Fv Lecture 5 - Host Defense Mechanisms, Immunity (1)

7/28/2019 Fv Lecture 5 - Host Defense Mechanisms, Immunity (1)

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Innate Immune Response

BIOL 2900


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Overview of Innate Defenses

First line of defense are barriers that shield

interior of body from external surroundings

Anatomical barriers include skin and mucous

membranes Provide physical separation

Membranes bathed in antimicrobial secretions


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Phagocytes are specialized cells that engulf

and digest microbes and cellular debris

Act as sentries

Alerted to signs of invasion

More phagocytes can be recruited from

bloodstream


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Cells of immune system have elaboratecommunication system

Communication achieved through

productions of proteins Proteins act as chemical messengers Called cytokines

Cytokines from one cell defuse to another Bind to cytokine receptor on cell

Receptor transmits signal to cell interior

Induces changes in cellular activities


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Inflammation is initiated by microbial

invasion or tissue damage

During inflammation, cells in blood vessels

undergo changes that allow certain

immune particles to leak out of the cell



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First Line of Defense

Physical barriers Skin is most visible barrier

Covers majority of surfaces in obvious contact with

environment Mucous membranes barrier that lines digestive

tract, respiratory tract and genitourinary tract Mucous protect these surfaces from infections


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Figure 15.3


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Skin Provides the most difficult barrier to penetrate Composed of two main layers

Dermis Contains tightly woven fibrous connective tissues

Makes extremely tough

Epidermis

Composed of many layers of epithelial cellsAs cells reach surface, they become increasingly flat

Outermost sheets of cells embedded with keratin

Makes skin water-repellent

Outer layers slough off taking microbes with it



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Mucous membranes Constantly bathed with mucus Helps wash surfaces

Some mucous membranes have mechanisms

to propel microorganisms and viruses to

areas where they can be eliminated



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Antimicrobial substances Both skin and mucous membranes are protected by variety of

antimicrobial substances including Lysozyme

Enzymes that degrade peptioglycan

Found in tears, saliva, blood and phagocytes

Peroxidase

Found in saliva, body tissues and phagocytes

Breaks down hydrogen peroxide to produce reactive oxygen

Lactoferrin Sequesters iron from microorganisms

Iron essential for microbial growth

Found in saliva, some phagocytes, blood and tissue fluids

Defensins

Antimicrobial peptides inserted into microbial membrane



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Normal flora Defined as microorganisms found growing on

body surfaces of healthy individuals

Not technically part of immune system However, provides significant protection

Protects through competitive exclusion Covers binding sites

Pathogens cant bind

Competes for nutrients

Nutrients unavailable for pathogens



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Cells of the Immune System

Always found in normal blood Numbers increase during infection

Some cells play dual roles in both innate

and adaptive immunity Blood cell formation called hematopoiesis

Blood cells including immune cells originate

from hematopoietic stem cells in bone marrow Blood cells stimulated to differentiate by

colony-stimulating factor


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General categories of blood cells Red blood cells (RBC) a.k.a erythrocytes

Carry oxygen in blood

Platelets Fragments of megakaryocytes

Important component in blood clotting

White blood cells (WBC) a.k.a leukocytes

Important in host defenses

Divided into four categories

Granulocytes - Mononuclear phagocytes

Dendritic cells - Lymphocytes



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Granulocytes Contain cytoplasmic graduals

Divided into three types Neutrophils

Basophils

Eosinophils


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Neutrophils Most abundant and important in innate response

Sometimes called polymorphonuclear neutrophilic

leukocytes (PMNs) Basophils

Involved in allergic reaction

Eosinophils Important in expelling parasitic worms

Active in allergic reactions


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Mononulcear phagocytes Constitute collection of

phagocytic cells called

mononuclear phagocyte

system Include monocytes Circulate in blood

Macrophages differentiate

from monocytes

Present in most tissues

Abundant in liver,

spleen, lymph nodes,

lungs and peritoneal

cavity


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In order for immune system to respond,

cells must communicate with environment

and with each other

Cell surface receptors are the eyes and

ears of the cell

Cytokines are the voice

Adhesion molecules act as the hands

Cell Communication


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Phagocytosis

Process of phagocytosis Chemotaxis Cells recruited to infection

Recognition/attachment

Use receptors to bind invadingmicrobes

Engulfment Phagocyte engulfs invader

forming phagosome

Phagosome lysosomefusion Phagosome binds lysosome,

forming phagolysosome

Destruction and digestion Organism killed due to lack of

oxygen and decreased pH

Exocytosis Phagocyte expels material to

external environment


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Phagocytosis Animation

http://www.sp.uconn.edu/~terry/Common/phago053.html

http://highered.mcgraw-hill.com/sites/0072495855/student_vi
http://www.sp.uconn.edu/~terry/Common/phago053.htmlhttp://highered.mcgraw-hill.com/sites/0072495855/student_view0/chapter2/animation__phagocytosis.htmlhttp://highered.mcgraw-hill.com/sites/0072495855/student_view0/chapter2/animation__phagocytosis.htmlhttp://www.sp.uconn.edu/~terry/Common/phago053.html


