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Cells and tissues of the immune system

The immune system consists of a series of organs, tissues, and cells widely distributed throughout the body.

IMMUNE SYSTEM CELLS
The immune system is made up of a variety of cells with different functions that interact with each other. They can be classified into two main groups:1,2

A. Nonspecific response cells: these are rapid response cells that do not identify specific pathogens, but rather groups of pathogens.

  1. Phagocytes: This name means “eat cells”. These are immune cells that devour, pathogens or their toxins through the process called phagocytosis.  Phagocytes usually patrol the body for pathogens, but they may also react to a group of specific molecular signals, called cytokines, produced by other cells. Types:1,2
    • Macrophages: They are found in tissues and together with neutrophils are the most efficient phagocytes. They come from monocytes that, after passing through the walls of the capillaries and penetrating the tissue, become macrophages.
    • Neutrophils: Neutrophils, like eosinophils and basophils, are known as granulocytes due to the presence of granules inside (cytoplasm). These granules contain a variety of toxic substances to kill or inhibit the growth of bacteria and fungi.
    • Dendritic cells: they also come from monocytes as do macrophages. They can ingest foreign substances and organisms, but they have the same phagocytosis capacity as macrophages. They are cells present in tissues that are in contact with the external environment, mainly the skin (where these cells take the name Langerhans Cells), and the internal mucosal lining of the nose, lungs, stomach and intestine. Dendritic cells are very important in the presentation of antigens, and serve as a link between the innate and adaptive immune systems.
  2. Basophils: are granulocytes. They secrete histamine which acts on inflammatory reactions. They are important in defence against parasites and in allergic reactions. They are closely related to mast cells.1,2
  3. Eosinophils: are another type of granulocytes. When activated, they secrete a series of highly toxic proteins and free radicals that are highly effective in killing bacteria and parasites, but are also responsible for the tissue damage that occurs during allergic reactions.1,2
  4. Mast cells: these are connective tissue cells that participate in inflammatory and allergic processes, discharging their toxic vacuoles into the environment. They also repel large parasites. They release histamine and heparin.1,2
  5. Natural killer cells or Natural Killer: these are cells with innate cytolytic activity and, unlike cytotoxic T lymphocytes, do not require pre-activation in order to lysate infected cells. They destroy certain types of tumour cells and cells infected by viruses.1,2

B. Specific response cells: these are slower responding cells (they take approximately one week) and they do recognise specific pathogens through their antigens. They are the cells responsible for the specific immune response, as they express receptors on their membrane that allow them to recognize the antigen in a specific way. Types:1

  1. B lymphocytes: These are a type of antigen-presenting cells*, participating in the activation of T lymphocytes. When activated in a dependent or independent way by T lymphocytes, they differentiate into plasma cells, which produce antibodies.
  2. T lymphocytes: Eliminate virus-infected cells and regulate the activity of other leukocytes or white blood cells.

*Antigen-presenting cells, such as dendritic cells, mononuclear phagocytes (monocytes and macrophages) and B lymphocytes, capture antigens in an innate or adaptive way and then process them so that they can be adequately recognised by T lymphocytes. Endothelial cells may also present antigens to T lymphocytes, contributing to the recruitment of lymphocytes at the site of infection.1


LYMPHOID ORGANS
The cells that form part of the immune system are in turn grouped into tissues and organs, which are called the lymphoid system. There are several lymphoid organs and tissues that are grouped into two groups: primary lymphoid organs and secondary lymphoid organs.1

  • Primary lymphoid organs.
    The primary or central organs and tissues (bone marrow and thymus) are responsible for lymphocytes (the process by which lymphocytes are formed).1

    1. Bone marrow: The bone marrow produces the precursors of all cell types of the immune system and is also where the B lymphocytes mature.
    2. Thymus: In the thymus the precursors of the T lymphocytes undergo various selection processes, and once mature (they come out as virgin T lymphocytes since they have not yet been activated) they migrate from there to the secondary lymphoid organs.
  • Secondary lymphoid organs.
    Several leukocytes coexist in the secondary or peripheral lymphoid organs and in them the microenvironmental conditions are created so that B and T lymphocytes can interact with other cells, in order to recognize the antigen in an adequate way. The most important secondary lymphoid organs are the spleen, lymph nodes and mucosal associated lymphoid tissue grouping (MALT). Each secondary organ specializes in the regional response to pathogens, depending on its route of access to the body.1

    1. Spleen: is formed by two regions: the red pulp and the white pulp. The red pulp participates in the destruction of deteriorated erythrocytes and is a large storehouse of erythrocytes, granulocytes and platelets. The white pulp is the lymphoid tissue that participates in the generation of immune responses against antigens that reach it via the bloodstream. In the spleen there are all the cell types necessary to generate cellular and humoral immune responses.1
    2. Lymph nodes: These are intercalated in the network of lymphatic vessels. They are in charge of filtering the antigens coming from the interstitial liquid and the lymph. It is divided into cortical area with B lymphocytes, paracortical area with T lymphocytes and central marrow containing B lymphocytes, T lymphocytes, macrophages and antibody-producing cells. In the T lymphocyte area there are abundant numbers of antigen-presenting dendritic cells that migrated from the skin or antigen contact areas to present the antigen to the T lymphocytes of the corresponding regional ganglion. In the area of B lymphocytes there is a peculiar type of cells presenting antigen to B lymphocytes, follicular dendritic cells (FDC). These are involved in the formation of germinal centres in the B area, both in the ganglion and in the spleen and in other peripheral lymphoid tissues. The germinal centres are places of active proliferation of B lymphocytes stimulated by the antigen presented by the FDC and in them the formation of the memory of B1 lymphocytes takes place.
    3. MALT: MALT consists of groups of non-encapsulated lymphoid tissue that are located in the proper lamina and submucosal areas of the gastrointestinal tracts (such as tonsils, Peyer’s plaques in the intestine and the cecal appendix), respiratory and genitourinary. Humoral responses (production of antibodies) triggered in the mucosa are mainly IgA. These immunoglobulins pass through the epithelium and help prevent the entry of infectious microbes. There are also intraepithelial T lymphocytes γδ, whose function may be the defence of host epithelial cells infected by certain viruses or bacteria.1

LYMPHOCYTE RECIRCULATION
The bone marrow continuously generates leukocytes which it releases into the circulatory torrent. Some circulate and extravasate into tissues (mast cells, macrophages, dendritic cells, eosinophils) waiting for an encounter with pathogens, until they die in a few weeks. Others remain in the circulation where they live for only a few days (granulocytes). The precursors of the T lymphocytes go to Thymus, where they are extravasated to undergo the maturation process and then return to the blood (if they survive selection). The mature (virgin) T and B lymphocytes, for their part, recirculate, a curious daily habit that consists of abandoning the blood precisely in the lymph nodes, going to the stromal of the node in search of a specific antigen to be activated, from there they are collected again to the efferent lymphatic vessel, to return to the blood at the level of the subclavian veins and again to begin. The idea is that as the lymphocyte circulates again and again through the lymph nodes, it increases the likelihood that the lymphocyte will encounter an antigen that it is able to recognize. Something that sometimes does not occur in the comparatively long life of the virgin lymphocyte (weeks).1


Bibliography

  1. 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.
  2. Alberts Bruce, Johnson Alexander, Lewis Julian, Raff Martin, Roberts Keth y Walter Peter. Biología molecular de la célula. 5ª edición. Editorial Omega, 2010.