23. Tumor Immunity & Paraneoplastic Effects, Oncogenic Viruses, & Diagnostic Tools in Neoplasia

the process by which the immune system attacks cells not recognized as self, including transplanted tissues, microbes, or foreign cells

immunosurveillance

What is the believed effect of immunosurveillance on tumor development?

it suppresses it

proteins, glycoproteins, glycolipids, or carbohydrates expressed on tumor cells

tumor antigens

What are the types of tumor antigens?

T
T

• tumor specific antigens

• tumor associated antigens

antigen that is specific to the tumor itself

tumor specific antigens

antigens that are expressed on both the tumor cells and normal cells

tumor associated antigens

True or false: Tumor antigens can be recognized by immune cells.

true

True or false: Sometimes the body is not very good at antitumor effector mechanisms. In some neoplasms, antitumor immunity leads to regression of the neoplasm and is key to fighting neoplasia.

true

What is the type of immune response and effectiveness dependent on?

animal and tumor antigen expressed

What immune response is the first line of defense?

innate immune response

What cells are involved in the innate immune resposne?

NK cells and macrophages

What are the components of the adaptive immune system?

cell mediated and humoral

Which component of the adaptive immune response is the most effective antitumor defenses?

cell mediated

Humoral is ________ mediated, and is not believed to be as ________.

antibody; effective

these cells recognize MHC molecules and stress induced ligands on tumor cells

NK cells

What happens when NK cells bind to the stress ligands? What does this allow to occur? What does this do?

forms an immunologic synapse; release perforin and granzyme; inhibits apoptosis

The mechanism of killing that NK cells use is shared with what other cell type?

cytotoxic T lymphocytes

What do macrophages respond to?

interferon gamma produced by T lymphocytes and NK cells

How do macrophages kill tumor cells?

through the release of ROS, lysosomal enzymes, nitric oxide, and tumor necrosis factor alpha

True or false: While macrophages can be tumorcidal, new research suggests that some macrophages will promote tumorigenesis by promoting angiogenesis, enhancing tumor cell invasion, and metastasis.

true

How do cytotoxic T lymphocytes (CD8+ T lymphocytes) predominantly mediate killing? What cell type is this mechanism similar to?

via perforin and granzyme; NK cells

How do B cells predominantly kill tumor cells?

through secreting immunoglobulins which activate the complement cascade and insert the membrane attack complex on tumor cells

How do tumor cells inhibit/manipulate immune responses?

A
A
T
I

• altered major histocompatability complex expression

• antigen masking

• tolerance

• immunosuppression

Tumor cells that fail to express MHC I are more likely to be killed by what cell type?

NK cells

In altered major histocompatability complex expression, what is down-regulated? What does this mean?

MHC I and MHC II expression; no MHC II means no TH (CD4) cell response

inhibits growths and function of macrophages and lymphocytes

TGF alpha production by tumor cells

During immunosuppresion, the expression of what triggers the apoptosis of T lymphs?

Fas ligand

Can tumors regress?

yes but is rare and overall uncommon

What certain tumor types more commonly regress?

papillomas and canine cutaneous histiocytomas

When happens when regression occurs?

the immune system attacks and removes the neoplastic cells

systemic clinical signs as a result of a tumor

paraneoplastic syndromes

True or false: Not every cancer produces one of these syndromes.

true

What is humoral hypercalcemia of malignancy also known as?

pseudo-hyperparathyroidism

In humoral hypercalcemia of malignancy, the neoplastic cells produced ________, which has a similar homology as PTH and thus has the same effects.

PTHrP

What neoplasias are associated with PTHrP production?

A
L
V

• anal sac gland adencarcinoma (AGASACA, canine)

• lymphoma

• various carcinomas

What do you run if humoral hypercalcemia of malignancy is suspected?

malignancy profile

What other disease acts through the mechanism of PTHrP?

schistosomiasis

space occupying neoplastic and nonneoplastic masses in the thoracic cavity that has been reported in dogs, cats, and horses and results in lameness due to periosteal new bone growth on the long bones

hypertrophic osetopathy

process of fat and muscle loss which occurs in chronic inflammatory states of cancer that is complex and multifactorial

cachexia

Cachexia is in part due to the increased production of what hormones and cytokines? What do these do?

T
I
I
P

• TNF alpha

• IL-1

• IL-6

• prostaglandins

raise basal metabolic rates and result in anorexia

primarily the loss of fat (eventually there is muscle atrophy) from malnutrition (inadequate caloric intake)

emaciation

True or false: Sometimes, neoplasia can have an etiologic agent.

true

viruses that are able to induce neoplasia

oncogenic viruses

What is the causative agent of Marek’s disease? What does it do?

gallid herpes virus 2 (alpha herpesvirus); suppresses the ability of the host immune system to eliminate neoplastically transformed T cells

What can the bovine leukosis virus (BLV) induce? What does it do? Where?

H
U
L
A
S

B-cell lymphoma; induces neoplastic transformation of lymphocytes

• heart

• uterus

• lymph node

• abomasum

• spinal cord

What is feline leukoemia virus (FELV) associated with?

leukemias and thymic lymphoma in cats