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76 Cards in this Set
- Front
- Back
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Q: For cytotoxic T (virus) immunity, what cells react with the antigen, what form is the antigen in and what killer cells affect infection?
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-CD8 immune, peptide in MHC1, CTL
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Q: For T helper (any pathogen) immunity, what cells react with the antigen, what form is the antigen in and what killer cells affect infection?
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-CD4 T helper, peptide in MHCII, none
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Q: For delayed type immunity, what cells react with the antigen, what form is the antigen in and what killer cells affect infection?
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-CD4 memory cell, peptide in MHCII, macrophage
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Q: For hypersensitivity (TB) immunity, what cells react with the antigen, what form is the antigen in and what killer cells affect infection?
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-CD8 memory cell, peptide in MHCI, macrophage
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Q: For DTH cytotoxic T (TB late) immunity, what cells react with the antigen, what form is the antigen in and what killer cells affect infection?
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-CD8 immune, glycolipid in CD1, CTL
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Q: For superantigen response (enteric Staphylococci) immunity, what cells react with the antigen, what form is the antigen in and what killer cells affect infection?
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-CD4 (nonimmune), unprocessed superantigen, none
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Q: For T regulatory (no pathogen) immunity, what cells react with the antigen, what form is the antigen in and what killer cells affect infection?
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-CD4s (self ags), peptide in MHCII, N/A
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Q: For T suppressor (TB) immunity, what cells react with the antigen, what form is the antigen in and what killer cells affect infection?
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-CD8 immune, peptide in MHC1, none
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Q: Define cell-mediated immunity.
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-is directly effected by cells, without involvement of antibody and contrasts with humoral immunity which is mediated directly by antibodies. Humoral immunity can be passively transferred from one animal (or person) to another by antibody alone. In cell-mediated immunity, ntigen-specific immune lymphocytes must be transfred to the confer immunity. The immune function cannot be transferred by antibodies and the cells must be from one inbred animal into another. The cells that transfer antigen-specific cell-mediated immunity are T lymphocytes.
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Q: What are some subsets of functional T cells?
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-T helper 17 lymphocytes (TH17 cells), cytotoxic T lymphocytes (CTLs), delayed type hypersensitivity (DTH) T cells, T regulatory cells, T suppressor cells, Immune memory T cells
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Q: Describe T helper 17 lymphocytes.
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-are CD4+ T helper cells that secrete IL-17 instead of gamma interferon or IL-4. These T cells are pro-inflammatory and are important in autoimmune diseases.
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Q: Describe cytotoxic T lymphocytes (CTLs).
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-kill other cells. Many CD8+ T cells recognize and kill virally infected cells. The infected cells have (endogenously produced) viral peptide antigens associated with MHC class I molecules. A newly recognized subset of CD8+ T cells kills cells bearing nonpeptide antIgens associated with CD 1 molecules. (There are rare CD4+ cytotoxic lymphocytes which kill cells bearing antigens in the context of class II MHC proteins.
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Q: Describe delayed hypersensitivity T cells.
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-DTH prevents the growth of intracellular bacteria. many of these intracellular bacteria infect macrophages. DTH immunity can be observed as an antigen-specific inflammatory skin lesion that appears 24-48 hours after exposure to antigenic challenge (which is why TB skin tests are read 2 days after injection). If the person is immune, pre-sensitized specific T helper cells will respond to the antigen. The DTH lesion is mediated by macrophages that are activated by Iymphokines from the antigen-specific T cells. (Macrophages themselves cannot recognize specific antigens.) DTH responses include those to tubercle bacilli (TB), Listeria, Salmonella, poison ivy and allergies to metal. Sometimes, CD8 T cells have roles in DTH,.
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Q: Describe T regulatory cells.
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-are CD4+ T cells that are generated in the thymus and maintain expression of CD25+ after they are released from the thymus. They regulate normal immune responses and prevent autoimmune responses.
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Q: Describe T suppressor cells.
