Cell-mediated Immunotherapy

Immunotherapy Treatment

The immune response is the one that helps the body react against foreign invasions by recognizing “non self” elements, such as proteins, viruses, bacteria, fungi, parasites or foreign cells (in the case of bone marrow or organ transplantation), and tries to neutralize or reject them.

When most of us think about immunity, we usually think about recovering from an infection or receiving a vaccine. So how can cell-mediated immunotherapy be used against so many different diseases caused by infective agents and cancers?

How Does Immunity Work?

There are two supplementary types of immunity that form the immune system: innate immunity and adaptive immunity. The first corresponds to immediate barriers against invading pathogens. These defense mechanisms are generic rather than specific: that is, they act in the same way regardless of the invader that is being dealt with. The innate immune system activates genes that induce the secretion of different molecules that can react against viruses, such as cytokines or interferons. The innate immune system also includes natural killer (NK) cells that can directly attack invaders like viruses or cancer cells.

Adaptive immunity, on the other hand, is an immune response that develops after several days after the initial invasion. Initially, other cells like dendritic cells, antigen presenting cells, or macrophages, process the antigens of the targeted foreign element, then and present smaller pieces of the larger molecules to T cells. Each T cell can see only a smaller part of the entire protein molecule named peptide. Then, each T cell starts dividing to create more of the same and together, all T cells each stimulated by another peptide create a response against the entire element. 

This process recruits and activates a large number of antigen-specific lymphocytes called helper T cells. They educate another type of lymphocytes called B-cells. These can be differentiated into plasma cells, which produce specific antibodies that will target the foreign invader.  In parallel, helper T cells also educate another type of T cell known as “killer cells” which can attack and kill the invader by direct attack. 

Therefore, there is a two-pronged fight against anything foreign: a cell-mediated one done by T cells, and a soluble attack by antibodies. The adaptive immune system doesn’t simply fight against an antigen – it is also tasked with “remembering” what worked before in order to ensure a faster response if the same antigen is ever encountered again. This is mediated by another type of T cells called memory T cells.

To sum up,  the immune system protects us against anything that could be harmful, through a sophisticated coordination effort between different types of cells that provide immediate, long-term and future protection against dangerous invaders and infective agents. 

The key types of cells that act in the immediate or innate immune system are NK cells and macrophages. Neutrophils, a type of blood cells, also play a role: these represent the first defense line against invading bacteria, and they kill bacteria directly, independently of T cells or antibodies. The cells responsible for reacting against invaders and infectious agents include dendritic cells responsible for education of helper T cells, killer T cells and memory T cells. These all respond and act together against all peptides to induce an effective immune response.   

Types of Immune System Cells

The key types of cells that act in the immune system are T-cells, B-cells, and dendritic cells. 

Dendritic Cells

These are the cells that are called antigen presenting cells and they process invaded antigens and presents the final product to helper cells. Helper T cells will educate B cells to produce specific antibodies against that antigen and educate cytotoxic T cells to attack and kill the invader that can be recognized by these antigens. 

Macrophages

These are the cells that process invaded particles and infective agents, and they can also help dendritic cells to present antigens to helper T cells. Some subsets of macrophages can also migrate to cancer metastases and protect the malignant cells by suppression of the immune system.

T-cells

T-cells are part of the white blood cells that originate from multipotent stem cells and are educated to become T cells in the thymus and then released into the circulation. They are present in the lymph nodes and in the spleen and circulate in the blood. There are several types of T-cells and they belong to the so-called adaptive immune system:

  • CD4 helper T cells: these are the first to recognize the special features of any foreign invaders that circulate in the blood or penetrate the body or as soon as any element modifies a patient’s normal cells, now being recognized as “non-self” or (modified self”.
  • CD8 “Killer” T cells: these have T cells that can attack and kill invading viruses or any target different from normal self.
  • Memory T-cells: These are T cells that store the information for production of specific antibodies and immune reaction against the same antigens encountered previously when the primary response occurred. Memory T cells are responsible for the so-called secondary immune response and as such, they react very fast and produce an effective immune response by activated T cells and by production of antibodies like the ones produced initially but much faster and reaching higher titers. Therefore, these are the cells responsible for protective long-lasting immunity.
  • Regulatory T cells: These are other kind of T cells that suppress the function of the immune system. Under normal circumstances they regulate the immune system to prevent over-reaction. In the case of autoimmune diseases, they can help minimize the reaction of the immune system against patients’ tissues or organs. In the case of cancer, they are the “bad T cells” because they suppress the ability of helper and killer T cells to react against a patient’s cancer. Therefore, one of the first important steps for application of anti- cancer immunotherapy is to suppress the bad suppressor cells, in order to free the good T cells to start reacting against cancer. 

B-cells

B cells are also lymphocytes that have the ability to differentiate into plasma cells and secrete specific antibodies against foreign antigens as per the instruction of antigen-specific T cells.

Natural Killer Cells

Also known as NK cells belonging to the innate immune system and they can kill viruses or foreign invaders directly with no need to get help from T cells.

Natural Killer T Cells

Also known as NKT cells and they share properties with NK cells and T cells. Some subtypes of NKT cells induce anti-cancer effects and some can regulate and control the immune system.

Each cell type includes a number of variable cell types that can be located in different locations and can have different functions but detailed analysis of all types of cells involved in the complex immune system is beyond the scope of this website.

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