Flashcards in T lymphocytes Deck (65):
What are the three family members of the lymphocytes?
What is meat by the term MHC restriction, in terms of T cells?
T cells are restricted in what they can respond to, since they require an MHC cell to activate them
What are the precursors to T cells called? Where are these produced, and where do they go to mature?
Prothymocytes, made in bone marrow, go to Thymus to mature
What are the two factors that differentiate T lymphocytes?
Functions and surface proteins
Where do T lymphocytes go once they mature in the Thymus/?
To lymphoid organs to await activation by antigen
Where are memory T cells found? What do they wait for?
Memory T cells tend to reside in the bloodstream until directed to enter non-lymphoid tissues to elicit cell-mediated immune responses.
What are the two subsets of T helper cells?
Th1 and Th2
What is the response generated by Th1? Th2?
Th1 = cell-mediated
Th2 = humoral immunity
True or false: Th1 cells are exclusive in the fact that they only direct cell mediated immunity
False--there are actually cytokines that Th1 cells produce that stimulate B cells to produce IgG
What is the role Th17 plays?
What is the function of T-follicular helper cells?
promote germinal center formation in lymphoid organs
What is the function of cytotoxic T cells?
Lyse virus infected cells
Which lymphocytes are responsible for the form of DTH by reacting to noninfectious foreign antigens in the skin and causing a contact dermatitis (like poison ivy)
Cytotoxic T cells
What are T regulatory cells?
Cells that secrete cytokines to inhibit immune responses, thus acting to downregulate immunity once a pathogen has been eliminated
What are alpha-beta T Cell Antigen Receptor?
the proteins on the surface of T cells that allow them to recognize and respond to antigen
How many specific antigens can individual T cells recognize?
The TCR for most T lymphocytes is comprised of what parts? What binds these parts together?
an alpha and beta heterodimer, bound together by disulfide bridges
How are different specific TCRs generated?
Each chain on TCRs are composed of constant and variable regions similar to immunoglobulins
There are two chains (alpha and beta) on each TCR. Are both involved in binding to an antigen+MHC protein, or just one?
True or false: The TCR is partly responsible for MHC restriction
False--not at all responsible. CD4 and CD3 are.
What produces MHC restriction?
CD4 and CD8 proteins
The cytoplasmic tails of the TCR chains are not long enough to act as signal transducers (t-rex!!). What transduces the signal from the TCR chains then?
What are the antigen receptor for B cells?
How many antigen bonding sites are on TCRs? B cell surface antibodies?
The TCR has a single antigen binding site, whereas the B cell antigen receptor has two antigen binding sites.
Are B cell antibodies secreted? How about the TCR protein on T cells?
B cell antibodies, yes
What are CD3 proteins? Are they variable between individuals? What subtypes exits? What sites exist in the tail that allows these proteins to act as signal transducers?
1. Proteins that mediate the response of TCR proteins
3. 1 gamma, 2 epsilon, and 2 zeta
4. Phosphorylation sites in the tails
Besides CD3 proteins, what other protein are needed to transduce a signal from TCR proteins?
Co-stimulatory molecules that stimulate their own pathway.
What is the function of CD28? What does it bind to?
co-stimulator of T cells that binds to B7 on macrophages/dendritics cells/others
What is CD40 ligand? What does it bind to?
Co-stimulator of T cells tha tbinds to CD40 protein on macrophages/dendritic cells
What is the CD4 transmembrane protein? What does it do (3)?
Single polypeptide that is expressed on 65% of T-cells
1. cell adhesion
2. Signal transduction in T-cell activation
3. Restricts T-cell response to recognizing only class II MHC
Besides T-cells, what other cell types have CD4 proteins? What is the consequence of this?
Macrophages, meaning that AIDS can target marcophages
CD4 acts to restrict T cell responses to recognizing only class II MHC proteins. CD4 binds to non-polymorphic (i.e. invariant) regions of class II MHC proteins. Why is this important?
Because CD4 is invariant and wouldn't be able to change to accommodate the many different class II MHC proteins that humans express
Most CD8-expressing cells are what cells?
Cytotoxic T cells
Structurally, CD8 is composed of what?