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-are functionally defined as a subset of CD8+ T cells that inhibit an immune response by influencing the activity of another immune subset of cells. They are usually measured by their ability to reduce proliferation of T helper cells or T cytotoxic immune ceils when they are challenged with antigen. They can also reduce B cell proliferation and antibody production.
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Q: Describe immune memory T cells.
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-last a lifetime. They are "restricted," i.e., they have to respond to antigen presented in the same MHC I or II format as the antigen was presented during initial exposure.
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Q: Class I MHC restriction.
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-CD8+ T lymphocytes display strict memory in terms of what they will kill. Most CD8+ T cells recognize "self' MHC class I proteins holding foreign peptides, such as viral peptides. The CD8+ T cells also recognize MHC class I proteins of foreign grafts. A CD8+ killer cell will kill only target cells that hold the identical foreign peptide in the identical MHC class I protein that first stimulated the particular T killer cell.
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Q: Describe Class II MHC restriction.
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-CD4+ specifically immune T cells will secrete lymphokines and proliferate only when given the original antigenic peptide in the context of the original, stimulatory MHC class II protein-antigenic complexes. The original peptide in the context of other MHC class II proteins will be unrecognized and fail to stimulate lymphokine production.
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Q: Describe CD1 restriction.
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-This restriction applies to T cells that recognize lipid glycolipid or hydrophobic peptide antigens held in CDt proteins. CD 1-restricted immune T cells will recognize only a complex of a CDl molecule holding a particular hydrophobic antigen, not the antigen alone or the CD 1 holding another hydrophobic antigen. Some T cells recognizing CD I-antigen complexes are CD4- CD8- ("double negative") T cells
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Q: What is lysis?
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-Lysis is the disruption of the plasma membrane of a cell. Cytoplasm leaks out of the cell.
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Q: What is necrosis?
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-Necrosis is a form of cell death in which the cell is injured by external events.
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Q: What is apoptosis?
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-Apoptosis is a form of cell death in which a cell is induced to commit suicide and dies from the inside out. The plasma membranes still contain the cytoplasm of the cell: the dead cell fragments into membrane-enclosed pieces which are cleared by phagocytic macrophages and neutrophils. This form of death has advantages since intracellular contents (for example, viruses) remain contained. Prior to the cell death, the nucleus appears condensed, the cell shrinks, and the plasma membrane blebs.
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Q: What must happen to the T cells before T cell function can occur?
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-T cell divide and increase in number before these T cell functions can occur. In generation of T help for antibody production, DTH, T killer and T suppressor "cellular" immune responses, selection and proliferation of antigen-specific T cells and generation of memory cells are essential to get the immune response. Antigen-specific immune responses require interleukins (such as the growth factor interleukin 2) to support their cell growth. Clonal expansion is the point of the figure that will be drawn in class. The antigens have to be presented or held by MHC proteins or CD 1 proteins.
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Q: What are the three forms that antigens are found in that are recognized by T cells?
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-peptide antigens in MHCII, peptide antigens in MHCI, and glycolipid and lipid nonprotein antigens in CD1
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Q: Describe peptide antigens that are in MHCII.
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-Processed exogenous protein antigens are made outside the cytoplasm of the antigen-presenting cell, digested to peptides in phagolysosomes of the antigen-presenting cell (i.e., "processed") and are combined with MHC class II to present them as exogenous, processed antigens. Dendritic cells and macrophage are very good antigen-presenting cells that internalize and process exogenous antigens. Exogenous or 'extracellar' antigens are synthesized outside the particular cell that "presents" the antigens. Usually exogenous antigens are synthesized by bacteria, yeast, plants, etc. and not by the cells of the host animal or person.
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Q: Describe glycolipid nonprotein antigens in CD1.
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-These antigens also get processed. The processing mechanisms are areas of current research. Processing may be exogenous or endogenous in origin. The glycolipids and lipids freed from bacteria such as tubercle bacteria are presented within the grasp of CD 1 proteins. CD 1 proteins hold much more hydrophobic antigens than MHC proteins.
