The Immune System

It is our natural shield against external aggressions and the goal of immunotherapy against cancer. What is the immune system and how it works.

Our body has an efficient defense system against external agents: it is the immune system, formed by different types of cells with varying functions and circulating molecules that work together to recognize and eliminate external agents such as bacteria, parasites, fungi and viruses but also cells infected with pathogens or cancer cells.

Our immune system is naturally vigilant and ready to respond in case of emergency by taking all the necessary steps to protect the body and keep it in good health.

The immune system is composed of two lines of defense: non-specific or innate immunity and specific or adaptive immunity.

Non-specific or innate immunity, also called natural immunity, consists of mechanisms pre-existing the encounter with a disease-causing agent, it is able to act quickly against the external agent, recognized as a threat. It is present at birth and includes both biological barriers (the skin, the mucous membranes lining body parts that open to the external environment - such as mouth, nose and ears - and secretions such as saliva and sweat) and circulating proteins acting as regulators and mediators of the body's inflammatory response. When a harmful agent overcomes this first line of defense, the body reacts by producing cells and substances that respond to the attack and repair the induced damage.

Specific or adaptive immunity, also called acquired immunity, develops after birth, during the first year of life, and it is empowered and "educated" in response to the infections and foreign agents it encounters. As it is a tailored response of the body that is based on the type of foreign agent, specific or adaptive immunity is much faster and effective than innate immunity can be enhanced by vaccination and has mechanisms creating memory of the agents encountered and of the specific response established. It is a targeted defence against specific antigens, i.e. substances that our body recognizes as foreign.

The specific or adaptive immune response mechanism is based on the action of T and B lymphocytes.

T lymphocytes (T cells) mature in the thymus and circulate in the blood and lymphatic system, where they recognize all the cells of the body as “self” and do not attack them.

T cells activate when the receptors that are present on their surface recognize the antigens (foreign agents) that are specific for that receptor.

There are different types of T lymphocytes, the best-defined populations are T-helper cells and cytotoxic T cells.

In order to recognize the antigen, T-helper cells need to come into contact with other cells which “present” that particular antigen (dendritic cells, macrophages, B lymphocytes). Macrophages, the scavenger cells of our body: they engulf and digest foreign material and then display antigen fragments on their cell’s surface for recognition by T-helper cells, which in turn activate and produce substances called cytokines. Cytokines assist other T-cell types in eliminating the foreign cells that invaded our body (cytotoxic activity).

B lymphocytes (B cells) mature in the bone marrow and tend to localize in lymph nodes, small organs that are found at different sites of the human body. For B-cell activation, too, contact with an antigen is required. Following antigen stimulation, B cells proliferate to form a progeny of identical cells called clones. A part of these clones activates into plasma cells that are responsible for the generation of specific antibodies against a given invader. The remaining part of these clones has a memory function and is essential to fend off future attacks from the same antigen in a quicker and more targeted manner.

Therefore, an efficient immune system has the ability to protect the body against attacks. Tumor cells have different characteristics compared to those of the counterpart made up of healthy cells of our body. Tumor cells present, thus, antigens and as such they are potentially capable of activating a response from an efficient immune system.

The body’s ability to recognize and destroy tumor cells is reduced when a state of immunodepression is present.

In spite of the reaction of our defense system, tumor cells can develop mechanisms through which they bypass the immune system’s control. After an initial phase, during which the immune response is able to fight and destroy the majority of tumor cells, surviving tumor cells mutate and become resistant to the immune system’s control. Usually, this is a long process which may take place over several years. Mutated tumor cells “cheat” the immune system, and since they can act virtually undisturbed, they spread uncontrollably and generate clinically detectable and diagnosable tumors.