Inflammation Week 2 PDF

The basics Cellular response 1/13/25 Lauri Keogh/Bio 4311/2024 1  INFLAMMATION non-specific response of the body to local injury (immune response to many things/identified as not us) Specific- immune system...

The basics Cellular response 1/13/25 Lauri Keogh/Bio 4311/2024 1  INFLAMMATION non-specific response of the body to local injury (immune response to many things/identified as not us) Specific- immune system response to a particular bad guy part of the body’s second line of defense/skin is first can also produce devastating effects (e.g. rheumatoid arthritis) can be brought on by various agents: Physical agents – trauma, ischemia , temperature extremes Chemical agents – strong acids & bases, venom Biological agents – bacteria, fungi etc.  INFLAMMATION suffix –itis used to indicate inflammation in a certain tissue (e.g. appendicitis) the inflammatory response can follow two patterns: acute (self-limiting)(good one) or chronic (self-perpetuating)(bad one/keeps coming back and does harm)(frictioning)(doesn’t have any good stuff like acute) Acute inflammation shows characteristic signs and symptoms that are produced by vascular and cellular responses to chemical mediators 1/13/25 3  ACUTE INFLAMMATION VASCULAR RESPONSE starts almost immediately after injury and consists of vasodilation of arterioles and venules that supply the area vasodilation leads to increased blood flow that produces redness and heat permeability of capillaries(gets leaky)increases, which allows fluid to escape into the tissue and cause swelling (for decreased use of the movement that injured you) pain and impaired function follow as a result of tissue swelling and release of INFLAMMATION chemical mediators 1/13/25 4  INFLAMMATION VASCULAR RESPONSE Why does fluid move into the tissue, can this be a good thing? § it dilutes the injuring agent § it carries plasma proteins & leukocytes to the site § it carries away bacterial toxins, dead cells and debris to the lymphatic system § Brings clotting agents and helps prevent the spread of microorganisms  depending on the severity injury, the vascular response can follow one of three different patterns: an immediate transient response, occurs when there is a minor injury an immediate sustained response, occurs with a more serious injury INFLAMMATION a delayed response, occurs in injuries such as sunburns Although inflammation may be local, it may also be Vascular Response widespread or systemic. Systemic effects include: fever (from infection) leukocytosis (high numbers of white blood cells in the blood circulation)(risk of clotting) increase in circulating plasma proteins 1/13/25 6 INFLAMMATION ACUTE INFLAMMATION - CELLULAR RESPONSE Mast Cells: found in connective tissues throughout the body, but are most abundant in the dermis of skin, and mucosa of GI and respiratory tracts contain granules with several chemical mediators: histamine and chemotactic factors (basophils contains) degranulation occurs as a result of physical injury*** including massage!!!****, chemical agents or immunologic means 1/13/25 7  Histamine: causes the dilation of blood vessels and increases vascular permeability Chemotactic factors: attract neutrophils and eosinophils to the injured site (taxi) Ø during an inflammatory response, mast cells will also synthesize other chemicals: leukotrienes, prostaglandins and platelet-activating factor, to augment the inflammatory response HISTAMINE 1/13/25 8 INFLAMMATION Neutrophils: Are a type of white blood cell and are classified as granulocytes along with eosinophils and basophils neutrophils (phagocytes) are usually the first cell on the scene and arrive a few hours after the initial injury their job is to clean up debris and dead cells 1/13/25 9  INFLAMMATION Monocytes: in the blood waiting till the get their signal white blood cell (leukocyte) follow neutrophils into site of injury within 24 hours mature into macrophages; these cells last longer than neutrophils macrophages help to destroy injurious agent by phagocytosis; also, take part in activating specific immunity and resolving inflammatory response  Natural Killer (NK) Cells: patrol the blood and lymph and have the ability to kill cancer cells and virus-infected cells before the adaptive mechanisms are activated they attack their targets non-specifically by identifying the lack of “self” cell surface receptors and recognizing cell surface carbohydrates on target cells INFLAMMATION killing is accomplished by release of cytolytic chemicals called perforins 1/13/25 11 INFLAMMATION Platelets: cytoplasmic fragments that circulate in bloodstream once an injury occurs they take part in clotting and releasing chemical mediators of inflammation (stick to each other till the hole is patched) 1/13/25 12  INFLAMMATION Response of White Blood Cells: included in the response of WBCs (mainly neutrophils and monocytes) are: Margination of WBCs to capillary walls, Emigration of WBCs, Chemotaxis, Phagocytosis Diapedesis (false foot) INFLAMMATION Margination (Pavementing) leukocytes slow their migration and then adhere to the endothelial cells via adhesion molecules release of chemical mediators – kinins, histamine, leukotrienes and cytokines – causes the leukocytes to increase their expression of adhesions molecules (CAMs); endothelial cells also express adhesion molecules diapedesis INFLAMMATION Emigration (diapedesis) emigration consists of leukocytes sending extensions through the permeable capillaries and moving through the walls and into the tissues in amoeboid fashion emigration occurs after adherence of the phagocyte to the endothelial cells 1/13/25 15 Chemotaxis INFLAMMATION movement of leukocytes toward the injured site due to chemical signals Chemotactic agents include: cytokines, bacterial and cellular debris and complement fragments (C3a, C5a)  Phagocytosis engulfing of bacterial and cellular debris by macrophages and neutrophils Eats anything that doesn’t belong in the area INFLAMMATION 1/13/25 17  a) adherence – binding of the phagocyte to the target; target is usually opsonized (coating) with complement or antibody that enhances recognition and binding of target cell by phagocyte (makes them easy to locate) b) engulfment – carried out by small pseudopods (of plasma membrane) that surround the adhered microorganism c) formation of phagosome - which fuses with lysosome (a) A macrophage (purple) uses its cytoplasmic extensions to pull spherical bacteria (green) toward it. Scanning electron micrograph (1750x). d) intracellular killing – either oxygen-dependent killing mechanism (e.g. Hydrogen peroxide/extra fuel to kill), lysosomal enzymes and other mechanisms INFLAMMATION  Phagocyte adheres to pathogens or debris. Phagocyte forms pseudopods that Phagosome eventually engulf the (phagocytic particles forming a vesicle) phagosome. Lysosome Lysosome fuses with the phagocytic vesicle, forming a phagolysosome. Acid hydrolase enzymes Lysosomal enzymes digest the particles, leaving a residual body. Exocytosis of the vesicle removes INFLAMMATION indigestible and residual material. (b) Events of phagocytosis.