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Q: Describe cytotoxic CD8+ T lymphocytes and the antigens they recognize.
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-kill virally infected cells. Viruses can infect almost any type of cells. The viruses are intracellular. It is the function of the MHC class I system to capture intracellular antigens and present them on the outside of the infected cell so that the circular T cells can detect those cells that harbor viruses.
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Q: What is the role of the CD8 proteins on the CTLs?
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-The CD8 proteins are co-receptors for antigen. CD8 molecules bind to MHCI molecules, to make it easier for the T cell receptors for antigens (TCR) to locate a 'cognate' antigen made of foreign peptide held by MHCI.. The CD8+ T cells also have CD3 and CD2 cell surface proteins.
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Q: What does the interaction of CD8+ CTL with viral antigens require?
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-requires that the endogenously produced viral peptides be presented by class I MHC proteins. CD8+ anti-viral CTL are MHC class I restricted in their killing.
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Q: What does the induction phase of CD8+ CTLs activate?
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-activates naive T cells into effector cells and/or memory cells. Clonal selection and clonal expansion are essential for generation of cytotoxic T lymphocytes CTLs). The CD8+ cells initially lack mediators and will acquire cytotoxic molecules to become the killers. In vivo, antigen-reactive cells are chosen for clonal expansion. CTL induction requires three cell types (the CD8 cells, I CD4 helpers, and APes for the CD4 helpers)
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Q: Describe the antigens for CTLs.
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-The target antigens for killer cells are antigens which are associated with the MHC class I proteins on the stimulator or "target" cell surface. These antigens will come from the viruses that infect the target cells. These killers need T helper cells to provide a source of IL-2, which is a growth hormone for all T cells (CD4+ or CD8+).
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Q: Why do T helper cells need IL-2?
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-IL-2 is needed because CD8+ cells make limited amounts of IL-2. CTL are extremely long lived cells: they appear to remain in resting form in blood circulation for years. In circulation, the memory CTL are quiescent. Cytokines like IL-2 as well as antigen are needed for memory cells to reactivate their cytolytic mechanisms.
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Q: What do the CTLS require at the site of toxicity?
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-only it target. The target is killed and the killer survives. The killer is free to keep killing many more targets. Cells which lack antigens are "innocent bystanders" and will not be killed. The targets die from perforin pores, or by Fas- or granzyme- stimulated apoptosis.
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Q: What are the 3 stages of CTL killing?
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-antigen-specific binding of target cells, programming for lysis, and killer cell independent lysis
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Q: Describe CTL killing.
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-Killer lymphocytes exocytose granules containing a pore-forming protein termed perforin. After granules are exocytosed the targets can die within minutes. Alternately, when granules are not exocytosed, a CTL membrane protein called Fas ligand (FasL) can bind to Fas on the target cells and trigger the targets to commit suicide via preset death programs. The death programs cause apoptosis, which is also involved in the cell death that occurs during tissue remodeling during fetal development. A common feature of apoptosis is DNA fragmentation that occurs before the plasma membrane of the cell becomes leaky. The DNA fragmentation produces ~200 base pair pieces of DNA.
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Q: What are granzymes?
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-Serine proteases termed granzymes are in the lymphocyte granules together with perforin. They can enter cells with membranes that have been permeabilizzed by perforin. When granzyme B enters the target cell, it induces an alternate form of apoptosis, producing typical DNA fragmentation. It is thought that granzyme B (which cleaves after Asp and Glu residues) activates the same caspase death pathway as does Fas triggering. ("Caspase" is the designation for a group of related cysteine aspartate-cleaving proteases.)
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Q: What type of cells does the perforin pathway kill?
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-The perforin pathway of killing is important in killing virally infected cells. It will kill almost any cell type of the body. (And almost every cell is susceptible to some viruses.)
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Q: What is the use for the Fas-induced death pathway?
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-The Fas-induced death pathway is primarily used a means to regulate and kill immune cells. FasL is a protein that is induced in the membrane of killer T cells. FasL binds specifically to the protein Fas that is found on many tissues. After the T cell receptor engages MHC plus peptide antigen, if the protein FasL binds, it can trigger the target (through its Pas) to die from apoptosis.
