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Specific Immune Response

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Natural Science
NATS 1670
Motti Anafi

The specific immune response Specific (Adaptive): • • Effects after few days • • Leads to a state of immune memory • • High specificity- improve during the course of respons - A response to a specific immune stimulus (antigen) - The immune system can "remember" invaders and react more promptly to second exposures to infection. -- Only an exposure to the same antigen will activate this memory response. - The specific immune system is NORMALLY distinguishes between self- and non-self and only reacts against non-self. Humoral adaptive immunity - ANTIGENS (Ag, antigenic determinants) - substances that induce a specific immune response and subsequently react with the products of a specific immune response. - ANTIBODIES (Ab, Immunoglobulins, Ig) - protein molecules that are produced by plasma cells in response to an antigen and can bind specifically to that antigen. -- Are proteins that serve as molecular weapons of defence. - antibodies have a specific shape and are made out of regions that are very specific to the pathogen and have a region that is different from other antigens. - Recognition: They can recognize their specific antigen. Their recognition works to create a pocket that the antigen can fit into. -- Have very specific shape -- Contain four polypeptide (protein) chains arranged in a Y shape -- The antigen binding site consists of combination of residues from the heavy and the light chain -- Have variable (top of Y) and constant regions (other part) Antibody Molcule Antigen Binding Site | | Y - Light Chain (two extended arms: V) - Heavy Chain ( the base of the two extending arms (|) NOV 23,2011 NATS NOVEMBER 23, 2011Humoral Adaptive Immunity-Antibodies recognize foreign pathogens and help to destroy theySteps: -Neutralization: the attachment protein is blocked by antibodies to stop the cells from infecting other cells. Antibodies can block bacteria and virus cells. -Agglutination: antibodies cells have two binding sites. Collect together many pathogens and then get rid of them at once.-Precipitation: clumps together molecules dissolved in bodily fluids and destroys them all together. -Activation of complement: you can create holes in the membrane of bacteria and it bursts and dies.-40 years ago the way to see interaction between bacteria and antibodies was by taking the bacteria and letting it grow, then adding a drop of antibodies. They you see the tube becomes cloudy nd you cant see through because interactions between bacteria type of interactions so you had to do these tests (Agglutination, Precipitation)at Function of Antibodies- an antibody molecule has two related functions in humoral immunity-recognize and bind to a certain antigen- By binding to it, help to counter its effect- Neutralization: Ab “neutralizes” toxins, binds to attachment molecules- Agglutination: Create complexes of cells- Precipitation: create complexes of molecules- Opsonization: Ab binds to pathogen surface molecules and link them to phagocyte cell.- Complement Activation: occurs on antibody bound to pathogens. Complement alsowork in the acquired immunity as well. ** Opsonization by Antibodies (Ab)- to increase the efficiency of the interaction Lymphocytes- we have billions of antigens and we need a strong immunity when a relevant infection is around- when were are making an antibody that is specific to an antigen, this antibody must be produced by 1 lymphocyte. This specific cells only knows how to make antibodies for one specific antigen, nothing else.- to recognize approximately trillion of possible antigens, individuals and specifically- each lymphocyte has 1 specific antibody that it expresses for its lifetime- this creates a bit of a problem because in order to make an effective amount of antibodies, to mount an effective response, we need to have sufficient cells specific for the antigen in question (100,000’s to millions)- it is not possible having 1 million x1 trillion (10~15) cells in the body just for specific immunological response. -our entire body consists of 10~14 cells. We need to be ten times as large just for the immunesystem- the body needs to find another way in order to give us this specific activity against all kinds of pathogens that are around now or may be around. - The Solution: Clonal Selection of Lymphocytes(what Prof said outloud) -we have trillions of cells that can recognize different antigens and they are located in lymphnodes doing nothing until the relevant antigen is around. When it’s around the antigen binds to the B Cell they create antibodies and secrete them out and the B Cells create 2 new cell( clone them selves) and have the ability to secrete antibodies outside of the cell. They’re still considered as B Cells but they get another name to describe that they are a bit different. As Summary of Clonal Selection: - the immune system has an extremely low frequency of cells specific for each of trillion of specificities (5-10/cell)- when a cell encounters its specific Ag, it replicates extensively, turning ~5-10 cells into millions of progeny- Rare antigen-specific cells can increase in number so that they get the ability to effectively fight the pathogen that elicited the response. www. Clonal selection and immunity - Primary response is about clonal selection -Our immune system has a chemical memory of infections. Immunological memory Immunological memory is the ability of the immune system to respond more quickly and effectively to pathogens that have been encountered previously -The primary immune response takes several days to produce effector cells via clonal selections. - clonal selection produces also memory cells, which can last decades in the lymph nodes. - The secondary immune response can be developed when the same antigen is encountered again. - Initiated much faster due to the presense of memory cells. - In the primary response the major class of AB produced is Igm. - In the secondary response it is IgG The Body's Defenses ALL IN ONE- Summary The First Line of Defense (nonspecific) • Skin • Mucous Membranes and their Secretions ◦ Stomach acid ◦ Mucous ◦ Tears ◦ Urine The Second Line of Defense (nonspecific) • Phagocytic White Cells ◦ neutrophils ◦ monocytes / macrophages ◦ eosinophils • Antimicrobial Proteins ◦ complement ◦ cytokines (interleukins)? ◦ interferon • The Inflammatory Response and Fever ◦ histamines ◦ cytokines (interleukins) ◦ pyrogens The Third Line of Defense: The Immune system (specific mechanisms) • Lymphocytes (Cellular response - a 2 prong attack on invaders) ◦ B-cells - antibodies ◦ T-cells - help stimulate B-cells, other T-cells directly attack infected cells or are involved in self-regulation of the immune system. • Antibodies (Humoral response) Basic Features of the Immune System The Immune system's primary role is to protect the body against damage from any source that