A-V Tumor immunology Flashcards
Metastasis
Spread of cancerous cells through lymph fluid or blood.
Neoantigens
Tumor antigens that are self-antigens with mutations and are recognized as foreign by the immune system.
CD8+ T-cells (in tumor immunity)
Recognize and kill tumor cells using perforin and granzyme cytotoxicity.
NK Cells (in tumor immunity)
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.
Macrophages (in tumor immunity)
Can kill tumor cells through ADCC, release lysosomal enzymes and ROS, and use TNF to induce thrombosis in tumor blood vessels.
CD4+ Th cells (in tumor immunity
Primarily involved in the activation of other effector cells, such as macrophages, to fight tumors.
Antibodies (in tumor immunity)
Can contribute to tumor destruction through complement activation and ADCC activation.
Tumor immune evasion
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.
PD-L1 and PD-L2 in tumor immunity
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.
Hot tumor
A tumor that is infiltrated by T-cells but exhibits immune escape, often through the expression of PD-L1.
Cold tumor
A tumor with no T-cell infiltration, leading to immune escape.
T-cell exclusion
A mechanism of immune escape where T-cells are unable to infiltrate the tumor, preventing killing of cancer cells.
Autoimmunity
A misdirected attack by the immune system on the body’s own tissues and organs.
Genetic risk factors for autoimmunity
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).
Enviromental risk factors for autoimmunity
Can include infections (e.g., Covid-19, Hepatitis C, EBV), traumatic insult (potentially introducing self-antigens), tissue inflammation, hormones, smoking, and the microbiome.
Immune tolerance in relation to autoimmunity
Autoimmunity represents a failure of immune tolerance, the mechanisms that prevent the immune system from attacking self-antigens.
Diabetes Type 1
An autoimmune disease involving the attack of β cells in the pancreas that produce insulin, leading to irreversible insulin deficiency.
Rheumatoid arthritis
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.
Multiple sclerosis
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.
Molecular mimicry (in autoimmunity)
A theory suggesting that microbial antigens can share structural similarities with self-antigens, potentially triggering an autoimmune response.
Type II hypersensitivity
A type of hypersensitivity reaction where antibodies bind to antigens on cells, leading to the activation of neutrophils and macrophages and cell destruction.
Type III hypersensitivity
A type of hypersensitivity reaction where large immune complexes form and deposit in tissues, causing neutrophil degranulation and tissue damage.
Treatment of autoimmune diseases
Primarily focuses on suppressing the immune response through various therapeutic targets. There is no cure, and treatment is typically lifelong.
What are tumor antigens also called, and what is their basic nature?
Tumor antigens are also called neoantigens, and they are essentially mutated self-antigens that are recognized as foreign by the immune system
Name three categories of tumor antigens based on their origin
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
Describe the mechanism used by CD8+ T-cells to kill tumor cells
CD8+ T-cells kill tumor cells through perforin and granzyme cytotoxicity
How do NK cells recognize and kill tumor cells that have reduced expression of MHC Class I molecules?
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
Explain the role of PD-L1 expression on tumor cells in immune evasion
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
What is meant by a “hot tumor” in the context of immune infiltration and escape
A “hot tumor” is characterized by being T-cell infiltrated but still exhibits immune escape mechanisms, such as the expression of PD-L1
Name two categories of genes as risk factors for developing autoimmune diseases
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
Provide an example of an environmental factor that may contribute to the initiation of autoimmune disease
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
What is the primary target of the autoimmune attack in Diabetes Type 1
Diabetes Type 1, there is an autoimmune attack of the β cells in the pancreas, which are responsible for producing insulin
Describe the involvement of autoantibodies in rheumatoid arthritis
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
True and False: Metastasis is defined as the uncontrolled growth of transformed cells
False; metastasis is the spread of cancer cells through fluid such as blood or lymph fluid
True or False: Neoantigens are recognized as self-antigens by the immune system
False; they are mutated self antigen that are recognized as foreign
True or false: CD8+ T-cells primarily kill tumor cells by releasing lysosomal enzymes
False; macrophages uses lysosomal enzymes
True or False: NK cells are inhibited when they encounter cells expressing MHC Class I molecules with self-peptides
True:
True or False: The secretion of immunosuppressive cytokines like TGF-β by tumor cells is a mechanism of tumor immune evasion
True
True or False: In a “cold tumor, “ there is typically a significant infiltration of T-cells
False; this is a hot tumor
True or False: Blocking inhibitory receptors on T-cells, such as PD-1, is a completely risk-free experimental cancer treatment
False; this can lead to autoimmune diseases
True or False: Autoimmunity represents a properly directed immune response against foreign pathogens
False; its an overreaction against self antigens
True or False: Diabetes Type 2 is an example of an autoimmune disease where the immune system attacks insulin-producing cells
False; this is the case for Type I
True or False: In rheumatoid arthritis, autoantibodies like RF and ACPA target foreign antigens in the joints
False
What are the stages of tumor immune evasion
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
How can cytokines be associated with autoimmune diseases?
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
True or False: autoimmune diseases is more common in women
True
Crohns disease
Autoreactive T-cells against antigens in the intestinal flora causes intestinal inflammation
Multiple sclerosis
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
