Inflammation & Immunity

7/29/2019 Inflammation & Immunity

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Inflammation and Immunity

Week 2 Chapter 9


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TheImmuneSystem


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Cells of the Immune System

Source: http://www.biologymad.com/


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Components of the Immune System

Immunity: protection from infectious disease Involves coordinated response of cells and molecules

Protection provided two lines of defense:

1. Innate defenses

Require no previous exposure to effectively respond to antigen NK cells

Phagocytic cells Neutrophils

Macrophages

2. Specific defenses

Respond more effectively to 2nd exposure

Highly restricted in ability to recognize antigens

B and T lymphocytes


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Types of immunty

Immune response

-T lymphocytes(identifies ad kills

with a toxic)

-B Lymphocytes

(identifies and killswith an antibody)

Physical Barriers

- Skin

- Normal Flora-Mucous membrane

Inflammation

-Neurtrophils

-NK cell-Monocyctes

(Macrophages)

Non-specfic (Doesn't identify enemy) Specific (identify enemy)


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Mononuclear Phagocyte System (Cont.)

Fig 9-1


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SECONDARY LYMPHOID ORGANS

(CONT.)

Lymph Nodes Contain large numbers of B cells, T cells, and macrophages Lymph fluid flows through for immune cells to filter, detect, and

react to foreign material

Found primarily in neck, groin, axillae, thorax, abdomenSpleen Located under diaphragm on left side of body Largest lymphoid organ Macrophages filter out foreign substances and old red blood

cells Lymphocytes contact blood-borne antigens (then may migrate

to other lymphoid organs)Peyer Patches (Intestine) Produce antibodies to microorganisms that invade mucosal

tissue


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Lymphoid System (Cont.)

Fig 9-3


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COMPONENTS OF THE IMMUNE SYSTEM

(CONT.)

LeukocytesMediate inflammation and immunity

Locate and eliminate pathogens and

foreign molecules Chemical mediators

Aid leukocytesComplement

Kinins

Clotting factors (helps to stop blood vessel

bleeding)

Cytokines (activate gene controlled cell

death)


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LEUKOCYTES

Primary effector cells of immunesystem

Formed from stem cells in bone

marrow Neutrophils Eosinophils Basophils and mast cells

Monocytes and macrophages Dendritic cells Lymphocytes

Natural killer cells

T Lymphocytes B L m hoc tes


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Leukocytes Contd

Neutrophils Are the early responders to infection Phagocytosis (eat pathogen) and also release

chemicals to destroy micro orgs

Can cause damage to normal tissue Attracted to areas of inflammation and bacterial

products by chemotactic factors (complement,cytokines)

Basophils and Mast Cells; release cytokins

Basophils in circulation, mast cells in connectivetissues Have receptors for IgE (immunoglobilin)

When bind allergen, degranulate and begin inflammatoryresponse ~ allergic reactions, also chronic inflammation


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Mediator Vasodilation Increased

permeability

pain other

Histamine

++ + -Major mediator

of inflammation.

Produces the

effect of inflmtn

Bradykinins ++ + ++

prostaglandins + + ++ Enhance effects

of the mediators.They often

targeted in turns

of eliveating the

inflammation

Mediator: a molecule that works in the process

Histamine: is a very strong vasodilator

Brady: when they form they re also strong vasodilators, they induce pain they bind

directly to the pain receptors

+: Yes

-: Nothig


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LEUKOCYTES CONTD

Monocytes Immature macrophages that circulate in

bloodstream; become macrophageswhen entertissue

Macrophages; developed from monocytes Large 2phagocytes; can ingest several times as

many microorganisms than neutrophils May proliferate at site of inflammation Cell surface covered with variety of receptor proteins

e.g. Fc receptors bind to constant fragment of Abswhich aid phagocytosis (opsinization coating with antibodies and proteins of the bacteria)

Release cytokines Promote inflammation, activate other WBCs

Antigen presentation


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MONOCYTES AND MACROPHAGES

Fig 9-7

Fig 9-9


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Summary function of

marcophages

1. They are powerful phagocytes

2. Are predominant in the inflammation

3. Important secretory function

!!!Without looking at the previous slides

explain in detail what these three points

mean!!!!!!!


