Processes in the Microcirculation During Inflammation

Chapter 6 This chapter outlines the concepts of innate immunity, inflammation, and wound healing. Innate immunity refers to the body's initial defense mechanisms against invasion and injury. Inflammation is the body's response to injury and infection, aimed at protecting and healing the body. Wound healing involves several phases, including hemostasis, inflammation, tissue formation, and remodeling. Bullet points Processes in the microcirculation during inflammation  Hemostasis (coagulation): Clotting cascade activation and platelet activation  Vasodilation: Increased blood vessel diameter, resulting in erythema and warmth  Increased vascular permeability: Enlarged spaces between endothelial cells, leading to exudation and edema  White blood cell adhesion: WBCs adhere to vessel walls, migrate through endothelial cells, and target microorganisms Pain and swelling in response to injury  Tissue injury and activation of pain fibers result in pain associated with injury  Inflammation can lead to loss of function  Lymphatic vessels may become inflamed, leading to lymphangitis or lymphadenitis Functions and benefits of inflammation  Prevents infection and further damage by diluting toxins and activating plasma protein systems  Limits the scope of the inflammatory process to prevent spread to healthy tissue  Prepares the injury for healing and repair by removing debris through drainage channels  Facilitates the development of adaptive immunity by initiating immune response and protecting against future exposures Plasma protein systems and inflammation  Three key plasma protein systems: complement system, clotting system, and kinin system  Each system consists of inactive forms of proteins and enzymes  Activation of components in a cascade sequence triggered by tissue damage  Systems have similar biologic functions in promoting inflammation Quick Check: Questions  Innate immunity and inflammation are nonspecific because they do not target specific pathogens  The five classic symptoms of acute inflammation are pain, swelling, redness, heat, and loss of function  Basic steps in acute inflammation: tissue injury, vascular changes, recruitment of immune cells, resolution  Benefits of inflammation: prevention of infection, limitation of inflammation scope, preparation for healing, facilitation of adaptive immunity Complement System  The complement system consists of a family of proteins that are activated in sequence  Activation of the complement system enhances the immune response against pathogens  Activated complement produces substances that can destroy pathogens directly and enhance the activity of other immune response components  Key molecules produced during complement activation include C3b, C5a, C3a, and C5a C3b  C3b serves as an opsonin, coating the surface of bacteria to increase their susceptibility to phagocytosis C5a  C5a functions as a chemotactic factor, attracting leukocytes to sites of inflammation C3a and C5a (Anaphylatoxins)  C3a and C5a induce rapid degranulation of mast cells, leading to histamine release  Histamine causes vasodilation and increased capillary permeability Membrane Attack Complex (MAC)  The MAC, composed of elements C6 through C9, leads to bacterial destruction by creating pores in cell or bacterial membranes  This facilitates the infusion of water into cells, resulting in cellular death Activation of Complement  Three major pathways control the activation of complement: classical, alternative, and lectin pathways  The classical pathway is activated by antibodies  The alternative pathway is antibody-independent  The lectin pathway is activated by lectins binding to carbohydrates on pathogens Complement pathway  Activated by antibodies or substances on infectious microorganisms  Three pathways: classical, alternative, and lectin  Result in opsonization, inflammation, cell lysis, and leukocyte chemotaxis Clotting system  Activated by tissue injury or infection  Two converging pathways: tissue factor and contact activation  Leads to the formation of a fibrin clot Kinin system  Interacts closely with the clotting system  Activated through Hageman factor  Forms bradykinin, which causes blood vessel dilation and other effects Control and interaction of plasma proteins  Plasma proteins interact and cascade to activate different systems  Proteins like factor XII and prekallikrein play important roles in initiating pathways Plasma Protein Systems  There are three plasma protein systems: complement system, coagulation system, and kinin system  Activation of one system leads to production of biologically active substances that activate other systems  Tight regulation of these processes is important for survival and to prevent harm to the individual  Enzymes in plasma destroy inflammatory mediators and downregulate the inflammatory response  Defects in these mechanisms can be genetic or acquired, leading to conditions like hereditary angioedema or widespread clotting Cellular Components of Inflammation  Inflammatory response involves cells from both innate and adaptive immune systems  Cells respond to molecules produced at the site of cellular damage and are recruited to help with the protective response  Inflammatory cells include mast cells, endothelial cells, platelets, phagocytes (neutrophils and macrophages), and lymphocytes  These cells act to confine damage, kill microorganisms, remove debris, and activate healing Vascular Tissues and Cells  Inflammation occurs in vascular tissue  Endothelial cells line blood vessels and play a role in maintaining blood flow  During inflammation, the vascular endothelium facilitates clotting and passage of cells and fluid into surrounding tissue  Mast cells are important mediators of inflammation  Macrophages are present in the tissues surrounding blood vessels