summary host defence against tumornmph.ppt

Host Defense Against Tumor� (Tumor Immunity) coordinated biologic process designed to recognize tumor cells and their products and to kill or damage the offending cells

1. Host Defense Against Tumor
(Tumor Immunity)
•Definition
coordinated biologic process
designed to recognize tumor
cells and their products and to
kill or damage the offending
cells.

2. Host Defense Against Tumor
Tumor Immunity
•Tumor Specific Antigens(TSA)
Present only on tumor cellsand
not on any normal cells and can be
recognized by cytotoxic T-lymphocytes.
•Tumor Associated Antigens
(TAA)
Not unique to tumors and are
also see on normal cells.

3. Tumor Antigens
•Tumor Specific Antigens (TSA)
•Cancer testis antigen
•Viral antigen
•Mucin
•Oncofetal antigens
•Antigens resulting from mutational in protein
B catenin, RAS, P53,CDK4

4. Tumor Antigens
•Tumor Associated Antigen=TAA
Present in normal cells & tumor cells
e.g. MART-1, gp100, tyrosinase expressed
in melanomas & normal melanocytes
T-cells directed against melanomas will
also destroy normal melanin containing
cells

5. Tumor Antigens
Tumor Associated Antigens(TAA)
•MART-1, gp100, tyrosinase
•Over expressed antigens
•Differentiation-specific antigens

6. Tumor Associated Antigens(TAA)
•Over expressed Antigens
e.g HER-2 (neu)in 30 % Breast cancer
( present in normal breast & ovary)
Human epidermal growth factor receptor 2-a gene
that plays a vital role in the dvt of breast cancer
HER2 breast Ca tend to be more aggressive

8. Tumor Associated Antigens(TAA)
•Differentiation-Specific
Antigens
e.g CD10& PSA
Expressed in normal B
cells & Prostate
Used as a marker for tumors
arise from these cells

9. ANTITUMOR EFFECTOR
MECHANISM
Cellular
•Cytotoxic T lymphocytes.
•Natural killer cells.
•Macrophages.
Humoral
mechanisms.complement
mediated or ADCC.

10. Mechanisms of Immunity to
Tumors
•Cytotoxic T lymphocytes (CTL)-
that are sensitized to TSAand
perhaps other tumor antigens kill
tumor cells. Play a role in virus induce
malignancy –HPV, Epstein Barr Virus,
HIV, HBV
•Natural Killer (NK) cells-can
attack tumor cells directly without
antibody coating or by Antibody
Dependent Cell Cytotoxicity (ADCC)
utilizing the Fc receptor on the NK
cells.

11. Mechanisms of Immunity
to Tumors
•Killer Macrophages-activated
by IFN-gelaborated by Helper T
lymphocytes. Participate in
ADCC and can lyse tumor cells
through release of TNF-a.

13. Immune surveillance:
•a constant monitoring process
aimed at eliminating emerging
cancers
recognition and
destruction of non-self
tumor cells .

14. Evidence for Immune Response
to Tumors
1) Infiltrate of lymphocytes and macrophages
associated with better prognosis in many
tumors.
2) Peripheral blood NK activity correlates with
survival.
3) Peripheral blood lymphocytes counts fall as
cancer overwhelms host; patients develop
anergy to skin tests.

15. Evidence for Immune Response
to Tumors
4) Non-specific vaccines can
stimulate macrophages and
improve prognosis. IFN-gand IL-
2 can stimulate NK cells and
improve outcome.
5) High incidence of some tumors
in immunosuppressed
individuals.
6) Spontaneous regression in some
tumors.

16. Sporadic cancers occur in
immune competent people
HOW ???
Escape mechanisms :
•Growth of antigen-negative
variants.
•HLA underexpression .
•No expression of costimulatory
molecule .
•Immunosuppression.
Immunosurveillance