A-V Tumor immunology

Question 1

Metastasis

Answer 1

Spread of cancerous cells through lymph fluid or blood.

Question 2

Neoantigens

Answer 2

Tumor antigens that are self-antigens with mutations and are recognized as foreign by the immune system.

Question 3

CD8+ T-cells (in tumor immunity)

Answer 3

Recognize and kill tumor cells using perforin and granzyme cytotoxicity.

Question 4

NK Cells (in tumor immunity)

Answer 4

Recognize and kill tumor cells via missing self-recognition (lack of MHC Class I), ADCC (Antibody-Dependent Cell-mediated Cytotoxicity) through FcγRIII binding to IgG antibodies and release of perforin, and FasL binding to Fas on tumor cells.

Question 5

Macrophages (in tumor immunity)

Answer 5

Can kill tumor cells through ADCC, release lysosomal enzymes and ROS, and use TNF to induce thrombosis in tumor blood vessels.

Question 6

CD4+ Th cells (in tumor immunity

Answer 6

Primarily involved in the activation of other effector cells, such as macrophages, to fight tumors.

Question 7

Antibodies (in tumor immunity)

Answer 7

Can contribute to tumor destruction through complement activation and ADCC activation.

Question 8

Tumor immune evasion

Answer 8

Mechanisms used by tumors to inhibit anti-tumor immune responses, such as antigen loss, failure to trigger APC co-stimulation, inhibition of MHC Class I expression, secretion of immunosuppressive cytokines (TGF-β, IL-10), induction of a physical barrier, and expression of PD-L1 and -L2.

Question 9

PD-L1 and PD-L2 in tumor immunity

Answer 9

Inhibitory ligands upregulated on tumor cells and Antigen-Presenting Cells (APCs) that bind to PD-1/2 on effector T-cells, leading to inhibitory signaling and preventing an antitumor response.

Question 10

Hot tumor

Answer 10

A tumor that is infiltrated by T-cells but exhibits immune escape, often through the expression of PD-L1.

Question 11

Cold tumor

Answer 11

A tumor with no T-cell infiltration, leading to immune escape.

Question 12

T-cell exclusion

Answer 12

A mechanism of immune escape where T-cells are unable to infiltrate the tumor, preventing killing of cancer cells.

Question 13

Autoimmunity

Answer 13

A misdirected attack by the immune system on the body’s own tissues and organs.

Question 14

Genetic risk factors for autoimmunity

Answer 14

Include MHC genes (both Class I and II associated), non-MHC genes like CTLA-4, AIRE, and FoxP3, as well as genes related to cytokines (e.g., IL-2/IL-2R) and complement components (e.g., C1q, C2, C4).

Question 15

Enviromental risk factors for autoimmunity

Answer 15

Can include infections (e.g., Covid-19, Hepatitis C, EBV), traumatic insult (potentially introducing self-antigens), tissue inflammation, hormones, smoking, and the microbiome.

Question 16

Immune tolerance in relation to autoimmunity

Answer 16

Autoimmunity represents a failure of immune tolerance, the mechanisms that prevent the immune system from attacking self-antigens.

Question 17

Diabetes Type 1

Answer 17

An autoimmune disease involving the attack of β cells in the pancreas that produce insulin, leading to irreversible insulin deficiency.

Question 18

Rheumatoid arthritis

Answer 18

A prevalent autoimmune disease characterized by the attack on peripheral joints, leading to inflammation, synovial membrane invasion, and eventual joint destruction. Specific autoantibodies like RF and ACPA are often present.

Question 19

Multiple sclerosis

Answer 19

An autoimmune disease where the immune system attacks the central nervous system (CNS), specifically the myelin sheets that insulate nerve fibers, leading to neurological dysfunction.

Question 20

Molecular mimicry (in autoimmunity)

Answer 20

A theory suggesting that microbial antigens can share structural similarities with self-antigens, potentially triggering an autoimmune response.

Question 21

Type II hypersensitivity

Answer 21

A type of hypersensitivity reaction where antibodies bind to antigens on cells, leading to the activation of neutrophils and macrophages and cell destruction.

Question 22

Type III hypersensitivity

Answer 22

A type of hypersensitivity reaction where large immune complexes form and deposit in tissues, causing neutrophil degranulation and tissue damage.

Question 23

Treatment of autoimmune diseases

Answer 23

Primarily focuses on suppressing the immune response through various therapeutic targets. There is no cure, and treatment is typically lifelong.

Question 24

What are tumor antigens also called, and what is their basic nature?

Answer 24

Tumor antigens are also called neoantigens, and they are essentially mutated self-antigens that are recognized as foreign by the immune system

Question 25

Name three categories of tumor antigens based on their origin

Answer 25

Based on the source, three categories of tumor antigens are: ◦ Products of genes that are required for malignancy, such as ras and p53 ◦ Proteins produced by mutated genes ◦Products of overexpressed genes

Question 26

Describe the mechanism used by CD8+ T-cells to kill tumor cells

Answer 26

CD8+ T-cells kill tumor cells through perforin and granzyme cytotoxicity

Question 27

How do NK cells recognize and kill tumor cells that have reduced expression of MHC Class I molecules?

