Innate Immunity Notes PDF

INNATE IMMUNITY At the end of the lesson students will be able to  Define Innate Immunity  Describe the components of the innate immunity  Recognize the effector mechanisms of the innate immunity INNATE IMMUNITY Natural or native immunity and provides first line of defense against any...

INNATE IMMUNITY At the end of the lesson students will be able to  Define Innate Immunity  Describe the components of the innate immunity  Recognize the effector mechanisms of the innate immunity INNATE IMMUNITY Natural or native immunity and provides first line of defense against any microbial infection, foreign material Protective mechanisms that do not require a prolonged period of induction Is a system able to recognize non-self structures but not self and react appropriately, autoimmunity is avoided. Pattern recognition receptors’ (PRRs) recognize pathogen associated molecular patterns’ (PAMPs) microbial structures Detect immunological ‘danger’ in the form of ‘damage associated molecular patterns’ (DAMPs) Exist before encountering with microbes and are rapidly activated by microbes and lately activate the adaptive immunity  Characteristics of the innate immunity Set up at birth and consists all elements with which we are born (inherited ability) Non-specific, and is resistance that exists prior to exposure to the microbe that occur early Does not improve after exposure to antigen Always present and have no lag period Limited diversity Available on short notice to protect and is antigen independent Heredity and has racial or species difference No immune memory (innate immunity dose not remember) Components of innate immune system First Line of Defense Physical Barriers: Skin The dry, acidic surfac e forms a hostile environment that is resists to microbial growth Continual loss of outer dead skin layers removes potential pathogens continuously Cells of the stratum corneum a tight barrier that prevents toxins and bacteria from entering the body The sebaceous glands in dermis of hair follicle produce sebum, maintain the pH between 3 and 5 inhibit growth of many potential pathogens. Sweat regulates body temperature flushes microbes and waste and lysozyme inhibit microbial growth Cont Mucous Membranes: Vulnerable due to very thin epithelial layer, moist surface Includes the linings of the respiratory, digestive & genitourinary tracts Continually produce mucus, a viscous glycoprotein that traps microbes and debris Epithelial cells with inner connective tissue, goblet cells -secrete mucus prevents desiccation, traps microbes, enzymes to kill microbes Acidic environment of stomach kills most microbes Mucus-coated nose hairs, trap microbes Ciliary escalator – ciliated cells of lower respiratory tract mucus-coated & push outward dust/microbes; sneezing/coughing speed up process Epiglottis – Covering over larynx: prevents food and microbes getting in Cont. Tears of lacrimal glands: Under upper eyelid wash over eye & drain into lacrimal ducts, Lysozyme (breaks peptidoglycan walls of bacterial cell walls) Urine: Flushing mechanism prevents microbial colonization, contains uric acid, urea (makes pH ~6.5), lysozyme Acidic environment of the vagina and cervical in healthy women, lactic acid secreted by the commensal bacteria Lactobacilli spp (pH 4.4 to 4.6) Saliva from salivary glands constantly washes over teeth and mouth, contains lysozyme and aggregate bacteria Gastric Juice: HCl, mucus and enzymes, low pH 1.5-3 Kills most microbes and toxins (except to S. aureus and C. botulinum) Some bacteria enter protected by food, H. pylori neutralizes acid and makes a niche for itself in stomach  Cont. Small intestine - Mucus - prevent attachment & entry - Pancreatic enzymes, bile, intestinal enzymes, and secretory IgA - M cells - endocytose pathogens, aids presentation to B and T lymphocytes Peristalsis – Movement of food by coordinated contractions –Defecation – Vomiting in response to microbial toxins Barriers along the privileged organs (Blood – brain barrier, blood – placenta barrier, blood – thymus barrier) Recognition of signals that indicate ‘all-is-well’ and an inhibitory signal that delivered to prevent activation of the immune response against host tissues. Cont. Normal Flora The “normal microbiota” are the microorganisms that live in/on the body of a healthy individual and inhibit the growth of pathogens Commensal microbes which are not pathogenic (disease-causing) except under special circumstances. The skin and the gastrointestinal tract are colonized by more than 500 commensal bacterial and other microbial species. These microbes "defend" their territory: *By virtue of their physical advantage of previous occupancy, especially on epithelial surfaces *By competing for essential nutrients * By producing inhibitory substances such as acid or colicins or toxins specific for other microorganisms e.g in the large intestine (E. coli) *Invasion by extraneous microbes due to alteration of normal resident flora, causing serious diseases, such as staphylococcal enterocolitis or candidiasis following oral antibiotics Cont. Ⅱ. Second Line of Defense consists A. Formed element of blood Platelets - involved in the process of blood clotting Erythrocytes - transport oxygen