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Q: Describe the steps involved when a killer T cell employs its FasL to kill other cells.
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-all it has to do is bind to other cells with Fas. The killer cell needs to further signaling to kill. It is the cells that have Fas that respond with intracellular signals. In other words, intracellular signal transduction goes on in the target with Fas and is absent from the effector which has FasL. (It should be noted that T cells may express Fas, and thereby can be killed by the Fas pathway)
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Q: What does the FasL-Fas system recognize CTLs as?
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-CTLs can be targets as well as killers in the FasL-Fas system. The T cells that have FasL are potential killers. The T cells that have Fas are potential victims. The Fas-positive cell, after its Fas-proteins are bound by FasL and cross-linked, will die when a signal activates caspase enzymes. The substrate of the last caspase protease in the cascade activates a DNAse that produces the DNA degradation typical of apoptosis. Fasdependent death is important for control of lymphoproliferation of both T cells and B cells.
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Q: When does CTL kill virally infected cells?
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-only after the host has become immune. Critical resistance of animals and men to viruses is cell-mediated and not antibody mediated. Only live virus induce strong CTL responses. Infected cells produce the endogenous viral antigens that will become associated with MHC class I cellular proteins. Heat killed viruses are noninfectious and fail to produce endogenous antigens. This is why live attenuated virusess make so much better vaccines than heat-killed viruses.
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Q: What is the purpose of the delayed type hypersensitivity (DTH)?
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-provdes defense against bacteria that live inside macrophages, Delayed type hypersensitivity restricts the growth of intracellular bacteria. The "antigen-sensitized T cell that triggers delayed type hypersensitivity to antigens is usually a TH1-helper cell, i.e. secretes gamma interferon (IFN).
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Q: What do DTH CD4+ T cells do?
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-DTH CD4+ T cells do not mediate killing themselves
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Q: What are the 2 cell types required for the production of the DTH response?
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-CD4 TH1 cells and the macrophages. In delayed type hypersensitivity, gamma IFN is the key mediator from the T cells which activates macrophage to become cytotoxic to their intracellular bacteria. Upon recognition of antigen in MHCII, the CD4 TH1 cells secrete gamma interferon. The CD4 DTH THI cells also secrete tumor necrosis factor-alpha (TNFalpha) which produces the local inflammation. Also, after activation, the macrophages secrete several different inflammatory factors. Sometimes CD8 T cells can recognize antigens in MHCI and produce gamma interferon, which allows the CD8 T cells to also initiate DTH. Once again, it is the macrophages that respond.
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Q: What is the biological function of DTH?
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-to arrest the growth of the intracellular bacteria that colonize the macrophage. The bacteria that live inside the macrophages include tubercle bacteria that cause TB, Listeria, and Salmonella. Human macrophage use oxidative mechanisms to arrest the growth of the bacteria, including nitrous oxide (N02-) and nitric oxide (N03-) oxidants that they produce from arginine. The NOx toxic oxidants have a short range because they are unstable, with half lives less than second. Thus nearby uninfected 'bystander' cells are not killed
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Q: What is needed for TB mycobacteria to be arrested?
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-TB mycobacteria may be only arrested (and not eliminated) by the activated macrophage that contains the bacteria. The intracellular bacteria can remain dormant throughout the life of the infected individual.
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Q: What are some other things that can induce DTH response?
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-Other DTH responses are induced by chemicals and irritants like poison ivy instead of by intracellular bacteria. In a test for a patient's DTH competence, the chemical dinitrochlorobenzene (DNCB) is painted onto the skin. The first application is termed "priming", which generates DTH memory cells. After a second application, or "challenge" with the DNCB, a DTH inflammatory response will occur 24-48 hrs later. Normal immune responders develop DTH.
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Q: What happens to antigen recognition during fulminant TB or leprosy?
