Immunology Adoptive Cellular Immunotherapy Flashcards
[…]
D
[…]
E
First gen only CD3 (no costim)
Second gen includes CD3 and CD28 (1 costim)
Third gen includes CD3, CD28 and CD137 (2 costim)
[…]
A&D
Not C!
C
[…]
D
Keyword is NOT
3 ways NK can effect its function?
3 ways NK can effect its function?
1) CDC (Cell mediated direct cytotoxicity)
2) ADCC (Ab Dependant Cellular Cytotoxicity)
3) **Cytokine-mediated function **
5 ways a tumour may escape immunity?
5 ways a tumour may escape immunity?
- Loss of tumour specific antigens
- Loss or reduced expression of MHC class I
- Secretion of immunosuppressive factors (e.g. TGF β) from the tumour
- Expression of inhibitory cell surface proteins eg CTLA-4, PD-L1
- Promote other cellular suppressors of immune responses, such as regulatory T cells
Concept of adoptive cellular immunotherapy?
Concept of adoptive cellular immunotherapy?
1) Collect immune cells from a patient and grow in the lab
2) put back the cultured immune cells into the patient to help immune system fight disease
How are NK cells involved in a tumor-antigen-specific antibody therapy?
Tumour antigen specific (TAS) antibodies bind to the […] on the tumour cell surface. A NK cell expresses […], which are mostly CD16. These receptors recognize, and bind to, the […], which has bound to the surface of a tumour cell. Once the Fc receptor binds to the Fc region of an antibody, the NK cells releases […] that induce the death of the tumour cell.
This process is called […]. Therefore, NK cell adoptive therapy can be combined with TAS antibody therapy to achieve better efficacy
How are NK cells involved in a tumor-antigen-specific antibody therapy?
Tumour antigen specific (TAS) antibodies bind to the tumour antigens on the tumour cell surface. A NK cell expresses Fc receptors, which are mostly CD16. These receptors recognize, and bind to, the Fc portion of an antibody, which has bound to the surface of a tumour cell. Once the Fc receptor binds to the Fc region of an antibody, the NK cells releases cytotoxic granules that induce the death of the tumour cell.
This process is called antibody dependent cell-mediated cytotoxicity. Therefore, NK cell adoptive therapy can be combined with TAS antibody therapy to achieve better efficacy
How can tumour cells inhibit immune response?
How can tumour cells inhibit immune response?
via expressing CTLA-4 and PD-L1. And also production of immunosuppressive cytokines such as TGF-B
PD-L1 is on tumour cells!! PD-1 Is on T cells.
Rmb this card? This card is evade immune response, this question is inhibit immune response.
- Loss of tumour specific antigens
- Loss or reduced expression of MHC class I
- Secretion of immunosuppressive factors (e.g. TGF β) from the tumour
- Expression of inhibitory cell surface proteins eg CTLA-4, PD-L1
- Promote other cellular suppressors of immune responses, such as regulatory T cells
How can tumour evade the immune response?
How can tumour evade the immune response?
- Loss of tumour specific antigens
- Loss or reduced expression of MHC class I
- Secretion of immunosuppressive factors (e.g. TGF β) from the tumour
- Expression of inhibitory cell surface proteins eg CTLA-4, PD-L1
- Promote other cellular suppressors of immune responses, such as regulatory T cells
How does NK cell differentiate tumour cells from healthy cells?
How does NK cell differentiate tumour cells from healthy cells?
MHC I on healthy cells stimulate negative signal in NK cell –> inhibits cell killing
Altered/reduced/absent MHC I on tumour cells unable to stimulate sufficient negative signal in NK cell –> tumour cell killing and apoptosis
“Healthy cells shows alot of “Please no” (MHC I) to passing by NK cells”
“Tumour cells act smart show different/less MHC I (some dont even show bro LOL) to avoid adoptive immunity police but that also means less “please no”s”
rly #不作死就不会死
How does NK cytokine mediated function work?
How does NK cytokine mediated function work?
Dc cell produce IL-12-> activate NKC-> produce IFN-y-> cause the macrophage to kill the phagocytosed microbes
Presence of CD56+ can be used to identify what cell used for ACI?
Presence of CD56+ can be used to identify what cell used for ACI?
NK cells!
Principle cell involved in using ACI (adoptive cellular immunotherapy) for tumours?
Principle cell involved in using ACI (adoptive cellular immunotherapy) for tumours?
CD8 cells
Process of CTL killing of tumour cell (IMPT!!!)
Process of CTL killing of tumour cell (IMPT!!!)
Phagocytosed tumour antigen
Presentation of antigen to tumour antigen-specific CD8+ T Cell
Migration of tumor-specific CTL to tumor
CTL killing of tumor cell (Degranulation, perforin, granzyme B, granulysin, caspases, apoptosis/FasL mediated apoptosis)
Strategies of adoptive cancer immunotherapy?
Strategies of adoptive cancer immunotherapy?
1) Host immune response to tumour antigens can be enhanced by immunizing with tumour antigen-pulsed DC as cancer vaccines
2) passive immunity to tumours can be induced by adoptive infusions of NK cells or T cells expressing tumour-sepcific antigen receptors through isolation, specific expansion or gene modification.
Includes TIL, TCR and CAR T cell therapy
What are CARs?
What are CARs?
CARs (Chimeric Antigen Receptors) are synthetic proteins with two components:
an extracellular antigen-recognizing domain, composed of fragments of monoclonal AB recognizing a specific protein on the surface of malignant cells (e.g CD19), and
an intracellular activation domain that ensures TCR signalling necessary to activate the effector function of the CAR T-Cell
First gen only CD3 (no costim)
Second gen CD3 + CD28 (1 costim)
Third gen CD3 + CD28 + CD137 (2 costim)
What are some strategies of adoptive cancer immunotherapy? (IMPT!!)
What are some strategies of adoptive cancer immunotherapy? (IMPT!!)
1) Tumor-infiltrating lymphocytes (TIL)
2) TCR Therapy
3) CAR-T Cell Therapy
*CAR = Chimeric Antigen Receptor *
What is ADCC? Briefly describe the process.
What is ADCC? Briefly describe the process.
Antibody Dependent Cell-mediated/cellular** C**ytotoxcity
1) Ab binds to antigen on target cell surface
2) Fc receptors on NK cells recognize AB
3) Crosslinking of Fc receptors signals the NK cell to kill target cell
4) Cell dies by apoptosis
