What are the 3 main types of T cells in the innate immune system?
- Helper (TH)
- Regulatory (Treg)
- Cytotoxic (TC)
What are the 3 main components of the innate (cellular) immune system?
- Antigen-presenting cells (dendritic cells, macrophages)
- Cytotoxic cells (NK cells, macrophages)
- Proteins (complement system)
How do Treg cells help to regulate the adaptive immune system?
By inhibiting TH and TC cells.
What 2 processes are stimulated by TH cells?
- Proliferation of plasma cells (B cells and other humoral immune cells)
- Killing of target cells by TC cells
What does HIF stand for (as in HIF1 & HIF2)?
What type of cell differentiates to become a tumour-associated macrophage (TAM)?
What are the most abundant immune cells involved in tumour development?
How do TAMs initially respond to the levels of hypoxia found in tumours?
By upregulating transcription factors, including HIF1 & HIF2, that in turn activate genes that promote tumour growth and proliferation.
What are the 4 main types of genes activated by transcription factors upregulated in macrophages in response to hypoxia in tumours?
- Mitogenic genes
- Proinvasive genes
- Proangiogenic genes
- Prometastatic genes
What are the 2 main molecules recognized by anti-tumour macrophages as part of normal innate immunity?
- Lipopolysaccharide (LPS)
- Interferon-γ (INF-γ)
What is the main function of anti-tumour macrophages (MACs) in the normal innate immune response?
To recognize LPS or INF-γ as a marker of foreign or abnormal material and to phagocytize an infectious pathogen or tumour cell once recognized.
What type of macrophage responds to LPS or INF-γ?
Anti-tumour macrophages (MACs).
What type of macrophage responds to hypoxia with an area of rapid tissue growth?
Tumour-associated macrophages (TAMs).
Why does hypoxia trigger an innate immune response by TAMs?
TAMs recognize the hypoxic tissue as a wound site and are attracted to it in order to fix the wound.
What is interleukin-10 (IL-10)?
A proangiogenic cytokine, released by TAMs in areas of hypoxia, that stimulates HIF1α and VEGF to promote angiogenesis.
What is the combined effect of TAM cytokines, such as IL-10, and glucocorticoids in a tumour microenvironment?
The cytokines are anti-inflammatory and the combination is immunosuppressive, resulting in lympocyte levels that are too low to resolve the invasion of tumour cells.
What are the effects of IL-6 and TGF-α released by TAMs in a tumour microenvironment?
They promote growth, division, and proliferation of cancer cells.
How do MACs attack unusual cells that may become cancerous?
By releasing TNF-α at low local levels, which induces apoptosis in target cells.
What is the effect of TNF-α released locally by MACs in a tumour microenvironment?
It induces apoptosis in cancer cells.
Which 3 metalloproteases are released by MACs to help phagocytize unusual, potentially cancerous cells?
Why is the release of ROS by TAMs more dangerous than the release of ROS by MACs?
MACs release relatively low levels of ROS that are easily managed by antioxidant enzymes and vitamins; TAMs release much higher levels that are
What is tissue factor?
A small protein that attracts wound-healing TAMs into a tumour microenvironment.
What 2 classes of molecules recruit TAMs to a tumour microenvironment?
- Tissue factor
What is the role of metalloproteases released by TAMs in a tumour microenvironment?
What types of pathways are stimulated by cytokines released by TAMs in a tumour microenvironment?
Mitogenic/growth factor pathways.
What is the estimated number of antigens that T and B cells could theoretically recognize, given their diversification by DNA rearrangement?
What are T-cell receptors (TCRs)?
Antibody-like molecules developed on the surface of cytoxic T (TC) cells that display an antigen-like recognition for a specific pathogen and allow the TC cell to recognize and bind target cells for removal.
What happens to Langerhans cells once they have taken up antigens?
They migrate to the lymphatic system and enter the lymph node to mature into dendritic cells, where they expose their found antigens to T cells.
What are MHC class II receptors?
Intracellular receptors in antigen-presenting cells that move oligopeptides from phagocytized foreign bodies to the cell surface.