Inflammation: Introduction

Dr Alok Tripathi
Dr Alok TripathiDirector at Academia para la Educación Profesional
Definition
“An inflammation
is a more or less
coordinated series
of responses by the
body to injuries and
infections”. Or
While various exogenous stimuli can cause
direct cell injury & the same stimuli also
incite a complex reaction in vascularized
connective tissues call inflammation
The characteristics of the
inflammatory response are
swelling, redness, heat,
& pain-acne
When tissue is
injured or invaded
by microbes, a
series of more or
less predictable
events ensues.
INFLAMMATION
Acute: Short duration
immediate & early
responses to injury
Chronic: Long duration
impacts even in
years
Inflammation
time -- hyperacute (peracute), acute,
subacute, and chronic inflammation;
the main inflammatory
manifestation - alteration,
exudation, proliferation;
the degree of tissue damage -
superficial, profound (bordered, not
bordered);
characteristic picture -
nonspecific, specific;
immunopathological
mechanisms
•allergic (reaginic) inflammation,
•inflammation mediated by cytotoxic antibodies,
•inflammation mediaded by immune complexes,
•delayed-type hypersensitivity reactions.
According to different criteria, inflammatory responses can
be divided into several categories. The criteria include:
An increased blood supply to the tissue ''in danger''.
It is performed by vasodilation.
The inflamed tissue looks like containing greater number of vessels.
Increased capillary permeability
caused by retraction of the
endothelial cells.
This permit comparatively larger
molecules to escape from the
capillaries, and thus allows the
soluble mediators of immunity to
reach the site of inflammation.
Leukocytes migrate out of the
capillaries into the surrounding
tissues.
In the earliest stages of
inflammation, neutrophils are
particularly prevalent, but later
monocytes and lymphocytes also
migrate towards the site of
infection.
Three major events occur during this response :
Main humoral and cellular components involved in the amplification
and propagation of both acute and chronic inflammation
There are two categories of factors capable to induce the
damage of cells and tissues - endogenous and exogenous.
Endogenous damaging factors include
immunopathological reactions, and some neurological and
genetical disorders. Exogenous factors can be divided into:
mechanical
(traumatic
injury),
physical
(extremely low or
high
temperature,
ionising
irradiation,
microwaves),
chemical (caustic
agents, poisons,
venoms,
genotoxic and
proteotoxic
compounds),
nutritive
(deficiency of
oxygen, vitamins
and basic
nutrients),
biological
(viruses,
microorganisms,
protozoan and
metazoan
parasites).
Factors involved in cell damage
The acute inflammatory response is an effective way to isolate an infection
and to attract the macrophages, neutrophils, and lymphocytes that can attack
and overcome it,
This can occur because of an
autoimmune
disease (such as
rheumatoid
arthritis),
because of
persistence of
an infection
(such as
tuberculosis),
because of
repeated tissue
injuries
("tennis
elbow"),
or because of
cancer.
Impact of acute Inflammation on Body of Host
Under some conditions it can persist for long
periods of time, becoming a chronic
inflammatory response.
Often the chronic inflammation causes a mass
of activated macrophages, lymphoctes, and
antigen that form a tumor-like lump called a
granuloma.
Apparently one of the central activators of a
chronic immune response is gamma-
interferon, which is also essential for normal
immune responses.
chronic inflammations are treated variously
with drugs like aspirin and ibuprofen (non-
steroidal anti-inflammatory drugs), steroids,
or drugs that block extravasation.
Impact of chronic Inflammation on Body of Host
Inflammation: Introduction
Acute Inflammation: Has 3 major components:
• Heat (colour)
• Redness (Nubor)
• Swelling (Tumor)
• Pain (Dolor)
• Loss of function
(Functio-laesa)
Alteration in
vascular caliber
that lead to local
increase in
blood supply
=Vasodilatatio
n
Structural
changes in
micro
vasculature that
permit plasma
protein to leave
the circulation
Emigration of
leukocytes from
microcirculation
& accumulation
in focus of
injury
These three
process
accounts for fine
classical local
sign of acute
inflammation :
After Adhering endothelial cells leukocytes squeezed between them & migrate through vascular wall into
interstitial tissues, a process called emigration.
