Inflammation

initiation of inflammation: injured tissue releases inflammatory chemical signals

-damage-associated molecular patterns (DAMPs) -express surface molecules not found on healthy cells

overview of the beginning of the inflammatory response:

1. tissue damage and bacteria cause resident sentinel cells [macrophages, mast cells, dendritic cells] 2. permeable capillaries allow an influx of fluid (exudate) and cells 3. neutrophils and other phagocytes migrate to site of inflammation (chemotaxis) 4. phagocytes and antibacterial substances destroy bacteria

increase in vascular permeability leads to

edema or swelling

an exudate rich in white cells and necrotic debris caused by migration of neutrophils and release of enzymes

pus

compounds that relay signals between cells or cell types

cytokines

when tissues are damaged, the injured cells release inflammatory chemical signals into the tissue and on their cell surface that attract the tissue phagocytic cells to the area, these components are called

damage associated molecular patterns or DAMPs

attracted by the chemoattractants released into the tissue, through a process known as _____, the neutrophil squeezes between the endothelial cells and enters the tissue

diapedesis

the functional part of inflammation is to deliver plasma components and cellular components of the blood to

extravascular tissues

high protein edema fluids containing immunoglobins

exudate

_____ is deposited to wall of injured area from rest of the body

fibrin

late chemical mediators (6-12 hours) include:

fibrin split products, arachidonic acid metabolites, bradykinin, complement, cytokines

if damage is extensive, _____ form scar tissue [replacement of functional tissue cells or "parenchyma" by connective tissue]

fibroblasts

primary process through which the body repairs tissue damage and defends against infection

inflammation

_____ activated on neutrophils surface by chemokines, bind to endothelial surface via intercellular adhesion molecules or ICAM resulting in tight binding of neutrophils to endothelium

integrins

original designation for low molecular weight proteins and signaling molecules secreted by cells of the immune system to act on hematopoietic cells

interleukins

_____ are normally inactive in plasma, tissue damage activates -> causes vasodilation and increased permeability

kinins

a cell adhesion molecule on the cell surface of the endothelial lining of the blood vessel, will interact with a glycoprotein on the surface of the neutrophils causing them to slow down and roll along the interior surface of the blood vessel

selectins

diffuse inflammatory infiltrate in tissue

cellulitis

low molecular weight protein cytokine that attracts cells of the immune system to the site of inflammation through chemotactic gradient (chemotaxis)

chemokines

match the compound to function activity:

-ICAM: neutrophil binding -selectin: neutrophil slowing -histamine: initiate vasoconstriction -fibrin: wall of damaged tissue -chemokine: attract neutrophils

cellular response in inflammation:

-mast cells: release histamine -macrophages/dendritic cells: release chemokines -neutrophils: infiltrate tissue -mononuclear cell infiltration [lymphocytes and macrophages]: attracted by chemotactic mediators

acute inflammation characteristics:

-neutrophils mobilized within 30-60 minutes -neutrophils emigration lasts 24-48 hours -number of neutrophils proportional to amount of chemotactic factors present in the area -macrophages and monocytes migrate several hours after initial injury, peak between 16-48 hours -clean up area, repair to normal structure

chronic inflammation characteristics:

-prolonged inflammation often due to non-resolution of infection and inflammatory mediators -primary cells are macrophages and lymphocytes -T lymphocytes activate macrophages -B cells producing antibodies -tissue destruction, loss of function

vasodilation results:

-redness "rubor" [3-60 seconds] -swelling "tumor" [1-5 minutes]

causes of inflammation include:

-trauma -tissue necrosis (tissue death) -infection -immune reactions

Three goals of inflammation

1. eliminate the initial cause of injury 2. remove necrotic cells and tissue 3. initiate the process of repair

phased of inflammation:

1. injured tissue cells result in the release of interleukin-1, tumor necrosis factor alpha, histamine 2. increased blood flow preceded by transient vasoconstriction 3. increased vascular permeability leading to edema 4. infiltration by polymorphonuclear leukocytes 5. infiltration by lymphocytes and macrophages 6. resolution [restoration of normal structure of tissue] OR scarring due to tissue destruction and replacement of nascent tissue type with fibroblasts and collagen

constituents of the immune response involved in the induction and resolution of inflammation

1. inside blood vessels -white blood cells: neutrophils [polymorphonuclear leukocytes or PMNs], lymphocytes, monocytes, eosinophils, basophils -platelets: pieces of megakaryocytes cytoplasm that aid in blood clotting -plasma: liquid portion that contains complement, clotting factors, kininogens [inactive proteins that can become active by enzymes]

put stages of inflammatory process in order of occurrence (collagen formation, vasodilation, neutrophil infiltration, mast cells release histamine, transient vasoconstriction)

1. mast cells release histamine 2. transient vasoconstriction 3. vasodilation 4. neutrophil infiltration 5. collagen formation

five cardinal signs of inflammation:

1. redness 2. swelling 3. heat 4. pain 5. loss of function

illustrates process of selectins encountered order

1. rolling 2. activation 3. arrest/adhesion 4. transendothelial migration

acute phase reactants: concentration increase/decrease by at least _____ percent

25

a cavity filled with pus

abscess

_____ are plasma proteins that increase [or decrease] in concentration during tissue damaging infections

acute-phase proteins

inflammation can be potentially _____

harmful {can also destroy normal tissue}

_____ released in response to tissue damage, produces vasodilation and increased permeability

histamine

early chemical mediators (within minutes) include _____

histamine

inflammatory chemical signal cause mast cells to degranulate and release _____

histamine

vasodilation results in _____ being able to exit capillaries and enter tissue

neutrophils

inflammation can result in _____ due to mechanical pressure from swelling and chemical mediators acting on nerve endings

pain

bacteria, parasites, fungi, and viruses can also have conserved patterns that are recognized by phagocytic cells, these are called

pathogen-associated molecular patterns or PAMPs (MAMPs or microbe associated molecular patterns)

initial _____ happens by the vessels [help minimize blood loss so clots can form in damaged vessels] followed by _____ {histamine} [to increase blood flow to the area resulting in redness + heat in the area] of vessel

vasoconstriction, vasodilation

histamine causes _____

vasodilation

effects of inflammation on vasculature

when an inflammatory process occurs, more fluid is flowing out of the vessels into the tissue than is flowing into the blood vessels by the osmotic pressure, so there is a net flow out of the blood vessels and into the interstitial fluid of the surrounding tissue