Tumor Immunology s1

7/29/2019 Tumor Immunology s1

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TUMOR IMMUNOLOGY

.


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TUMOR ANTIGENS

Has tumor cell antigen ?

The variety of tumor antigens ?

The relationship between tumor antigenand carcinogenesis.

What is tumor marker ?

May tumor antigen stimulate Immune

Responses ? Evasion of immune responses by

tumor cells.


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GENERAL FEATURE OF

TUMOR IMMUNOLOGY Tumor express antigens that are

recognized as foreign antigen by the

immune system. Immune respons frequently fail to

prevent the growth of tumor.

The immune system can be activatedby external stimuli to effectively killtumor cells.


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1.Product o f mutated

oncogenes and tumor

supp ressor genes

Oncogens &

Tumor SuppGenes

(mutation)

Tumor Antigens

which related

to carcinogenesis.Cell Membrane

Carcinogen

Ras

p53,

Myc


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2.Product o f o ther mutated

genes

Other genes

(random

mutation)

Cell Membrane

Tumor antigens

which not related

to carcinogenesis

Carcinogen

TSTAs


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3.Abberant ly Exp ressed

Normal Cel lu lar Genes

GeneMutations

Cell Membrane

Tumor antigens

(Normal protein

but inappropriateexpression)

Carcinogen

Tyrosinase

MAGE

4 T A t i E d d


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4.Tumor An t igens Encoded

by Genome of Oncogenic

Viruses

Viral Genes

Cell Membrane

Tumor antigens

(Foreign antigens)

Oncogenic

Viruses

(EBV,HPV)

EBNAs(6)

LMPs(2)

VCAs


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5.Onco fetal An tigens

Silenced

Normal

Genes

Cell Membrane

Tumor antigens:Normal protein in high

level during

development (fetal)

Carcinogen

AFP

CEA


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6.Altered Glycoprotein &

Glycolipid Antigens.

Genesmutations

Cell Membrane

Carcinogen

Tumor Antigens:abnormal form of

GP & GL and/or

higher than normal

level.

GM2,GD2&GD3

CA-125,CA-19-9

MUC-1


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7.Tissue Spes if ic

Dif feren t iat ion Ant igens

NormalGenes

Cell Membrane

Carcinogen

Tumor Antigen:normally produced by

differentited cells

CD-10(CALLA)

CD-20


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TUMORANTIGENS

Carsinogen treatment

genetic alterations

( gene amplification,deletian &

translocation)

expression ofaltered

protein,glycoprotein & glycolipid

(antigen) in tumor cells.


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TUMOR ANTIGENS

1. Tumor antigen recognized by

immune system which may stimulate

the immune responses (Macrophage,

NK Cells, Antibody and T cells). to kill

tumor cells.(Immunosurvei lance

theory)


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TUMORANTIGENS

TUMOR CELLS

Immune responses

Mcell NKcell Tcell AB

antigen antigen


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TUMOR ANTIGENS

2. Tumor antigen could not be

recognized as foreign by immune

system but spesific for particular

tumor.

TUMOR MARKER

DIAGNOSE ANDTHERAPY


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TUMORANTIGENS

TUMOR CELLS

ANIMAL

Antigen Antibody

Diagnose &

Therapy


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Funct ion of Tumor Ant igens

AntigensImmune

Respone1. Product of mutated oncogenes

and tumor suppressor genes.

Therapy

2. Product of other mutated genes

3. Abberantly expressednormal cellular proteins.

4. Tumor antigens encoded by

genomes of oncogenic viruses.

5. Oncofetal Antigens.

6. Altered glycolipid and

Glycoprotein Antigens

7. Tissue Spesific Differentiation

Antigens.

No Yes

Yes

Yes Yes

Yes Yes

Yes

Diagnose

Yes Yes Yes

Yes Yes

Yes

No No

No

No No

Yes

Yes


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IMMUNE RESPONSE TO

TUMOR

1. Macrophage

.

3. Cytolytic T Lymphocyte

2. Natural Kiler (NK) Cell

4. Helper T Lymphocyte

5. Antibody


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Macrophage1. Phagocytosis

Lysis of

tumor cells

Tumor cells

Lysozymes

Tumor cells Macrophage

2. Production of Cytokine TNF(Tumor Necrocis Factor).

TNFRATumor Cell

A. TNF

Thrombosis intravasculer

Necroses of Tumor Cells

B.

