Flashcards in Objectives and Vocabulary for Week # 11 Deck (59):
Where does activation of naive T lymphocytes occur?
Typically in the secondary lymphoid organs, when they come in contact with APCs, specifically DCs.
What is the role of effector CD4+ and CD8+ effector cells?
CD4+ cells activate macrophages, B Cells, and other cells; CD8+ cells kill infected cells and activate macrophages.
What are the first and second signal in T lymphocyte activation?
1) Antigen recognition by the T cell receptor (specifically dendritic cells) 2) Co-stimulation
What happens to T cells that have signal 1, but not signal 2?
1) Die by apoptosis or 2) enter into a state of prolonged unresponsiveness.
T cell surface marker that binds to B7-1/2 (CD80 and CD86), which is present on the surface of APCs.
(CD80 = B7-1 and CD86 = B7-2); expressed on the surface of APCs (DCs, Macrophages, and B lymphocytes); upregulated by TLR recognition of pathogen and the secretion of IFNg (Example of innate aiding adaptive); B7-2 is expressed constitutively at all levels and is then upregulated quickly after APC activation.
Bcl-2 and Bcl-Xl
anti-apoptotic proteins, promote survival; enhanced proliferation; increased metabolic activity; production of IL-2; and the differentiation of the naive T cells into effector and memory cells.
(inducible co-stimulator, CD278); ligand is ICOS-L (CD275), which is expressed on dendritic cells, B cells, and other cell populations; responsible for the development and activation of follicular helper T cells, which is needed to create high affinity B cells.
Cytotoxic T Lymphocyte antigen 4; inhibitory receptor; recognize B7 molecules just like CD28, but instead of activating T cell, it inactivates T cells by competitively inhibits CD28, remove B7 molecules from the surface of APCs, or deliver inhibitory signals that block activating signals from the TCR and CD28
Programmed death 1; inhibitory receptor; PD-ligand interactions inhibit the activation of effector cells, especially in peripheral tissues.
Present on the surface of T cells. Interacts with CD40 on the surface of APCs. Activates APCs to make them more potent by enhancing their expression of B7 molecules and secretion of IL-12 that promotes T cell differentiation.
Activated T cells enable APCs to become more powerful stimulators; CD40L and CD40 interaction Activates APCs to make them more potent by enhancing their expression of B7 molecules and secretion of IL-12 that promotes T cell differentiation.
Describe the changes in outer surface of the T cell as it is activated. What are their purposes?
1) CD69 expression increased, causing decreased amounts of S1PR1 (sphingosine 1-phosphate receptor aids in migration out of lymph node) which keeps the lymphocyte in the cell. 2) CD25 (IL-2RA) Increased expression allows for T cell to respond to IL-2 3) CD40L enables CD4+ T cells to interact with macrophages and B cells. Enables APCs to become better APCs 4) CTLA-4, increased expression to regulate T cell response. 5) reduced expression of CCR7 and L- selectin (both are responsible for migration into the lymph nodes) 6) Increased expression of LFA-1 and VLA-4 receptors for E and P selectin respectively, responsible for migration to peripheral sites of infection 7) Increased expression of CD44 a receptor for the extracellular matrix molecule Hyaluronan, helps retain effector T cells in the tissues at sites of infection and tissue damage.
IL-2 and its role in T lymphocyte activation
1) Role: growth, survival, and differentiation factor for T lymphocytes 2) Produced by: mainly T cells (autocrine/paracrine function) 3) IL-2R receptors: present briefly on naive and effector T cells, while regulatory T cells always express high affinity IL-2 receptors;
How does IL-2 stimulate the survival, proliferation, and differentiation of antigen-activated T cells?
Aids in the production of anti-apoptotic protein Bcl-2; increases the production of effector cytokines IFNg IL-4
What cytokine is required for the survival and function of regulatory T cells?
IL-2; IL-2 has also been shown to stimulate proliferation and differentiation of NK cells and B cells.
Roles of effector T cells (CD4+ and CD8+)
CD4+: Activated B lymphocytes, Macrophages, and Dendritic cells CD8+: cytotoxic and kill infected cells
Transcription factor that promotes the differentiation of memory cells.
Integral part of the adaptive immunity, characterized by their ability to survive in environments with little to no available antigen and mounts enhanced responses to pathogens previously encountered.
What proteins are released that keep memory T cells alive, even without survival signals?
Bcl-Xl and Bcl-2 are anti-apoptotic proteins, which prevent the release of cytochrome c from the mitochondria, which prevents apoptosis due to the lack of survival signals.
What cytokine is most important for the maintenance of memory CD4+ and CD8+ T cells?
IL-7, which is also important in early lymphocyte development and survival of naive T cells
Which cytokines induce the expression of anti-apoptotic proteins?
IL-7 and IL-15
What receptors are up-regulated in response to T cell recognition of antigen, to keep the T cells at the site of infection? What are their ligands?
1) VLA-4/5 and CD44 2) Fibronectin/(VCAM-1) and hyaluronan are the ligands respectively.
Delayed-Type Hypersensitivity, tissue damage caused by an immune response, damaged caused by CD4+ recruitment of leukocytes, which is characteristic of inflammation.
