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Ch. 4 "Cytokines and Chemokines"-Tony Ramos # (p.105-108 and…

- - - - as you can see, immune cells are places all over the body, so it would seem they are at a disadvantage when it comes time to work together, seeming as they are so far apart. so the key to their success is to be able to communicate quickly and efficiently and that all cells can go where they are needed, and kick pathogen ass
        
        molecules that help communication among immune cells are referred to as cytokines. they do the following three:
        
        the interaction of a cytokine with its receptor on a target cell can cause changes in the expression of adhesion molecules and chemokine receptors on the target membrane, thus allowing it to move from one location to another.
        
        cytokines can also signal an immune cell to increase or decrease the activity of a particular enzyme or change its transcriptional program, thereby altering and enhancing its effector functions.
        
        finally, they can instruct the cell when to survive or when to die with a process known as apoptosis--programmed cell death
        
        early attempts classified cytokines as interleukins which basically meant they communicated between white blood cells (WBCs)
        
        chemokines is like a subgroup of cytokines in the regard that chemokines are specific to the purpose of mobilizing immune cells from one organ, or indeed, from one part of an organ, to another.
        chemokines belong to the class of molecules called chemoattractants, molecules that attract cells by influencing the assembly, disassembly, and contractility of cytoskeleton proteins and the expression of cell-surface adhesion molecules. chemokines attract cells with the appropriate chemokine receptors to regions where the chemokine concentration is highest.
        
        chemokines, for example, are important in attracting cells of the innate immune system to the site of infection and inducing T cells to move toward antigen-presenting cells in the secondary lymphoid tissues.
        
        cytokines communicate in three different types of ways, that really are distinguished by the distance of communication. they are the following:
        
        endocrine--acting on cells from a distance, thus need to travel through the blood stream/circulate to reach their target
        
        paracrine--cytokines that act on neighboring cells by simply diffusing molecules through tissue fluids or across an immunological synapse
        
        autocrine--occurs when a cell needs to promote a positive feedback loop by self stimulation.
        
        Review Figure 4-1
  - - - a. cytokines mediate the activation, proliferation, and differentiation of target cells
        
        cytokines regulate the intensity and duration of the immune response by stimulating or inhibiting the activation, proliferation, and/or differentiation of various cells, by regulating the secretion of other cytokines or of antibodies, or in some cases by actually inducing programmed cell death in the target cell.
        
        stopped on right side of page 107
        
        Refer to Figure 4-2:
        
        inducing stimulus -->
        
        cytokine gene activation -->
        
        cytokine secretion -->
        
        cytokine is receipted on target cell -->
        
        signal induces gene or enzyme activation -->
        
        finally a biological effect is set into motion
        
        this is an example of a signal transduction pathway
- - - - These changes act to transmit or transduce the ligand-binding signal into the interior of the cell, leading to alterations of cellular functions. In the nervous system, we could call the signaling molecules neurotransmitters; in the endocrine system, hormones.
        
        In the immune system, the foreign molecules that signal the presence of non-self entities are antigens, and the small molecules that communicate among the various populations of immune cells are cytokines. Specialized cytokines that induce chemo-attraction or -repulsion are termed chemokines.
        
        The essential concepts that underline cell signaling in the immune system can be summarized as follows:
        
        A cellular signal is any event that causes a cell to change its metabolic or proliferative state.
        
        Signals are usually generated by the binding of a ligand to a complementary cell-bound receptor.
        
        A cell can become more or less susceptible to the actions of a ligand by increasing (up-regulating) or decreasing (down-regulating) the expression of the receptor for that ligand.
        
        The ligand may be a soluble molecule, or it may be a peptide, carbohydrate, or lipid presented on the surface.
        
        The ligand may travel long distances from its entry point through the body in either the bloodstream or lymphatics before it reaches a cell bearing the relevant receptor.
        
        Ligand-receptor binding is noncovalent, although it may be of quite high affinity.
        
        Ligand binding to the receptor induces a molecular change in the receptor. This change may be in the form of a conformational alteration in the receptor, receptor dimerization or clustering, a change in the receptor's location in the membrane, or a covalent modification.
        
        Such receptor alterations set off cascades of intracellular events that include the activation of enzymes, and changes in the intracellular locations of important molecules.
        
        The end result of cellular signalling is often, but not always, a change in the transcriptional program of the target cell.
        
        Sometimes a cell must receive more than one signal through more than one receptor in order to effect a particular outcome.
        
        Integration of all the signals received by a cell occurs at the molecular level inside the recipient cell.
    - - The surface of a receptor molecule binds to its complementary ligand surface by the same types of noncovalent chemical linkages that enzymes use to bind to their substrates.
        
        These include hydrogen and ionic bonds, and hydrophobic and van der Waals interactions.
        
        The key to a meaningful receptor-ligand interaction is that the sum total of these bonding interactions hold the two interacting surfaces together with sufficient bodning energy, and for sufficient time, to allow a signal to pass from the ligand to the cell bearing the receptor.
        
        Because these noncovalent interactions are individually weak, many such interactions are required to form a biologically significant receptor-ligand connection. Must be very close to each other.
        
        Look up the figure on pg. 70 yourself.
  - - - The interaction of a cytokine with its receptor on a target cell can cause changes in the expression of adhesion molecules and chemokine receptors on the target membrane thus allowing it to move from one location to another.
        
        Cytokines can also signal an immune cell to increase or decrease the activity or particular enzymes or to change its transcriptional program, thereby altering and enhancing its effector function.
        
        Finally, they can instruct a cell when to survive and when to die.
      - Interleukins- the name means the communication between white blood cells.
        
        Although the term cytokine refers to all molecules that communicate among immune cells, the name chemokine is used specifically to describe that subpopulation of cytokines that share the specific purpose of mobilizing immune cells from one organ, or indeed, from one part of an organ to another.
        
        Chemokines belong to the class of molecules called chemoattractants, molecules that attract cells by influencing the assembly, disassembly, and contractility of cytoskeleton proteins and the expression of cell-surface adhesion molecules.
        
        The classification and nomenclature of chemokines is more logical than that of interleukins and is based on their biochemical structures. Although chemokines technically fall under the umbrella classification of "cytokines", normal usage is evolving such that the term chemokine is used when referring to molecules that move immune cells from place to place, and the term cytokine is employed when referring to any other messenger molecules of the immune system.
        
        Cytokine Classification:
        
        [Stopped here]
        
        Cytokines that act on cells some distance away from the secreting cell, such that they must pass through the bloodstream before reaching their target, are referred as endocrine.
        
        Those that act on cells near the secreting cell, such that the cytokine merely has to diffuse a few Angstroms through tissue fluids or across the immunological synapse, are referred to as paracrine.
        
        Sometimes, a cell needs to receive a signal through its own membrane receptors from a cytokine that it, itself, has secreted. This is called autocrine.