As the stasis developed, leukocytes (principally neutrophils) begin to settle out of the flowing blood &
accumulate along the vascular endothelial surface, a process called migration.
This cause RBC to become more concentrated, thereby increase blood viscosity & slowing the circulation.
These changes are manifested microscopically numerous dilated small vassals, pocket with erythrocytes called stasis.
Subsequently, microvasculature become more permeable resulting in extraduction of protein rich fluid into
extra-vascular tissues.
After an inconstant & transient vasoconstriction of arterioles, vasodilatation occur.
Arterioles are involve first resulting in opening of new micro-
vascular beads in the area of infection
Local increase in blood flow cause the redness (erythrema) and
warmth characteristically seen in acute inflammation
Vascular Changes: A-Change in vascular flow & Caliber
Vasodialation
+Increased Blood Flow
Vascular Hydrostatic
Pressure
Filtration of Fluid From
Capillary=Fluid:
Transdute =Ultrafiltrate
of Blood Plasma
Increased Vascular
Permeability
Permit the flow of
protein rich fluid &
even cells into
interstitum
This movement of fluid
cause the reduced in
intravascular OP while
interstitial OP increases
OUTFLOW of water &
Ions into extra-vascular
tissue which
accumulation is called
EDMA
Vascular Changes: B-Increased Vascular Permeability
INCREASED
ECLIPASED
Permit
Endothelial Cell Contraction
In-vitro System
Direct Endothelial Injury
Leukocytes Dependent Endothelial Injury
Increase Transcytosis
How Permeability Increases?
leads to widening of
intracellular gap elicited
by histamine,
bradekinine,
leukotrinase, etc., & it is a
reversible process.
Cellular contraction
occur rapidly after
binding of mediators
to a specific
receptors (short-
lived)
Only these
endothelial lining of
venules 20-60m
undergo contraction;
while endothelium
in capillary &
arteries are remain
unaffected.
1-Endothelial Cell Contraction
Functional mechanism is another mechanism
resulting vascular permeability
2-In-vitro System
Cytokines like TNF,
IL-1 etc 
Structural
reorganization of
cytoskeleton 
Endothelial Cell
Junction are
disrupted
Start after 2-4 hrs & persists upto 24 hrs
3-Direct Endothelial Injury Seen after serious injury
Causing Vascular leakage by endothelial cells necrosis & detachment
Detachment is often associated with palate adhesion & Thrombosis
This reaction is known as Immediate Sustain response which affect
vacuoles, capillary and arterioles
This may cause Delayed Prolong Leakage that begain after 2-12 hrs &
last for several hrs or even a day
e.g. Mild to modrate thermal injury, X-ray/UV radiation & Certain bacterial
toxins
It is Attributable to apoptosis & action of Cytokines
4-Leukocytes Dependent Endothelial Injury
May occur as a consequences of Leukocytes
accumulation during inflammatory responses
Such Leukocytes may activate the release of
TOXIC OXYGEN SPECIES & PROTEIOLYTIC
ENZYMES
which thus cause endothelial injury or
detachment, largely restricted to those tissues
where leukocytes can adhere to endothelium
Inflammation: Introduction
1-the activation of a number of
proteolytic enzymes including
plamin, fibrin, kallikrein, and
complement
2-These cause localized increases
• in vascular permeability,
• smooth muscle contraction (blood vessels
are made of two kinds of cells-- smooth
muscles and endothelial cells), and
• production of chemotactic molecules like
some fragments of the complement proteins
(C3a, C5a).
3-These chemotactic molecules lure
(attract=ensnare) various cell types
out of the blood stream, by binding to
specific receptors on their cell surface
and inducing a migratory behavior
out of the blood stream into the
tissues.
