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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
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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
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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
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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
Insert 21_18 here
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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
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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
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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.
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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.