Apoptosis of tumor cells


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Helper T Lymphocy te

MHC-II TCRHelper T Lymp

(CD-4)

Macrophage

(APC)

Tumor Antigens

Costimulator

Production of TNF

Production of

Interferon-gamma

Activation of

Macrophage and NK Cells.

Lysis of Tumor Cells

Apoptosis

of Tumor Cells

Necroses of

Tumor Cells

Activation ofCTL


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Cytolyt icT Lymphocyte

MHC-II TCR T Lymp

(CD-4)

Macrophage

(APC)

Tumor Antigens

MHC-I TCR CTL

(CD-8)

Tumor Cells

Tumor Antigens

Helper factors

A. Introduction of antitumor T cell r esponse

B. Ef fector phase of anti tumor CTL response.

Lysis of

Tumor Cells

Costimulator


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Natu ral K il ler (NK) Cells

No expression of MHC-I

IgG antibody-coated tumor cells

IgGFcRes

NK Cells

Tumor cells

(ADCC)

NK Cells

Adhesion molecules

Cytokines

(IL-1,IL-12,INF-G)Lysis of

tumor cells

Tumor cells

= tumor antigen


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ANTIBODY

IgG antibody-coated tumor cells

IgGFcResNK cells/

ADCC

Lysis of

tumor cells

Macrophages

Com-

plement

IgG or IgM

antibody-coated tumor cells

Tumor cells

Tumor cells

= tumorantigen


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EVASION OF IMMUNE

RESPONSES BY TUMORS


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1.Class I MHC exp ression may be

downregu lated on tumor cel ls ..

MHC-I TCR

CTL(CD-8)

Tumor Cells

Tumor AntigensLysis of

Tumor Cells

TCRCTL

(CD-8)

Tumor Cells

No expression of

Tumor Antigens

No Lysis of

Tumor Cells


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3. No exp ress ion o f MHC-II o r

cost imulator

MHC-II TCR Helper

T Lymp

(CD-4)

Macrophage

(APC)

Tumor Antigens

Costimulator

Production of TNF

Production of

Interferon-gamma

Activation of

Macrophages and NK Cells.

Lysis of Tumor Cells

Apoptosis

of Tumor Cells

Activation ofCTL

Necroses of

Tumor Cells


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4. The produce of tumor may supp ress

ant i tumor immune response.

MHC-II TCR T Lymp

(CD-4)

Macrophage

(APC)

Tumor Antigens

MHC-I TCR CTL

(CD-8)

Tumor Cells

Tumor Antigens

Helper factorsB. Ef fector phase of anti tumor CTL response.

Lysis of

Tumor Cells

Costimulator

TGF-

TGF-TGF-

A. I ntroduction of antitumor T cell r esponse


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5. Tumor ant igens may induce

speci f ic immunolog ic to lerance.

TUMOR CELLS

Immune responses


antigen antigen

6 The Cell su rface an tigens of tumors


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6. The Cell su rface an tigensof tumorsmay be hidden f rom the immune system

(antigen masking, fibrin cocoon & antigen-

antibody complexs)

TUMOR CELLS

Immune responses


antigen


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CONCLUSION

Tumor cells may express a variety of tumorantigens.

Some of the tumor antigens may recognizedas foreign by immune system.

Tumor cells have abilities to escape fromimmune responses.

Immune responses frequently fail to prevent

the growth of tumor cells. Some of tumor antigens are usefull as tumor

marker for diagnosis and therapy.


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Recommended Text Book.

Abul K Abbas and Andrew H. Lichtman:

BASIC IMMUNOLOGY

2nd

ed, 2006-2007Function and Disorders of the Immune

System.

SAUNDERS ELSEVIER


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Recommended Text Book.

Abul K Abbas and Andrew H. Lichtman:

BASIC IMMUNOLOGY

2

nd

ed, 2006-2007Function and Disorders of the Immune

System.

SAUNDERS ELSEVIER

Tumor Immunology s1

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