4-The first cells to extravasate are
neutrophils followed subsequently
monocytes (macrophages that
haven't yet made a commitment)
and lymphocytes. Several
coordinated activities mediate this
process.
Reactions in Inflammation:When tissue is injured or invaded by
microbes, a series of more or less predictable events ensues.
5-First, bradykinin, fibrin, and complement
act on endothelial cells to increase their
permeability.
Second, release of "mediator" molecules by
activated macrophages induces increased
permeability of the blood vessel, and serves
as chemotactic factors for cells.
Several of the macrophage released
cytokines, including IL-1, IL-6 and TNF-
alpha, have widespread activities
throughout the body, not just at the site of
the injury.
6-Some of these activities recruit
•leukocytes-increased vascular permeability
•and adhesion molecules on endothelial cells;
•some induce "systemic" non-specific actions
•like fever and production of
•"acute phase proteins" that inhibit microbial growth:
•some help activate a specific immune responses;
•and some even help promote the healing response,
such as proliferation of fibroblasts
Reactions in Inflammation:When tissue is injured or invaded by
microbes, a series of more or less predictable events ensues-2
Third, the recruited leukocytes
enter the damaged tissue and
can begin to attack the
microorganisms causing the
infection, digest damaged cells
and tissues, and initiate an
immune response.
However, antigen-presenting
cells such as macrophages are
necessary to this activation;
macrophages can pick up
bacteria or other foreign
materials at the site of injury
and reenter the blood stream
where they can eventually
encounter and present to
lymphocytes.)
Reactions in Inflammation:When tissue is injured or invaded
by microbes, a series of more or less predictable events ensues.
Extravasation of leukocytes and lymphocytes, for example, seems to depend on a
complex series of interactions between the membranes of the blood cells and the endothelial cells of
the blood vessels. A variety of cell surface receptors, cell adhesion molecules, and secreted
chemokines induce tight, specific interactions among the cell types, followed by migration between
endothelial cells and out of the blood vessel.
In addition to direct cell-cell interactions, there are also long range interactions that direct
cells out of the blood stream and into the tissues at specific locations. These are mediated by
chemokines (a special subclass of cytokines) that are released by a variety of lymphoid and myeloid
cell types and that act through chemokine receptors to act as "chemo-attractants", luring cells along
a concentration of chemokines to a particular location.
All chemokine receptors known are G-protein coupled receptors that activate a variety of
second messenger systems to mediate, among other things, directional cell movement.
While the acute inflammatory response is an effective way to isolate an infection and to attract the
macrophages, neutrophils, and lymphocytes that can attack and overcome it, under some
conditions an inflammatory response can persist for long periods of time, becoming a chronic
inflammatory response. This can occur because of an autoimmune disease (such as rheumatoid
arthritis), because of persistence of an infection (such as tuberculosis), because of repeated tissue
injuries ("tennis elbow"), or because of cancer. Often the chronic inflammation causes a mass of
activated macrophages, lymphoctes, and antigen that form a tumor-like lump called a granuloma.
Apparently one of the central activators of a chronic immune response is gamma-interferon, which
is also essential for normal immune responses. Chronic inflammations are treated variously with
drugs like aspirin and ibuprofen (non-steroidal anti-inflammatory drugs), steroids, or drugs that
block extravasation. Presumably inhibitors of IFN- would also be effective, but I don't know of
any that are available. The hottest news in anti-inflammatory drugs are the so called Cox
(cyclooxygenase) inhibitors that are much more specific than other NSAIDs in blocking
inflammation.
 http://www.gluegrant.org/flash/injury.swf
 http://www.biostudio.com/index_%20inflammation%
20mac.htm
 http://library.med.utah.edu/WebPath/INFLHTML/IN
FL070.html
Inflammation
Triggered by tissue damage due to infection, heat,
wound, etc.
