Tumor Immunology Hypersensitivity Flashcards
What is a tumor
An abnormal growth resulting from uncontrolled proliferation with no physiologic funtion
other name for a tumor
Neoplasm (new growth)
What is Cancer
Malginant tumor
Difference between Benign and Malignant Tumors
Slow growth: Rapid Growth
Well-defined capsul: Not encapsulated
Not invasive: invasive
Well differentiated: pooly differentiated (anaplasia)
Low Mitotic index: High Mitotic index
Does not metastasize: Can spread distantly (metastasis)
what is cancer a predominantly a disease of
Aging
How does Cancer proliferate
Clonal
why does cancer spread so rapidly
as a mutation it is benifical to the cell to grow fast, so it has a selective advantage ocer its neighbored (increased groth or decreased apoptosis)
What needs to occur to have Full blown cancer
4-7 mutations in a step wise accumulation of alterations occuring in specific genes
What are Carcinogens
Agents that can cause genetic mutation or alterations of gene expression that can lead to the development of cancer
Examples of Carcinogens
Chemical (Alcohol, asbestos, benezene, tobacco, aluminum)
Radioactive (plutonium-239, radon-222, iodine-131)
Pathogens (Epstein-Barr Virus, H. pylori, Hep B and C, HPV)
What do Cancer-Causing Mutations affect
Activation of growth-promotion pathways
Block antigrowth signals
Prevent apoptosis
Turn on telomerase and new blood vessel growth
Allow tissue invasion and distant metastasis
What are tumor associated antigens
Normal proteins that are expressed in abnormally high levels, in an abnromal location, or during an abnormal stage of cellular development
What are tumor specific Antigens
Macromolecuels (PR or carbs) that are unique to the tumor
What suppresses many developing malignancies
An efficient immune system
Defects in the immune system increase the risk of what type of cnacer
Viral assocaited
What is antitumor immunity
Innate and adaptive responses that can contribute to tumor destrucution and elimiation
Can Tumors evade the immune system
Yes
What is Protumor immunity
Evidence that some immune responses can perpetuate tumor development (Chronic inflammation)
Innate cells invovled in Antitumor Immunity
MAcrophages (M1)
Neutrophils (N1)
Dendritic Cells
NK cells
What can innate antitumor cells recognize
DAMPS that may be upregulated during tumor growth
How do DAMPS forom tumors contribute to inflammation
Via IFN gamma, IL-12, TNF-alpha, ROIs, and RNIs
How are NK cells activated to a tumor
IFN gamma
What are Nateral Killer Cells biolgoically
Lymphoid cells that contain perforin and grnzymes
what do NK cells recognize
MHC I but are not ag specific
What is the ROll of NK cells in fighting off tumors
Important for removing virally-infected and tumor
cells
How to NK cells kill
Antibody binds antigen on the surface of target cells
Fc Receptors on NK cell recognizes bound antibody
Cross linking of Fc Receptors signals the NK cells to kill the target
Target cell dies by apoptosis
What drives the Th1 response to tumors
IFNgamma and IL-12
what lymphocytes are invovle in adaptive antitumor immunity
Cytotoxic T lymphocytes (CTLs)
What must be broken for a T cell to be invovled in ANtitumor immunity
A break in central tolerance in order for a T cell to be involved
Cells in Protumor Immunity
MAcrophages (M2) Dendritic CElls Regulatory T cells Th2 cells Myeloid-derived suppressors cells
Roll of Macrophages (M2) in protmor Immunity
PRomote Angiogenesis and invasiveness
Roll or Dendritic cells in Protumor Immunity
Suppress T cell functions
Problem with inflammation relation with cancer
an important factor in the development of cancer
what does Active inflammation do for cancer
Predisposes a person to cancer by stimulating a wound-healing reponse that includes proliferation and new blood vessel growth
Susceptible organs to get cancer from inflammation
GI tract, Pancrease
Thyroid gland
PRostate, urinary bladder
Pleura, skin
Anti-tumorigenic effect of Dendritic cell
Release Cytotoxic Cytokines