Th1 cell (Signature cytokine, Immune reactions; Host defense, and Role in diseases)
1) IFNg 2) Macrophage activation / IgG production 3) Intracellular microbes 4) autoimmune diseases; tissue damage associated with chronic infections
Th2 cell (Signature cytokine, Immune reactions; Host defense, and Role in diseases)
1) IL-4, IL-5, IL-13 2) Mast cells, eosinophil activation; IgE production; "alternative" macrophage activation 3) Helminthic parasites 4) allergic diseases
Th17 cell (Signature cytokine, Immune reactions; Host defense, and Role in diseases)
1) IL-17A, IL-17F, IL-22 2) Neutrophilic, monocytic inflammation 3) extracellular bacteria; fungi 4) autoimmune inflammatory diseases.
What chemokine receptors are on the surface of Th2 cells? What do they do?
Chemokine receptors CCR3, CCR4, and CCR8, which recognize chemokines that are expressed at sites of helminthic infection or allergic reactions, primarily in mucosal tissues
What chemokine receptors are on the surface of Th17 cells? What do they do?
Chemokine receptor CCR6, which binds to CCL20, which is produced by various tissue cells and macrophages in some bacterial and fungal infections.
What cytokines drive the differentiation of naive T cells to Th1 cells? Where are they produced?
Th1 differentiation is driven mainly by IL-12 and IFNg and occurs when microbes activate DCs, macrophages, and NK cells
What cytokine is secreted by NK cells that are important to cell mediated immunity?
IFNg, causes Th1 differentiation and causes DCs and macrophages to produce IL-12
How do Th1 cells promote differentiation of only their class of effector cells?
Th1 produces IFNg, which leads to more Th1 differentiation, but also inhibits Th17 and Th2 differentiation.
What transcription factors are activated for Th1 differentiation?
1) IFNg leads to STAT1 and T-bet differentiation leading to greater IFNg production 2) IL-12 leads to STAT4 production, which also leads to IFNg production.
What is the principal function of Th1 cells?
Activate macrophages; activate immunoproteosome; promotes the expression of MHC; increased expression of co-stimulators
What is the principle cytokine that activates macrophages?
What type of cells produce IFNg?
Th1, NK, CD8+,
IFNg's role in Class switching
IFNg acts on B cells to promote switching to certain IgG sublasses, IgG1 and IgG3 possibly IgG2a or IgG2c inhibits IL-4 dependent isotypes, such as IgE
What is the role of IFNg in Th cell differentiation?
IFNg promotes Th1 differentiation and inhibits the development of Th2 and Th17 cells.
How does IFNg promote antigen presentation?
IFNg stimulate the expression of MHC proteins, TAP, the proteosome, HLA-DM, and B7 costimulators on APCs
What role does IL-10 play in Th1 regulation?
IL-10 is produced by Th1 cells, and inhibit the ability of DCs and Macrophages to activate Th1 cells. Negative feedback loop
Describe Th1 mediated Classical Macrophage activation
CD40L from the T cell interacts with CD40 on the surface of macrophages. IFNg produced by the T cell also interacts with the APC. The macrophage response is the production of ROS, NO, lysosomal enzymes, secretion of cytokines IL-1, IL-12 and TNF and chemokines; increased expression of B7 costimulators, and MHC molecules.
Th2 Overview. Responsibility and Effector functions
mediator of phagocyte independent defense (mostly parasites); eosinophils and mast cells play the most important role; also key in the development in allergic disease (produce IgE)
How does the development of Th2 cells occur?
Th2 differentiation occurs in response to IL-4 and occurs in response to helminths and allergens
How does IL-4 stimulate Th2 differentiation?
Activates the transcription factor STAT6, which together with TCR signals, induces the expression of GATA 3; GATA-3 a transcription factor that acts as a master regulator of Th2 differentiation;
Master regulator of Th2 differentiation; leads to increased IL-4, IL-5, and IL-13; blocks Th1 differentiation by down-regulating IL-12R
Master regulator of Th1 differentiation; production of IFNg
What are the functions of Th2 cells?
Stimulate IgE, mast cell, and eosinophil mediated reactions that serve to eliminate helminthic infections.
Functions of IL-4
Th2 differentiation and function; produced mainly by Th2 and activated mast cells; stimulates B cells to class switch, and produce IgE/allergic responses; also important for class switching to IgG4 in humans, and IgG1 in mice; inhibits switching to IgG2a and IgG2c (both of those classes are induced by IFNg/Th1)
IL-4 and IL-13
1) Together inhibit defense against intracellular microbes (both inhibit production of IFNg) 2) Stimulate the recruitment of leukocytes; 3) IL-4 increases peristalsis in the gastrointestinal tract, while IL-13 increases mucus secretion from airway and epithelial cells.
Activation of macrophages via the IFNg/Th1 route; cause Macrophages to carry out microbicidal functions; inhibited by IL-13 and IL-4
IL-4/IL-13; Th2 mediated activation of macrophages; response is tissue repair, anti-inflammatory effects, wound repair, and fibrosis; inhibited by IFNg.
Th17 subset overview
primarily involved in recruiting leukocytes (IL-17 mediated neutrophil inflammation) , inducing inflammation, and combating extracellular bacteria and fungi.
What three cytokines lead to Th17 differentiation?
IL-6, IL-1, IL-23
How are Th17 cells inhibited?
Inhibited by IL-4 and IFNg (Th2 and Th1 respectively)
What transcription factors are important for Th17 development?
Stat 3 (IL-6) and RORgt (TFG-b)
What cytokines do Th17 cells produce?
IL-17 and IL-22
What cytokines do Th2 cells produce?
IL-4, IL-5, IL-13
What cytokines do Th1 cells produce?