Four Major Symptoms of Inflammation:
1. Redness
2. Pain
3. Heat
4. Swelling
May also observe:
5. Loss of function
Functions of Inflammation
1. Destroy and remove pathogens
2. If destruction is not possible, to limit
effects by confining the pathogen and its
products.
3. Repair and replace tissue damaged by
pathogen and its products.
Stages of Inflammation
1. Vasodilation: Increase in diameter of blood vessels.
Triggered by chemicals released by damaged cells:
histamine, kinins, prostaglandins, and leukotrienes.
2. Phagocyte Migration and Margination: Margination
is the process in which phagocytes stick to lining of
blood vessels.
Diapedesis (Emigration): Phagocytes squeeze
between endothelial cells of blood vessels and enter
surrounding tissue.
Inflammation: Introduction
Stages of Inflammation
(Continued)
Phagocytes are attracted to site of infection through
chemotaxis.
Phagocytes destroy microbes, as well as dead and
damaged host cells.
3. Tissue Repair: Dead and damaged cells are
replaced.
Antimicrobial Substances:
I. Complement System: Large group of serum
proteins that participate in the lysis of foreign cells,
inflammation, and phagocytosis.
Two mechanisms of complement activation:
1. Classical Pathway: Initiated by an immune reaction
of antibodies.
2. Alternative Pathway: Initiated by direct interaction
of complement proteins with microbial
polysaccharides.
Both pathways cleave a complement protein called C3,
which triggers a series of events.
Inflammation: Introduction
Inflammation: Introduction
Consequences of Complement
Activation:
1. Cytolysis: Due to the formation of a membrane attack
complex (MAC) which produces lesions in microbial
membranes.
2. Inflammation: Complement components (C3a)
trigger the release of histamine, which increases
vascular permeability.
3. Opsonization: Complement components (C3b) bind
to microbial surface and promote phagocytosis.
4. Inactivation of Complement: Regulatory proteins
limit damage to host cells that may be caused by
complement.
Inflammation: Introduction
Inflammation: Introduction
II. Interferons: Antiviral proteins that interfere with
viral multiplication.
 Small proteins (15,000 to 30,000 kDa)
 Heat stable and resistant to low pH
 Important in acute and short term infections.
 Have no effect on infected cells.
 Host specific, but not virus specific.
Interferon alpha and beta: Produced by virus
infected cells and diffuse to neighboring cells.
Cause uninfected cells to produce antiviral
proteins (AVPs).
Interferon gamma: Produced by lymphocytes.
Causes neutrophils to kill bacteria.
1 of 34

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Inflammation: Introduction

  • 1. Definition “An inflammation is a more or less coordinated series of responses by the body to injuries and infections”. Or While various exogenous stimuli can cause direct cell injury & the same stimuli also incite a complex reaction in vascularized connective tissues call inflammation The characteristics of the inflammatory response are swelling, redness, heat, & pain-acne When tissue is injured or invaded by microbes, a series of more or less predictable events ensues. INFLAMMATION Acute: Short duration immediate & early responses to injury Chronic: Long duration impacts even in years Inflammation
  • 2. time -- hyperacute (peracute), acute, subacute, and chronic inflammation; the main inflammatory manifestation - alteration, exudation, proliferation; the degree of tissue damage - superficial, profound (bordered, not bordered); characteristic picture - nonspecific, specific; immunopathological mechanisms •allergic (reaginic) inflammation, •inflammation mediated by cytotoxic antibodies, •inflammation mediaded by immune complexes, •delayed-type hypersensitivity reactions. According to different criteria, inflammatory responses can be divided into several categories. The criteria include:
  • 3. An increased blood supply to the tissue ''in danger''. It is performed by vasodilation. The inflamed tissue looks like containing greater number of vessels. Increased capillary permeability caused by retraction of the endothelial cells. This permit comparatively larger molecules to escape from the capillaries, and thus allows the soluble mediators of immunity to reach the site of inflammation. Leukocytes migrate out of the capillaries into the surrounding tissues. In the earliest stages of inflammation, neutrophils are particularly prevalent, but later monocytes and lymphocytes also migrate towards the site of infection. Three major events occur during this response :
