T-Cell Immunity Flashcards
What is the site of naive T cell activation?
Secondary Lymphoid tissue
What are the phenotypic markers used to define naive T cells?
CCR7 and L-selectin
To what chemokines does CCR7 bind? What are the sources?
CCR7 binds to CCL19 and CCL21 bound on HEV and produced by activated dendritic and stroma cells of the lymphoid tissue
What are the ligands for L-selectin and where are they located?
HEV addressins CD34 or Glycam-1
In addition to the bindings of CCR7 and L-selectin, what is required for T cells to move into tissues?
LFA-1 (expressed by all T cells) is activated by endothelial chemokines and binds to ICAMs 1 and 2 to allow for diapedesis
How do interactions between T cells and APCs change upon recognition of cognate antigen?
T cell is initially bound to the dendritic cell via a low-affinity LFA1: ICAM-1 interaction; Subsequent binding of TCRs signals LFA1 to undergo conformational change that increases the affinity of the interaction and prolong the cell: cell interaction
What mediates the secondary signal needed for activation of naive T cells?
Professional APCs express co-stimulators B7.1 and B7.2 expressed after activation which binds to CD28 on the T cell.
What consequence of CD28 binding to B7 helps to dampen the reponse?
Interaction between B7 and CD28 signals T-cell expression of CTLA-4 which binds more strongly to CD28 and inhibits the interaction with B7
What are the professional antigen presenting cells found in secondary lymphnode tissue?
Dendritic cells, macrophages, and B cells
What is the most efficient antigen presenting cell?
Dendritic cell
What is an immunological synapse?
The region of contact between and T cell and APC
How is intracellular signaling of T cell activation initiated?
ITAMs on the cytoplasmic tails of CD3 and zeta chain are phosphorylated by LcK. Also bound to the ITAMs and phosphorylated by LcK is tyrosine ZAP-40 which further propagates the signal
What is the end point of signaling through ZAP-40?
Activation of 3 transcription factors: NFAT, AP-1, and NFkB
What is the first major product synthesized by T cell upon activation that is necessary for proliferation and differentiation?
IL-2
Why does IL-2 only bind to effector T cells and not naive T cells?
It must bind to high-affinity receptor- naive expresses low affinity and upon activated increases the affinity
What is triggered by high affinity binding of IL-2 to an effector T cell?
Clonal expansion
What pharmaceuticals inhibit IL-2 production?
Cyclosporine, tacrolius, and rapamycin
What is the T cells response to recognition of antigen in the absence of costimulation?
They become anergic
True or false: B7 is only expressed on APCs during infection.
True
What is the process of peripheral tolerance development in T cells?
When a self reactive T cell recognized self antigen it becomes anergic; also through action of certain T helpers
What determines the differentiation pattern of an activated CD4+ T cell?
Determined by the local secondary lymphoid milieu set up by the innate immune system
What cytokines induce the differentiation of TH1 cells? What are their signature cytokines produced? What is their function?
IL-12 and IFN-gamma; IFN-gamma; Macrophage activation for bacterial and viral infections
What cytokines induce the differentiation of TH17 cells? What are their signature cytokines produced? What is their function?
IL-6 and TGF-b; IL-17 and IL-6; Help neutrophil respond to extracellular bacterial and fungal infections
What cytokines induce the differentiation of TH2 cells? What are their signature cytokines produced? What is their function?
IL-4; IL-4 and IL-5; Activate cellular and antibody response to parasites
What cytokines induce the differentiation of T follicular cells? What are their signature cytokines produced? What is their function?
IL-6; IL-21 as well as signature cytokines of origin TH cell; responsible for activation of naive B cells and class switching
What cytokines induce the differentiation of Treg cells? What are their signature cytokines produced? What is their function?
TGF-B; TGF-B and IL-10; keep effector T cells in check and prevent autoimmunity
True or False: Activation of CD4+ cells requires more co-activation than CD8+ T cells
False- CD8 require more
Briefly, what are the two ways naive CD8+ cells?
