2. First responders: the innate immune response

How does the immune system know when to respond? ‘First responders: the innate immune response’ considers this fundamental question that is central to understanding both normal (e.g. to infections) and abnormal (e.g. in auto-immune diseases) responses; and designing vaccines and new therapies in cancer and infectious diseases. It looks at how ‘danger’ is sensed by the immune system through pathogen-associated molecular patterns and damage-associated molecular patterns. Having been alerted, it is important that rapid action is taken to limit the spread of a pathogen. A number of responses can be initiated immediately, forming a critical part of our innate immunity, which are followed by the acute phase response.

7. The immune system v2.0: biological and immune therapies

This VSI examines the basic building blocks of the immune system, how they work as a team, and what happens when the teamwork breaks down. Researchers apply this basic knowledge working to influence outcomes of disease—immunologically and otherwise. ‘The immune system v2.0: biological and immune therapies’ considers three major inter-related areas where our knowledge of immunology is being applied to current challenges: boosting immunity in the case of vaccines, harnessing immunity for cancer treatment, and developing novel treatments for blocking immunity and auto-immunity. It also looks at the ageing immune response and how it may be corrected to treat or prevent disease.

4. Making memories

The ability of the immune system to sense pathogens and how they can be targeted specifically needs to be tightly coordinated in space and over time. ‘Making memories’ considers how the immune response develops following exposure to a virus. To make effective memory, the immune response needs to be induced correctly or ‘primed’ during the initial stages of an infection. The first step is for the immune system to develop a response relating to the activation of the innate immune system. Without this, the adaptive response is often subsequently overwhelmed. The mechanics of memory formation and how this is then harnessed in current vaccines are described.

3. Adaptive immunity: a voyage of (non-)self-discovery

How does the immune system respond to such diverse threats, including viruses never encountered previously by us as a species? The inherent diversity in the immune system can be explained by examining how the adaptive immune system is built, in particular the receptors on B and T lymphocytes. ‘The adaptive immune system: a voyage of (non-)self-discovery’ describes B and T cells, receptors, and the creation of antibodies. Antibody genes are not created as a single unit but are made up from smaller parts, generating many more possible combinations. The antibodies that are created from the genetic template are further honed, becoming highly specific to their target.

6. Too much immunity: auto-immunity and allergic diseases

Given the capacity to cause tissue damage and inflammation, every immune response must be appropriately and specifically tuned. Failure to tune appropriately leads to a range of immunologically driven diseases that, given the general improvements in health status and many major infections in Western populations, have taken on increasing significance. ‘Too much immunity: auto-immunity and allergic diseases’ considers how the immune system acts to turn off unwanted responses, and what goes wrong when this fails. This includes looking at classical auto-immune diseases, other diseases where there is excessive inflammation, and allergic diseases where there is an exaggerated response to harmless antigens, dominated by a particular style of immunity.

1. What is the immune system?

The immune system resists threats from outside as well as from within the body. ‘What is the immune system?’ considers the basic mechanisms of immunity and describes the specific structures in the immune system where more complex activities take place. The critical cells—‘white blood cells’ or leukocytes—are generated in the bone marrow. Leukocytes are highly diverse, each with its own specialist function, but broadly divided into the myeloid (develops in the marrow) and the lymphoid (develops in lymphoid structures including the thymus, lymph nodes, and spleen) leukocyte. We have both ‘innate’ (which we are born with) and ‘adaptive’ (which encompasses learned, very specific responses to individual infections) immunity.

5. Too little immunity: immunological failure

The immune system is continuously active, preventing severe infection from the micro-organisms that colonize our skin and our gut, and suppressing the chronic virus infections most of us picked up as infants. In certain individuals, or under certain conditions, the immune response may, however, fail and this can lead to severe disease—the exact disease depends on the precise mechanism of the failure. ‘Too little immunity: immunological failure’ examines how such failures may occur, specifically through genetic changes, such as redundancy and polymorphisms, and through HIV infection and AIDS. It also considers what we may learn from them about the working of the normal immune system.