  • 4. Main humoral and cellular components involved in the amplification and propagation of both acute and chronic inflammation
  • 5. There are two categories of factors capable to induce the damage of cells and tissues - endogenous and exogenous. Endogenous damaging factors include immunopathological reactions, and some neurological and genetical disorders. Exogenous factors can be divided into: mechanical (traumatic injury), physical (extremely low or high temperature, ionising irradiation, microwaves), chemical (caustic agents, poisons, venoms, genotoxic and proteotoxic compounds), nutritive (deficiency of oxygen, vitamins and basic nutrients), biological (viruses, microorganisms, protozoan and metazoan parasites). Factors involved in cell damage
  • 6. The acute inflammatory response is an effective way to isolate an infection and to attract the macrophages, neutrophils, and lymphocytes that can attack and overcome it, This can occur because of an autoimmune disease (such as rheumatoid arthritis), because of persistence of an infection (such as tuberculosis), because of repeated tissue injuries ("tennis elbow"), or because of cancer. Impact of acute Inflammation on Body of Host
  • 7. Under some conditions it can persist for long periods of time, becoming a chronic inflammatory response. Often the chronic inflammation causes a mass of activated macrophages, lymphoctes, and antigen that form a tumor-like lump called a granuloma. Apparently one of the central activators of a chronic immune response is gamma- interferon, which is also essential for normal immune responses. chronic inflammations are treated variously with drugs like aspirin and ibuprofen (non- steroidal anti-inflammatory drugs), steroids, or drugs that block extravasation. Impact of chronic Inflammation on Body of Host
  • 9. Acute Inflammation: Has 3 major components: • Heat (colour) • Redness (Nubor) • Swelling (Tumor) • Pain (Dolor) • Loss of function (Functio-laesa) Alteration in vascular caliber that lead to local increase in blood supply =Vasodilatatio n Structural changes in micro vasculature that permit plasma protein to leave the circulation Emigration of leukocytes from microcirculation & accumulation in focus of injury These three process accounts for fine classical local sign of acute inflammation :
  • 10. After Adhering endothelial cells leukocytes squeezed between them & migrate through vascular wall into interstitial tissues, a process called emigration. As the stasis developed, leukocytes (principally neutrophils) begin to settle out of the flowing blood & accumulate along the vascular endothelial surface, a process called migration. This cause RBC to become more concentrated, thereby increase blood viscosity & slowing the circulation. These changes are manifested microscopically numerous dilated small vassals, pocket with erythrocytes called stasis. Subsequently, microvasculature become more permeable resulting in extraduction of protein rich fluid into extra-vascular tissues. After an inconstant & transient vasoconstriction of arterioles, vasodilatation occur. Arterioles are involve first resulting in opening of new micro- vascular beads in the area of infection Local increase in blood flow cause the redness (erythrema) and warmth characteristically seen in acute inflammation Vascular Changes: A-Change in vascular flow & Caliber
  • 11. Vasodialation +Increased Blood Flow Vascular Hydrostatic Pressure Filtration of Fluid From Capillary=Fluid: Transdute =Ultrafiltrate of Blood Plasma Increased Vascular Permeability Permit the flow of protein rich fluid & even cells into interstitum This movement of fluid cause the reduced in intravascular OP while interstitial OP increases OUTFLOW of water & Ions into extra-vascular tissue which accumulation is called EDMA Vascular Changes: B-Increased Vascular Permeability INCREASED ECLIPASED Permit
  • 12. Endothelial Cell Contraction In-vitro System Direct Endothelial Injury Leukocytes Dependent Endothelial Injury Increase Transcytosis How Permeability Increases?
