Download - Defense Sysem
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HOST DEFENSE
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Three lines defense
1stline of defense : Non-specific: Natural barriers (Physical; Chemical and
Genetic ?? barrier's ).
2ndline of defense : Non-specific: Phagocytic Whiteblood cells( WBC),
Antimicrobial proteins and Inflammatory process.
3rdline of defense: Lymphocytes and Antibodies.
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1stline of defense :
Non-specific: Natural barriers (Physical; Chemical and
Genetic ?? barrier's ).
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Most microorganisms express repeating patterns of molecularstructures termed Pathogen Associated Molecular Patterns (PAMPs)
The biological system has evolved mechanisms capable of recognizingthese repeating patterns termed Pattern Recognition Receptors(PRRs)
Examples of Pattern Recognition Receptors:- Mannose-Binding Lectin (MBL)- Macrophage Mannose Receptor- Scavenger Receptors- Toll-like Receptors (TLRs)- Nod-like Receptors (NLRs)- RNA helicases (RIG-I, MDA-5)
Pathogen Recognition
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2ndline of defense
Non-specific: Phagocytic Whiteblood cells( WBC)
Inflammatory process and
Antimicrobial proteins
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Macrophage destroying bacterial cells
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Form a cascade effect - if only a few are activated, they will trigger others to become active in
great numbers
Some punch holes in bacterial walls (forms holes where cellular components leak out)
Some promote inflammation
Concentration gradients attract phagocytes to irritated or damaged tissue
Encourage phagocytosis in phagocytes (promotes "eating")
Some bind to the surface of invading organisms
Chemokines- create a chemical gradient to attract neutrophils and other leucocytes to the wound
site Inflammation
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Causes localized redness, swelling, heat, and painChanges in capillary wall structure allow interstitial fluid and WBC's to leak out intissuePromotes macrophage (phagocytic WBC's) activityMacrophages secrete Interleukins(communication proteins among WBC's)
Interleukin-1: increases body temperature (i.e. causes a fever)This enhances the WBC's ability to protect the bodyCauses drowsiness - reduces the body's energy usage and stress
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Molecular cues that stimulate lypmphocytes to create animmune response
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3rdline of defense:
Lymphocytes and Antibodies.
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Cell-mediated immune response
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B Cell & Antibodies
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2ndline of defense
Phagocytosis
- the process by which particular substances orcells are ingested and destroyed by
specialized cells
- neutrophils, macrophages (monocytes, tissue
macrophages)
P th R iti
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Most microorganisms express repeating patterns of molecularstructures termed Pathogen Associated Molecular Patterns (PAMPs)
The biological system has evolved mechanisms capable of recognizingthese repeating patterns termed Pattern Recognition Receptors(PRRs)
Examples of Pattern Recognition Receptors:- Mannose-Binding Lectin (MBL)- Macrophage Mannose Receptor- Scavenger Receptors- Toll-like Receptors (TLRs)- Nod-like Receptors (NLRs)- RNA helicases (RIG-I, MDA-5)
Pathogen Recognition
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Once the PRRs are activated by the PAMPs,
phagocytosis is initiated
Phagocytosis is active process:
- Internalization of pathogen into phagosome- Acidification of phagosome
- Fusion of phagosome with lysosomes thatcontain anti-microbial compounds
(phagolysosome)- This may be sufficient to kill the pathogen
- If not, reactive oxygen and nitrogenspecies may need to be generated
Macrophage Microbial Killing
Ph t i d E i f
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Phagocytosis and Evasion ofPhagocytosis
ANIMATION Phagocytosis: Microbes That Evade It
ANIMATION Virulence Factors: Inactivating Host Defenses
ANIMATION Virulence Factors: Hiding From Host Defenses
ANIMATION Phagocytosis: Mechanism
ANIMATION Phagocytosis: Overview
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Process of Phagocytosis
Phagocytes engulf and kill microorganismsSteps o f phagocy tos is :
Chemotaxis
Recognition and attachment
Engulfment and creation of phagosome
Fusion of phagosome with lysosome Destruction and digestion
Residual body Exocytosis
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Phagocytosis
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Process of Phagocytosis
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Inflammation
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Inflammation
Inflammationis the body's reaction to injury
and is known as the body's second line of
defense which results in:
Increased blood supply to the area.
