1. ‫الرحيم‬ ‫الرحمن‬ ‫اللة‬ ‫بسم‬‫الرحيم‬ ‫الرحمن‬ ‫اللة‬ ‫بسم‬

2. Tumor immunologyTumor immunology

3. Tumor immunologyTumor immunology
** Pathological cell massesPathological cell masses derived by abnormal andderived by abnormal and
uncontrollable clonal expansion of single celluncontrollable clonal expansion of single cell
* Transformation of normal cells to malignant cells by:* Transformation of normal cells to malignant cells by:
a-a- Spontaneous mutationSpontaneous mutation during daily cell divisionduring daily cell division
chemical carcinogenschemical carcinogens
b- It may beb- It may be induced byinduced by physical carcinogensphysical carcinogens
virusesviruses
* Cells become* Cells become antigenically differentantigenically different from normal cellsfrom normal cells
* They are* They are recognizedrecognized andand destroyeddestroyed byby immune systemimmune system

4. Etiology Of TumorEtiology Of Tumor
1) Inherited :1) Inherited :
Expression of inherited oncogeneExpression of inherited oncogene
e.g. viral gene incorporated into host genee.g. viral gene incorporated into host gene
2) Viral:2) Viral:
- Human papilloma, herpes type 2, HBV, EBV (DNA)- Human papilloma, herpes type 2, HBV, EBV (DNA)
- Human T-cell leuckemia virus (RNA)- Human T-cell leuckemia virus (RNA)
3) Chemical:3) Chemical:
- Poly cyclic hydrocarbons cause sarcomas- Poly cyclic hydrocarbons cause sarcomas
- Aromatic amines cause mammary carcinoma- Aromatic amines cause mammary carcinoma
- Alkyl nitroso amines cause hepatoma- Alkyl nitroso amines cause hepatoma
4) Radiological:4) Radiological: Ultraviolet & ionizing irradiationUltraviolet & ionizing irradiation
5) Spontaneous:5) Spontaneous: failure in the cellular growth controlfailure in the cellular growth control

5. Tumor Associated AntigensTumor Associated Antigens
!) Viral Antigen :!) Viral Antigen :
a- Viral proteins and glycoproteinsa- Viral proteins and glycoproteins
b- New antigens produced by virally infected hostb- New antigens produced by virally infected host
cells under control of viral nucleic acidcells under control of viral nucleic acid
2) Tumor specific antigens :2) Tumor specific antigens :
- Tumor cells develop new antigen specific to- Tumor cells develop new antigen specific to
their carcinogenstheir carcinogens
3) Tumor specific transplantation antigens :3) Tumor specific transplantation antigens :
- Tumor cells express new MHC antigens due to- Tumor cells express new MHC antigens due to
alteration of normally present MHC antigensalteration of normally present MHC antigens

6. Tumor Associated AntigensTumor Associated Antigens
4) Oncofetal antigens:4) Oncofetal antigens:
a- Carcino-embryonic antigens (CEA)a- Carcino-embryonic antigens (CEA)
- Normally expressed during fetal life on fetal gut- Normally expressed during fetal life on fetal gut
- Reappearance in adult life:- Reappearance in adult life:
GIT, pancreas, biliary system and cancer breastGIT, pancreas, biliary system and cancer breast
b- Alpha fetoprotein:b- Alpha fetoprotein:
- Normally expressed in fetal life- Normally expressed in fetal life
- Reappearance in adult life; hepatoma- Reappearance in adult life; hepatoma

7. Immune Surveillance SystemImmune Surveillance System
* During neoplastic transformation, new antigen develop* During neoplastic transformation, new antigen develop
* The host recognize them as nonself antigens* The host recognize them as nonself antigens
* Cell mediated immune reactions attack these* Cell mediated immune reactions attack these
nonself tumor cellsnonself tumor cells
* Immune response act as surveillance system* Immune response act as surveillance system
to detect and eliminate newly arising neoplastic cellsto detect and eliminate newly arising neoplastic cells

8. Immune Surveillance SystemImmune Surveillance System
This system include :This system include :
1) Natural killer (NK) cells1) Natural killer (NK) cells
They kill directly tumor cells,helped by interferon, IL-2They kill directly tumor cells,helped by interferon, IL-2
2) Cytotoxic T-cells2) Cytotoxic T-cells
They also kill directly tumor cellsThey also kill directly tumor cells
3) Cell mediated T-cells (effector T-cells)3) Cell mediated T-cells (effector T-cells)
They produce and release a variety of lymphokines :They produce and release a variety of lymphokines :
a-Macrophage activation factora-Macrophage activation factor that activate macrophagthat activate macrophag
b-Gamma interferon and interleukin-2b-Gamma interferon and interleukin-2 that activate NKthat activate NK
c-Tumor necrosis factor (cachectine)c-Tumor necrosis factor (cachectine)

