Innate Immunity: Inflammation & Wound Healing (Chapter 6) PDF

Innate Immunity: Inflammation & Wound Healing Chapter 6 Learning Objectives 1. Identify 1st, 2nd and 3rd lines of body defence 2. Describe the stages of the inflammatory process 3. Discuss the pathophysiology of altered body defence 4. Discuss the cellular components of...

Innate Immunity: Inflammation & Wound Healing Chapter 6 Learning Objectives 1. Identify 1st, 2nd and 3rd lines of body defence 2. Describe the stages of the inflammatory process 3. Discuss the pathophysiology of altered body defence 4. Discuss the cellular components of inflammation 5. Describe the local and systemic manifestations of inflammation 6. Differentiate acute and chronic inflammation 7. Describe the role of inflammation in the process of tissue repair 8. Differentiate active, passive, cell mediated and humoral immunity 9. Discuss the pathophysiology of inflammation. 10. Describe clinical manifestations of the immune response. 11. Identify characteristics of infection. 12. Differentiate between inflammation and infection. 13. Discuss how human defenses are effective against the development of infection. 14. Compare and contrast primary and secondary immunity. 15. Discuss the transmission and clinical manifestations for HIV/AIDS. 16. Describe medical treatment for autoimmunity and immune deficiencies. Immunity Two types: INNATE (natural/native), and ACQUIRED (adapted/specific) Lines of defence in the body towards unknown pathogens First Line: Innate immunity; physical, mechanical and biochemical barriers Second Line: Inflammation Third Line: Acquired immunity Innate Immunity (First Line) Includes natural barriers (physical & biochemical) and inflammation IN PLACE AT BIRTH Surface physical barriers harbours a group of microorganisms known as the “normal flora” that can protect us from pathogens If the pathogen breaks through the surface barriers, the inflammatory response is the second line of defence activated! Inflammatory Response (Second Line) Activated to: protect the body from further injury prevent infection of injured tissue promote healing This response is a rapid activation of biochemical & cellular mechanisms that are non-specific towards a wide variety of causes of tissue damage. Adaptive/Acquired Immunity (Third Line) This process is slower and more specific; targets particular microorganisms and eradicating them Involves a “memory”, which results in a more rapid response during future exposure to the same microorganism First Line of Defence PHYSICAL BARRIERS BIOCHEMICAL BARRIERS Skin Epithelial cell-derived barriers; Linings of the GI, GU, and saliva, tears, earwax, sweat, and respiratory tracts mucus Mucus and cilia Normal microbiome; unique to MECHANICAL BARRIERS individual and location Coughing & Sneezing Vomiting Sloughing of cells Normal Microbiome (Normal Flora) The skin and mucous membranes are colonized by mutualistic microorganisms that provide protection by - releasing chemicals that facilitate immune responses - preventing colonization by pathogens - facilitating digestion in the GI tract Some of these organisms are opportunistic microorganisms, and can cause disease if there is a break in the individual’s defences (ex. Pseudomonas) Second Line of Defence: Inflammation Inflammation is a systematic process that responds to cellular or tissue damage; benefits include - Preventing infection & limiting further damage - Destroying contaminating infectious microorganisms - Initiating the adaptive immune response, and - Beginning the healing process *Signs of acute inflammation include: redness, heat, swelling, pain, and sometimes loss of function Inflammatory Changes @ Arterioles, Venules & Capillaries 1. VASODILATION a. Increases blood flow to the injured site 2. INCREASED VASCULAR PERMEABILITY a. Fluid leaks out of the vessel, causing edema at the site of injury b. This fluid is drained by the lymphatic vessels 3. WHITE BLOOD CELL ADHERENCE a. To the inner walls of vessels Cellular Components of Inflammation Tissue close to the vessels include: 1. Mast Cells; activator of inflammation 2. Dendritic Cells; connect the innate and acquired immune responses Blood contains: 1. Erythrocytes (red blood cells, RBC) 2. Platelets 3. Leukocytes (white blood cells, WBC) Cytokines signal the immune system; they are crucial in controlling the growth & activity of other immune system cells & blood cells Leukocytes Granulocytes These cells act at the site of - Includes basophils, eosinophils, injury to and neutrophils 1. Confine the extent of Monocytes damage 2. Kill microorganisms - Precursor of macrophages 3. Remove the cellular debris Lymphocytes 4. Activate healing, tissue regeneration or repair - Participate in the innate immune response (natural killer cells) & acquired immune response (T and B cells) Phagocytes The primary role of most granulocytes (neutrophils, basophils & eosinophils) and monocytes/macrophages is PHAGOCYTOSIS. This is the process by which a cell ingests and disposes of damaged cells and foreign material 5 steps to Phagocytosis 1. Recognition & adherence to the target 2. Engulfment (ingestion) 3. Formation of a phagosome 4. Fusion of phagosome with lysosomal granules within the phagocyte 5. Destruction of the target Acute Inflammation: Local Manifestations Acute