NURSING 2LA2 Study Guide - Final Guide: Complement System, Mast Cell, Platelet-Activating Factor
28 Nov 2016
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Patho Final Exam Review
Inflammation
− Inflammation: protective response designed to eliminate the initial cause of injury, remove damaged
tissue, and generate new tissue. Occurs in vascularized tissues and organs (perfused w blood)
− Human Defense Mechanisms: can be specific (immune response) or non-specific (inflammatory
response). Can be innate (present at birth) or acquired (after birth). Three types of defense
mechanisms: Natural barriers include mechanical and chemical types. Mechanical means of ridding
the body of pathogens (ex. coughing, urinating, etc.). Chemical barriers include mucous, perspiration,
tears, etc. that destroy bacteria. Inflammation is primary focus of module. Immunity is acquired,
specific, and adaptive ability. Our immune system makes antibodies targeted toward that antigen.
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Humoral Immunity: complement factors in inflammation and action of antibodies in immunity.
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Cellular Response: cell-derived process. Inflammation = neutrophils and macrophages. Immune
response = lymphocytes.
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Goals of Inflammation: movement of the necessary blood and cellular components to the site of the
injury; delivery of nutrients and blood cells to eradicate the offender; dilution, confinement and
elimination of the offending agents; stimulation and facilitation of components of the immune system;
and promotion of healing with generation of new tissue.
− There are three major events that occur pretty much simultaneously and include:
• The first is an increased metabolic rate. We increase our heat production, our oxygen and glucose
consumption and our production of wastes during injury.
• Dilation of blood vessels helps speed up delivery of inflammatory components to the site of injury.
• Increased capillary permeability which allows for movement of white cells (specifically neutrophils),
proteins, and nutrients out of the blood vessels and into the tissue where they can go to work.
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Causes of Inflammation: microbes, immune reactions between antigen and antibody, trauma, burns,
physical or chemical agents and tissue necrosis. Other causes include temperature extremes, oxygen
deprivation, nutrient deprivation, genetic or immune defects, and ionizing radiation.
−
Cells Involved in Inflammation:
• Endothelial Cells: line the walls of blood vessels. The space between them is very tight, limiting the
movement of cells and particles across the vessel wall. In addition to this traffic control function,
endothelial cells also: produce antiplatelet agents to prevent formation of clots, produce both
vasoconstrictors and vasodilators to regulate flow, regulate leukocyte extravasation through the
use of adhesion molecules, regulate immune cell proliferation through secretion of colony
stimulating factors, and participate in the repair process through angiogenesis and formation of an
extracellular matrix.
• Platelets: Referred to as thrombocytes and they circulate passively until activated by products of
tissue degradation. Their primary role is one of hemostasis or the stemming of blood flow. Once
activated, they produce potent inflammatory mediators which result in increased vascular
permeability, chemotaxis, adhesive and proteolytic properties of the endothelium.
• Neutrophils: Represent one type of granulocyte; considered the chief phagocytic leukocytes. Early
in the inflammatory response, these cells are attracted to the site of injury by chemotactic factors.
Because of their lysosomal enzymes, they are called upon to destroy invaders and remove
subsequent debris. Once they themselves die off, they become exudate, or pus. In inflammation,
neutrophils are released from bone marrow. Short-lived because they are incapable of division, and
when they die off, they release macrophage chemotactic factor to attract macrophages to the site
of injury. In the presence of severe inflammation, as demand for neutrophils increases, the bone
ao a’t uite keep up ad eleases iatue eutophils alled ads.
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• Monocytes/Macrophages: Monocytes are also leukocytes derived from bone marrow, but contain
larger and fewer lysosomes. Typically, monocytes exit the circulation in response to inflammation
and take up residence in various tissues as the more mature macrophage. Monocytes are an
immature form of macrophage. Macrophages arrive at the site of inflammation a little later than
the neutrophils. They replace the neutrophils as they die off. Macrophages are often associated
with chronic inflammation. Monocytes/macrophages produce very potent vasoactive mediators
(prostaglandins, leukotrienes, platelet activating factor, inflammatory cytokines and growth factor)
and they engulf more material than neutrophils. Their lifespan is 3-4x longer than neutrophils.