  • 13. leads to widening of intracellular gap elicited by histamine, bradekinine, leukotrinase, etc., & it is a reversible process. Cellular contraction occur rapidly after binding of mediators to a specific receptors (short- lived) Only these endothelial lining of venules 20-60m undergo contraction; while endothelium in capillary & arteries are remain unaffected. 1-Endothelial Cell Contraction
  • 14. Functional mechanism is another mechanism resulting vascular permeability 2-In-vitro System Cytokines like TNF, IL-1 etc  Structural reorganization of cytoskeleton  Endothelial Cell Junction are disrupted Start after 2-4 hrs & persists upto 24 hrs
  • 15. 3-Direct Endothelial Injury Seen after serious injury Causing Vascular leakage by endothelial cells necrosis & detachment Detachment is often associated with palate adhesion & Thrombosis This reaction is known as Immediate Sustain response which affect vacuoles, capillary and arterioles This may cause Delayed Prolong Leakage that begain after 2-12 hrs & last for several hrs or even a day e.g. Mild to modrate thermal injury, X-ray/UV radiation & Certain bacterial toxins It is Attributable to apoptosis & action of Cytokines
  • 16. 4-Leukocytes Dependent Endothelial Injury May occur as a consequences of Leukocytes accumulation during inflammatory responses Such Leukocytes may activate the release of TOXIC OXYGEN SPECIES & PROTEIOLYTIC ENZYMES which thus cause endothelial injury or detachment, largely restricted to those tissues where leukocytes can adhere to endothelium
  • 18. 1-the activation of a number of proteolytic enzymes including plamin, fibrin, kallikrein, and complement 2-These cause localized increases • in vascular permeability, • smooth muscle contraction (blood vessels are made of two kinds of cells-- smooth muscles and endothelial cells), and • production of chemotactic molecules like some fragments of the complement proteins (C3a, C5a). 3-These chemotactic molecules lure (attract=ensnare) various cell types out of the blood stream, by binding to specific receptors on their cell surface and inducing a migratory behavior out of the blood stream into the tissues. 4-The first cells to extravasate are neutrophils followed subsequently monocytes (macrophages that haven't yet made a commitment) and lymphocytes. Several coordinated activities mediate this process. Reactions in Inflammation:When tissue is injured or invaded by microbes, a series of more or less predictable events ensues.
  • 19. 5-First, bradykinin, fibrin, and complement act on endothelial cells to increase their permeability. Second, release of "mediator" molecules by activated macrophages induces increased permeability of the blood vessel, and serves as chemotactic factors for cells. Several of the macrophage released cytokines, including IL-1, IL-6 and TNF- alpha, have widespread activities throughout the body, not just at the site of the injury. 6-Some of these activities recruit •leukocytes-increased vascular permeability •and adhesion molecules on endothelial cells; •some induce "systemic" non-specific actions •like fever and production of •"acute phase proteins" that inhibit microbial growth: •some help activate a specific immune responses; •and some even help promote the healing response, such as proliferation of fibroblasts Reactions in Inflammation:When tissue is injured or invaded by microbes, a series of more or less predictable events ensues-2
  • 20. Third, the recruited leukocytes enter the damaged tissue and can begin to attack the microorganisms causing the infection, digest damaged cells and tissues, and initiate an immune response. However, antigen-presenting cells such as macrophages are necessary to this activation; macrophages can pick up bacteria or other foreign materials at the site of injury and reenter the blood stream where they can eventually encounter and present to lymphocytes.) Reactions in Inflammation:When tissue is injured or invaded by microbes, a series of more or less predictable events ensues.
