigen (local response), T cell activation, some individuals are resistant to a pathogen
How are CD8+ T cells and CD4+T Cells distinguished?
co-receptor expression, MHC restriction, and their effector functions
What are the components of CD8+ T cell?
mainly cytotoxic T cells (CTL), granzymes help perforin cause apoptosis as in NK cells
What are the components of CD4+ T cell?
mainly helper cells to regulate immune responses with cytokines, includes Th1 and Th2 subsets
What is the CD4+ T cell subset Th1 composed of?
cell-mediated immunity and enhances inflammation; interferon-y and TNF-a activate macrophages, IL-2 stimulate proliferation of Th1, CTL and NK cells
What is the CD4+ T cell subset Th2 composed of?
induces humoral immunity; IL-4 and IL-5 promote antibody production by B cells, deliver the costimulatory signal to B
When do CD4+ T cells become Th1 or Th2?
after they exit the thymus, is dependent on cytokines produced by APC
What induces Th1 and Th2 cells?
IL-12 & interferon-y induce Th1 cells
IL-4 induces Th2 cells