Innate Immunity Lecture Notes PDF

Innate (Non-Specific) Immunity By Prof. Dr. Nagwa Gamil Rizk Ghaly  Lecture Outline Types of host immune defenses. Determinants of innate immunity. First line of defense: - Mechanical defenses - Chemical defenses Second line of defense: - Phagocyt...

Innate (Non-Specific) Immunity By Prof. Dr. Nagwa Gamil Rizk Ghaly  Lecture Outline Types of host immune defenses. Determinants of innate immunity. First line of defense: - Mechanical defenses - Chemical defenses Second line of defense: - Phagocytosis - Inflammation - Complement - Fever  Overview of the Immune System Innate immune system is non-specific defense against invading organisms. Adaptive immune system is specific defense, and also afford protection against re-exposure to the same pathogen. Both have cellular and humoral components by which they carry out their protective function. There is interplay between both systems.  Differences Between Innate& Adaptive Immune Systems Innate Immunity Adaptive Immunity 1- Defenses are present & 1- Requires time to react to an ready to be mobilized upon invading organism. infection. 2- Not antigen specific & 2- Antigen specific & reacts only reacts to a variety of with the organism that induced organisms. the response. 3- Does not demonstrate 3- Demonstrates immunological immunological memory. memory. It remembers the invading organism and reacts more rapidly on subsequent exposure to it.  Natural (Innate) or Non-specific Immunity Present since birth Does not depend on previous exposure to any particular pathogen Genetically controlled Modified by factors as age, hormones, nutritional status  Acquired (Adaptive) or specific Immunity Not present since birth Depends on previous exposure to particular pathogen Specific; active against the inducing pathogen Genetically controlled, influenced by hormones & cytokines Formed of 2 arms: humoral (Ab-mediated) and cell mediated immunity Involves the development of memory cells Three Lines of Defense Against Infection Innate Immunity Adaptive Immunity 1. First Line of Defense: Non-specific natural barriers which restrict entry of pathogen. Examples: Skin and mucous membranes. 2. Second Line of Defense: Innate non-specific immune defenses provide rapid local response to pathogen after it has entered host. Examples: Fever, phagocytes (macrophages and neutrophils), inflammation, and interferon. 3. Third line of defense (Adaptive Immune Response): Antigen-specific immune responses, specifically target and attack invaders that get past first two lines of defense. Examples: Antibodies and lymphocytes.  First Line of Defense A. Mechanical Defenses 1. Skin: it has two Layers; - Epidermis: Thin outer layer of epithelial tissue. Contains Langerhans cells, dead cells, and keratin (waterproof). Superficial cells continually peel off when die, thus eliminate the organisms colonizing the skin - Dermis: Thick inner layer of connective tissue. Infections are rare in intact skin. Exceptions: Hookworms can penetrate intact skin Dermatophytes: “Skin loving” fungi Intact Skin is an Effective Barrier Against Most Pathogens 2. Mucous Membranes: Line gastrointestinal, genitourinary, and respiratory tracts. – Two layers: Outer epithelial and inner connective layer. – Epithelial layer secretes mucus which maintains moist surfaces. – Although they inhibit microbial entry, they offer less protection than skin. – Several microorganisms are capable of penetrating mucous membranes: Papillomavirus , Treponema pallidum , Enteroinvasive E. coli Entamoeba histolytica 3. Lacrimal apparatus: tears; continual washing away of pathogens, have bactericidal enzymes, blinking prevents microbes from settling on the eye surface. 4. Saliva: washes microbes from teeth and mouth mucous membranes. 5. Mucus: thick secretion that traps many microbes. 6. Nose hair: coated with mucus, filter dust, pollen, and microbes. 7. Ciliary escalator: cilia on mucous membranes of lower respiratory tract move upwards towards throat at 1-3 cm/hour. Natural Immunity - Cilia 8. Coughing and sneezing: expel foreign objects. 9. Epiglottis: covers larynx during swallowing. 10. Urination: cleanses urethra. 11. Vaginal secretions: remove microbes from genital tract. 12. Wax in ear: traps microorganisms. Epiglottis Protects Respiratory System from Infection During Swallowing  B. Chemical Defenses: 1- Sebum: Oily substance produced by sebaceous glands that forms a protective layer over skin. Contains unsaturated fatty acids which inhibit growth of certain pathogenic bacteria and fungi. 2- pH: Low, skin pH usually between 3 and 5. Caused by lactic acid and fatty acids. 3- Perspiration: Produced by sweat glands. Contains lysozyme and acids. 4- Lysozyme: Enzyme that breaks down gram- positive cell walls. Found in nasal secretions, saliva, and tears. 5- Gastric Juice: Mixture of hydrochloric acid, enzymes, and mucus. pH between 1.2 to 3 kills many microbes and destroys most toxins. Many enteric bacteria are protected by food particles. Helicobacter pylori neutralizes stomach acid and can grow in the stomach, causing gastritis and ulcers. 6- Transferrins: Iron-binding proteins in blood which inhibit bacterial growth by reducing available iron. 7- Interferons: Family of proteins which are important non-specific defense mechanisms against viral infections.  