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P12: Role of Immune System in fighting cancer - Coggle Diagram
P12: Role of Immune System in fighting cancer
Components of Immune System
Innate Immunity
: First line of defense
Non-specific, no immunological memory, immediate response.
Consists of cells and proteins that are readily available to fight microbes at the targeted site. (eg. Phagocytes, dendritic cells, NK cells, granulocytes)
Physical barrier (skin, mucosal membrane); Chemical barrier (IgA, mucus, digestive enzymes); Biological barrier (microflora).
Adaptive Immunity
: After subsequent exposure to antigens
Specific to antigen, delayed response, immunological memory after exposure
B and T cells involved --> Recognize specific antigens --> Launch stronger attacks after each exposure
Humoral response
: Involves secreted Antibodies (Antibody mediated response) --> Defend host via neutralization, opsonization, and complement system activation.
Cellular response
: APC present antigens to T cells --> release cytokines --> Activate immune cells
CD8 T cells will interact with MHC Class I
CD4 T cells will interact with MHC Class II
Cancer Destruction by Immune System
Dendritic cell & CD4 helper-T cell
Dendritic cells (APC) present tumor antigen on MHC Class II
Recognition of antigen presented on MHC Class II by CD4 Helper-T cells --> causes the release of cytokines (IL2- Interleukin-2)
Co-stimulatory molecules (B7 on DC, CD28 on T cell) --> Activates naive CD4 T cells --> releases interferon gamma to activate B cells (APC)
CD8 T cell Activation
Cytokines released by CD4 Helper-T cell --> Promotes proliferation & differentiation of cytotoxic T cells
Cytotoxic T lymphocyte (contain T cell receptors) --> recognize tumor antigen presented on MHC Class I
Cytotoxic T cells --> releases granzymes (induce apoptosis) & protein perforin (form pores by punching holes in target cell membrane)
Cytokine Therapy
is a form of
immunotherapy
. By understanding the mechanisms of action of cytokines such as IL2 & IFN-gamma, it enables me to better understand how cytokine therapy would work to fight cancer.
B cell Activation
After activation by CD4 Helper Tc --> B cells produces Ab
Ab binds to antigen presented on tumor cell surface --> signals NK to attack
Ab also triggers: Neutralization (Blocks glycoprotein of virus) , Opsonization (enhance phagocytosis), and activation of Complement system.
Immunoediting
Dynamic process consisting of immunosurveillance and tumor progression.
Made up of 3 phases:
Elimination
,
Equilibrium
,
Escape
Tumor cells are able to avoid tumor destruction via the 3 phases.
Elimination
: Eliminate the target tumor cells but not the entire tumor.
Equilibrium
: Acquire genetic mutation and does not express the tumor antigen --> will not be targeted by CD4/CD8 cells --> Tumor dormancy and editing occurs
Escape
: Tumor cells proliferate continuously and escape the detection by immune cells.
How does tumors escape immune recognition?
Immunoevasion
Repression of Antigen Presentation
Tumor cells disrupt Antigen presentation system --> Escape detection & destruction by immune cells --> Promotes tumor cell survival
Downregulation of MHC Class I --> antigen cannot be expressed --> disrupt antigen presentation
Repression of NKG2D ligand
Downregulate Natural Killer cell ligand (Rae1) that binds to NKG2D on NK cells --> Avoid detection by NK cells
Inactivate immune cells
Treg (CD4 Helper Tc) and cancer cell releases immunosuppressive cytokines (
IL-10
&
TGF-beta
) --> suppress naive T cell activation
Tregs express
CTLA-4
(co-inhibitory ligand) on their surface --> compete with T cells for B7 binding -->
downregulate B7 (CD80) expression
by APC --> Stop T cell activation --> Unable to destroy tumor cell.
Induced Immunocyte Apoptosis
Fas & FasL are death signals.
Tumor cells produce FasL and binds to Fas receptor on T cell's surface --> Tumor cells express FasL --> Induce apoptosis of T lymphocytes
Why immune system recognize cancer cells as foreign?
For the activation of the immune system.
Tumor Specific Antigen (TSA)
--> Antigen found ONLY on tumor cells. (eg. Hyperactive RAS protein, BCR-ABL oncoprotein)
Tumor Associated Antigen (TAA)
--> Antigens expressed on some healthy cells and excessively on tumor cells. (eg. HER2 receptors on breast cancer cells)
Monoclonal Antibodies
Aids in suppression of cancer
Monoclonal Ab can work alone or conjugate to cytotoxic agents --> destroy tumors
Specialized Ab can work with other components of immune system --> destroy tumors
"Naked Monoclonal Antibodies" (mAbs)
Able to block specific target on cancer cells
Targeted Ab --> A form of cancer immunotherapy --> causes disruptions to activity of cancer cells --> activate immune responses
Eg 1:
Blocks PD-L1/PD-1
enable T cells to kill tumor cells.
Eg 2:
Block co-inhibitory molecule CTLA-4
enable T cells to kill tumor cells.
Antibody-Drug conjugate (ADCs)
Antibody-Drug conjugate targets and bind to cancer cell --> delivers toxic drug --> kills cancer cells
Bispecific Antibodies (BiTEs)
Targets both cancer and immune cells.
Targets front end region of 2 different Ab --> Brings T cells into close proximity --> Allow elimination of cancer cells
Monoclonal antibodies
is form of
immunotherapy
. This allows me to explore the 3 different mechanisms and actions of monoclonal Ab that helps in the elimination of cancer cells as the monoclonal Ab can mimic the immune system's ability to eliminate antigens.