1) Dendritic cells infected w/ some viruses can directly activate naive CD8+ cells on their own stimulating their production of IL-2
2) Dendritic cells infected with other viruses active virus-specific CD4 T cell to secrete IL-2
Which types of effector T cells stay in 2ndary lymphoid tissue to carry out their function?
Tfh
True or False: Effector T cells require no costimulation.
True
Through what distribution method (e.g., endocrine) do cytokines most typically move?
Paracrine and autocrine
What molecules mediate the effector T cell function?
Cytokines and Cytotoxins
What are cytotoxins in the context of effector T cells?
Specialized proteins that kill and are premade in 2ndary lymphoid tissue so that when CD8+ cells enter the blood stream they already have their toxins
What is the protein kinase associated with the cytoplasmic tail of most cytokine receptors?
JAKS
What is the JAK-STAT pathway?
Cytokine binding dimerizes cytokine receptor and the cytoplasmic JAKS come together, activate each other and phosphorylate the cytokine receptor. STATs bind to the phosphorylated receptor and are also phosphorylated by JAKs. Phosphorylated STATs form dimers which translocate to the nucleus to affect gene transcription
What is the site(s) of synthesis for CD8+ T cell cytokines and cytotoxins?
Cytokines @ infection site; Cytotoxins @ secondary lymphoid tissue
What stimulates the release of cytotoxic granules from CD8+ T cells?
Recognition of infected cells and formation of immune synapse initiating intracellular signaling
True or False: Once CD8+ cells release their cytotoxic granules they undergo apoptosis?
False- they can just make more :)
What effects are mediated through IFN-gamma?
Antiviral properties, increased MHC Class I expression, activates macrophages
What are the two mechanisms by which CTLs induce apoptosis?
Cytotoxic granule release (perforin and granzymes); Fas-Fas ligand interactions
What is Fas? What is Fas Ligand?
Fas is a receptor only expressed by damaged cells, Fas-ligand is a chemokine expressed only by activated CD8 cells
True or False: Apoptosis by Fas-Fas L ligation help maintain lymphocyte homeostasis?
True
What stimulates effector T cells to express Fas?
Cessation of antigenic stimulation
What is autoimmune hyperproliferative syndrome (ALPS)?
Uncontrolled lymphocyte (B and T cells) proliferation in the absence of infection or malignancy
What causes ALPS? What are the symptoms and lab signs?
One nonfunctional copy of the Fas genes; Splenomegaly, lymphadenopathy, susceptibility to autoimmunity and lymphoma, elevated serum Igs, increased B cells, large numbers of T cells
What are the two signals needed by macrophages to be activated by Th1 cells?
Primary from IFN-gamma and 2ndary by CD40 ligand
What are granulomas- what are their structures? When are they formed?
Occurs wen an intracellular pathogen successfully resists the killing activity of activated macrophages and so the immune system walls off the pathogen into a granuloma consisting of an inner core of infected macrophahes surrounded epitheloid cells and CD4 cells
When does caseation necrosis occur?
If the granuloma grows large enough to cut off their own blood supply
What is linked recognition?
The concept that both Tfh cells ad the naive B cell that they help recognize different epitopes of the same antigen
How are B cells activated through Tfh assistance?
Naive B cells process and present antigen via MHC II to Tfh cells; the recognition of the antigen by the TCR activates the B cell through CD40 and CD40L interactions
What is cognate interaction?
Interaction between a T cell and a B cell recognizing different epitopes on the same antigen
How does Th2 secreted IL-4 help against parasitic infections?
Stimulates class switching to IgE production and works with basophils, mast cells, and eosinophils to eliminate the parasitic pathogens
How do Th17 help respond to extracellular bacteria and fungal infections?
Secretion of IL-17 induces epithelial and stromal cells to produce chemokines that recruit neutrophils
What compounds are characteristically produced? by Treg cells?
CD25, FOxP3, IL-10 and TGF-b
What is IPEX?
Immune dysregulation, polyendocrinopathy, enteropathology, X-linked disease- caused by lack of T regs
