Innate Immunity

Dr. Catanzaro posted and edited
Written By: Preeti Gokal Kochar

As noted in the previous post, the immune system can be divided into two branches; innate and adaptive, both are involved in fighting cancer.  In this post, the focus will be on the innate branch of the immune system.

Innate immunity is the first line of defense against infectious agents and consists of natural anatomical barriers, such as skin and mucous membranes, physiological barriers like elevation of temperature and acid in the stomach to digest harmful bacteria.  It provides immediate and non-specific defense against infectious organisms.

First characteristic of innate immunity:

It contains phagocytic cells that identifies common features of infectious agents and responds by engulfing bacterial and damaged cells. Phagocytic cells, namely, natural killer cells, dendritic cells and macrophages are the components of the innate immune system most directly involved in tumor immunology.

Second characteristic of innate immunity:

It contains a group of inactive proteins, also known as the complement system, in the blood that is activated in the presence of pathogens and cause cell lysis (cell destruction).  Tumor cells have complement regulatory proteins on their cell surface – proteins that inhibit the activation of complement- and thus escape complement-mediated lysis.

Pattern-recognition receptors, present on the cell surface, and antimicrobial proteins present inside cells, are part of the innate immunity and both target pathogenic bacteria.  

The cells of the innate branch have specific roles: 

(1) Natural Killer (NK) Cells
Target cells for NK cells include virally-infected cells and tumor cells.  NK cells don’t require a previous encounter in order to kill tumor cells. These cells have killer activating receptors and cause lysis of target cells using specialized enzymes, perforin and granzymes. Killer inhibitory receptors are also present on the NK cell surface, which prevent lysis of cells with MHC molecules.

 (2) Dendritic Cells (DCs)
Using their pattern-recognition receptors (e.g. toll-like receptors) they detect bacteria and viruses. When encountered, the pathogens are phagocytosed and their proteins are processed and inserted into the DC surface to be presented to T cells. Dendritic cells are professional antigen-presenting cells (APC). They activate helper T cells and Cytotoxic T cells and also activate B cells. They are the first line of defense, because they are found in tissue, i.e. skin, mucosal and respiratory membranes. In the blood, DCs are found in the immature state. 

(3) Macrophages
Macrophages have granules filled with digestive enzymes making it possible for them to fight bacteria and also ingest damaged cells by phagocytosis. In addition to being strongly phagocytic, they present antigens to T cells and thus have a role in adaptive immunity. Macrophages can destroy tumor cells and play a crucial role in the inflammatory response. They are derived from monocytes and have several different names (e.g. Kupffer's cells, histiocytes, alveolar macrophages) depending on the tissue in which tissue they are found.

Cancer Vaccines

Engaging the Cancer Fight

Engaging the cancer fight is not a simple process as it involves genetic, biological, metabolic and biochemical controls. Traditional therapies offer little hope in eradicating cancer, thereby, requiring a more specific defense. Cancer cells are cells that have acquired a “bad” DNA message. The DNA damaged cells mutate and produce offspring that are more aggressive and invasive. The immune system is designed to detect foreign invaders and defend against them. However, one of the complications in cancer is that the cells that have acquired a “bad” DNA message and have been damaged are not easily recognized and evaded by the immune system. These wayward destructive cells then become tolerated by the immune system and have freedom to go anywhere they wish.

The Two Important Platforms of Cancer Research

It becomes necessary to engage defense on two main platforms. The first is detection of cells with the “bad” DNA message and second recruiting all of the active defense cells and the necessary immune mechanisms that initiate eradication of the cell with the “bad” (cancer cell) message. DNA is the genetic matrix material of every living cell. DNA is known as the “double helix” and replicates in a uniform regulated fashion. When DNA is damaged it becomes overexpressed and the checkpoints in replication are altered causing the continuous replication of single-strand DNA. This damage to DNA is caused by mutations, which impairs the cells normal signaling balance. DNA then continues to replicate in the nucleus of the harmed cell and impairs every function of the cell. Additionally, the harmed cell’s life and replication cycles are overexpressed and each offspring produced from the original harmed cell can express the same mutation as well as additional mutations making it virtually impossible to respond to one type of treatment approach. Therefore, it becomes essential to re-think the development of cancer treatment making it necessary to address different cancer types with their set mutations specifically.

As noted above DNA damage detection and discovery of repair mechanisms are of primary importance. When DNA replication and regulatory communication checkpoints are distorted or impaired there are numerous specific proteins altered. Research and discovery of these regulatory proteins of DNA is vital importance. The figures below demonstrate DNA damage and its consequences on cell health and development.