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39 Cards in this Set

  • Front
  • Back
Types of Tumor Antigens
• Products of mutated genes
• Abnormal expression of normal genes
• Oncogenic virus genes
• Oncofetal antigens
• Altered glycolipid and glycoprotein antigens
• Tissue-specific differentiation antigens
Products of Mutated Genes
• The amino acid sequence determines what peptides are bound to what MHC molecules
• A change in the sequence will change what peptides can be presented.
Altered Glycolipid and glycoprotein antigens
• Most human tumors express increased levels or abnormal forms or cell surface glycoproteins and glycolipids
o Gangliosides (GM2, GD2, GD3), blood group antigens, mucins
Tissue Specific Differentiation Antigens
• Cell surface markers or intracellular proteins/receptors that are found only on/in specific lineages of cells.
o CD10 or CD20 on B cell derived lymphomas, Tyrosinase in melanomas, CD4 on T cell derived leukemias
List the Innate Immune Responders
- NK cells
- NK Receptors
- Macrophages
What is NK Cells Mechanism of Recognition?
Altered cell surface glycoproteins, Loss of class I MHC, Bound antibodies
What is the Mechanism of Killing for NK Cells?
Release of cytotoxic granules
What are NK Receptors?
Some of the NK cell receptors are heterodimer of two different protein families
What are the two types of NK Receptors?
- NKG2 family (6 members)
- Ly49 family (? Family):
What is NKG2 family inhibitory and activating?
A and B are inhibitory,
C and D are activating
What are Ly49 family inhibitory and activating?
A and G are inhibitory
D and H are activating
What is the Mechanism of Recognition for Macrophages?
Bound antibodies, receptor interactions (Can express NKG2D receptors)
What is the mechanism of killing for Macrophages?
Phagocytosis, NO production
What are Adaptive Immune Response types?
- CD8 + Cytolytic T cells
- B lymphocytes
What is the Mechanism of Recognition for CD8 + Cytolytic T cells?
Tumor antigens presented in Class I MHC
What is the Mechanism of Killing for CD8 + Cytolytic T cells?
Release of cytotoxic granules
What is the Mechanism of Recognition types for B lymphocytes?
Cell surface tumor antigen, T cell help
What is the Mechanism of Killing for B lymphocytes?
ADCC, antibody dependent cell mediated cytoxcity, complement activation?
How Tumors evade recognition and destruction?
• Tolerance
• Regulatory T cells
• Loss of class I MHC
• Loss of tumor antigens
• Suppressive secretions by tumor cells
List a Regulatory T cell
CD4 CD25+ autoreactive T cells
What is the role of CD4 CD25+ autoreactive T cells?
Role is to inhibit the activation of other autoreactive T cells.
What happens when there is a loss of Class I MHC?
• Tumors often lose expression from non-vital genes due to rapid mutations and selection by the immune system
• Loss of Class I MHC is positively selected for by protecting the cell from CTL killing

• With lost of Class I MHC: CTL Killing goes down, NK cell killing goes up
What happens when there is a loss of tumor antigen?
• Tumors often lose expression from non-vital genes due to rapid mutations
• Loss of any protein is positively selected for if it is not essential for growth and is being responded to by the immune system
Secretion of Suppressive COmpounds by tumor cells-- list mechanisms by which tumors escape immune recognition
- Low immunogenicity
- Antigenic modulation
- Tumor-induced immune suppression
What happans in Low immunogenicity?
- No peptide MHC ligand
- No adhesion molecules
- No co stomulatory molecules
What happens to Antigenic modulation?
- Anti body against tumor cell- surface antigens can induce endocytosis and degradation of the antigen.
- immune selection of antigen loss variants
What happens to Tumor indued immune suppression?
- factors (e.g. TGF-B) secreted by tumor cells inhbit T cells directly
For Chronic Inflammation, What does Macrophage released factors cause?

(role of Immune system in promoting tumor growth)
Promote angiogenesis (make new blood vessels) and tissue remodeling, promote DNA damage (oxygen free radicals).
Ex:
hep B infection, H. Pylori infection
List the Immune Therapy for Tumors
• Tumor Vaccination
• Augmenation of tumor responses
• Blocking inhibitory pathways
• Non-specific stimulation
• Passive Immunotherapy: Adoptive cell culture, Graft vs. Leukemia Reaction, Anti-tumor Ab Therapy
• Problems with chemotherapy
For Tumor Vaccination What are the steps?
1. Dendritic cells from patient are removed and “loaded” with tumor antigens, then returned
2. A plasmid that will express a tumor antigen is used as a vaccine.
• Dendritic cells from a patient are transfected with the same plasmid before return.
What happens in Augmentation of Tumor responses?
• Tumor cells are removed and forced to express immune modulating genes, then returned.
What happens in Blocking Inhibitory Pathways?
• Normal pathways that are used to inhibit or down-regulate an immune response include CD152/CTLA-4
• Antibodies are injected to block this receptor, allowing the immune system to respond to the tumor (self)

• The immune system is full of self regulating networks meant to prevent unnecessary activation or prolongation of an immune response.
• CD152 is upregulated with activation and binds the same targets (CD80/CD86) as CD28, but slightly better.
what happens in Non Specific Stimulation?
• Antigen non specific stimulators of the immune system are injected in the tumor: Cytokines, BCG, Anti-CD3 antibodies
List Pasttive Immunotherapy
- Adoptive Cell Culture
- Gradft vs. Leukemia Reaction
- Anti-tumor Antobodies
what is Adoptive Cell Culture?
: Lymphocytes are removed, activated by tumor antigens, and expanded in vitro, then returned to patient.
What is Graft vs. Leukemia Reaction?
Alloreactive T cells are administered along with stem transplants
What is Anti-Tumor Antibodies?
Antibodies to tumor cell markers are injected t induce humoral immunity
What are the problems with Chemotherapy?
- Chemotherapeutic agents typically cause apoptotic cell death
- More cells than just tumor cells need to divide in the body normally
- Cells dying from necrossi promote inflammation
- Cells dying from apoptosis inhit inflammation
In problems with chemotherapy, what type of dying cells promote phagocytosis?
- Cells dying from necrossi promote inflammation
- Cells dying from apoptosis inhit inflammation