Answer 27

NK cells utilize a "missing self" recognition strategy. When tumor cells turn down the expression of MHC Class I, there is no binding to the inhibitory receptor on the NK cell, leading to the killing of the cell

Question 28

Explain the role of PD-L1 expression on tumor cells in immune evasion

Answer 28

According to the source, the expression of PD-L1 on tumor cells can bind to PD-1/2 on effector T-cells. This binding delivers an inhibitory signal to the T-cell, resulting in no antitumor response

Question 29

What is meant by a "hot tumor" in the context of immune infiltration and escape

Answer 29

A "hot tumor" is characterized by being T-cell infiltrated but still exhibits immune escape mechanisms, such as the expression of PD-L1

Question 30

Name two categories of genes as risk factors for developing autoimmune diseases

Answer 30

Two categories of genes associated with the risk of autoimmunity are MHC genes (including MHC Class I and Class II associated genes) and non-MHC genes like CTLA-4 and AIRE

Question 31

Provide an example of an environmental factor that may contribute to the initiation of autoimmune disease

Answer 31

Infections such as Covid-19, Hepatitis C, EBV, and Coxsackie B as potential environmental factors that can contribute to the initiation of autoimmune diseases .Traumatic insult leading to the introduction of self-antigens not normally encountered by the immune system could be a factor

Question 32

What is the primary target of the autoimmune attack in Diabetes Type 1

Answer 32

Diabetes Type 1, there is an autoimmune attack of the β cells in the pancreas, which are responsible for producing insulin

Question 33

Describe the involvement of autoantibodies in rheumatoid arthritis

Answer 33

B-cells are involved in rheumatoid arthritis, leading to the production of specific autoantibodies such as RF (Abs against self-IgG) and ACPA (IgG that target proteins containing citrulline). These autoantibodies can even be found before the onset of the disease

Question 34

True and False: Metastasis is defined as the uncontrolled growth of transformed cells

Answer 34

False; metastasis is the spread of cancer cells through fluid such as blood or lymph fluid

Question 35

True or False: Neoantigens are recognized as self-antigens by the immune system

Answer 35

False; they are mutated self antigen that are recognized as foreign

Question 36

True or false: CD8+ T-cells primarily kill tumor cells by releasing lysosomal enzymes

Answer 36

False; macrophages uses lysosomal enzymes

Question 37

True or False: NK cells are inhibited when they encounter cells expressing MHC Class I molecules with self-peptides

Answer 37

True:

Question 38

True or False: The secretion of immunosuppressive cytokines like TGF-β by tumor cells is a mechanism of tumor immune evasion

Answer 38

True

Question 39

True or False: In a "cold tumor, " there is typically a significant infiltration of T-cells

Answer 39

False; this is a hot tumor

Question 40

True or False: Blocking inhibitory receptors on T-cells, such as PD-1, is a completely risk-free experimental cancer treatment

Answer 40

False; this can lead to autoimmune diseases

Question 41

True or False: Autoimmunity represents a properly directed immune response against foreign pathogens

Answer 41

False; its an overreaction against self antigens

Question 42

True or False: Diabetes Type 2 is an example of an autoimmune disease where the immune system attacks insulin-producing cells

Answer 42

False; this is the case for Type I

Question 43

True or False: In rheumatoid arthritis, autoantibodies like RF and ACPA target foreign antigens in the joints

Answer 43

False

Question 44

What are the stages of tumor immune evasion

Answer 44

1 - Elimination phase. When tumor cells first arise, immune cells will recognize and eliminate them 2 - Equilibrium phase. Tumor cell variants that are more resistant to being killed starts to arise. Different types develop. 3 - Escape phase. One variant escapes the killing mechanisms or reqruit Tregs as protection

Question 45

How can cytokines be associated with autoimmune diseases?

Answer 45

Both over and underexpression of cytokines can lead to autoimmune disorders. Overexpression of inflammatory cytokines such as TNF-alpha is associated with IBD. IL-2 and IL-7 is also associated with IBD. Underexpression of suppressor cytokines such as TGF-beta is also associated with IBD

Question 46

True or False: autoimmune diseases is more common in women

Answer 46

True

Question 47

Crohns disease

Answer 47

Autoreactive T-cells against antigens in the intestinal flora causes intestinal inflammation

Question 48

Multiple sclerosis

Answer 48

Autoreactive T-cells against brain and spinal chord antigens cause destruction of myelin sheaths, leading to muscle weakness and other symptoms. Blood brain barrier allows immune cells and antibodies to pass over