proves dangerous including viruses, bacteria, fungi, and other microorganisms as well as internal threats such as cancer. Evolution continues to improve the countermeasures parasites use to invade our bodies. Although our immune system is also capable of evolving to meet this challenge medical and technological advances so far have kept the legions of invaders at bay. How long will the uneasy peace last against constant new threats such as AIDS and E. Bola. How does the immune system identify and respond to pathogens? The first step involves the preparation of a molecule of foreign protein, referred to as an antigen, for identification. Macrophages such as the interdigitating dendritic cells and other so-called antigen-presenting cells, APCs, such as macrophages scavenge materials from the blood and tissues and digest them. Once inside these cells, small pieces of the antigens (peptides) enter a special processing center, a vacuole called the compartment for peptide loading or CPL, where they are bound to a special class of membrane proteins called major histocompatibility complex (MHC) molecules. The CPL somehow attaches the antigen to a class II MHC molecule and embeds it into the plasma membrane for all passing immune cells to see. It is this antigenic flag around which various lymphocytes rally. MHC molecules are organized into 3 classes. (Class I molecules are found on all nucleated cells, class II are found on B-cells and macrophages, and class III are the various soluble proteins that make up complement.) Class I MHC molecules act as a badge identifying all nucleated cells as "self". T-cells have molecules called T-cell receptors which fit like lock and key to the Class I or Class II MHC molecules on normal healthy cells. But these T-cell receptors are actually a dual site, capable of recognizing a specific antigen which is attached to the MHC molecule. T-cells can only be activated when the antigen-MHC site is occupied (first signal), and a second, less understood, site is also involved (second signal). Conversely, anytime a T-cell gets the first signal but not the second it will be inactivated - perhaps by apoptosis. (A receptor protein coded CD28 is implicated) The body's third and perhaps the ultimate line of defense is its immune system. It is distinguished from the nonspecific defenses by four features: specificity, diversity, self/non-self recognition, and memory. a. Specificity - the immune system's ability to recognize and eliminate particular microorganisms and foreign molecules called antigens. b. Diversity - the ability of the immune system to respond to millions of kinds of invaders, each recognized by its antigenic markers by a unique antibody producing lymphocyte. c. Self/Non-Self recognition. Why doesn't the immune system attack our own cells? The standard explanation is that the immune system is "trained" during its early development to recognize the difference between self and non-self. This is called self-tolerance. It is presumed that any lymphocytes with receptors for molecules present in the body (self) before birth (and perhaps after) are somehow destroyed. Thus there are no antigen receptors for an animal's own molecules. However it may be that the immune system responds to danger, actual damage detected as a special chemical signature caused by the rupture of injured or dying cells. d. Memory - refers to the immune system's ability to remember antigens it has encountered and to react quickly and effectively against them a second time around. This is known as acquired immunity. Acquired immunity may be active; conferred by recovery from a particular infectious disease; or passive&emdash;transferred from one individual to another&emdash;often obtained through vaccination. It the case of infants mom's antibodies can pass through the placental barrier. When a lymphocyte first encounters an antigen it recognizes and is stimulated to divide it initiates the Primary Immune Response. The process involves clonal selection, the rapid development of a single line or lines of T- and B- lymphocytes from a vast and diverse army. But before this occurs all pathogens must slip by the: I. The First Line of Defense 1. The skin is an effective physical barrier by being both tough (keratin resists the digestive enzymes of invading bacteria) and poisonous (certain fatty acids are toxic to bacteria as are secretions from sweat and oil glands which lower the pH of the skin somewhere between 3 and 5&emdash;a hostile environment for most pathogens). 2. The secretions of the mucous membranes in the respiratory system effectively trap invading bacteria which can then be swept away by the ciliate lining. 3. The nasal passages and sinuses are now known to make nitrous oxide and other nitrogen compounds which are toxic to a wide range of infectious microorganisms. "Unlike the nose, which harbors many types of bacteria, the sinuses...remain curiously free of intruders." The reason, recently discovered, is that the sinuses produce nitric oxide, NO, a gas considered a pollutant in the atmosphere is lethal even in small doses to bacterial and viruses, binding strongly to their vital enzymes. NO is made by the sinus' epithelial cells. (July '96, Discover) 4. Most invaders cannot withstand the strong acid (HCl) found in the stomach. 5. Anti-bacterial enzymes known as lysozymes are found in tears and other body secretions. Lysozymes (digestive enzymes) found in the respiratory tract and around the eyes attack the cell walls of many bacteria. 6. Urinary passages are protected by the flushing action of urine. 7. The vagina and lower intestine are protected by the symbiotic association of mutualistic bacteria which help crowd out dangerous species by using up available resources, out-competing the invaders or by creating a hostile environment. 8. The inflammatory response and fever. Certain white blood cells release molecules called pyrogens which set the body's thermostat at a higher temperature. While a high fever is dangerous a moderate one inhibits the growth of some microorganisms (possibly by decreasing availability of iron) and can facilitate phagocytosis. II. Secondary /Tertiary Defenses: Nonspecific and Specific 1A. Nonspecific, Chemical Secondary Defenses 1. Histamine - speeds release of other agents both chemical and cellular and initiates the inflammatory response. Histamines (which are blocked by antihistamines) initiate the redness and swelling associated with inflammation and infection. Histamine is released by injured basophils and mast cells that are found in connective tissue. Histamine triggers local vasodilation and makes the capillaries leakier. Prostaglandins which are also released promote blood flow to the injury. 2. Cytokinins (kinins or lymphokines)- attract phagocytes, increase inflammatory response. Released by injured cells, these short polypeptides increase circulation and capillary permeability; attract white blood c
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