Antigen presentation to T cells
PRo-tumorigenic roll of Dendtriic Cells
Suppress T cell function
Promote tumor growth and progression
Anti-Tumorigeneic role of T cells
Directly lyse cancer cells
Release cytotoxic cytokines
Pro-tumorigenic roll of T cells
Release tumor promoting cytokines
Anti-tumorigenic Roll of Treg
Restor homeostasis to reduce chronic inflammaion
Pro-tumorigenic roll of Treg
Suppresses anticancer immune responses
Stimulate inflammatory cytokine producion
Anti-tumorigenic roll of macrophages
RElease cytotociv cytokines
Antigen presentation to T cells
PRo-tumorigenic roll of MAcrophages
PRomote Angiogeneisis, tumor proliferation, chemotaxis, invasiveness, and metastis
Anti-tumorigenic roll of Myeloid derviced suppressor cells (MDSC)
Limited
Pro-tumorigenic Roll of MDSC
Suppress T cell function
REcruit immunosuppressive immune cells
Anti-tumorigenic roll of NK cells
Relase Cytotociv cytokines
Directly Cytotocix to Cancer cells
Pro-tumorigenic roll of NK cells
Limited
Conventional Cancer treatmetns
Surgery
Chemo
Radiation
When is surgery not good for cancer treatment
NOt good for diffuse cancers
Problem with Chemo to treat cancer
Non-specific
How does Chemo fight cancer
TArgets rapidly growing cels, but can also damages normal cels too such as immune cells, GI and Hair
Benifit of Ratiation over Chemo
More target than Chemo
How does Radiation Work to fight cancer
Radioactive substances generate ROIs that can severely damage tumor DNA causign the cells to die
Why is Monoclonal Ab good to fight cancer
Advantageous due to specificity, but first need to find a specific target
what must be found to use Monoclonal Ab
Tumor specific or tumor-associated antigens
What is HErceptin (trastubzumab) used to treat
Breast cancer treatment for patients with tuomrs that overexpres HER2
What is HErceptin (trastuzumab)
A monoclonal Ab that binds to HER
How does Herceptin work
PRomotes NK cell mediated ADCC
INterferes with HER2-directed Signa that promote tumor growth
How to do adoptive T cell transfer therapy
Remove T cells from patient
–Isolate T cells taht recognize cancer or T cell can be genetrically engineered to recognize cancer cells
Clonally expand cancer-specific T cells
Infuse PAtient with Cancer specific T cells
Types of Adoptive T cell transfer therapies
TIL (Tumor Infiltrating Lymphocytes)
TCR (T cell receptor)
CAR (Chimeric Antigen Receptor)
What type of Adoptive T cell transfer is the most advances
CAR T cell therapy
What is the main side effect of CAR T-cell therapy
Cytokine relase syndrome in which a patient feels flu symptoms for 5-7 days
What is CAR T-cell therapy approved for
PEdiatric Acute lymphoblastic Leukemia (ALL) and for adult with advanced lymphoma
3 main causes of hypersensitivies
Reaction to Sself (autoimmunity)
Reaction against Micrboes
Reaction against Envirnomental Antigens
Other name for Type persensitivityI HY
Allergy, Atopy, immediate hypersensitivity
when does Type I hypersensitivity occur
within minute after reexposure to antigen/allergen
What is The Type I Hypersensitivity response
Rapid IgE and Mast cell mediated vascular and smooth muscle reaction that is often followed by inflammation
What determines what reactions may affect due to type I hypersensitivity
depending on the route of allergen entry
Commonness of Tyep I hypersensitivity
Most common disorder of the immune system of about 20% of the population
Typr I hypersesnsitivity General sequence of envents
- Initial exposure to antigen and production of IgE antibodies
- Binding of IgE ab to Fc receptors on mast cells
- Cross-linking of bound IgE upon reexposure to allergen
- Release of mast cell mediators
What is Sensitization
Intial exposute to antigen and production of IgE antibodies in Type I Hypersensitivty
What occuring in Sensitization
Antigen presention to Th2 cell or Tfh cell Antigen bound B cell and Il-4 and CD40L causes class switching to IgE
Release of Mediators from mast cells in Type I Hypersensitivity leads to what
A biphasic Response