C- Normal flora: Produce bactericidal substances; salivary streptococci produces H2O2, lactobacilli make acidic pH of the vagina. Normal flora prevent other microorganisms from establishing an infection – “competitive exclusion” ; as they compete with pathogenic bacteria for nutrients or attachment sites on cell surfaces.  Factors Modify Defense Mechanisms Age Hormones Drugs and chemicals Malnutrition Fatigue and stress Genetic determinants  Second Line of Defense If bacteria are not successfully killed locally, may further invade the host by way of the lymphatics to the regional lymph nodes. – within lymph nodes the bacteria meet other phagocytic cells – bacteria may overcome these and gain access to the bloodstream where they meet circulating phagocytes (neutrophils and monocytes). – may pass through the bloodstream and reach organs such as the liver and spleen where they come into contact with tissue macrophages. – although a powerful defense system, this final phagocytic barrier may be overcome, with seeding of the microorganism to organs such as bone, brain, and kidney, terminating in fatal septicemia.  Second Line of Defense 1) Phagocytosis 2) Non-specific killer cells 3) Inflammation 4) Complement 5) Fever 6) Interferons All work tightly with specific immunity  1- Phagocytosis 1. Initiation is caused by damage to the tissues; trauma or as a result of microbial multiplication. 2. Chemotaxis, attraction of leukocytes or other cells by chemicals. 3. Opsonization - Opsonization coating a pathogen by substances so as to enhance phagocytosis. 4. Adherence - firm contact between phagocyte and microorganism. 5. Engulfment into cytoplasm and enclosed in a vacuole. 6. Digestion enzymatic or hydrogen peroxide contents in vacuole destroy the microorganism. Phagocytosis Mechanism of Phagocytosis Mechanism of Phagocytosis Macrophage Phagocytosis is carried out by white blood cells: macrophages, neutrophils, and occasionally eosinophils. – Neutrophils predominate early in infection. – Wandering macrophages: Originate from monocytes that leave blood and enter infected tissue, and develop into phagocytic cells. – Fixed Macrophages (Histiocytes): Located in liver, nervous system, lungs, lymph nodes, bone marrow, and several other tissues.  Phagocytic Cells: Macrophages (Monocytes), Neutrophils, and Eosinophils (Macrophages)  Langerhans cells in skin Phagocytes in blood Microglial cells in CNS  2- Non-specific Killer Cells Natural killer (NC) cells Large granular lymphocytes (LGL) Killer (K) cells Activated macrophages Eosinophils They are capable of recognizing the surface changes on tumor, & viral infected cells and damage these target cells in a non-specific manner; (innate immunity).  3- Inflammation four classic signs : redness, swelling, heat and pain. Inflammatory Response: 1- Dilation of capillaries (hyperemia) to increase blood flow to area (nutrients, O2, antibodies, complement, immune cells) 2- Increased capillary permeability allowing white cells to go to injured area, a process known as “diapedesis” 3- Chemotaxis - chemicals released which cause phagocytic white cells to migrate to the area. 4- Formation of exudate - same composition as plasma and it contains antibacterial substances, phagocytic cells, drugs and antibiotics, if present. Inflammation  Inflammatory Response Histamine & Capillaries dilate Chemotactic Phagocytes prostaglandins Clotting begins factors attract consume released phagocytic cells pathogens & cell debris  Fever Pluses Minuses Inhibit microbial growth Malaise Enhance immune cell Body aches performance chills Speed tissue repair “Breaking” fever or “crisis of fever”: body begins to cool by sweating, “color returns” as blood vessels in skin open Indicates infection is overcome  Antimicrobial substances Coagulation system Lactoferrin and transferrins Lysozyme Interferons The complement system 1. Coagulation system: After tissue injury, the coagulation system is activated. Some of the products of the coagulation system are directly antimicrobial. For example, β-lysin, a protein produced by platelets during coagulation can lyse many Gram-positive bacteria. 2. Lactoferrin and transferrin: By binding iron, an essential nutrient for bacteria, these proteins limit bacterial growth. 3. Lysozymes They are found in high concentrations in tears. They are found in almost all body fluids except urine, CSF and sweat. In addition, they are present intracellularly within phagocytes. They have mucolytic activity, splitting off the cell wall of Gram-positive bacteria causing lysis. 4. Interferon: It is a glycoprotein having molecular weight of 28,000- 45,000 daltons. It act nonspecifically to inhibit the spread of viral infections α-IFN and β-IFN: Produced by virus infected cells. Mode of action is to induce uninfected cells to produce antiviral proteins (AVPs) that inhibit viral replication. γ-IFN: Produced by lymphocytes. Causes neutrophils and macrophages to phagocytize bacteria. Also involved in tumor immunology. 5. The complement system The complement system is the major humoral nonspecific defense mechanism. It is a complex series of 30 serum proteins. The complement system has three major activities : a. Initiation of the inflammation. b. Identifying materials for removal by phagocytic cells (opsonization). c. Lysing a susceptible bacterial cell.