inflammation continues only until the threat to the host is eliminated (8-10 days). Local manifestations result from vascular changes & corresponding leakage of circulating components into the tissue: - Heat - Swelling - Redness - Pain - Exudative fluids  Exudative Fluids Exudate results from increased vascular permeability and varies depending on the inflammatory response & what caused the injury Serous Exudate: watery & clear, such as fluid in a blister; indicates early inflammation Fibrinous Exudate: thick & clotted; severe or advanced inflammation Purulent Exudate: pus & green/yellow; large number of leukocytes accumulate (bacterial infection) Hemorrhagic Exudate: blood; filled with erythrocytes  Acute Inflammation: Systemic Manifestations FEVER - Induced by specific cytokines (released from neutrophils and macrophages) known as pyrogens - Pyrogens act directly on the hypothalamus (controls the body's thermostat) LEUKOCYTOSIS - Increase in the number of circulating WBCs PLASMA PROTEIN SYNTHESIS - These proteins can either be proinflammatory or anti-inflammatory Chronic Inflammation If the acute response is inadequate, a chronic inflammation may develop. The difference between the two is duration. Chronic inflammation lasts 2 weeks or longer. Often related to an unsuccessful acute inflammatory response. - Characterized by pus formation, purulent discharge & incomplete wound healing Wound Healing The most favourable outcome of inflammation is a return to normal structure and function & the destroyed tissues are capable of regeneration. Regeneration: replacement of the damaged tissue with healthy tissue Resolution: the restoration of tissue, may not be possible of extensive damage is present; in that case repair takes place Repair: replacement of destroyed tissue with scar tissue - Scar tissue is composed primarily of collagen to restore the strength of the tissue, but not its function. Healing by Primary Intention VS. Secondary Intention Primary Intention - Wounds that heal under conditions of minimal tissue loss (simple incision) Secondary Intention - Wounds that require much more tissue replacement (open wound) Healing includes; filling the wound, sealing the wound (epithelialization), and shrinking the wound (contraction) Wound Healing Phase I: Inflammatory Phase Begins almost immediately Includes - coagulation or hemostasis - Infiltration of cells that participate in wound healing (platelets, neutrophils & macrophages) - Platelets = clot formation, and as they break down they release growth factors that initiate proliferation of undamaged cells Wound Healing Phase II: Proliferation Phase Begins 3-4 days after injury, takes up to 2 weeks Includes - Macrophage invasion (dissolving the clot) - Recruitment and proliferation (reproduction) of fibroblasts (connective tissue cells) - Fibroblast collagen synthesis - Granulation tissue growth (healthy wound healing) *PROTECT IT!* - Epithelialization (epithelial cells grow into the wound) - Contraction of the wound (closure) Wound Healing Phase III: Remodelling and Maturation Begins several weeks after injury, and is complete within 2 years Includes - Cellular differentiation - Scar formation (scar tissue contracts, and capillaries disappear) - Scar remodelling (tissue regeneration and wound contraction) Dysfunctional Wound Healing Causes include: Ischemia Excessive bleeding Obesity Predisposing disorder such as diabetes mellitus Wound infection Inadequate nutrients Numerous medication Tobacco smoke Wound disruption Impaired contraction Wound Disruption Dehiscence: event where the wound pulls apart at the suture line - Generally occurs 5-12 days after suturing - Wound infection occurs with approximately ½ of dehiscence occurrences Risk Factors: - Obesity - Excessive strain S/S: increased drainage from site, and patients perception that “something gave way” **requires prompt surgical attention** Impaired Contraction Contracture of Scar Tissue: excessive contracture, resulting in loss of movement around joints (burns) Internal example include duodenal strictures caused by dysfunctional healing of a peptic ulcer Proper positioning, range of motion exercises, and surgery are some ways to overcome excessive skin & internal contractures Pediatric & Geriatric Considerations Innate Immunity in Newborns - Acquired from the mother through breast milk & the placenta - Establishment of the gut microbiome is facilitated by breast milk - C-section newborns have reduced gut microbial diversity Innate Immunity in Geriatrics - Cells have diminished function - At risk for impaired healing if they have a chronic illness (diabetes, peripheral vascular disease) - Medications may interfere with healing Case Study (Breakout Rooms) John Doe is a 55-year-old man recently admitted to the hospital for an elective laparotomy (open abdominal surgery) to remove polyps from his large intestine. John has a medical history of type 2 diabetes. On the third postoperative day, the nurse notices the wound is dehisced, and there is purulent drainage coming from where the wound edges are no longer closely approximated. John’s pain has also increased, and he is requiring more analgesic to relieve it. The physical is notified and orders the removal of some staples with packing of the wound and changing the dressing every shift.