wc hum phys 26 feb

HS 345: HUMAN PHYSIOLOGY

WILMINGTON COLLEGE

LISA REGULA MEYER

Cellular Immunity

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Properties of Immunity

1. Specificity

2. Versatility

3. Memory

4. Tolerance

Immunity

Response to threats on anindividualized basis

Adaptive Immunity

Active Immunity Passive Immunity

Adaptive immunity is not present at birth; youacquire immunity to a specific antigen only whenyou have been exposed to that antigen or receiveantibodies fromanother source.

Develops in responseto antigen exposure

Develops afterexposure toantigens inenvironment

Develops afteradministration ofan antigen toprevent disease

Conferred bytransfer of maternalantibodies across placenta or inbreast milk

Conferred byadministration ofantibodies tocombat infection

Naturally acquiredactive immunity

Artificially inducedactive immunity

Naturally acquiredpassive immunity

Artificially inducedpassive immunity

Geneticallydetermined−noprior exposure orantibodyproductioninvolved

Innate Immunity

Produced by transferof antibodies fromanother source

Adaptive Defenses

Cell-MediatedImmunity

Direct Physical andChemical Attack

Antibody-MediatedImmunity

Attack by CirculatingAntibodies

Destructionof antigens

Phagocytesactivated

T cellsactivated

Communicationand feedback

Antigen presentationtriggers specificdefenses, or animmune response.

Activated Bcells give riseto cells thatproduceantibodies.

Activated T cells findthe pathogens andattack them throughphagocytosis or therelease of chemicaltoxins.

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Major Components of Cellular Immunity

CytokinesMHC proteinsLymphocytes

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Cytokines

Chemical messengers released by tissue cells

To coordinate local activities

To act as hormones to affect whole body

Functions of Cytokines

1. Stimulate T cell divisions

Produce memory TH cells

Accelerate cytotoxic T cell maturation

1. Attract and stimulate macrophages

2. Attract and stimulate activity of cytotoxic T cells

3. Promote activation of B cells

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Types of Cytokines

InterleukinsLymphokinesMonokinesChemokinesInterferons

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MHC Proteins

The membrane glycoproteins that bind to antigens

Genetically coded in chromosome 6

The major histocompatibility complex (MHC)

Differs among individuals

Antigen PresentationT cells only recognize antigens that are bound to

glycoproteins in plasma membranes

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Class I MHC

Found in membranes of all nucleated cells

Pick up small peptides in cell and carry them to the surface

T cells ignore normal peptides

Abnormal peptides or viral proteins activate T cells to destroy cell

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Class II MHC

Found in membranes of antigen-presenting cells (APCs)

Found in lymphocytes

Inserted in plasma membrane to stimulate T cells

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Lymphocytes

Lymphoid Stem Cells

Group 1

Remains in bone marrow and develop with help of stromal cells

Produces B cells and natural killer cells

Group 2

Migrates to thymus

Produces T cells in environment isolated by blood–thymus

barrier

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T Cells make up 80% of circulating lymphocytes

Cytotoxic Attack cells infected by viruses Produce cell-mediated immunity

Memory Formed in response to foreign substance Remain in body to give “immunity”

Helper* Stimulate function of T cells and B cells

Suppressor* Inhibit function of T cells and B cells

*Regulatory T Cells control sensitivity of immune response

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Overview

Antigen presentationAntigen recognitionT Cell activation

Antigen binding Co-stimulation

T Cell proliferationT Cell differentiation

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Cell-Mediated Immune Response

Antigen Presentation First step in immune response

Extracted antigens are “presented” to lymphocytes

Or attached to dendritic cells to stimulate lymphocytes

Can be phagocytic or non-phagocytic antigen-presenting

cells

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Phagocytic APCs

• Free and fixed

macrophages

In connective tissues

• Kupffer cells

Of the liver

• Microglia

In the CNS

Non-phagocytic APCs

Langerhans cells

In the skin

Dendritic cells

In lymph nodes and

spleen

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Antigen Recognition Inactive T cell receptors

Recognize Class I or Class II MHC proteins

Recognize a specific foreign antigen

Double recognition

Binding occurs when MHC protein matches antigen

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CD Markers

• CD8 Markers Found on cytotoxic T

cells and suppressor T cells

Respond to antigens on Class I MHC proteins

• CD4 Markers Found on helper T cells Respond to antigens on

Class II MHC proteins

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Co-Stimulation

For T cell to be activated, it

must be costimulated

By binding to stimulating

cell at second site

Which confirms the first

signal

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Proliferation and Differentiation