Macrophages are responsive to lymphocytes from T cells which enhance their efficacy and work
with the immune system by processing and presenting antigens to the lymphocytes.
• Eosinophils: They are granulocytes with many lysosomes. They contain biochemical mediators of
inflammation. They are particularly good at tackling parasitic infections. Eosinophils circulate in the
blood until they are needed to response to injury. Then, they migrate to the tissues where they
modulate release of inflammatory mediators and degrade vasoactive molecules, controlling the
vascular effects of histamine and serotonin.
• Basophils: Similar in function to eosinophils. They produce lipid mediators and cytokines to induce
the inflammatory response. They are important in the allergic and hypersensitivity reactions. They
also interact with the immune system in that they bind to IgE through receptors on their cell
surface. This action triggers the release of histamine and vasoactive agents.
• Mast Cells: Considered most important activators of inflammatory response (especially for
hypersensitivity & allergies), by performing 2 functions: degranulation and synthesis of mediators.
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Mast Cells: Located in connective tissue, close to a blood vessel. Derived from same hemopoeitic stem
cells as basophils. Mast cells produce lipid mediators and cytokines that induce inflammation. When
activated, they release their granular contents (histamine, serotonin, cytokines such as TNF-alpha, etc.)
into the circulation and exert their effects immediately. They also synthesize lipid mediators from cell
membrane precursors, such as prostaglandins, and stimulate cytokine and chemokine synthesis by
other cells such as monocytes and macrophages. They bind to one of immune globulin, IgE to trigger
the release of histamine and vasoactive substances from basophils. Responsible for release of
eosinophil chemotactic factor-A which serves to attract eosinophils to the site of inflammation.
− Plasma Protein Systems: three interrelated plasma protein systems that exist in an inactive state.
− Complement System: Components include 20 different proteins. They are capable of direct
destruction of pathogens or can activate and work with other components of the inflammatory
response to effect the same results. Complement fragments contribute to the inflammatory response
by causing vasodilation, increasing vascular permeability, and enhancing activity of phagocytes.
Activation of C3 and C5 results in formation of opsonins, chemotactic factors (draw other important
inflammatory mediators to site of injury as needed) and anaphylatoxins (cause rapid degranulation of
mast cells). Opsonins coat bacteria and tag them for destruction. The final endpoint of the
complement cascade is formation of the membrane attach complex (MAC). Its job is to create holes in
the membranes of pathogens, allowing entry of water, causing the cells to explode. Three possible
avenues through which the complement cascade can be activated: (1) classical pathway is activated by
antibodies (destruction of bacteria); (2) lectin pathway is activated by bacterial carbohydrates and no
antibodies are required; and (3) alternative pathway is activated by gram negative bacterial and fungal
cell wall polysaccharides; no antibodies are required. Complement cascade has 4 major effects: (1)
opsonisation; (2) mast cell degranulation through anaphylatoxic activity; (3) leukocyte chemotaxis; and
(4) cell lysis.
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Clotting System: activated by substances released during tissue destruction and infection. Two
pathways (intrinsic and extrinsic) that converge at the place where factor X becomes Xa. Factor Xa and
thrombin both act to provide the link between the coagulation system and inflammation.
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Inflammation is enhanced by many of the by-products or fragments that are produced during the
clotting cascade. Similarly, plasmin works with the complement cascade to activate C3a and C5a
causing the release of histamine, enhancing the inflammatory response. The primary goal of the
clotting system then, is to produce a fibrous clot. The fibrinous network that forms serves to prevent
the spread of infection by trapping the offending agent and retaining it at the site of inflammatory
activity, to prevent bleeding and to provide the framework for eventual healing and repair.
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Kinin System: interacts closely with the clotting system. Clotting and kinin system are both initiated by
activated factor XII (factor XIIa). In this cascade, vasoactive peptides are generated from plasma
proteins called kininogens by the action of proteases called kallekreins. The end result is production of
bradykinin which causes vasodilation, increases vascular permeability, causes smooth muscle
contraction, enhances leukocyte chemotaxis and stimulates pain receptors. Kinins are eventually
degraded by kininases, to maintain homeostasis.
