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Immunity to Infection • • • • Obviously protecting the host from infection is the main goal for the immune system The immune system as an integrated defense mechanism. The first thing to remember is that most microorganisms arriving at the external surfaces of the body fail to establish a colony. Just as in military strategy, the hardest thing for an invader to do is to establish a beachhead. So one cardinal property which distinguishes microorganisms capable of colonising hosts from the much larger number which can not is their ability to overcome the physical and physiological barriers which protect the surfaces of the body. Immunity to Infection • • • • Even then the majority of colonising organisms do not penetrate the body's surface Indeed the presence of these harmless commensal bacteria makes a significant contribution to keeping out undesirables. Pathogens, then are that rather select group which can both colonise and invade the body There are a very small number of exceptions to this (almost all gut bacteria) which can cause disease by secreting toxins which damage the host without the organisms themselves penetrating the body surface. Immunity • resistance to particular pathogens or to their toxins or metabolic by-products • based on the ability to distinguish “self” from “non-self” • antigens elicit immune responses Antigens • proteins • polysaccharides • glycoproteins • glycolipids • most effective are large and complex • haptens are small molecules that are not antigenic by themselves 4 Body Defenses Against Infection • Pathogen • Disease causing agent • Bacteria, Viruses, Parasites, Fungi • innate defenses • general defenses • protects against many pathogens • adaptive defenses • immunity • more specific • carried out by lymphocytes Innate Defenses • • • Early Immune responses (4-96 hrs) The immediate defenses are available instantly or within an hour or so of invasion The recognition of foreign antigens triggers the adaptive immune response by the de novo synthesis of cytokines etc. Innate Defenses • Species Resistance • resistance to certain diseases to which other species are susceptible • Mechanical Barriers • skin • mucous membranes • Chemical Barriers • enzymes in various body fluids such as Amylase • pH extremes in stomach • Fever • inhibits microbial growth • increases phagocytic activity Innate Defenses Inflammation • Acute inflammation is a short-term process, usually appearing in a few minutes or hours • Ceasing once the injurious stimulus has been removed • It is characterized by five cardinal signs: rubor (redness), calor (increased heat), tumor (swelling), dolor (pain) functio laesa (loss of function). Innate Defenses Inflammation • tissue response to injury • helps prevent spread of pathogen • promotes healing • blood vessels dilate • capillaries become leaky • white blood cells attracted to area • clot forms • fibroblasts arrive • phagocytes are active 'Natural' antibody • Even when an organism is encountered for the first time there may be some IgM antibody which may bind to its' surface structures • This is called 'natural' antibody • low affinity • It should be recognised that even very low affinity reactions with IgM can trigers the reactions Innate Defenses Phagocytosis Destruction of foreign particles • Neutrophils • Monocytes • Macrophages Innate Defenses Phagocytosis • • • • • • Macrophages: resident in almost all tissues particularly in large numbers in mucosal tissues Neutrophils are present in the blood in very large numbers Neutrophils can be rapidly recruited to any site which innitiate inflamatory reactions and/or activates complement Both types of phagocyte possess receptors which enable them to bind and phagocytose microbial organisms These receptors recognise molecules such as carbohydrate structures which are not present on host cells Once organisms are engulfed, they are subject to a battery of chemical and enzymatic attacks which in many cases destroys them. Innate Defenses Interferon • Interferon alpha/beta are produced by a variety of cells (Leukocytes & fibroblasts) in response to viral infection • They have an important role in limiting viral infection in the early phase (before specific immunity is available) • They do this both directly and indirectly. 1. They act on a wide variety of cell types to induce the synthesis of a series of proteins which interfere with viral replication both by degrading RNA and by inhibiting 2. They also potently activate NK cells. protein synthesis. Innate Defenses Natural Killer Cells (NK Ceels) • • • • • • A type of lymphocyte Lyses of viral-infects cells and cancer cells These lymphocytes lack some antigen specific receptors of T and B cells. They are part of the innate immune system They play an important role in viral infections. They are activated by the cytokines IL12 and IFN alpha/beta. Innate Defenses Complement