Immunology- Tumors

Front 1

Tumors are the result of what?

Back 1

DYSregulated growth- a clone of cells that replicate

Front 2

Cancer and tumors

Back 2

uncontrolled tumor growth

UNCONTROLLED

Front 3

Malignant vs. Bening Tumor

Back 3

Not invasive, not capable of indefinite growth

Front 4

What are the three types of cancer?

Back 4

1) Carcinoma
2) Lymphoma/Leukemia Cells
3) Sarcomas

Front 5

Carcinoma

Back 5

Endodermal or ectodermal tissue

Skin, epithelial lining of organs- breast, colon, lung, prostate (~80%)

Front 6

Lymphomas/Leukemia

Back 6

from HEMATOPOIETIC CElls (myeloid vs. lymphoid leukemia)

Lymph nodes
lymphode cell

Front 7

Sarcoma

Back 7

From mesodermic tissue- BONE

Front 8

What are 3 causes of cancer?

Back 8

1) Induce cell proliferation
2) loss of tumor suppressor gene function
3) loss of control of cell death- bcl2

Front 9

Cancer is a result of

Back 9

1) spontaneous or inherited mutation
2) Chemical carcinogens
3) virus transformation

Front 10

Genes that were normal before them became an ONCOGENES

Back 10

PROTO oncogenes

Front 11

What are mutations that induce cell proliferation

Back 11

A) Growth factor receptors (NEU)

Breast cancer- is over production of NEU

B) Tyrosine kinases in GF signaling (Src, abl)

C) GTP-binding proteins involved in growth induction

Front 12

Proteins involved in mutation in tumor suppressor genes (mutates to lose inhibition of cell growth)

Back 12

p53, RB

These normally regulate cell growth- but don't regulate as they should

Front 13

Gene amplification of genes controlling cell death mutation involves what protein

Back 13

bcl2

Front 14

Anti-apoptotic protein

Back 14

bcl2
Inhibits apoptosis and promotes growth

Increase bcl2, increase tumor generation (Lymphoma)

Front 15

The development of cancer requires

Back 15

MULTIPLE HITS

Front 16

15% of all cancers are from

Back 16

Viruses that integrate into genome and induce transformation

Front 17

What are examples of viruses that cause TUMOR

Back 17

HPV- cervical
Epstein Barr Virus
nasopharyngeal carcinoma
Burkitt lymphoma
Hepatitis B virus- Liver cancer

Front 18

Human T-lymphotropic virus (HTLV)

Back 18

human, single-stranded RNA retrovirus that causes T-cell leukemia and T-cell lymphoma in adult

Front 19

How do we know that a protective response can be mounted against tumors?

Back 19

Tumor rejection antigens
Tumor specific antigens
Tumor associated antigens

Front 20

Why won't response to irradiated tumor will not eliminate unrelated tumors of different cell types?

Back 20

Response to UNIQUE tumor rejection ANTIGENS elmiminates tumor

Front 21

Response to unique tumor rejection antigen

Back 21

ELIMINATES TUMOR

Front 22

Tumor antigen CEA

Back 22

reactivates embroynic gene xpression in tumor cell- present new antigens to adult immun esystem

Front 23

Overexpress normal self-peptide by a tumor cell changes peptide presentation density allowing T cell recognition

Back 23

HIGHER levels of expression

Front 24

If you have mutated peptide, then you have

Back 24

alterations in CHO

Alteration in glycosylation machinery- alter structure, making it susceptible to different ways of cleaving.

Different cleaves, different MHC T cell presentation (foreign)

Front 25

MUC-1

Back 25

underglycosylated mucin


Different kinds: Over and differently glycosylated

Exposure of cleavage site for processing, recognition by acid residue sequences

Front 26

Three immune responses to tumors?

Back 26

CTL killing
Nk Killing
Macropahges secreting stuff

Front 27

CTL killing involves what?

Back 27

LAK cells

Front 28

LAK cells

Back 28

Lymphokine activated killer cells are white blood cells that help to identify and destroy cancer cells in the body.

Front 29

Nk killing occurs

Back 29

directly or via FCR
direct or ADCC (FcR)

Front 30

What do macrophages secrete

Back 30

lyctic enzymes, NO, Ros, TNF alpha

Front 31

Mechanisms by which tumors escape immune recognition

Back 31

1) Antigenic modulation

Antibody against tumor-cell surface antigens can induce ENDOCYTOSIS and DEGRADATION of antigen

Immune selection of antigen-loss variants

Front 32

Antigenic moduation

Back 32

INGEST
CLUSTER
down regulate

now the immune system can no longer see it
Protected
So ab' is not enough to generate Complement activation
Not in right place to allow for phagocyte or NK mediated killing

Front 33

Immune may also generate proteases

Back 33

ECTOpreateases that cleave up antigen

Front 34

Tumors have low immunogenicity

Back 34

Down regulate
Loss of HLA class I expression in prostate gland

Front 35

Tumors and HLA class I

Back 35

lymphocytes coming in to combat tumor


No HLA 1 to present foreign peptide
Must have CD8s to work

Front 36

Macrophages and low immunogenicity of tuomrs

Back 36

The successful Macrophages against tumor cells secrete soluble TNF receptor

Kill tumors by secreting TNF alpha, induces apoptosis in tumor cells
Tumor cells clip that off by clipping protease
No longer have receptor- no apoptosis
TNF-alpha binding- neutralize

Front 37

Low immunogenicity of Tumors because they don't have

Back 37

PEPTIDE
MHC ligand
Adhesion molecules
Co-stimulatory molecules

Front 38

Tumors escape immune suppression DIRECTLY via

Back 38

TGF-beta by tumor cells inhibits T cells directly

Blocking factors- like sTNF alpha receptor

Front 39

How are NK cells activated?

Back 39

Tumor specific antibody
binds to tumor cell

NK cells with Fc receptors (CD16) activated to kill tumor cells

Front 40

If tumor specific Ab has CONJUGATED

Back 40

Cojugate is internalized, killing the cell

Front 41

Tumor specific antibody conjugated to RADIONUCLIDE

Back 41

radioactive antibody binds to the tumor cell

Radiation kills tumor cell and neighbor tumor cell

Front 42

Monoclonal Antibodies-

Back 42

AVASTIN


HERCEPTIN
RITUXAN

Front 43

Presence of TRA and no accompanying costimulatory molecules

Back 43

Tumor rejection antigen

Can't turn on naive CD8 T cells
Anergic
Tumor grows progressively