− Hageman factor (XII) activates the following four components of the plasma protein systems: (1)
clotting cascade through factor XI; (2) fibrinolytic system through conversion of plasminogen; (3) kinin
system by prekallekrein activator; and (4) C1 and the complement cascade.
− Homeostasis helps control the effects of inflammation so that they are self-limiting.
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Inflammatory Mediators: plasma-derived mediators are synthesized in the liver. Cell derived
mediators of inflammation are derived from both pre-formed cells (mast cells, platelets and
neutrophils and macrophages) or newly synthesized in response to need from leukocytes,
macrophages, lymphocytes and endothelial cells.
− Cell Derived Mediators of Inflammation:
• Histamine: present in preformed cells and is one of the first mediators released during acute
inflammation. Histamine is most prevalent in well perfused connective tissue. Histamine binds to
H1 receptors on endothelial cells, causing vasodilation which helps increase blood flow to the
microcirculation. It contributes to increased vascular permeability by causing retraction of
endothelial cells. It causes smooth muscle constriction of bronchioles, making breathing difficult
during an acute inflammatory reaction. Antihistamine meds are capable of binding to the H1
receptor to compete with histamine to antagonize the effects of the acute inflammatory response.
• Serotonin: Released mainly by mast cells, basophils, and platelets and causes smooth muscle
contraction, small blood vessel dilation, and increased vascular permeability. Similar to histamine.
• Lysosomal Enzymes: Are small membrane enclosed sacs that contain very powerful enzymes. These
lysosomes are capable of fusing with phagocytes for the purpose of destroying foreign invaders.
• Arachidonic Metabolites: They are released from mast cells and initiate complex reactions that
lead to the production of other inflammatory mediators (prostaglandins and leukotrienes).
• Prostaglandins: Synthesized from arachidonic acid metabolites and serve to induce inflammation
and enhance the effects of histamine and other inflammatory mediators. They promote
vasodilation and bronchoconstriction and increase neutrophil chemotaxis, cause pain through
direct action on nerves and fever.
• Thromboxane A2: Produced primarily by platelets at the site of injury and promotes platelet
aggregation, bronchoconstriction, and vasoconstriction.
• Leukotrienes: They increase vascular permeability, induce smooth muscle contraction and constrict
pulmonary airways, thus playing a major role in mediation of asthma and anaphylaxis. They affect
the adhesion properties of endothelial cells and the extravasation and chemotaxis of neutrophils,
eosinophils, and monocytes. Leukotrienes help to prolong the inflammatory response.
• Platelet Activating Factor: Generated from lipids stored in the cell membrane and induce platelet
aggregation. Serves to activate neutrophils and may act as a chemoattractant for eosinophils.
• Cytokines and Chemokines: Are proteins that play a role in both acute and chronic inflammation
and immunity. They are either pro-inflammatory or anti-inflammatory. They are produced by many
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Document Summary
Inflammation: protective response designed to eliminate the initial cause of injury, remove damaged tissue, and generate new tissue. Occurs in vascularized tissues and organs (perfused w blood) Human defense mechanisms: can be specific (immune response) or non-specific (inflammatory response). Can be innate (present at birth) or acquired (after birth). Three types of defense mechanisms: natural barriers include mechanical and chemical types. Mechanical means of ridding the body of pathogens (ex. coughing, urinating, etc. ). Chemical barriers include mucous, perspiration, tears, etc. that destroy bacteria. Our immune system makes antibodies targeted toward that antigen. Humoral immunity: complement factors in inflammation and action of antibodies in immunity. There are three major events that occur pretty much simultaneously and include: the first is an increased metabolic rate. Causes of inflammation: microbes, immune reactions between antigen and antibody, trauma, burns, physical or chemical agents and tissue necrosis. Other causes include temperature extremes, oxygen deprivation, nutrient deprivation, genetic or immune defects, and ionizing radiation.