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LYMPHOCYTES

Three major types NK cells: function in innate immunity

Released into circulation Important in killing tumor and virally infected cells without

previous exposure T cells: responsible for specific adaptive immunity

Mature in thymus Two major classes T helper cells: have CD4 proteins Cytotoxic T-cells: have CD8 proteins

B cells: responsible for specific adaptive immunity Remain in bone marrow during maturation Recognize Ag with B cell receptor (BCR) Process and present Ag to T H Clone to produce Ab in response to Ag binding, cytokines

and T H cell stimulation (require co-stimulation)


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T and B Lymphocytes

Fig 9-12 Fig 9-15


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T Cells Mature

in Thymus

Stem Cells

of the Bone

Marrow

Identify

Antigens

B Cells Replicate

to form

Plasma cells

B Memory

Cells

Released into

blood, spleen,lymph

Macrophages

carry foreigncells to T

Helper cells

T Helper cells (Th)

produce proteins

Secrete

Interleukins

Secrete

lymphokines

Release

Antibodies

Stimulates

Phagocytosis

Effector Tc

Cells

Tm Memory

Cells

B Cells Mature

in Marrow

Replicate

Cytotoxic (killer)

T (Tc) Cells

Antibody MediatedImmunity Cell MediatedImmunity

Lymphocyte

Maturation


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CHEMICAL MEDIATORS OF IMMUNE

FUNCTION

ComplementComplement cascadeMembrane attack complex (MAC)

Opsinization Kinins (bradykinin)

Vasodilation, permeability, pain

Clotting factors Cytokines and chemokines

Coordinate and enhance both innateand specific immune defenses


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Complement


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INNATE DEFENSES AND INFLAMMATION

Three purposes of inflammatory response1. Neutralize and destroy invading and

harmful agents2. Limit spread of harmful agents to other

tissue3. Prepare damaged tissue for repair

Five Cardinal Signs of Inflammation Redness Swelling Heat Pain Loss of function


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Inflammation ContinuedTissue Injury

Release of Histamine,

Bradykinin and PGs

Release of

Leukocytosisinducing factor

Vasodilation

CapillaryPermeability

Chemotaxis Increased WBCs

in blood

neutrophilsand monocytes

migrate toinjured area

Phagocytosisby neutrophils

andmacrophages

Heat andRedness

Capillariesleak fluid

andprotein

(exudate)

Pain andSwelling

Blood clotwalls-off

injured area

Increasedmetabolic rate,

oxygen andnutrientdelivery

Healing


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Inflammation

Increased vascular

permeability

Emigration of leukocytes

Emigration or diapedesis Chemotaxis

Phagocytosis; clean up dead

cells

Healing

Mediators Histamine

Bradykinins Prosta landins PGs

Fig 9-19


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CARDINAL EVENTS OF INFLAMMATION


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PROSTAGLANDINS

Prostaglandins (PGs) are fatty acids produced from the phospholipid

derivative arachidonic acid

The enzyme cyclooxygenase (COX) converts arachidonic acid intodifft PGs, each with their own biological activities

Aspirin and other NSAIDs inhibit both COX I and COX II renaland gastrointestinal abnormalities along with the anti-

inflammatory, anti-fever and analgesic effects

Hence, some current anti-inflammatory drugs are being developed

that are specific COX II inhibitors e.g. celebrex, Valdecoxib

Two difft COX enzymes have been characterized:

COX I produces PGs that regulate blood flow to the kidneys and

stimulate mucous production in the digestive tract COX II produces PGs that are involved in pain, inflammation,

fever and uterine contractions

Other anti-inflammatory drugs that are active in the PG pathway

include steroids that inhibit the release of arachidonic acidfrom phospholipid stores


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Innate Defenses and Inflammation (Cont.)

