Immunology HML2053 Lecture Notes PDF

Immunology HML2053 1 LO2: Describe the non-specific defense (innate) mechanism of the host Week 7: List the stages of inflammation and describe the roles of vasodilation, and cytokines in inflammation 2  Definition...

Immunology HML2053 1 LO2: Describe the non-specific defense (innate) mechanism of the host Week 7: List the stages of inflammation and describe the roles of vasodilation, and cytokines in inflammation 2  Definition of Inflammation Definition: The body normally responds to any local injury, irritation, microbial invasion, or bacterial toxin by a complex series of events collectively called inflammation or inflammatory response. Causes: 1. Microbial infection 2. Physical & mechanical agents (e.g. heat, radiant energy, electricity, cuts, blunt trauma) 3. Chemical agents (acids, bases, gases) 4. Immunological (hypersensitivity)  Aim of inflammation The primary purposes are: 1. Localize an infection (Limit the effects on the body by walling off the Injurious agent & its by-product). 2. Prevent the spread of microbial invaders. 3. Destroy the injurious agent & remove it & its by-products (Toxins) from the body. 4. Repair or replace the damaged tissue.  Symptoms or Response: 5 Cardinal/ essential signs of inflammation (Derived from the Latin words): 1. Calor (heat) 2. Dolor (pain) 3. Rubor (redness) 4. Tumor (swelling) 5. Loss of function  Three major events in acute inflammation are: 1. An increase in diameter of capillaries (vasodilation) 2. Increased permeability of capillaries. 3. Egress (exit) of WBCs from the capillaries. http://www.sumanasinc.com/webcontent/animations/content/inflammatory.html  Three types of changes in blood vessels: 1. ↑ in diameter of blood vessels ↑ Local blood flow (heat, redness) ↓ in velocity of blood flow. 2. Activation of endothelial cells lining the blood vessels (by expression of adhesion molecules)  promotes binding of circulating WBCs. Extravasation: Combination of decreased velocity of blood flow & induced adhesion molecule allow WBCs to attach to the endothelial cells & migrate into the tissues. Initiated by cytokines (active macrophages) 3. Increased vascular permeability Separation of tightly joined endothelial cells lining the blood vessels leading to exit of fluid & protein from blood & their local accumulation to the tissue (Swelling; edema + pain).  Order of cells involved 1. Neutrophils; destroy or remove the offending agent 2. Monocytes; finish removal of residual debris & stimulate tissue repair. 3. Later Eosinophils & lymphocytes.  Inflammatory mediators: These are the chemical mediators which are responsible for the changes in the blood vessels. Widely distributed in an inactive form throughout the body & released or activated at site of inflammation 1. Lipid mediators: (prostaglandins, leukotrienes, platelets-activating factor (PAF)) 2. Cytokines & chemokines: (chemoattractant cytokines) e.g. cytokine tumor necrosis factor-α (TNF-α) Mediator Main source Function Mediator Main source Function  Activation of complement pathway As a result of cleavage product: C5a Several activities: 1. ↑ Vascular permeability 2. Induce expression of some adhesion molecules 3. Powerful chemoattractant for neutrophils & monocytes “phagocytes" 4. Activates local mast cells Function of inflammatory exudates: 1. Dilution of bacterial tissue-damaging toxins. 2. Creating physical obstruction to limit spread of bacteria by fibrin deposition as a result of clotting factors. 3. Continuous drainage of antigen by lymphatic vessels.  Role of kinin & coagulation systems in inflammatory response Wound injury to blood vessels  activates Kinin & coagulation systems Kinin system: Enzymatic cascade of plasma proteins that is triggered by tissue damage to produce bradykinin; causes vascular permeability that promotes the influx of plasma proteins to the site of injury + pain  (limit spread of infection). Coagulation system: Enzymatic cascade of plasma proteins that is triggered following damage to blood vessels. Leads to formation of fibrin “clot” thus  preventing pathogen from entering blood stream “ Not spread”  Summary of inflammation: Redness, Pain, Heat & Swelling (edema); due to: 1. Acute-phase proteins activated e.g. (complement, cytokine & kinins) 2. Vasodilation (Histamine, kinins, prostaglandins & leukotrienes) 3. Margination “adhesion” & emigration of WBCs 4. Tissue repair Chemicals Released by Damaged Cells: 1. Histamine Vasodilation, increased permeability of blood vessels 2. Kinins Vasodilation, increased permeability of blood vessels 3. Prostaglandins Intensify histamine & kinin effect 4. Leukotrienes Increased permeability of blood vessels & phagocytic attachment http://www.youtube.com/watch?v=suCKm97yvyk  Chronic inflammation When causative agent not easily removed or reintroduced i.e. present for long time → more tissue destruction “granuloma formation” Collection of inflammatory cells with surrounding fibrosis & loss of function (e.g. Tuberculosis). Chronic activation of immune response: e.g. rheumatoid arthritis, chronic glomerulonephritis. Treatment: Anti-inflammatory agents e.g. aspirin, ibuprofen Cortisone, cytotoxic drugs. Other humoral factors involved in innate immunity.  