and carbon-dioxide Leukocytes: Granulocytes (visible granules, Neutrophils- (phagosytosis), Basophils (produce histamine), Eosinophils- produce toxic against parasites Agranulocytes (granules not visible)- Monocytes (phagocytosis when matured to macrophages), Dendritic Cells (phagocytosis) Lymphocytes: Natural killer cells (destroy target cells by cytolysis apoptosis) B. Phagocytes Cells that perform phagocytosis * Neutrophils: early during infection first phagocytes at site of infection * Monocytes/Macrophages in tissue/organ phagocytosis when infection progresses  Cont. Phagocytosis: Mechanism Recognition: by process of chemotaxis: attracted to site of infection by cytokines (released from WBCs, Cell damage, Microbial products) Phagocytes recognize pathogen-associated molecular patterns (PAMP) via pattern recognition receptors (PRRs). Adherence: attachment to microbial surface via Toll-like receptors (TLRs), activate inflammation; Scavenger receptors initiate phagocytosis, Opsonins- opsonization Ingestion: pseudopodia engulf microbe into phagosome Digestion: fusion of phagosome with lysosome form phagolysosome and – Enzymes digest microbe – Residual body excreted Cont.  Cont. Soluble Factors Acute phase proteins which consists of an increase in the levels of various plasma proteins (e.g., C- reactive protein and mannose-binding protein). Synthesized by the liver in response to certain cytokines, namely, IL-1, IL-6, and TNF, produced by the macrophage after exposure to microorganisms. Acute-phase proteins bind to the surface of bacteria and activate complement, which can kill the bacteria Interferons (alpha, beta & gamma) Chemokines (chemotactic activity, e.g. IL-8, CXCL12) Enzymes (Lactoperoxidase ,Lactoferrin ,Myeloperoxidase) Complement (serum proteins C1-C30 but C5b-C9 form membrane attack complex)  Cont. Complement activation occurs by the classical, alternative, or lectin pathways, each initiated differently Classical path way activated by immunoglobulins (IgM and IgG) Alternative pathway doesn’t need Ab, but initiated by cell-surface constituents of bacteria, yeasts, viruses Lectin Pathway originated when host proteins bind to microbial surfaces The pathways join at enzyme C3 convertase and form C5 convertase that cleave C5 to C5a and C5b C5b attaches to C6, C7, form C5b67 complex & bind to C8 and C9 Form a cylindrical transmembrane channel, C5b678(9)n, the membrane attack complex (MAC) Inflammation Is the reaction of the body to injury, such as invasion by an infectious agent, exposure to a noxious chemical or physical trauma. Inflammation is response based an exposure and is an attempt to restore homeostasis Inflammation can be induced by immune recognition that is hypersensitive to environmental components/auto inflammatory or autoimmune (=disease) Acute inflammation: Is intense and Infecting agent removed in short time Chronic inflammation: less intense, more destructive and infecting agent/ inducer of inflammation cannot be removed or after long time Inducing factors: *Endogenous factors : tissue necrosis, immunological (hypersensitivity) bone fracture. *Exogenous factors: mechanical (e.g. cut), physical injury (e.g. burn), chemical injury (corrosive chemicals), biological (i.e. infectious agents). Cont. Hallmark signs of Inflammation;  Tumor: swelling (due to influx of plasma proteins and phagocytic cells into the tissue spaces)  Rubor: redness (due to local vessel dilatation)  Calor: heat (due to blood vessels dilation)  Dolor: pain (due to local release of enzymes and increased tissue pressure)  Functio-laesa: Loss of function of the inflamed area Cont  Events in the inflammatory response: 1. Vasodilation & increased blood vessel permeability 2. Phagocyte migration & phagocytosis 3. Tissue repair  Purpose of inflammation: 1. Terminate infection Remove it and its byproducts from the body 2. If abolishing is not done successfully, confine the infectious agent and by products and keep from spreading 3. Restoration or replace damaged tissue Steps Step 1: Vasodilation & increased vessel permeability Histamine: released from injured cells/inflammatory cells granules (basophils, mast cells) and increased vasodilation Kinins: In plasma attract phagocytic granulocytes to injured site Prostaglandins: From damaged cells , intensify the effects of histamine and kinins Leukotrienes: From damaged basophils, mast cells increase vessel permeability; attach phagocytes to pathogens Cytokines: activated fixed macrophages, increase vasodilation and permeability Clotting factors: enter infection site; clot prevents spread of pus: (dead cells and body fluids); abscess(cavity after tissue breakdown) Cont Step 2: Phagocyte migration and phagocytosis Phagocytes appear on the scene within 1 hour Margination cytokines alter blood vessel lining, cause phagocytes to stick to vessel walls at inflammation site Phagocytes traverse vessel walls to get into affected area (diapedesis), extravasation or transmigration) Phagocytes engulf invading microbes Granulocytes (neutrophils) are first on scene; die off rapidly Macrophages enter at a later stage - larger and more phagocytic - Phagocytize destroyed tissue, granulocytes, remnants of invaders  Cont Stage 3: Tissue repair Is