Types of Inflammation Acute

Short in duration,lasting less than 2weeks

Involves a discreteset of events Chronic

More diffuse Extends over longer

period May result in scartissue formation ordeformity

Granulomas

Gould


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INFLAMMATION MANIFESTATIONS

Inflammatory Exudates Transport leukocytes and antibodies

Dilute toxins and irritating substances

Transport nutrients for tissue repair Types

Serous exudateSerosanguineous drainage

Fibrinous exudate Purulent exudate

abscess

Hemorrhagic exudate


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Systematic Manifestations

of Inflammation

Localized Occur with acute and chronic inflammation

Can lead to systemic involvement

Systemic Fever, neutrophilia, lethargy, muscle catabolism

Erythrocyte sedimentation rate (ESR)

The systemic effects responses are

generated by cytokines released by WBCs: Fever, neutrophilia, lethargy, muscle catabolism

Erythrocyte sedimentation rate (ESR)


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Specific Adaptive Immunity

Specific immune system capable of

Recognizing foreign invaders with specificity

Destroying foreign invaders

Retaining memory of the encounter

Allows for more effective defense

(adaptive) to be achieved after

subsequent exposure


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MHC CLASS I PRESENTATION

Nucleated cells continuously produce MHCI proteins (on the rough endoplasmic reticulum (ER) wherethey)

combine with peptide fragments in cytoplasm

for presentation on cell surface MHC I -peptide complexes inspected by TC-

cells Binding of TC-cells to MHC I-antigen complex

triggers release of enzymes and perforinswhich lyse the target cell

Abnormal proteins Produce immune response

MHC I peptide antigens have intracellular origin Viral rotein common source of forei n MHC I


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MHC Class I Presentation Contd


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MHC CLASS II PRESENTATION

MHC II Proteins Present antigens obtained from extracellular

sources

Extracellular antigens must first be ingested byantigen-presenting cell

Antigen presenting cell degrades Ag intofragments in endocytic vesicle

MHC II proteins form complexes wit Ag fromphagosome on way to plasma membrane

T helper cells detect MHC II antigencomplexes


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MHC Class II Presentation (Cont.)


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T Helper Cells (CD4+)

Recognize antigen in association

with MHC II molecules

CD4 protein necessary to enable

T helper cells to bind to MHC II

protein; T-cell receptors

recognize specific antigen

presented

T-cell receptors bind to

corresponding antigen andgenerate signaling cascade in T

helper cell cytoplasm

Fi 9-31


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Recognize antigen displayed in association with

MHC I protein

CD8 protein needed for MHC I binding TCR specifically recognizes presented antigen

Binding Triggers cytokine release

need costimulation by IL-2 cytokines andcostimulators usually present on surfaces of

presenting and responding cells

Activated cytotoxic T cells

Proliferate into memory cells and effector cells

Cytotoxic T Cells (CD8+)


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Cytotoxic T Cells (CD8+) (Cont.)

Perforins Proteins manufactured

in cytotoxic T cell

Store in cytoplasmgranules with granzymes

Granules (vesicles) Bind to target cell,

migrate to contact site,and release to target cell

membrane


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Activation requires help from T helper cell Ag binding to B-cell receptor (variable region) necessary

but not enough stimulus to produce effective B-cell clone B cell engulfs, processes, and presents antigen to T helper

cells Initiates cell-to-cell contact between B and complementary

T cell helper

Antigen Recognition by B Cells

Fig 9-37


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Cell-to-cell binding interactions stimulate intracellular

signaling pathways in B- and T-helper cell

Promote clonal expansion and differentiation

B cells need specific cytokines to proliferate and begin

antibody synthesis

become plasma cells

On the subsequent exposure,

the Memory Cells rapidly clone

and produce many moreantibodies

The Secondary response is

greater than the Primary Response

Antigen Recognition by B Cells

(Cont.)

Fig 9-44


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ANTIBODY STRUCTURE (CONT.)