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-in fulminant tuberculosis or leprosyl, the patients are anergic and unable to respond to many different antigens, including tubercular antigens (or DNCB). The inability of patients to respond in the clinical DNCB test is an indicator of clinical anergy. Thus for these TB patients, a negative DTH test with purified protein derivative (PPD) of tubercle bacteria will be misleading, and the patient could actually have fulminant tuberculosis. Isolation of the bacteria is one way to establish a diagnosis in patients with fulminant TB.
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Q: What are the different subsets of T cells that recognize CD1 proteins with lipid antigens?
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-CD4- CDS- T cells (with TCRs) recognize lipid antigens held in CDl molecules secrete cytokines but do not ki1l the intracellular bacteria.
-The CD8+ T cells which cognize lipid antigens held in CDl molecules contain cytotoxic granules. Cytotoxic granules perforinand another protein called granulysin. Perforin permeabilizes the infected macrophagess to let granulysm into the macrophage. Then granulysin kills the tubercle bacilli. |
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Q: What do superantigens do to T cells?
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-Superantigens activate T cells but bypass the need for antigenic peptides in MHC and the need for antigen-specific immune T cells.
-Superantigens provide an intercellular clamp between the T cell antigen receptors (TCR) of some of the CD4+ T cells and the MHCII molecules. It is hard to say whether the effects benefit the host or the pathogens which secrete the superantigens. Enteric Staphylococci secrete many different superantigens. The effects of the cytokines released from the T cells happens fast when the superantigens are from enteric Staphylococci. Additional superantigens may be encoded by viruses and her bacteria that are found outside the gut. The cytokines released by T cells cause fever and various other side effects. |
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Q: How do superantigens different from normal antigens?
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-superantigens are not processed, superantigens fit outside the antigenic peptide-binding cleft of MHC class II proteins, superantigens bind to only part of TCRs, the V regions of the beta chain of T cell antigen receptors
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Q: Describe the importance of the superantigens being not processed.
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-In their native state, super antigens bind to MHC class II proteins that are already on the surface of cells. They use these MHC class II proteins to activate T cells. The whole superantigen binds to the MHC class II proteins
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Q: Describe the binding of superantigen to TCR Vbetas.
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-Different superantigens bind to different TCR VB's encode by different VB genes. Superantigens bind to their cognate VB's no matter what the TCR alpha chain is and no matter what D and J regions are in this TCR V beta chain. As a result, superantigens activate all of those T cells which have the particular Vbeta. One superantigen can bind to several, but not all, Vbetas. The independence from the TCR alpha chain means as many as 10-20% of all T cells can be activated by Staph enterotoxin superantigens. The superantlgen Staphylococcus enterotoxins cause food poisoning. The large numbers of T cells stimulated cause a massive T cell response with enormous production of interleukins. The interleukins lead to diarrhea, fever and other responses.
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Q: What do superantigens trigger?
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-Superantigens can trigger cytokine secretion from pre-existing T cells that have expanded in response to previous antigens. When they do so, they circumvent the time needed to clonally expand T cells.
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Q: What are some examples of superantigens?
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-Staphylococcal enterotoxins A-E are superantigens. After clamping MHC II , molecules to T cells with various VB TCR regions, they stimulate interleukin release. The released T cell interleukins trigger many responses, including diarrhea which will flush out substantial numbers of the bacterial population. Fever also enhances clearance of bacteria.
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Q: Describe toxic shock syndrome toxin-1 as a superantigen.
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-Another superantigen is the toxic shock syndrome toxin-I, also produced by Staphylococcal bacteria which selectively binds to the TCR Vbeta2 region. Some viruses, such as Epstein Barr Virus and Rabies Virus, produce viral superantigens that clamp MHCII molecules to other TCR Vbetas.
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Q: Describe T regulatory (Treg) cells.
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-T regulatory (Treg) cells are naturally occurring cells that are thought to prevent autolmmunlty.