healing process whereby the tissue maintenances itself after injury by replacing dead or damaged cells in affected area Maintenance of homoeostasis by clotting in any damaged regions of the CS The inflammatory phase response clears the wound site and prevents infection. The proliferative phase used to reconstitute the wound site The re-modelling phase used to strengthen tissue and restore function Repair capacity depends on tissue type Stroma = supportive connecting tissue - Eg. capsule around the liver that encloses and protects it; not involved in liver functions Parechyma = functioning portion of tissue - Eg. Hepatocyte cells of liver that perform the liver’s functions If parenchymal cells are active in repair perfect reconstruction; if stroma cells are more active scar  Antigens and antibodies LESSON OBJECTIVES  Defining the terms (antigen, Immunogen, Hapten, antibody, immunoglobulins adjuvant etc.)  Describe chemical properties and types of antigens Discussing the involvement and role of antigen, Immunogen and Hapten) to the immune system Describing the structure and types of immunoglobulins Discuss on function of immunoglobulins to the immune system  Discuse Antigen Antigens: are substances / molecules which can be specifically recognized as "foreign’’ by the immune system Immunogens are antigens that capable of triggering an immune response  Immunogen , stimulates the production of an antibody with which it reacts specifically and in an observable manner All substances which are immunogenic are also antigenic; but not the reverse An antigen has specific target determinants ‘’Epitope’’ by which it bound to a particular antibody molecule Cont Epitope or Antigenic Determinant - The smallest part of an antigen or immunogen that can be recognized by B and T receptors. Epitopes are – small chemical groups on the antigen molecule that can react with and elicit antibody production An antigen can have one or more epitopes, most antigens have many determinants; ie, they are multivalent The epitope on monovalent antigen is different from those on bivalent antigen Each antibody only recognize one epitope at a time rather than the whole multivalent antigen  The interaction occurs in the way of ternary complex Epitope on an antigen bind to Paratope in the variable domain of an antibody or T- cell receptor Agretope on antigen bind to Desetope on MHC Histotope on MHC bind to TCR looks at the. CHEMICAL NATURE OF ANTIGENS A. Proteins The vast majority of immunogens are proteins. These may be pure proteins or they may be glycoproteins or lipoproteins. In general, proteins are usually very good immunogens. B. Polysaccharides Pure polysaccharides and lipopolysaccharides are good immunogens. C. Nucleic Acids Nucleic acids are usually poorly immunogenic. However, they may become immunogenic when single stranded or when complexed with proteins. D. Lipids In general lipids are non-immunogenic, although they may be haptens.  Types of antigens Exogenous antigens: antigens enters to the body from external. Eg. bacteria, viruses The uptakes of these antigens by APCs are mainly mediated by the phagocytosis Exogenous antigens are presented in MHC-II; they are recognized by T-cells with a TCR and an associated with protein called CD4 Endogenous antigens: body’s own altered cell or sub fragments or compounds produced. Eg Histocompatibility Leukocyte antigens Endogenous antigens are presented by MHC-I; they are recognized by T-cells with a TCR and an associated with protein called CD8 Autoantigens: usually a normal protein/complex of proteins (DNA or RNA) & recognized as not self by the immune system These antigens should not be, under normal conditions, the target of the immune system, Due to genetic & environmental factors, the normal immunological tolerance for such antigen has been lost Eg. Nucleoproteins, Nucleic acids, etc. Complete Antigen: Posses antigenic properties denovo, i.e. able to generate an immune response by themselves. High molecular weight (more than 10,000) May be proteins or polysaccharides  Cont Incomplete antigen (Hapten) is a molecule that can not induce an immune response by itself but can react with specific antibody. Low Molecular Weight (Less than 10,000) Haptens can induce a response if combined with larger molecules (normally proteins) which serve as carrier. Structurally these conjugates are characterized by having native antigenic determinants of the carrier as well as new determinants created by the hapten (haptenic determinants)  In such conjugates the type of carrier determines whether the response will be T-independent or T-dependent Haptens are usually small, many drugs, eg, penicillins and the catechol in the plant oil that causes poison oak & poison ivy is a hapten.  Cont. T-independent antigens are antigens which can directly stimulate the B cells to produce antibody without the requirement of help of T helper cell These antigens are characterized by the antigenic determinant of the type repeated many times  Many of these antigens can activate B cell clones specific for other antigens (polyclonal activation) Only induce B cell to produce IgM, can not induce CMI and have no immune memory T independent antigens are generally more resistant to degradation