defense sysem

8/12/2019 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.

defense sysem

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