External and internal defences
In the skin and mucous membranes, being in contact with the outside, live most of the microbes that cause diseases. But only a few have access to the internal environment. Therefore, agents of the immune system are needed to participate in the defence against these pathogens. Therefore, the agents of the immune system can be classified almost militarily by their defensive role on our exterior (on the skin or mucous membranes) or on our interior (in the internal environment). They are respectively the first line of defence (external defences, such as the skin) and the second and third lines of defence (internal defences, such as phagocytes or antibodies).
External defenses
The skin and mucous membranes (moist epithelium, like the inside of the mouth) are the external defensive structures.
- The skin is a very effective physical barrier, as microbes can only pass through it if there are breaks or wounds. That is why the survival of people who suffer burns depends on the damaged body surface: the larger the surface, the greater the likelihood of infection.
- Mucous membranes are more fragile because they must allow the passage of nutrients (digestive mucosa) or gases (respiratory mucosa). In fact, most infections usually start by this route. But the mucous membranes, unlike the skin, produce secretions with antimicrobial activity (chemical barrier, such as lysozyme or defensins). In addition, the competition between commensal microbes prevents the proliferation of opportunistic pathogenic microbes (microbiological barrier).
Internal defenses.
The internal defences, i.e. the immune agents that protect us from inward epithelials, are the following, classified as innate or adaptive:
A. Innate or nonspecific immunity (second line of defense, recognizes molecular patterns). All living beings have it to a greater or lesser extent. Innate means that we are born with it. It lacks immunological memory, but on the other hand it is fast (it acts in seconds). Innate immunity is therefore able to fight infection from the very beginning and during its first stages (0-5 days). (for example, Gram- bacteria). Composed by:
- Molecules such as complement or some cytokines (such as interferon alpha). Complement is a group of serum proteins capable of binding to pathogens and destroying them. Cytokines are small immune hormones synthesized by various cells to communicate with other cells.
- Cells such as phagocytes or NK lymphocytes (Natural Killer, natural cytolytics or natural cytotoxics)
B. Adaptive immunity, specific or acquired (third line of defence, recognises antigens). It is exclusive to vertebrates. It takes a week to develop and is responsible for immunological memory. An example is antibodies. Adaptive means that it adapts to the pathogen. It specifically alludes to the fact that it identifies very specific pathogens (for example, Yersinia pestis, the Gram bacteria responsible for the plague), which it recognises by their antigens. Acquired means that we have to earn it, since we are not born with it. Composed of:
- Molecules such as antibodies or certain lymphocyte cytokines (such as gamma interferon)
- Cells such as B or T lymphocytes.
These immune agents in turn specialize in extracellular or intracellular pathogens according to the following table, using various mechanisms.
| Immunity | Pathogens | Molecules | Cells |
| Innate | Extracellular | Complement | Hepatocyte |
| Intracellular | Alpha interferon | NK Lymphocytes | |
| Adaptive | Extracellular | Antibodies | B Lymphocytes |
| Intracellular | γ Interferon | T Lymphocytes |
The first and second lines of defense are mostly innate and relatively unspecific, but rapid, while the third line of defense is slower but very specific and also has memory (such as antibodies).
The agents of innate immunity always act the same (they have no memory), regardless of the pathogens and the number of previous contacts. They use always identical receptors that recognize molecules common to groups of pathogens. Two examples are mannose, a sugar found on the surface of many microbes, but not in our own cells, and lipopolysaccharide (LPS) from the wall of Gram- bacteria. The phagocytes have mannose receptors and LPS receptors in their membranes. When the phagocyte finds hands or LPS on a particle, it means that it is facing a pathogen, although it does not know which one (it lacks specificity) and then quickly activates its phagocytosis to eliminate it.
Unlike innate immunity, adaptive immunity has enormous specificity and memory, as it is able to distinguish very similar pathogens by the antigens that distinguish them. It also manages to improve that recognition with each new contact and remember it for many years. However, adaptive immunity being specific only serves that particular pathogen, since it does not protect you from others.
The innate and acquired immune system act together
Lymphocytes usually only react to foreign antigens if the innate immune system has been previously activated. Innate rapid immune responses to infection depend on pattern recognition receptors produced by cells of the innate immune system. These receptors recognize patterns of immunostimulant molecules associated with pathogens that are absent in our body. These are often repeated patterns also called pathogen-associated molecular patterns (PAMP) such as those found in the molecular structure of nucleic acids, lipids, polysaccharides and proteins of microorganisms.2
Some of these receptors are located on the surface of the most efficient phagocytes (macrophages and neutrophils), where they favour the phagocytosis of pathogens, which will then be taken to their lysosomes where they will be eliminated. Other receptors are secreted and bind to the surface of microorganisms; in this way they are eliminated by phagocytes or by blood proteins of the complement system (they are plasma proteins involved in different enzymatic cascades, whose functions are to enhance the inflammatory response, facilitate phagocytosis and direct the lysis of cells including apoptosis). Finally, there are other receptors such as Toll-like receptors (TLR: Toll-like receptors) that activate intracellular signalling pathways leading to the secretion of extracellular signalling molecules, which favour inflammation and participate in the activation of acquired immune responses.2
Dendritic cells are the most efficient cells of the innate immune system in responding to PAMPs and activating acquired immune responses. They are found in most tissues and express large amounts of TLRs and other pattern recognition receptors, presenting microbial antigens to T lymphocytes in secondary lymphatic organs. In most cases, microorganisms, their products or fragments of infected cells are recognized and phagocyted at the site of infection, and then migrate to nearby peripheral lymphoid organs; in other cases, microorganisms or their products are captured directly in a peripheral lymphoid organ such as the spleen. In any case, microbial PAMPs activate dendritic cells which, in turn, can directly activate T-lymphocytes in peripheral lymphoid organs so that they respond to microbial antigens displayed by dendritic cells on their surface. Once activated, the T lymphocytes migrate to the site of infection where they assist in the elimination of microorganisms. Other activated T-lymphocytes remain in the lymphoid organ where they help keep dendritic cells active, activate other T-lymphocytes and activate B-lymphocytes to produce antibodies against microbial antigens.2
Therefore, innate immune responses are activated primarily at the sites of infection (or lesion), while acquired immune responses are activated mostly in peripheral lymphoid organs such as lymph nodes and spleen.2
Bibliography
- Regueiro González J.R., López Larrea C., González Rodriguez S. y Martínez Naves E. Inmunología: Biología y patología del sistema inmunitario. 4ª edición. Editorial Médica Panamerica, 2010
- Alberts Bruce, Johnson Alexander, Lewis Julian, Raff Martin, Roberts Keth y Walter Peter. Biología molecular de la célula. 5ª edición. Editorial Omega, 2010.