Modes of the Immune Response Lecture Notes PDF

Lec. 4 Modes of the immune response Assistant Professor Dr. Zahra A. Amin Clinical analysis Department College of Pharmacy Hawler Medical University Lecture Outlines Modes of the immune response 1) Non-specific immune response ---First Line ---Second Line -Phagocytosis -Inflammation -Fever The immun...

Lec. 4 Modes of the immune response Assistant Professor Dr. Zahra A. Amin Clinical analysis Department College of Pharmacy Hawler Medical University Lecture Outlines Modes of the immune response 1) Non-specific immune response ---First Line ---Second Line -Phagocytosis -Inflammation -Fever The immune system has two types of defense: 1. The first one representing a non-specific (no memory) response to antigen (substance to which the body regards as foreign or potentially harmful) known as the innate immune system. 2. The second one is the adaptive immune system a specific (memory) , which displays a high degree of memory and specificity. Lines of Defense Against Infection: 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: Antigen-specific immune responses, specifically target and attack invaders that get past first two lines of defense. Examples: Antibodies and lymphocytes. Three Lines of Defense Against Infection I. First Line of Defense Are structures, chemicals, processes that work to prevent pathogens entering the body like Skin and Mucous Membranes. A. Mechanical Defenses 1. Skin has two Layers: A. Epidermis: Thin outer layer of epithelial tissue. Contains Langerhans cells, dead cells, and keratin (waterproof). B. 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 A. Mechanical Defenses(Continued) 2. Mucous Membranes: Line gastrointestinal, genitourinary, and respiratory tracts, it have two layers: A. Outer epithelial: 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 Enteroinvasive E. coli Entamoeba histolytica B. inner connective layer. A. Mechanical Defenses (Continued) 3. Lacrimal apparatus: Continual washing and 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. A. Mechanical Defenses (Continued) 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. Lacrimal Apparatus 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 grampositive cell walls. Found in nasal secretions, saliva, and tears. B. Chemical Defenses (Continued) 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. C-Microbial Antagonism Normal microbiota help protect the body by competing with potential pathogens. Various activities of the normal microbiota make it hard for pathogens to compete. Consumption of nutrients makes them unavailable to pathogens. Create an environment unfavorable to other. microorganisms by changing pH. Helps stimulate the body’s second line of defense. Promote overall health by providing vitamins to host. D- Physical barriers Some of previously mentioned barriers of the body are also considered physical barriers: Natural barriers include the skin, mucous membranes, tears, earwax, mucus, and stomach acid. Also, the normal flow of urine washes out microorganisms that enter the urinary tract. II. Second Line of Defense Operates when pathogens succeed in penetrating the skin or mucous membranes (1st line of deffense). Nonspecific defense Composed of cells, antimicrobial chemicals, and processes but no physical barriers Many of these components are contained or originate in the blood II. Second Line of Defense: Phagocytosis: Derived from the Greek words “Eat and cell”. 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): Fixed macrophages do not move throughout the body and often phagocytize within a specific organ Include alveolar macrophages (lungs), microglia (central nervous system), Küpffer cells (liver) Phagocytosis Is the process by which immune cells engulf microorganisms and particles. Firstly, the phagocyte must move towards the microbe under the influence of chemotactic signals, e.g. complement. For the process to continue, the phagocyte must attach to the microbe either by recognition of the microbial sugar residues (e.g. mannose) on its surface or complement/antibody, which is bound to the pathogen. Phagocytosis History:  Phagocytes were first discovered in 1882 by Ilya Metchnikov, while he was studying starfish larvae.  1908 he awarded a nobel price in Physiology and Medicine. Phagocytosis Following attachment, the phagocyte’s cell surface invaginates and the microbe becomes internalized into a phagosome. The resultant phagosome fuses with multiple vesicles containing O2 free radicals and other toxic proteins known as lysosomes to form a phagolysosome. The microbe is subsequently destroyed. Phagocytes Are the white blood cells that protect the body by ingesting harmful foreign particles. Examples: neutrophils, monocytes, macrophages…..etc The Phagocytic Process Phagocytosis involves the following sequence of events: 1. Chemotaxis: Phagocytes are chemically attracted to site of infection. 2. Adherence (Opsonization): Phagocyte plasma membrane attaches to surface of pathogen or foreign material. 3. Ingestion: Plasma membrane of phagocytes extends projections (pseudopods) which engulf the microbe and enclose it in a sac called phagosome. 4. Digestion: Inside the cell, phagosome fuses with lysosome to form a phagolysosome. 5. Exocytosis: after digestion, the residual body with undigestable material is discharged. The sequence of phagocytosis Opsonization Opsonization (“to make tasty” – a Greek word) Opsonins are molecules, which enhance the efficiency of the phagocytic process by coating the microbe and effectively marking them for their destruction. Important opsonins are the complement component C3b and antibodies. Inflammation Nonspecific response to tissue damage resulting from various causes like infection, heat, wound.. etc. Characterized by redness, heat, swelling, and pain It has two types A) Acute inflammation: Develops quickly and is short lived, Is usually beneficial, Important in the second line of defense, Dilation and increased permeability of the blood vessels, Migration of phagocytes, Tissue repair. B) Chronic inflammation: Develops slowly and lasts a long time, Can cause damage to tissues. Functions of Inflammation 1. Destroy and remove pathogens 2. If destruction is not possible, to limit effects by confining the pathogen and its products. 3. Repair and replace tissue damaged by pathogen and its products. Stages of Inflammation 1. Vasodilation: Increase in diameter of blood vessels. Triggered by chemicals released by damaged cells: histamine, prostaglandins, and leukotrienes. 2. Phagocyte Emigration and Margination: Margination: is the process in which phagocytes stick to lining of blood vessels. Diapedesis (Emigration): Phagocytes squeeze between endothelial cells of blood vessels and enter surrounding tissue. Phagocytes are attracted to site of infection through chemotaxis. Phagocytes destroy microbes, as well as dead and damaged host cells. 3. Tissue Repair: Dead and damaged cells are replaced. Symptoms of inflammation: There are four major symptoms of inflammation: 1. Redness 2. Pain 3. Heat 4. Swelling May also observe: 5. Loss of function Events in Inflammation Chemical Mediators of Inflammation 1. Vasodilating chemicals: histamine, serotonin, prostaglandin. 2. Chemotactic factors: fibrin, collagen, bacterial peptides. 3. Substances with both vasodilating and chemotactic effects: complement fragment C5a and C3b, interferon, interleukins, leukotrienes, platelet secretions. Fever: A body temperature over 37C Results when chemicals called pyrogens trigger the hypothalamus to increase the body’s temperature There are two types of natural pyrogens: (1) endogenous pyrogens that the host's pyrogen cytokines (2) exogenous pyrogens that are microbial substance (e.g. lipopolysaccharides in the cell wall of certain bacteria). These pyrogens cause the production of Interleukin-1 Fever Production IL-1 production causes the hypothalamus to secrete prostaglandin which resets the hypothalamic “thermostat” Communication with the brain initiates muscle contractions, increased metabolic activity, and constriction of blood vessels which raises the body’s temperature Chills associated with fever are due to the reduced blood flow of constricted vessels Decrease in IL-1 production results in the body’s temperature returning to normal. Benefits of Fever Enhances the effects of interferons Inhibits growth of some microorganisms May enhance the performance of phagocytes, cells of specific immunity, and the process of tissue repair Questions?