An immune response is the coordinated set of biological processes through which the immune system detects a substance or condition, activates appropriate defensive mechanisms, removes or controls the target and eventually regulates the response. Immune responses can be directed against infectious pathogens, foreign substances, abnormal cells or, inappropriately, the body's own tissues. They involve recognition receptors, signalling molecules, immune cells, antibodies, complement and changes in tissue physiology. Immune responses are commonly divided into innate and adaptive components.
Innate responses can begin rapidly and recognise broad patterns associated with pathogens or damage, while adaptive responses involve highly specific lymphocyte receptors and can generate immunological memory. The outcome is determined by the type of stimulus, its location, dose, persistence and the physiological context in which recognition occurs.
The first stage is detection. Innate immune cells possess pattern recognition receptors that identify pathogen associated molecular patterns or damage associated molecular patterns. Examples include microbial nucleic acids, components of bacterial cell walls and molecules released from damaged host cells. Recognition activates intracellular signalling pathways that can induce cytokines, chemokines, antimicrobial molecules and inflammatory mediators. Adaptive lymphocytes recognise specific antigens through B cell and T cell receptors.
B cells can recognise antigen structures directly through their receptors, while T cells generally recognise antigen derived peptides presented by major histocompatibility complex molecules. Recognition alone is not always sufficient for activation because regulatory and costimulatory signals help determine whether a response should proceed and what form it should take.
Innate immune responses can involve inflammation, complement activation, phagocytosis and natural killer cell activity. Phagocytes such as neutrophils and macrophages can engulf and destroy microorganisms or remove damaged material. Complement proteins can become activated through several pathways and can promote inflammation, opsonisation and membrane attack against susceptible organisms. Natural killer cells can identify certain infected or abnormal cells and induce their death. These mechanisms provide rapid defence while also influencing the subsequent adaptive response. Innate responses are generally less antigen specific than adaptive responses, but they are not random or nonspecific in the everyday sense. They use sophisticated receptor systems that recognise recurring molecular patterns and cellular states characteristic of infection or tissue damage.
Adaptive immune responses involve clonal selection and expansion of lymphocytes. A lymphocyte whose receptor recognises an appropriate antigen can receive activating signals and proliferate, generating many cells with related antigen specificity. B cells can differentiate into plasma cells that produce antibodies and memory B cells that support future responses. T cells can differentiate into helper, cytotoxic, regulatory and memory populations according to signals received during activation.
Helper T cells can support B cell maturation and coordinate immune responses, while cytotoxic T cells can kill infected or abnormal cells. Regulatory mechanisms limit activation and help prevent unnecessary tissue damage. Adaptive responses therefore combine specificity, amplification, differentiation and memory rather than simply switching immune activity on or off.
Immune responses require extensive cellular communication. Cytokines can alter immune cell activity, growth and differentiation, while chemokines guide cell migration toward tissues where immune activity is required. Antigen presenting cells communicate information about encountered antigens to T cells. Antibodies can connect antigen recognition with effector mechanisms such as phagocytosis and complement activation. Cell surface receptors determine how immune cells interact with each other and with infected or abnormal cells. This communication allows the response to be spatially organised. A local infection may initially produce a local inflammatory response, while severe or extensive stimulation can generate systemic effects such as fever and changes in blood cell production. The immune response is consequently a dynamic network of signals rather than a single biochemical event.
Termination and resolution are important components of an immune response. Once the threat has been controlled, inflammatory signalling can decrease, activated immune cells can undergo programmed cell death, regulatory pathways can become more prominent and tissue repair can proceed. Failure to terminate a response can contribute to chronic inflammation or tissue damage. Conversely, premature suppression can allow pathogens to persist. The balance is particularly important in infections where both the pathogen and immune response can contribute to disease. Some immune responses are protective even when they do not completely eliminate a pathogen because they can reduce pathogen replication or limit tissue damage. The final outcome therefore reflects interactions among pathogen biology, immune mechanisms and host tissue responses.
Immune responses can produce memory. After an initial adaptive response, some B and T cells become long lived memory cells, while some plasma cells persist and continue antibody secretion. Upon later exposure to the same or closely related antigen, these cells can respond more rapidly than naive lymphocytes. This principle underlies vaccination and explains why previous exposure can change the course of subsequent infection. Memory is not necessarily permanent or equally effective against all pathogens. Antigenic variation can reduce recognition, and the magnitude or quality of memory can change over time. The response to a repeated exposure can therefore be stronger, faster or qualitatively different without guaranteeing complete protection.
Immune responses can be beneficial, neutral, insufficient or harmful depending on context. A response that eliminates a pathogen while preserving tissue function is protective. An inadequate response can permit uncontrolled infection, while an excessive response can cause inflammatory tissue damage. Allergic responses involve inappropriate or exaggerated responses to otherwise harmless substances, and autoimmune responses involve recognition of self tissues under circumstances in which tolerance mechanisms fail. Transplant rejection involves immune recognition of foreign tissue. These examples show why immunology focuses on specificity and regulation as well as defence. An immune response is not synonymous with disease or inflammation, because it can occur without overt illness and can involve many mechanisms besides inflammation.
