 the sequence of events in an inflammatory reaction:

1. the offending agent, located in the extravascular tissues, is recognized by host

cells and molecules
2. leukocytes and plasma proteins are recruited from the circulation to the site
where the offending agent is located
3. the leukocytes and proteins are activated and work together to destroy and
eliminate the offending agent
4. the reaction is controlled and terminated
5. the damaged tissue is repaired
Fundamental properties of inflammation
 components of the inflammatory response
o blood vessels
o leukocytes
 harmful consequences of inflammation
 local and systemic inflammation
 mediators of inflammation
 acute and chronic inflammation
o acute: innate immunity: develops within minutes and hours and lasts several
hours or a few days
o chronic inflammation: adaptive immunity: longer duration
 termination of inflammation and initiation of tissue repair
 Cells involved in the inflammation process
o Neutrophils
 Bacteria killing machine
 Blood and bone marrow-normally found
 End cell and lives only 12-20 hours
 Presence in the tissue signals inflammation
 Two types of cytoplasmic granules
 Primary granules (azurophil): lysozymes
 Secondary (specific) more numerous and contain antibacterial
proteins (lactoferrin, lysozyme, cobalamin)
 Kill bacteria by bombarding them with reactive oxygen species
 Super oxide
 Hydrogen peroxide
 Hydrochlorous acid
 Phagocytosis their content is spilled out the cell making neutrophils a
potentially harmful cell (can kill innocent bystander cells)
o Eosinophils
 Worm killers
 Not efficient at killing bacteria
 Similar to neutrophils: bilobed nucleus, but lives much longer (weeks in
tissue)
 Normally found in the blood and tissues like the mucosa of the GI tract
  Many + charged cationic proteins
 Major basic proteins
 Eosinophil cationic protein
 Eosinophil peroxide
 Eosinophil-derived neurotoxin
 Degranulate in local vicinity of parasites
 Cationic part binds the negatively charged proteins on parasites and kills
them
 Examples of inflammations with eosinophilic predominance
 Asthma
 Parasitic infections
 Hypereosinophilic syndrome is infiltration by eosinophils of many organs
including the heart.
 Can cause fibrosis which can be life threatening
o Monocytes and macrophages
 Master minds of inflammation
 Monocytesmacrophages (differentiation in tissues)
 Half life of blood monocyte is 1 day
 Macrophages several months or years
 Reticuloendothelial system
 Can phagocytize bacteria as neutrophils but as effectively
 Better at killing hard to kill intracellular bacteria
 Not end cells and can multiply
 Macrophages are second responders to finish what neutrophils started
and then take over
 Major player in chronic inflammation
o What activates a macrophage?
 Microbial products
 Cytokines
o Activated macrophages have multiple biological properties besides phagocytosis
 Antigen presentation
 Turn on angiogenesis
 Unleash fibrosis
 Produce inflammatory mediators
 Enzymes and cytokines
 Activated macrophages can become dangerous like neutrophils
 Platelets and endothelial cells
o Platelets are stiff disc passively dragged around in the blood stream
 Essential for stopping a hemorrhage
 Plug gaps in vessel walls
 Blood clotting
 Mediators of inflammation
 o Endothelial cells are a barrier that must be crossed by the two components of
inflammatory exudate: plasma and leukocytes
 When activated by cytokines they respond
 Produce prostaglandins and adhesions molecules
 Leukocytes migrate out of the blood vessels and into the tissue
 Fibroblasts, mast cells, basophils
o Fibroblasts: connective tissue: glucoaminoglycans, collagen, and elastin
 Contribute most during the terminal period of inflammation when the
damaged tissues are replaced with scar (collagen) tissue produced by
fibroblasts
 Wound healing
o Mast cells and basophils
 Mast: Live in tissues
 Basophils: live in blood
 Both are similar in structure and function but produced from different
bone marrow precursors
 Structure: large granules programed to release histamine, heparin and
other mediators
 Mast cells express a high affinity receptor for the Fc region of IgE, IgE
binding to fc receptor activates mast cells causing a release of histamine
causing vasodilation, leaky vessels, and inflammation)
 Mediators of inflammation
o Initiate and regulate inflammatory reactions
 Most mediators of acute inflammation are:
o Vasoactive amines
o Lipid products (prostaglandins, leukotrienes),
o cytokines (and chemokines)
o products of complement activation
 Either derived from plasma proteins or secreted by cells
o Cell-derived: intracellular granules and can be rapidly secreted by exocytosis
(histamine) or are synthesized de novo (prostaglandins, leukotrienes, and
cytokines)
 Sentinels: major precursors that detect invaders and damage in tissues
that is the macrophages, DCs, and mast cells
o Plasma derived (complement): mainly in the liver and are present in circulation
as inactive precursors that must be activated usually a series of proteolytic
cleavages, to acquire their biologic properties
o Most short lived
o One mediator can stimulate the release of other mediators
Mediator: Histamine
Source: Mast cells, basophils, platelets
Action: vasodilation, increased vascular permeability, and endothelial activation
Mediator: prostaglandins
Source: mast cells and leukocytes
Action: vasodilation, pain, fever

Mediator: leukotrienes
Source: mast cells and leukocytes
Action: increased vascular permeability, chemotaxis, leukocyte adhesion, and activation

Cytokines:
Source: macrophages, endothelial cells, mast cells
Action: local: endothelial cell activation (expression of adhesion molecules)
Systemic: fever, metabolic, abnormalities, hypotension, shock

Chemokines
Source: leukocytes, activated macrophages
Action: chemotaxis, leukocyte activation

Platelet activating factor

Source: Leukocytes, mast cells
Action: vasodilation, increased vascular permeability, leukocyte adhesion, chemotaxis,
degranulation, oxidative burst

Complement
Source: plasma (produced in liver)
Action: leukocyte chemotaxis and activation, direct target killing (membrane attack complex)
vasodilation (mast cell stimulation)

Kilins
Source: plasma produced in liver
Action: Increased vascular perm, smooth muscle contraction, vasodilation, pain.

Vasoactive amines
 Histamine and serotonin
 Histamine is stored in granules of mast cells, basophils, and platelets
 Serotonin is stored in the granules of platelets and enterochromaffin cells of the gut and
bronchi
 First mediators to be released during inflammation
 Actions: both are mediators
o Contract large arteries
o Dilate small arterioles
o Increase permeability of venules due to endothelial contraction
o Allow plasma and cells to leak out into site of inflammation (fluid exudation)
Eicosanoids
 Are build into the structure of the cell membranes (ER and Plasma mem)
 One of the two FA legs of the phospholipid molecule is arachidonic acid
 Arachidonic acid
 Cyclooxygenase pathway: prostaglandins and throboxanes
 Lipooxygenase pathway: leukotrienes
 Lipoxin cell-cell interaction pathway: lipoxins
All of these cells if stimulated enough stimulate the release of eicosanoids