Immunosuppression & Immune Tolerance Report 3HMT - Carbungco & Enverga

8/9/2019 Immunosuppression & Immune Tolerance Report 3HMT - Carbungco & Enverga

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Immunomodulation

Carbungco, Michael Paolo C.Enverga, Mariel C.

3H Medical Technology


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Reduction of thehost s immuneresponsiveness

Necessary to allow

the recipient toaccept an allogenicgraft

Maintenancetherapy after

transplant

Reversal of established

rejection

Immunosuppression


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Artificially InducedImmunosuppression

P hysical

Surgicalanipulation

IonizingRadiation

Chemicaland

Biological

Lympholytic Agents

Lymphocytotoxic Agents Anti odies


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P hysical

Physical

Surgicalmanipulation

Bursa of Fabricius and

Thymus

Removal of peripheral

lymphoid tissue

Ionizingradiation


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Chemical and Biologic


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Block the expression of the immune response throughcell lysisMore effective in disrupting the initiation of theimmune response

Action:

Ionizing radiation A ntibodies: A ntilymphocyte serum or antithymocyteserum

Types:

y p olytic A ents


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Interfere with DNA synthesisSuch as purine and pyrimidine analogues andfolic acid antagonists (Methotrexate) Anti meta olites

Interfere with cell division by altering guanineso that DNA based-pairing errors occurCyclophosphamide Alkylating Agents

Effective in suppressing graft rejection reactionsInhibitory effect on IL-2 actionCyclosporine Anti ioticsLympholytic in laboratory animalsCauses lymphopenia and monocytopenia shortly after injection in humansCortisone

ym ocytoto ic Agents


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Azathioprine (AZA)mycophenolate mofetil andmethotrexate are relatively specific cell-cycle inhibitorsAffecting mainly theresting and DNA synthesisphases.

Cyclophosphamide (CY) is

a nonspecific cell-cycleinhibitor and affects allphases.

G0 , dormant phase; G 1,resting phase; G

2,

premitotic phase; M,mitotic phase; MMF,mycophenolate mofetil;MTX, methotrexate; S,DNA synthesis phase


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React with lymphoid cells such as antilymphocyte globulin orantilymphocyte serum in transplant patients.

A ntilymphocyte globulinIgG polyclonal antibody directed at T cells at the time of

transplantation and of lymphoid irradiation before transplantationSuppression of cell mediated immune response

Preformed antibody followed by injection of specific antigen will block ISin the hostInjected Antibody binds up the antigen and prevents its access tolymphoid tissuesPrinciple to which Rho (D) Ig (RhoGam) was developed to combat

erythroblastosis fetalis

Antibodies specific for the antigen combining site (idiotype) of antibody injected to an animal

May specifically abort response

An tib i s


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BLOOD AN U ION


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ImmunologicTolerance


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ImmuneTolerance

aturally cquire /utotolerance

Escape may resultin autoimmune

iseases

Specifically In uce/ cquire Immune

tolerance

venue for t erapy of autoimmuneiseases, aller iccon itions an

allo raft rejection


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Also called Neonatal or Natural tolerance ac uired early in life

Animals ac uired autotolerance in utero

During fetal development, the ability to recognize ones own tissues is

ac uired

Individuals do not ordinarily produce antibodies against their owntissue antigens (Self antigens)

Au t t l r n c


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C l na l l ti n r


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GRADATIONS OF TOLERANCE

Individual is unable to respond to some of antigenic epitopes but can respond to othersepitopes

IMMUNE DEVIATION / SPLIT TOLERANCE

State where one of the immune responsescan be interfered with but not with another

IgM response can be blocked but NOT the IgGresponse; Cell mediated response may be

blocked but NOT humoral response

I une le ran ce


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Clonal deletion Clonal abortion

Clonal anergy Continuous inhibitionof cellular activity

ImmuneTolerance


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Active Suppressor T-cell can provoke a tolerance

A sence of components necessary for a B-cell response to antigen

Dependent on maturity of the cell

As B cell matures, it ecomes less suscepti le to tolerization

Tolerance vary during maturation

B-cell Tolerance


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P athways

B celltolerance

Clonal A ortion

ClonalExhaustion

FunctionalDeletion

Anti ody forming

cell (AFC)lockade


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MH C

TCR Antigen

T -cell T -cell

Anergy R esponsiveness

7-2

C D28/ CT LA-4

APC


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A ntigens required to produce tolerance are specific for each individual T-cell subset.

no marked difference in tolerance at different stages of maturation

Threshold of tolerance for T-cells is lower

T-cell Tolerance


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P athways

T celltolerance

Clonal A ortion

T cellsuppressionFunctionalDeletion


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Immature T cell clones may be aborted in asimilar manner to B cells

Subsets of mature T cells may beindividually deleted leading to the loss of

only one of the functions of the T cell group

Suppressor T cells actively suppress theactions of other T cell subsets or B cells

Clonal A ortion

FunctionalDeletion

T cellsuppression

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Immunosuppression & Immune Tolerance Report 3HMT - Carbungco & Enverga