Five classes Serve different immune functions

During the course of an Ab response, canundergo class switching ~ specific cytokines

Still recognizes the same Ag Presence of one class over another

indicates stage in course

IgG

IgM

IgA

IgD

IgE

Fig 9-41


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IgG

Most common type; Smallest; Easily escapes

bloodstream to enter interstitial fluid. Protection and

immunity, neutralizes. Can cross placenta.

IgM

10% of circulating immunoglobulins; Mostly found inintravascular pool; cannot penetrate capillary wall

(pentamer); First to be produced on exposure to

antigens or after immunization; Major antibody found

on B-cell surfaces; Works best to activate complement.

First responder.


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Ig A Produced by plasma cells located in tissue under

skin/mucous membranes

Primarily found in saliva, tears, tracheobronchial

secretions, colostrum, breast milk, and GI/GU secretions.

Can cross placenta.

IgD Found in tiny amounts in serum

Located primarily on B cell membranes (with IgM); fxn

not clearly understood

Thought to be cellular antigen receptor that acts to

stimulate B cell to: Multiply, Differentiate, Secrete other

specific immunoglobulins


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IgE Bound by Fc tail to receptors on basophil and mast

cell surfaces Trace amounts identified in serum

Helps in immunity against helminthic parasites;

responsible for initiating inflammatory and allergic

reactions

Functions as signaling molecule

Causes mast cell degranulation when antigen

detected at mast cell surface Type 1 hypersensitivity


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Antibody Functions

1. Precipitation2. Agglutination3. Neutralization

4. Opsonization5. Complement activation Each arm of immunoglobulin Y structure

can bind an antigenic epitope

Allows antibodies and antigens to bindtogether into large insoluble complexesthat precipitate out of body fluids enhance function of innate phagocytic cells

Fig 9-43


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What Antibodies do:


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TYPES OF IMMUNITY

Specific Immunity can be acquired in four ways:

1. Active natural immunity: exposure to an antigen

stimulates specific immune cells to produce antibodies

and memory cells

2. Active artificial immunity: a specific antigen ispurposefully introduced into the body to stimulate the

specific immune cells e.g. immunization (i.e.

vaccination): dead or attenuated pathogens are

introduced3. Passive natural immunity: antibodies are passed from

mother to infant in utero and in breast milk

4. Passive artificial immunity: injection of antibodies

developed in one person or animal to another e.g. rabies

antiserum, snake antivenom, hepatitis B treatment

Note the differences between active and passive immunity

VACCINES


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VACCINES

Vaccine: an artificially introduced

microbial antigen capable of

inducing active immunity without

causing disease

Organism Disease Vaccine Type

Bacterial Vaccine:Corynebacterium diphtheriae Diphtheria Toxin

Clostridium tetani Tetanus Toxin

Berdetella pertusis Whooping cough Killed organisms

Haemophilus influenzae MenigitisCapsular

polysaccharide

Streptococcus pneumoniae PneumoniaCapsular

polysaccharide

Neisseria meningitidis MenigitisCapsular

polysaccharide

Salmonella typhi Typhoid fever Killed or live organisms

Vibro cholerae Cholera Killed organisms

Bacillus anthracis Anthrax Killed organisms

Viral Vaccines:Rubeola virus Measles Live virus

Mumps virus Mumps Live virus

Rubella virusGerman

measlesLive virus

Varicella-zoster virus Chickenpox Live virus

Poliovirus Poliomyelitis Live or killed virus

Influenza virus Influenza Killed virus

Hepatitis A virus Hepatitis A Killed virus

Hepatitis B virus Hepatitis B Recombinant

Rabies virus Rabies Killed virus

Vaccines are composed of either:

live attenuated microorganisms inactivated (killed) microorgs

modified exotoxins (toxoids)

recombinant (genetically

A good vaccine:

is highly immunogenic

stimulates both Ab and cellular

immunity (long-term) is safe and free of side effects

is administered appropriately

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Inflammation & Immunity