What is the most abundant white cell in the blood?
What is the primary function of the neutrophil?
Destruction of tumor cells and pathogens
What is the difference between a macrophage and a monocyte?
A macrophage is a matured monocyte that has penetrated into the tissue
What are characteristics of NK cells?
These are activated by encounter with infected cells or tumor cells, kill target cells and secrete INF gamma
What are the two subsets of T-cells?
CD4+ and CD8+
CD4 T-cells are known as what?
CD8 T-cells are known as what?
Why can inflammation be referred to as a double edged sword?
Inflammation is required for tumor formation and destruction, but can contribute to tumorgenesis
What are the characteristics of acute inflammation?
Happens within minutes, vasodilation and leads to recruitment of neutrophils
What are the characteristics of chronic inflammation?
Fibrosis, angiogenesis, tissue remodeling Also leads to the recruitment of macrophages and lymphocytes
What is the process by which asbestos can lead to mesothelioma?
Small fibers of asbestos can be inhaled, and these are phagocytosed by macrophages and induce chronic inflammation. This then leads to activation of fibroblasts that cause fibrosis. Asbestos cannot be destroyed so the inflammation continues
How do T cells recognize tumor cells?
T-cells recognize antigen via the TCR (T cell receptor).
What is an antigen?
A peptide derived from degraded protein
How is an antigen presented to the T-cell?
Via the major histocompatability complex (MHC).
MHC I is expressed by what cells and presented to what cells?
Most nucleated cells and are presented to CD8+ T-cells
MHC II is expressed by what cells and presented to what cells?
MHC is expressed by professional antigen presenting cells (APCs - macrophages, dendritic and B cells) and are presented to CD4+ T cells
Tumor cells tend to express which type of MHC?
Stimulation through the TCR alone leads to what?
Anaergy - a state of unresponsiveness
T cell activation requires what?
TCR and co-receptor signaling leading to activation and differentiation
NK cells are regulated by what?
Activating receptors and inhibitory receptors
Is the activating or inhibitory signal dominant to NK cells?
Inhibitory signal is dominant
Loss of MHC-1 on a target cell has what effect on NK cells?
Loss of MHC-1 leads to release of inhibitory signal and permits MK cell activation
Explain elimination vs equilibrium
Elimination - CD8 T cells and NK cells eliminate tumor cells
Equilibrium - When lymphocytes can no longer destroy the tumor, there is a prolonged period in which tumors remain but do not grow
The balance between CD8 T cells and NK cells is mediated by what?
MHC class I
Tumor cells often down what?
MHC class I
How do CD4+ cells regulate T cells?
High levels of expression of FoxP3 and CD25 which suppresses that activity of T cells, macrophages, and other immune cells
What is T cell exhaustion?
Repeated stimulation of T cells that eventually results in anaergy
What is the role of CTLA-4?
It binds B7-1/2 and blocks co-stimulation by CD28.
Anti-CTLA4 (ipilimumab) does what?
Blocks CTLA-4 activity allowing for co-stimulation through CD28.
What is PD-1?
It is the inhibitory co-receptor on T cells. It binds to PD-L1/2.