Immunology

Our immune system has diverse strategies to prevent infection. The functions of the immune system can be broadly divided into:

Innate immune system: responds rapidly to microbes, but does not alter significantly on repeat exposure. Important aspects of this are:

• phagocytosis, or engulfment of microbes by cells.
• triggering inflammation in response to microbes or tissue damage.
• releasing substances that limit microbial invasion and recruit immune cells.

Adaptive immune system: develops ‘memory’ to microbes, allowing subsequent immune responses to the same microbe to be faster and larger. This immunological memory can last a lifetime.

Important aspects of adaptive immunity are:

• cells with receptors that recognise specific microbial proteins.
• antibodies, which are soluble proteins that can bind a specific microbial protein.

Innate immune responses typically occur more rapidly than adaptive responses. The innate and adaptive immune systems have many interactions, and can involve some of the same cells and molecules.

The immune system involves many different types of cells working together. Many of these are ‘white blood cells’ that develop from blood stem cells in the bone marrow.

Our researchers are contributing to the understanding of how immune cells develop and function. In doing this, they have revealed many sub-types of these cells.

Important immune cells include:

Phagocytes

These are innate immune cells that can engulf (phagocytose) microbes or other particles. They are important in triggering inflammation, and some can alert adaptive immune cells to an infection. Important phagocytes include:

• dendritic cells
• neutrophils
• basophils
• macrophages

Lymphocytes

These cells include adaptive and innate immune components, with many functions in controlling, stimulating and executing immune responses. Long-lived memory lymphocytes are the source of lifelong immunity to certain infections.

The broad types of lymphocytes are:

• B cells, adaptive immune cells that produce antibodies that specifically bind other proteins, such as on the surface of a microbe.
• T cells, adaptive immune cells that are stimulated by dendritic cells or other phagocytes to become activated against a particular microbe.
• Natural killer cells, which can have innate or adaptive roles in eliminating infections, and also killing cancer cells.

There are many factors released by immune cells that are important for immune reactions. These include:

• cytokines, hormone-like signalling proteins that allow cells to communicate with each other via cytokine receptors on the cell surface.
• antibodies, a type of protein released by B cells. Each antibody can bind a specific protein, called the ‘antigen’, with different antigens recognised by different antibodies. This identifies the antigen as ‘foreign’. The binding of an antibody to a microbe can hamper the microbe’s growth and survival.

For good health, both innate and adaptive immune responses need to:

• start and conclude rapidly to minimise damage to the body’s own cells.
• only occur in situations of genuine danger, in response to an invading microbe. Immune responses to harmless substances or the body’s own tissues causes disease.

The immune system contains many safeguards that regulate its functions. Many strategies are used to prevent harmful immune responses. This includes systems for destroying or silencing potentially harmful cells that could attack the body’s own tissues.

Usually the immune system can distinguish our own tissues from invading microbes, and respond appropriately, killing the microbes or infected cells but not harming uninfected or otherwise healthy cells. Defective control of the immune response, leading to misdirected, excessive or inadequate immune responses, underly many immune disorders.

Inflammatory disorders occur when the immune system causes excessive inflammation that damages the body. This may be triggered by an infection, such as in rheumatic fever or occur for no known reason, such as in inflammatory bowel disease.

Autoimmunity is a type of inflammatory disorder that occurs when the immune system mistakenly attacks the body’s own tissues. These disorders are caused by lymphocytes or antibodies reacting to the body’s own tissues.

Significant autoimmune diseases include:

• lupus
• type 1 diabetes
• rheumatoid arthritis
• coeliac disease

Allergy occurs when the immune system over-reacts to harmless factors in our diet or environment.

Immunodeficiency is a weakened immune system. This causes a person to be infected by microbes more easily than a healthy person.

Occasionally an immune cell develops changes in its genetic material that allow it to grow uncontrollably, and become long-lived. This can lead to cancers of the immune system, such as:

• leukaemia
• lymphoma
• myeloma

The normal functioning of our immune system is vital to our health. Immune cells can also be harnessed to treat disease, a field called immunotherapy. Examples of immunotherapy include:

• vaccines expose the immune system to substances that closely resemble a particular microbe, allowing the safe development of adaptive immunity. This protects the body from infection when the microbe is later encountered.
• targeted therapy can use antibodies to specifically bind to disease-causing molecules or cells. Many targeted therapies for cancer are being developed that bind to specific proteins on the cancer cell’s surface. Another strategy is to target immune cell communication molecules (such as cytokines) to enhance or inhibit the strength of response to cancer or autoimmune diseases.
• immunosuppression turns off the function of immune cells. Most immunosuppressive medications have widespread effects on immune cells, and can perturb protective as well as harmful immune responses.
• preventive vaccines switch off a harmful immune response by providing signals to the immune system that a substance is not harmful. Our researchers have developed potential preventive vaccines that are in clinical trials for coeliac disease and type 1 diabetes.