27 Cancer Immunology I Flashcards
What are the PRIMARY organs of the immune system?
What is the FUNCTION of each organ?
BONE MARROW = immune cells BORN here
THYMUS = immune cells “educated” herex
Name the SECONDARY endocrine organs
Spleen
Lymph nodes
Tonsils
Peyer’s Patches
What is the general FUNCTION of secondary endocrine organs
Immune cells aggregate to provide PROTECTION
Stem cells give rise to what 2 immune cell LINEAGES
- Lymphoid lineage
2. Myeloid lineage
What cells make up the LYMPHOID lineage
- B + T lymphocytes
* NK cells
What cells make up the MYELOID lineage
All INNATE immune cells
- mφ (APC)
- Dendritic (APC)
Define INNATE immunity and its main FUNCTION
Exists BEFORE exposure to antigen
Digest + PRESENT ANTIGEN to develop adaptive immunity
Function of MACROPHAGES
- Digest + PRESENT antigens
* RECRUIT other immune cells
Function of DENDRITIC cells
Digest + PRESENT antigens
Function of NK cells
Detects diseased cells with NO MHC
MHC is down-regulated in cancer cells
Functions of Complement system
- Opsonisation of pathogens
* Kill pathogens (channel)
Function of MAST cells
Degranulation to release histamine, chemokines, cytokines
= INFLAMMATION
= RECRUIT other immune cells
Functions of neutrophils
- FIRST response cells
* RECRUIT other immune cells
What cells are in ADAPTIVE immunity
What are the FUNCTIONS of each cell type
B cells = make antibodies
T cells = KILLS cells presenting foreign antigens on MHCI/II
DIfference between MHC1 and MHC2?
MHC1 found on ALL cells
MHC2 found on APCs only
LIST the 4 phases of adaptive immunity
RAEH Recognition Activation Effector Homeostasis
What happens in the RECOGNITION phase
APCs process + present antigens on MHCI/II
What happens in the ACTIVATION phase
SELECTED lymphocytes that recognise the antigen undergo CLONAL EXPANSION and differentiate into:
- EFFECTOR cells
- MEMORY cells
For example, naive B cells can become what 2 cell types?
PLASMA (effector) = make antibodies
MEMORY B cells = adaptive immunity
What happens in the EFFECTOR phase
Lymphocytes ELIMINATE the antigen
What happens in the homeostasis phase
Immune system returns to BASAL STATE
Activated cells die by APOPTOSIS
When the T-cells are “EDUCATED” in the thymus, what types of T-cells are selected AGAINST
- WEAK/NO binding
* SELF-reactivity
2 types of mature T-lymphocytes
CD4 helper T-cells
CD8 cytotoxic T-cells
Functions of CD4 helper T-cells
- Recognise antigens presented by MHCII (APCs)
- Secrete cytokines + HELP other immune cells function
- Differentiate into many Th types
What 4 cell types do Th cells differentiate into?
What are their functions?
Th1 = activates cytotoxic-T to kill pathogens
Th2 = activates B cells (humoral adaptive immunity)
Th17
Treg = SUPPRESS immunity
Function of CD8 cytotoxic T-cells
Recognise antigens presented on MHCII (APCs)
How do APCs stimulate cytotoxic T-cells to kill pathogens?
Th cells recognise antigens on MHCII
Th matures into Th1 cells = activates cytotoxic T-cells
2 pathways by which cytotoxic T-cells cause APOPTOSIS?
Release granules with PERFORIN + GRANZYMES
Fas/death-R activation
Action of perforin?
Punch HOLE
= influx to cause ⬆️osmotic P = LYSIS
Define Immune surveillance theory
That the PRIMARY role of the immune system is to SURVEY for and eliminate TUMOR cells
List some pieces of EVIDENCE for immune surveillance
- Cancer patients have TUMOR-specific antibodies + cytotoxic T-cells
- Nearly 100% mice with NO adaptive immunity = CANCER
Name the 2 classes of tumor ANTIGENS
TSA = Tumor SPECIFIC antibodies TAA = Tumor ASSOCIATED antibodies
What is the difference between TSAs and TAAs
TSA = mutated protein ONLY found in tumor TAA = NORMAL protein OVEREXP in tumors
Give examples of TSAs and TAAs
TSA = mut-Ras, Bcr-Abl, mut-p53 TAA = RTKs, Erbb2
What is the DIFFICULTY surrounding TAAs
HARD to mount immune response to NORMAL SELF-proteins
2 types of immuneTx approaches
Define each
ACTIVE immunoTx = stimulate patient’s OWN immune system against tumor
ADOPTIVE immunoTx = transfer “designer” agents to patient
Example of ACTIVE immunoTx
Vaccines
Examples of ADOPTIVE immunoTx
Antibodies
LAK/TIL
In the 1990s, a new anti-cytokine COMBO therapy was found
What combination therapy was this?
LAK/TIL and anti-IL2
Why is it important to also inhibit IL2?
IL2 stimulates proliferation
Concept of cancer vaccines?
EXTRACT tumor cells to raise ANTIBODIES against their antigens
= ENHANCE tumor response
What is a main LIMITATION of cancer vaccines?
Does NOT address EVASIVE mechanisms
Name 2 types of cancer VACCINES
BiovaxID
Provenge
What type of cancer does BiovaxID target?
Personalised antibody vaccine for follicular Non-Hodgkins LYMPHOMA
How is the BiovaxID vaccine made?
Extract B-cells making antibodies against tumor antigens
FUSE with immortal cell = HYBRIDOMA
What is done to ENHANCE SPECIFICITY of the antibodies
Conjugate KLH = enhance specificity
What is provenge
Personalised DENDRITIC cell vaccine for PROSTATE cancer
What antigen is provenge raised against?
PAP = antigen on ALL prostate cancer cells
What is conjugated to PAP?
GM-CSF
Function of GM-CSF?
Promotes DENDRITIC maturation for enhanced Provenge function
Name 2 other stategies other than vaccines
- mRNA strategies
* Oncolytic viruses (oncoVEX)
How do mRNA strategies work?
mRNA profiling
= find MUTANOME
= personalised Tx
What are Oncolytic viruses (oncoVEX)?
Viruses that replicate + LYSE in cancer cells ONLY
What happens upon LYSIS of cancer cells?
Release antigens to APCs = trigger immune response
2 things we can use Oncolytic viruses to DELIVER?
- TOXINS delivered to cancer selectively
* GM-CSF delivered to induce APCs (enhance immune response)