After activation, activated T cells enlarge and multiply

Newly expanded population of T cells differentiate into Cytotoxic T cells Memory T cells Regulatory T cells

Suppressor T cells Helper T cells

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Activation of CD8 T Cells

Activation of CD8 T Cells Activated by exposure to antigens on MHC proteins

One responds quickly

Producing cytotoxic T cells and memory T cells

The other responds slowly

Producing suppressor T cells

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Cytotoxic T Cells

Seek out and immediately destroy target cells

1. Release perforin

To destroy antigenic plasma membrane

1. Secrete poisonous lymphotoxin

To destroy target cell

1. Activate genes in target cell

That cause cell to die

Antigen Recognition Activation andCell Division

Infected cell

InactiveCD8

T cell

Viral orbacterial antigen

Antigen recognition occurswhen a CD8 T cell encountersan appropriate antigen on thesurface of another cell, boundto a Class I MHC protein.

Antigen recognition resultsin T cell activation and celldivision, producing active TC

cells and memory TC cells.

Active TC cell

Memory TC cells(inactive)

Infectedcell

CD8protein

Class IMHC

T cellreceptor

CD8T cell

Antigen

Costimulationactivates

CD8 T cell

Before activationcan occur, aT cell must bechemically orphysicallystimulated bythe abnormaltarget cell.

Costimulation

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Activation of CD4 T Cells

Active helper T cells (TH cells)

Secrete cytokines

Memory helper (TH) cells

Remain in reserve

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Activation by Class I MHC proteins

Antigen bound toClass I MHC protein

Indicates that the cell is infectedor otherwise abnormal

CD8 T Cells

Cytotoxic T Cells Memory TC Cells

Attack and destroyinfected and

abnormal cellsdisplaying antigen

Awaitreappearanceof the antigen

Control or moderateimmune response by

T cells and B cells

Suppressor T Cells

Activation by Class II MHC proteins

Helper T Cells

Stimulate immuneresponse by

T cells and B cells

Awaitreappearanceof the antigen

Memory TH Cells

CD4 T Cells

Indicates presence of pathogens,toxins, or foreign proteins

Antigen bound toClass II MHC protein

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B Cell Sensitization

Corresponding antigens in interstitial fluids bind to B cell receptors

B cell prepares for activation Preparation process is sensitization During sensitization, antigens are:

Taken into the B cell Processed Reappear on surface, bound to Class II MHC protein

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Helper T Cells Sensitized B cell is prepared for activation but needs helper T

cell activated by same antigen

B Cell Activation Helper T cell binds to MHC complex

Secretes cytokines that promote B cell activation and division

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B Cell Division

Activated B cell divides into:

Plasma cells

Memory B cells

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Plasma Cells Synthesize and secrete antibodies into interstitial fluid

Memory B Cells Like memory T cells, remain in reserve to respond to next

infection

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Pathologies of Cellular Immunity

HIV/AIDSDiGeorge SyndromeWiskott-Aldrich syndrome

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Combines Responses to Viral Infection

Similar to bacterial infection

But cytotoxic T cells and NK cells are activated by contact

with virus-infected cells

BACTERIA

Phagocytosis bymacrophages and APCs

Antigenpresentation

Activation ofcytotoxic T cells

Activation ofhelper T cells

Activation of B cells

Antibodyproduction byplasma cells

Destruction ofbacteria bycell lysis or

phagocytosis

Opsonizationand phagocyte

attraction

Formation ofantigen−antibody

complexes

Defenses against bacteria involve phagocy-tosis and antigen presentation by APCs.

Release of interferons

Infection oftissue cells

Appearance of antigenin plasma membrane

Infection of or uptakeby APCs

VIRUSES

Antigenpresentation

Activation ofhelper T cells

Activation of B cells

Antibodyproduction byplasma cells

Destruction ofviruses or

prevention ofvirus entry into cells

Increasedresistance toviral infection

and spread

Stimulationof NK cells

Activation ofcytotoxic T cells

Destruction ofvirus-infected cells

Defenses against viruses involves direct contact with virus-infected cellsand antigen presentation by APCs.