  • 21. Extravasation of leukocytes and lymphocytes, for example, seems to depend on a complex series of interactions between the membranes of the blood cells and the endothelial cells of the blood vessels. A variety of cell surface receptors, cell adhesion molecules, and secreted chemokines induce tight, specific interactions among the cell types, followed by migration between endothelial cells and out of the blood vessel. In addition to direct cell-cell interactions, there are also long range interactions that direct cells out of the blood stream and into the tissues at specific locations. These are mediated by chemokines (a special subclass of cytokines) that are released by a variety of lymphoid and myeloid cell types and that act through chemokine receptors to act as "chemo-attractants", luring cells along a concentration of chemokines to a particular location. All chemokine receptors known are G-protein coupled receptors that activate a variety of second messenger systems to mediate, among other things, directional cell movement. While the acute inflammatory response is an effective way to isolate an infection and to attract the macrophages, neutrophils, and lymphocytes that can attack and overcome it, under some conditions an inflammatory response can persist for long periods of time, becoming a chronic inflammatory response. This can occur because of an autoimmune disease (such as rheumatoid arthritis), because of persistence of an infection (such as tuberculosis), because of repeated tissue injuries ("tennis elbow"), or because of cancer. Often the chronic inflammation causes a mass of activated macrophages, lymphoctes, and antigen that form a tumor-like lump called a granuloma. Apparently one of the central activators of a chronic immune response is gamma-interferon, which is also essential for normal immune responses. Chronic inflammations are treated variously with drugs like aspirin and ibuprofen (non-steroidal anti-inflammatory drugs), steroids, or drugs that block extravasation. Presumably inhibitors of IFN- would also be effective, but I don't know of any that are available. The hottest news in anti-inflammatory drugs are the so called Cox (cyclooxygenase) inhibitors that are much more specific than other NSAIDs in blocking inflammation.
  • 23. Inflammation Triggered by tissue damage due to infection, heat, wound, etc. Four Major Symptoms of Inflammation: 1. Redness 2. Pain 3. Heat 4. Swelling May also observe: 5. Loss of function
  • 24. Functions of Inflammation 1. Destroy and remove pathogens 2. If destruction is not possible, to limit effects by confining the pathogen and its products. 3. Repair and replace tissue damaged by pathogen and its products.
  • 25. Stages of Inflammation 1. Vasodilation: Increase in diameter of blood vessels. Triggered by chemicals released by damaged cells: histamine, kinins, prostaglandins, and leukotrienes. 2. Phagocyte Migration and Margination: Margination is the process in which phagocytes stick to lining of blood vessels. Diapedesis (Emigration): Phagocytes squeeze between endothelial cells of blood vessels and enter surrounding tissue.
  • 27. Stages of Inflammation (Continued) Phagocytes are attracted to site of infection through chemotaxis. Phagocytes destroy microbes, as well as dead and damaged host cells. 3. Tissue Repair: Dead and damaged cells are replaced.
  • 28. Antimicrobial Substances: I. Complement System: Large group of serum proteins that participate in the lysis of foreign cells, inflammation, and phagocytosis. Two mechanisms of complement activation: 1. Classical Pathway: Initiated by an immune reaction of antibodies. 2. Alternative Pathway: Initiated by direct interaction of complement proteins with microbial polysaccharides. Both pathways cleave a complement protein called C3, which triggers a series of events.
  • 31. Consequences of Complement Activation: 1. Cytolysis: Due to the formation of a membrane attack complex (MAC) which produces lesions in microbial membranes. 2. Inflammation: Complement components (C3a) trigger the release of histamine, which increases vascular permeability. 3. Opsonization: Complement components (C3b) bind to microbial surface and promote phagocytosis. 4. Inactivation of Complement: Regulatory proteins limit damage to host cells that may be caused by complement.
  • 34. II. Interferons: Antiviral proteins that interfere with viral multiplication.  Small proteins (15,000 to 30,000 kDa)  Heat stable and resistant to low pH  Important in acute and short term infections.  Have no effect on infected cells.  Host specific, but not virus specific. Interferon alpha and beta: Produced by virus infected cells and diffuse to neighboring cells. Cause uninfected cells to produce antiviral proteins (AVPs). Interferon gamma: Produced by lymphocytes. Causes neutrophils to kill bacteria.