Acute-phase proteins Proteins present in high concentration during infection “How”!! 1. Presence of endotoxin from the pathogens stimulates macrophages 2. Active Macrophages  release endogenous interleukin-1 (IL-1) 3. This stimulates the liver to produce increased amount of “acute phase proteins” Examples: 1. C-reactive proteins “CRP”: Bind to phosphoryl-choline residues in the cell wall of certain microorganisms. Tested in the patients’ serum as a sign of inflammation. 2- Interferon: antiviral agent; 3 types: 1. Alpha (α) 2. Beta (β)  both (α & β part of innate immunity) 3. Gamma (γ)  T cell (acquired immunity) Function: 1. Alpha & Beta IFN: Cause cells to produce antiviral proteins  that inhibit viral replication. 2. Gamma IFN: Causes neutrophils & macrophages to phagocytose bacteria. 3- Complement: Group of serum proteins present in low concentration in normal blood plasma. These proteins make up what is called “Complement system” So named because it is ‘complementary’ to the action of immune system.  Fever Fever: is an abnormal increase in body temperature caused by virus or bacteria or a response to tissue injury. NOTE: Inflammation is local response of the body to injury. Fever is the systemic or overall response of the body. Body temperature is controlled by hypothalamus (body’s thermostat). Hypothalamus normally sets at 37°C. Bacterial products like LPS, gram-negative endotoxin, cause phagocytes to release interleukin–1 (IL-1). IL-1 resets the thermostat to a higher temperature. Hypothalamus releases prostaglandins that reset the hypothalamus to a high temperature  Fever Body invaded by pathogen → 39oC → to adjust to the increase, the body responds with blood vessels constriction & increase rate of metabolism & shivering. Body increases rate of metabolism & shivering which raise temperature. When IL–1 is eliminated, body temperature falls: 1. Crisis: As infection subsides, heat losing mechanisms like “vasodilation & sweating” go into operation. Skin is now warm & sweaty, indicates that body temperature is falling. 2. Chill: Body temperature is high but skin remains cold & shivering occurs. When body temperature reaches the setting of the thermostat, the chill disappears.  Fever Up to a certain point, fever is a defense mechanism (How!!) 1. Antiviral effects  interferons increased 2. Inhibits growth of bacteria. Advantages: 1. Increase transferrins (bind serum iron) 2. Increase IL–1 activity Disadvantages: 1. Tachycardia 2. Acidosis & electrolyte imbalance 3. Dehydration 4. Convulsions & coma 5. Death (above 44-46oC)  Activity! Define Inflammation? Enumerate three causes of Inflammation? Describe the primary purposes (aim) of Inflammation? What are the symptoms or response of Inflammation? Compare between acute and chronic inflammation? Describe the three major events of acute inflammation? Describe the three types of changes in blood vessels? Mention the order of cells involved in inflammation?  Activity! Enumerate four Inflammatory mediators then for each a) Describe the main source of its production b) Function Define Acute-phase proteins? Describe the following: a) Role of kinin system in inflammatory response? b) Role of coagulation system in inflammatory response? c) C-reactive proteins “CRP”? d) Interferon? e) Complement?  Activity! Illustrate the difference between inflammation and fever? Define fever? Explain the advantages and disadvantages of fever as one component of the immune system? Explain the mechanism of increasing and decreasing the body temperature in fever?  References Turgeon, Mary Louise. (2018) Immunology and serology in laboratory, 6th ed. ISBN 9780323402873 Levinson, Warren E, (2016). Review of Medical Microbiology and Immunology, 14th ed. McGraw-Hill. ISBN: 9781307198379 Abbas, Abul K./ Lichtman, Andrew H. (2011). Cellular and molecular immunology (with student consult online access) (7th Revised ed./e). Elsevier Health Sciences. ISBN: 9780808924258 Eales, L. J. Immunology for life scientists. John Wiley. 1997. ISBN: 0471962252. Playfair, J. H. I. / Chain, B. H. Immunology at a glance. Blackwell Science. 2001. ISBN: 0632054069. Sompayrac, Lauren M. How the immune system works. Blackwell Science. 1999. ISBN: 0632044136. 800 MyHCT (800 69428) [email protected] www.hct.ac.ae Happiness Center PO Box 25026 Abu Dhabi, UAE HCT_UAE hctuae 27