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Inflammation

Inflammation occurs in

response to tissue

damage

Four cardinal signs Heat

Pain

Redness

Swelling Loss of function

Fifth sign that can also be

present


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Inflammation

The inflammatory process Initiation leads to a cascade of events Results in dilation of blood vessels, leakage of fluid from

vessels and migration of leukocytes and phagocytes

Leakage of phagocytes from blood vessels called diapedesis

Certain pro-inflammatory mediators cause the

diameter of blood vessels to increase Results in increased blood flow

Increased blood flow responsible for cardinal signs of inflammation


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Inflammation

Outcomes of inflammation Intent is to limit damage and restore function Inflammation itself can cause considerable damage

Release of toxic products and enzymes from phagocytic cellsis responsible for tissue damage

If inflammation is limited to area of injury,damage is usually nominal

If inflammation results in delicate systems,consequences are more severe

Inflammation around brain and spinal cord can lead to

meningitis


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Fever

One of the strongest indicators of infection Especially of bacterial infection

Important host defense mechanism Temperature regulation center of body responds

to fever-inducing substances called pyrogens Fever-inducing cytokines termed endogenous

pyrogens

Microbial products termed exogenous pyrogens

Resulting fever inhibits growth of pathogens by Elevating temperature above maximum growth

temperature Activating and speeding up other body defenses


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Adaptive Immune Response


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Strategy of Adaptive

Immune Response

First response to particular antigen called

primary response May take a week or more to develop

Immune system remembers pathogen on

subsequent exposure Termed secondary response


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Nature of Antigens

Coined from compounds that elicit

antibody production Antibody generator

Includes an enormous variety of materials

Today, term used to describe any

compound that elicits an immune

responseAntigen that causes immune response

termed immunogen


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Nature of Antibody

Protective outcomes ofantibody-antigen binding Neutralization Prevents toxin from interacting with

cell

Immobilization and preventionof adherence

Antibody bonding to cellular structures

to interfere with function

Agglutination and precipitation Clumping of bacterial cells by specific

antibody

Bacteria more easily phagocytized


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Protective outcomes of

antibody-antigen binding Opsinization Coating of bacteria with antibody to

enhance phagocytosis

Complement activation Antibody bonding triggers classical

pathway

Antibody-dependent cellular

cytotoxicity Multiple antibodies bind a cell which

becomes target for certain cells

Nature of Antibody


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Nature of Antibody

Ab divided into five

classes Class is based on

constant region of the

Ab

Classes include: IgG

IgA

IgM

IgD

IgE


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Five classes of Ab IgM First Ab to respond to infection

5 13% of Ab in circulation

Only Ab that can be formed by the fetus

Nature of Antibody


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Five classes of Ab IgG Dominant Ab in circulation

80 85% Ab in circulation

Only Ab that can cross the placenta

The antibody of memory!!!!!

IgA Found in secretions - Breast milk, mucous, tears and

saliva

10 - 13 % of Ab in circulation

Nature of Antibody


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Five classes of Ab IgD


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Applications of

Immune Responses


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Principles of Immunization

Naturally acquired immunity is acquisition ofadaptive immunity through natural events

Immunization mimics these events by inducing

artificially acquired immunity Natural or artificial immunity can be divided into

Active immunity

Passive immunity


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Active immunity Results from immune response upon exposure to an

antigen

Active immunity can develop naturally Following illness

Or artificially After immunization


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Passive Immunity Occurs naturally during pregnancy IgG from mother crosses placenta

Infers protection to the baby

Occurs naturally as result of breast feeding IgA antibodies in breast milk given to child

Artificial passive immunity involves transfer of antibodiesproduced by another person or animal

Can be used to prevent disease before or after likely exposure


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Vaccines and Immunization

Attenuated vaccines Weakened form of pathogen Generally unable to cause disease

Strain replicates in vaccine recipient Causes infection with undetectable or mild symptoms

Results in long lasting immunity


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Attenuated vaccines Advantages Single dose usually sufficient to

induce long-lasting immunity

Due to multiplication of microbe

in body

Continued stimulation of

immune system

Vaccine has added potential for

being spread

disease after immunization

could be spread to un-

immunized individuals

inadvertently

Disadvantages Have potential to cause

disease in

immunocompromised

individuals

Pregnant women should

also avoid immunization

with attenuated vaccine

Attenuated vaccines in

use include Sabin polio vaccine

MMR

Yellow fever


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Inactivated vaccines Unable to replicate in vaccinated individual

Retains immunogenicity of infectious agent Immunogenic not pathogenic

Inactivated vaccines fall into two categories Whole agents

Contain killed organisms of inactivated virus

Cholera, plague, influenza and Salk polio are whole agents

Fragments

Portions of organisms or agents including toxins proteins and cell

wall components

Includes toxoids, protein subunit vaccines and polysaccharide

vaccines



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Table 17.5

Documents

Fv Lecture 5 - Host Defense Mechanisms, Immunity (1)