A homodimer or heterodimer
What are the three functions of CD8 proteins?
1. Cell adhesion to increase the strength of binding between CD8+ T cells and antigen-presenting cells or CTL target cells.
2. signal transducer to aid in T cell activation.
3. Restricts T cell regocnition to only class I MHC proteins
When does T cell activation begin?
When TCR binds to an MHC-bound antigen
True or false: Clustering of the TCR's with multiple MHC-peptide complexes on an antigen presenting cell has been shown to be important in activating signal transduction
Through which pathway do TCR proteins activate transcription?
Phospholipase C and MAP kinase cascade
What induces transcription of IL-2 cytokine?
Transcription factor AP-1
What is IL-2 cytokine?
provides autocrine growth of T cells by transcribing receptor and gene
What is the result of IL-2 production in T-cells?
Autcrine stimulation, resulting in mitosis a crap-ton of times
What are the two subsets of T helper cells?
Th1 and Th2
What directs the production of Th1 vs Th2?
the presence of either interleukin-12 (IL-12) or interleukin-4 (IL-4).
What does IL-12 do? What produces it?
Directs T-cells to become Th1 cells.
Macrophages/dendritic cells produce it when they see antigen
What does IL-4 do? What produces it?
Directs T-cells to become Th2 cells
Not known what produces it
T helper cells are derived from what?
antigen naïve CD4+ T cell precursors (called a Th0 cell),
What is the default pathway of helper T-cell maturation?
What is needed for precursors of helper T cells to be directed toward Th1 production?
Inflammation/macrophages etc to produce IL-12
Peptides present in large quantities on antigen presenting cells tend to induce (???) responses, whereas those in small amounts on antigen presenting cells elicit (???) responses. (fill in the blanks)
Peptides present in large quantities on antigen presenting cells tend to induce Th1 responses, whereas those in small amounts on antigen presenting cells elicit Th2 responses.
Peptides that bind strongly to the T cell antigen receptor cause (???) responses and those that bind weakly produce (???) responses.
Peptides that bind strongly to the T cell antigen receptor cause Th1 responses and those that bind weakly produce Th2 responses.
What cytokine do Th1 cells produce? Th2?
Th2- IL-4, IL-5 and IL-13.
What does the interferon-gamma that is produced by Th1 cells do? (2)
1. activates the microbicidal activities of macrophages
2. stimulates B cells to produce IgG antibody which can opsonize microbes, thereby enhancing phagocytosis
IL-2, together with interferon-gamma, generates what?
cytotoxic T lymphocytes
Th2 cytokines promote the production of what?
IgE antibody, and mast cell-mediated immune reactions
Why are immune responses generally dominated by either a Th1 or Th2 response?
Th1 will inhibit Th2, and vice versa
TH17 cells develop from uncommitted naive T cells when exposed to which cytokines?
IL-1, IL-6 and transforming growth factor-beta (TGF-β)
When are IL-1 and IL-6 cytokines produced? What produces them?
produced by dendritic cells during anti-microbial defense and are considered inflammatory cytokines
What is the function of IL-23? What cells produce it
Stabilizes TH17 phenotype, produced by dendritic cells
CTL typically have what CD protein expressed on the surface? What MHC protein does this recognize?
CD8+, which recognizes class I MHC proteins
How are CTLs activated?
The TCR of a pre-CTL binds the peptide/class I MHC complex of a target cell, as well as CD28 (on the CTL) binding the target cell B7 costimulatory proteins
What promotes CTLs maturation?
CD4+ Th1-derived interferon-gamma and IL-2
There is evidence that CTL subsets exist that can trigger Th1 or Th2 responses. Which response is generated in the less severe form of leprosy? In the more severe form?
Less severe = Th1
More severe = Th2
("They did not choose wisely")
What are the five steps involved in CTL killing?
1. TCR- MHC class I binding
2. CTL activation
3. Lethal hit delivered
4. CTL disengage
5. Death of cell
What are the two proteins involved in CTL killing, and what is the function of each?
Perforin perforates target cell, allowing for:
Granzyme B entry causes activation of Caspase pathway --->mitochondria release apoptosome