-Treg's are CD4+ T cells, but differ from CD4+ T helper cells. In circulation (i.e., the peripheral immune system outside the thymus), T regulatory cells are normally CD25+ (expressing the high affinity IL-2R alpha chain) while the lather T cells in circulation lack CD25. (The presence of CD25 confers rapid responsiveness to low levels of IL-2.) T regulatory cells also have the cell surface markers CTLA-4 and glucocorticoid induced TNF receptor (GITR), which most of the other circulating CD4+ T helper cells lack. Tregs also express a transcription factor that the other types of T cells lack, Foxp3. |
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Q: What do Tregs do?
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-T regulatory cells down regulate the proliferation of T helper cells and CD8+ T cells when these cells respond to antigen. The T regulatory cells require antigen recognition and TCR stimulation to be down regulatory. They recognize antigen in MHC II, as would be expected for a CD4+ T cell. It is likely that they recognize auto antigens presented in MHCII.
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Q: What do CD4+25+ T cells require direct contact with the immune cells they regulate?
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-the naturally occurring CD4+ 25+ T cells require direct contact with the immune cells they regulate. Their effects appear to be independent of the cytokines IL-10 and TGFbeta. How the naturally occurring T reg's down regulate immune responses is unknown, but some T reg's can be induced to express perforin and thus may kill antigen-presenting cells to down regulate immune responses.
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Q: When are inducible or adaptive T regs induced?
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-There are also 'inducible' or ' adaptive' T regs that are induced after antigen encounter. These cells may secrete the cytokines IL-IO and TGFbeta and use them for suppression of lymphocyte cell division
-Tregs are CD4+ cells and are induced by antigen in MHC II, and differ from the "T suppressors" described below. |
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Q: Describe Thelper17 cells.
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-Thelper17 cells are CD4+ cells that secrete IL-17 upon antigen stimulation. TH1 and TH2 T cells do not secrete IL-17. As CD4+ T cells, they recognize antigens held in MHC II molecules. Thelper17 cells are induced in the presence of IL-6 and TGFbeta. They are usually induded early in an immune response.
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Q: What do Thelper17 cells secrete?
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-At the site of an infection, where antigen is presented by APCs, TH17 cells secrete 1L-1 7.
-Receptors for IL-17 are found on many cells, including fibroblasts, endothelial cells and keratinocytes. These cells produce many cytokines, to promote inflammation and recruit neutrophils. In addition, the keratinocytes when provided IL-17 and anther cytokine secrete beta-defensins, which kill bacterial. Thus the IL-17 response was probably designed for defense against bacteria. IL-17 responses may also promote pathology, depending on the conditions that created the antigens and the inflammatory state. |
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Q: Describe suppressor T cells.
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-Suppressor T cells, like CTLs, are CD8+ T cells and thus differ from the CD4+ Tregs. Although they are functionally different from CTL, they cannot be phenotypically distinguished. Suppression means that these cells reduce the proliferation of other immune cells, either T helpers, CTL, or B cells reacting to their appropriate antigens. The induction of suppression is antigen-specific. The factors secreted by suppressor cells are nonspecific, affecting any Tor B cells proliferating to any antigen.
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Q: What does the induction of Ts involve?
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-The induction of Ts involves T s clonal expansion, to antigens associated with class I MHC proteins, and 1L-2 from T helper cells.
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Q: Describe the mediators of suppression of the dividing lymphocytes.
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-are soluble
-Cell contact is unnecessary. One possibility is transforming growth factor-beta (TGF-beta). TGF-B was initially named because it allowed cells to behave like tumor cells and grow independent of 'anchorage' to tissue culture dishes. However, it is now known that TGF-B will also suppress cell growth, depending on the culture conditions. In the case of lymphocytes, high concentrations of TGF-B suppress T and B lymphocyte cell division. IL-10 is another possible T cell suppressor factor |
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Q: How is the proliferation of T or B cells evaluated?
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-In vitro assays for suppression evaluate the proliferation (3H-TdR uptake) of T or B cells in the presence of antigens or mitogens. Mitogens are substances that cause resting lymphocytes to undergo cell division. Some plant proteins are mitogens, some bacterial products are also mitogens.
