Immunology is the study of the complex biological system called the immune system, which serves to recognize and tolerate whatever belongs to the host organism, and recognize and reject infectious agents (viruses, bacteria, fungi and parasites), cancer cells, and toxins. The host possesses three strategies to manage infectious agents: avoidance, resistance, and tolerance. Avoidance prevents exposure to the microbes. Resistance eliminates pathogens in the case of infection. Tolerance enhances tissue resilience to resist microbe-induced damage. Generally, immune protection is enabled through the synergistic actions of the adaptive immune system and its counter-partner, innate immunity. In this topic, we will discuss how exactly the immune system enables multicellular organisms to maintain homeostasis.
History of immunology
The notion of immunity (from latin "immunitas" — liberation) — that surviving a disease gives one better protection against it later — was an empirical observation for a long time. The first written evidence of variolation (transfer of smallpox pustules to a healthy individual via inhalation or skin transfer) appears in ancient China, and this practice later spread to the Middle East and Europe.
The emergence of immunology as science is attributed to the experiments of E. Jenner in England in the late 18th century. He observed that exposing a person to a mild version of pox from cows (vaccinia) protected them against smallpox, which was a severe and often fatal disease in humans. The process was named vaccination, and that term is still used to describe the inoculation of healthy individuals with weakened infectious agents to protect from disease.
To name just a few major contributions to the field: R. Koch and L. Pasteur proved that infections are caused by specific microorganisms; E. von Behring and S. Kisato discovered that serum of animals immune to diphtheria and tetanus posses an "antitoxic" activity that can protect people from those diseases (later discovered to be antibody activity); E. Metchnikoff discovered that microorganisms can be engulfed and digested by specific phagocytic cells, named macrophages; and P. Ehrlich, who identified white blood cells as effector cells of immunity and introduced the term "antibody."
Immune system
The immune system has two major lines of defense: the innate and adaptive immune responses, which functionally complement each other. They differ in their pathogen recognition systems, mediators, effector cells, response times, and ability to generate immunological memory. Innate immunity majorly relies on the work of phagocytes: these cells do not require intercellular communication to provide an immune response and are distributed throughout the barrier tissues such as skin, oral mucosa, respiratory epithelium, and intestinal mucosa. In contrast, adaptive immunity requires constant dialogue between different types of lymphoid cells that travel through the blood and interact with each other in the lymphoid organs, including the bone marrow, spleen, thymus, and lymph nodes.
Most cells of the immune system develop and mature in the bone marrow, a semi-solid tissue located within the spongy portions of bones. Bone marrow is primarily found in the ribs, vertebrae, sternum, and bones of the pelvis. It is a hub for hematopoietic stem cells (HSCs) — multipotent cells that can develop into all types of blood cells, including myeloid-lineage and lymphoid-lineage cells (pic.1), which are key players in the innate and adaptive immune responses, respectively. Myeloid progenitors are the precursors for macrophages, granulocytes (collective name for neutrophils, eosinophils, and basophils), mast cells, and dendritic cells. Lymphoid progenitors in the bone marrow develop into natural killer (NK) cells and T and B lymphocytes. There are some cells in the body that provide immune functions but develop outside the bone marrow as self-renewing populations; for example, microglia of the central nervous system.
Apart from bone marrow, another primary lymphoid organ is the thymus. Immature precursors of T lymphocytes migrate from the bone marrow to the thymus where they undergo maturation and differentiation. The secondary lymphoid organs include: lymph nodes, spleen, mucosal lymphoid tissues of the gut, nasal and respiratory tract and other mucosa. Communication between primary and secondary lymphoid organs is mediated through the specialized system of lymphatic vessels, as well as blood vessels.
Innate immunity
Innate immunity is the first immunological response that occurs and is intrinsic for all metazoan organisms. It is initiated when the anatomical and chemical barriers of the immune system are evaded. The innate immune response is preprogrammed to react to broad categories of target pathogens that share common structures, so called pathogen-associated molecular patterns (PAMPs). Immune cells recognize these using their pattern recognition receptors (PRRs). Lipopolysaccharides and double-stranded RNA produced during viral infection are common examples of PAMPs.
Stages of innate immune response include:
- Recognition of foreign agents.
- Rapid recruitment of immune cells to the infection sites by producing chemical factors (cytokines and chemokines).
- Activation of complement system (biochemical cascade, identifying and coating pathogenic agent).
- Prepare pathogen for phagocytosis (engulfing and killing microbes by phagocytic cells) and lysis.
Phagocytic actions can also activate adaptive immune system through the activation of antigen-presenting cells (APCs). Innate immunity is mediated by numerous effector cells, such as phagocytes (macrophages, granulocytes, and dendritic cells), mast cells, basophils, eosinophils, natural killer (NK) cells etc. Innate immunity is an antigen-independent, rapid response with no immunological memory, meaning every confrontation with a foreign agent will induce the cascade over again.
Adaptive immunity
Adaptive immunity is activated by APCs when innate immunity is not effective in the elimination of foreign agents. The adaptive immune response is programmed to recognize groups of molecules called antigens. Generally, antigens are proteins, glycoproteins, and polysaccharides characteristic to pathogens, but also other chemical structures, for example nickel, penicillin, and organic chemicals. This immune response is mediated by a family of proteins called immunoglobulins. Acquired later in evolution than innate immunity, adaptive immunity is machinery that generates diverse, antigen-specific receptors on its effector cells, T and B lymphocytes. The hallmark of the adaptive immune system is the generation of immunological memory: once exposed to an infectious agent, the organism will develop a faster and stronger response when faced with the pathogen again. This is due to memory B and T cells that develop from the adaptive immune response and provide long-term protection against reinfection. In contrast to innate immunity, the adaptive response takes hours and days to develop. Adaptive immunity acts more efficiently due to the vastness of specific antigen recognition, while the collection of receptors on innate immune cells is limited. Another difference from the innate system is that the adaptive immune system can also cause autoimmunity, or the recognition of the host's own molecular structures as dangerous agents. Autoimmunity causes many prevalent diseases, including rheumatoid arthritis and Type I diabetes.
Conclusion
Immunology is the study of the defense mechanisms organisms use to protect themselves from pathogens. The bone marrow and thymus are the centers for the formation and maturation of cells involved in the immune responses. There are two immune responses with different mechanisms. The innate immune system provides the first response with non-specific pathogen recognition and elimination pathways. Adaptive immunity is a slower, but highly specialized response mediated by specific antigen receptors expressed on effector cells to eliminate pathogens. Defects in the immune system can cause overactive immune responses, autoimmune diseases, or immunodeficiency disorders.