9. Immune Surveillance SystemImmune Surveillance System
4) B-cells :4) B-cells :
- Tumor associated antigens stimulate production of- Tumor associated antigens stimulate production of
specific antibodies by host B-cellsspecific antibodies by host B-cells
- These specific antibodies bind together on tumor cell surface- These specific antibodies bind together on tumor cell surface
leading to destruction of tumor through:leading to destruction of tumor through:
a- Antibody mediated-cytotoxicity :a- Antibody mediated-cytotoxicity :
killkill
Cytotoxic T-cells IgG-coated tumor cellsCytotoxic T-cells IgG-coated tumor cells
b- Activation of macrophagesb- Activation of macrophages
releaserelease
Sensitized T-cells macrophage activating factorSensitized T-cells macrophage activating factor
IgG-coated tumor cells macrophagesIgG-coated tumor cells macrophages
activateactivate
c- Activation of classical pathway of complementc- Activation of classical pathway of complement leading toleading to

10. Tumor EscapeTumor Escape
Mechanisms by which tumor escape immune defenses:Mechanisms by which tumor escape immune defenses:
1) Reduced levels or absence of MHCI molecule1) Reduced levels or absence of MHCI molecule onon
tumor so that they can not be recognized by CTLstumor so that they can not be recognized by CTLs
2) Some tumors stop expressing the antigens2) Some tumors stop expressing the antigens
These tumors are called “antigen loss variants”These tumors are called “antigen loss variants”
3) Production of immunosuppressive factors by tumor3) Production of immunosuppressive factors by tumor
e.g. transforming growth factor (TGF-e.g. transforming growth factor (TGF-ββ))
4) Tumor antigens may induce specific immunologic4) Tumor antigens may induce specific immunologic
tolerancetolerance

11. Tumor EscapeTumor Escape
5) Tumor cells have an inherent defect in antigen5) Tumor cells have an inherent defect in antigen
processing and presentationprocessing and presentation
6) Blocking of receptors on T-cells by specific antigen6) Blocking of receptors on T-cells by specific antigen
antibodies complex (antibodies complex (after shedding of tumor Ag)after shedding of tumor Ag)
prevents them from recognizing and attackingprevents them from recognizing and attacking
tumor cellstumor cells
7) Antigens on the surface of tumors may be masked7) Antigens on the surface of tumors may be masked
by sialic acid-containing mucopolysaccharidesby sialic acid-containing mucopolysaccharides
8) Immune suppression of the host as in transplant8) Immune suppression of the host as in transplant
patientspatients who show a higher incidence of malignancywho show a higher incidence of malignancy

12. Tumor MarkersTumor Markers
* Tumor markers :* Tumor markers :
Tumor antigensTumor antigens
* They are either or* They are either or
Tumor productsTumor products
(enzymes and hormones)(enzymes and hormones)
* Tumor products are released in the serum of patients* Tumor products are released in the serum of patients
* They are used to* They are used to confirm diagnosisconfirm diagnosis andand follow upfollow up thethe
response toresponse to therapytherapy

13. Tumor AntigensTumor Antigens
1) Alpha fetoprotein antigen (AFP)1) Alpha fetoprotein antigen (AFP) in cases of hepatomain cases of hepatoma
2) Carcinoembryoinic antigen (CEA)2) Carcinoembryoinic antigen (CEA) in gastrointestinalin gastrointestinal
tumors, tumors of biliary system and cancer breasttumors, tumors of biliary system and cancer breast
3) Cancer antigen 1253) Cancer antigen 125 (CA 125)(CA 125) in ovarian carcinomain ovarian carcinoma
4) Cancer antigen 15-3 (CA15-3)4) Cancer antigen 15-3 (CA15-3) in breast cancerin breast cancer
5) Cancer antigen 19-95) Cancer antigen 19-9 in colon and pancreatic tumorin colon and pancreatic tumor
6) Prostatic specific antigen (PSA)6) Prostatic specific antigen (PSA) in prostatic tumorsin prostatic tumors

14. Tumor ProductsTumor Products
a) Hormones :a) Hormones :
-- Human chorionic gonadotrophins (HCG)Human chorionic gonadotrophins (HCG) are secretedare secreted
in cases of choriocarcinomain cases of choriocarcinoma
- Thyroxin (T3 & T4)- Thyroxin (T3 & T4) is secreted in cases of canceris secreted in cases of cancer
of thyroid glandof thyroid gland
b) Enzymes :b) Enzymes :
- Acid phosphatase- Acid phosphatase enzymes in cases of cancer prostaeenzymes in cases of cancer prostae
- Alkaline phosphatese, lipase and amylase- Alkaline phosphatese, lipase and amylase enzymes inenzymes in
cases of cancer pancreascases of cancer pancreas

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