Increased capillary permeability.
Migration of leukocytes into the surrounding
tissue. These three events manifest symptoms which
include pain, heat, redness and swelling.
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Definition
Inflammation is a non specific, localized immune reaction of the
organism, which tries to localized the pathogen agent. Many
consider the syndrome a self-defense mechanism.
It consist in vascular, metabolic, cellular changes, triggered by the
entering of pathogen agent in healthy tissues of the body.
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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.
Cli i l t f i fl ti
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Clinical symptoms of inflammation:pain, redness, heat, swelling
1. Increased vascular diameter, increased blood flow (heat, redness)
2. Activation of vascular endothelium to express adhesion molecules, increasesleukocyte binding
3. PMNs are first cell type recruited to site, followed later by monocytes
4. Increased vascular permeability results in local swelling and pain
Microvascular coagulation helps prevent pathogen spread into bloodstream(physical barrier)
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Antimicrobial Substances:
Large group of serum proteins that participate in
the lysis of foreign cells, inflammation, and
phagocytosis.
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Antimicrobial Substances
1. The complement system
2. Interferons
3. Transferrins
4. Antimicrobial peptides
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The complement system
The complement components are present in serum ininactive form
The complement is activated in a cascading manner
Complement proteins are synthesized mainly in the liver,but tissue macrophages and fibroblasts can synthesize
some complement proteins as well
The
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TheComplement
System
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The complement system
3 pathways of complement activation:
1/ Class ical
2/ A lternative
3/ Lectin
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Complement System
Series of 30 plasma (serum) proteins, activated ina cascade
Three effects of complement system:
1. Enhances inflammatory response, e.g.:
attracts phagocytes2. Increases phagocytosisthrough
opsonizationor immune adherence
3. Creates Membrane Attack Complexes (MACs)
Cytolysis
Opsonins (complement proteins or antibodies) coat bacteria
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Opsonins (complement proteins or antibodies) coat bacteria
and promote attachment of micro-organism to phagocyte
Opsonization
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Classical Pathway
Alt ti P th
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Alternative Pathway
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Alternative Pathway
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Lectin Pathway
Activation begins when mannan-binding protein (MBP) binds to the mannosegroups of the microbial carbohydrates.
Two more lectin pathway proteins called MASP1 and MASP2 (equivalent to C1rand C1s of the classical pathway) now bind to the MBP.
This forms an enzyme similar to C1 of the classical complement pathway that isable to cleave C4 and C2 to form C4bC2a, the C3 convertase capable of
enzymatically splitting hundreds of molecules of C3 into C3a and C3b. The beneficial results are the same as in the classical complement pathway
above: trigger inflammation (C5a>C3a>c4a);
chemotactically attract phagocytes to the infection site (C5a);
promote the attachment of antigens to phagocytes via enhanced attachment oropsonization (C3b>C4b);
serves as a second signal for the activation of naive B-lymphocytes (C3d);
cause lysis of gram-negative bacteria and human cells displaying foreign epitopes(MAC);
and remove harmful immune complexes from the body (C3b>C4b).
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Figure 7.11: Complement cascade pathways.
Adapted from S. Smith. Immunologic Aspects of Organ Transplantation.
Organ Transplant. Medscape, 2002.
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Comparison of 3 Pathways
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Both Classical and Alternative Complement Pathways
Trigger the Cleavage of C3
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Classical and Alternative Complement Pathways
Cause Inflammation, Opsonization, and Cytolysis
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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.