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Q: What is the best evidence for T suppressor cells?
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-Leprosy and TB ,patients are the best evidence that we have for T suppressor cells. For example, TB antigens elicit suppressive factors from cells of TB-infected individuals but not from patients who have never been exposed. The secreted suppressive factors will suppress cell division stimulated by any antigen or mitogen. In fulminant TB, too much suppressive factors are generated and the patients are unresponsive to almost all antigens.
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Q: What are some properties of all T cells?
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-All T cells have TCR antigen receptors, CD3 and CD2 molecules, T cells have either the alpha-beta or delta-gamma TCR receptors. Most T cells are either CD4 or CD8 but some are "double negative" (C4- C8-). The T cell surface proteins have the following roles:
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Q: What roles do the T cell surface proteins have?
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-T cell receptor for antigen (TCR), co-receptor proteins that direct recognition by the TCR, accessory molecules of T cells, signal transduction molecules of T cells
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Q: What are some co-receptor proteins that direct recognition by the TCR?
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-CD4 molecules, which do not vary among individuals, bind to a domain of MHC class II proteins that is conserved in all MHC class II alleles. This recognition directs binding of CD4+ T cells only to MHC class II-bearing cells. CD4 is an accessory molecule that directs TCR (T cell antigen receptor) recognition.
-CD8 molecules, which do not vary among individuals, can bind to a domain of MHC class I proteins that is conserved in all MHC class I alleles. CD8+ cells do not bind to MHC class II proteins. CD8 is the other accessory molecule that direct TCR (T cell antigen receptor) recognition. |
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Q: Describe LFA-1 molecules of T cells.
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-promotes adhesion of T cells to other cells bearing ICAM-l, intracellular adhesion molecule-1. These other cells can be macrophage with ICAM-l or cytokine-stimulated endothelial cells lining blood vessels that have newly synthesized ICAM-l as a result of inflammation. LFA-l/ICAM-l initial adhesion makes it more likely that the TCR or other cellular receptors on cells will subsequently engage.
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Q: Do the alpha-beta or gamma-delta T cell antigen receptor proteins transducer signals into the T cells?
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-The T cell antigen receptor proteins, alpha-beta or gamma-delta pairs, cannot transduce signals into the T cells. Other molecules in the T cell receptor complex are needed to transduce the message that antigen has been bound.
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Q: What do the CD4 and CD8 T cell proteins do?
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-CD4 and CD8 proteins act as signaling molecules. Both are co-receptors for antigen and work together with the TCRs. CD4 and CD8 are adhesion molecules which bind MHCII or MHCI, respectively, increasing binding strength. They act as signaling molecules (after the antigen TCRs are engaged) by stimulating kinase activity in cells. The TCR by itself is unable to signal when it has engaged MHC-antigen.
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Q: What do the CD3 cell proteins do?
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-CD3 proteins are associated with the TCR and also help transduce the signal when antigen is bound to cells. CD3 is always on TCR-bearing cells. The CD4 and CD8 molecules cooperate with CD3 molecules in signal transduction
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Q: What do the CD2 cell proteins do?
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-CD2 promotes adhesion of all T cells to other cells bearing the ligand LFA-3. Engagement of CD2 initiates signals in the T cell cytoplasm that lead to gene activation.
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Q: What is the medical revelance of T cellular immunity?
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-T cell responses, once initiated, last a lifetime. If inflammatory responses are T cell responses, like allergies to metals (which are DTH responses), they will recur upon re-exposure to antigen. Also, in the DTH cell responses to TB without drug therapy, the TB bacteria are only arrested and not cleared. The infected person can relapse in old age or if immunocompromised.
-The pathogenesis of HIV reflects the importance of the CD4 cells. In AIDS, the human immunodeficiency virus (HIV) depletes CD4 cells from the body. Restoration of CD4 competent cells is key to survival and to recovery. -The CD1 antigen recognition system opens a new means for development of vaccines, including vaccines against the bacteria that cause TB and leprosy. |
