The Structure of the Immune System

08.08.2023

Immunomodulating Effects of Fungal Beta-Glucans: From Traditional Use to Medicine


Source: Nutrients Authors: van Steenwijk H, Bast, A and de Boer A.

Beta-glucans derived from mushrooms are bioactive long-chain polysaccharide compounds, insoluble in water and with immunomodulatory properties. Knowledge of the action and functions of beta-glucans, which have been used in traditional medicine for centuries, is developing thanks to modern immunological and biotechnological methods.

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Immunomodulating Effects of Fungal Beta-Glucans: From Traditional Use to Medicine

This review has highlighted the potential application of fungal beta-glucans—immunomodulators that have been used in traditional Chinese medicine for centuries—in nutrition and medicine. From this review, it can be concluded that fungal glucans may play a promising role within both perspectives, and that there are possibilities to give traditional medicine an immunological application in both medicinal products and foods. Depending on the dosage, formulation, efficacy, safety profile, and route of administration, the immunomodulating effects that can be expected from fungal beta-glucans can either be considered a pharmaceutical effect (treating or curing a disease) or as a health effect originating from foods, focusing on the prevention of negative health effects.

In Europe, claims on health benefits are strictly regulated, with EFSA reviewing the scientific evidence that supports putative statements about health effects. As shown in this paper, all applications for putative health claims related to stimulation of the immune system and defense against pathogenic microorganisms have so far been rejected. Since EFSA has only approved immune claims for six vitamins and four essential trace elements, it can only be speculated that the temptation to add these ingredients to products is growing, rather than stimulating research into innovative foods. Comparing the evidence base of the putative health effects of fungal beta-glucan supplements with the guidance documents on immune support health claims, but even more importantly, the guidance documents on substantiating immune stimulation and pathogen defense by food products, it is shown that fungal glucans could play a role in supporting and maintaining health and, thus, can be seen as a good health-promoting substance from food—which could mean that this effect may also be claimed if approved.

In addition to these developments related to food uses of beta-glucan-containing supplements, beta-glucans could also hold a novel position in Western medicine, as the concept of trained immunity is relatively new and has not been investigated to a larger extent. The new insights and developments in trained immunity may lead to the possible application of fungal beta-glucans as NSIs in Western medicine. Due to the experience from Asian medicine and the relatively favorable safety profile, lentinan (i.v.) could potentially be a suitable fungal glucan within this new field of immunity. However, additional (preclinical) safety studies must first be performed to be eligible as a medicine in Europe. Imprime PGG, which is currently going through the stages of drug development, is another fungal beta-glucan worth investigating. Finally, given the different ways to purify and process beta-glucans, one of the biggest challenges remains the standardization and proper characterization of the active compounds themselves. However, with the help of modern immunological and biotechnological methods, increasing insights are gained into immunomodulating fungal beta-glucans, with potential applications both in foods and pharmaceutical products.

Immunomodulating Effects of Fungal Beta-Glucans: From Traditional Use to Medicine Nutrients. 2021 Apr; 13(4): 1333. Published online 2021 Apr 17. doi: 10.3390/nu13041333

B cells (B Lymphocytes)

Lymphocytes B and T are the two main types of lymphocytes. B cells work mainly by secreting substances called antibodies into body fluids. Antibodies capture antigens circulating in the blood. However, they do not have the ability to penetrate cells. The task of attacking target cells – either virus-infected cells – or cancer-infested cells is left to T cells or other immune cells (described below).

Each B cell is programmed to produce one specific antibody. For example, one B cell produces an antibody that blocks a virus that causes the common cold, while another produces an antibody that attacks a bacterium that causes pneumonia.

If a B cell encounters a trigger antigen, it causes the growth of many large cells known as plasma cells. Each plasma cell is a specialized antibody factory. Each plasma cell is a descendant of a B cell and produces millions of identical antibodies that are released into the blood. The antibody fits the antigen like a key fits a lock. Some fit very precisely, others more like a pick. But wherever an antibody and an antigen come together, the antibody marks the antigen for destruction. Antibodies belong to a family of large molecules known as immunoglobulins. Different types of antibodies perform different functions in the immune defense strategy.

IgA

Immunoglobulin A has a critical role in immune defense particularly at the mucosal surfaces. IgA is found in many body secretions, including tears, saliva, respiratory and intestinal secretions, and colostrum (the first milk produced by lactating mothers). Very little IgA is present in the serum. IgA is produced by B cells located in the mucous membranes of the body. Two molecules of IgA are joined together and associated with a special protein that enables the newly formed IgA molecule to be secreted across epithelial cells that line various ducts and organs. Although IgG is the most common class of immunoglobulin, more IgA is synthesized by the body daily than any other class of antibody. However, IgA is not as stable as IgG, and therefore it is present in lower amounts at any given time.

IgG

Immunoglobulin G is the most common class of immunoglobulin. It is present in the largest amounts in blood and tissue fluids. Each IgG molecule consists of the basic four-chain immunoglobulin structure. There are four subclasses of IgG, each with minor differences in its H chains but with distinct biological properties. IgG is the only class of immunoglobulin capable of crossing the placenta; consequently, it provides some degree of immune protection to the developing fetus. These molecules also are secreted into the mother’s milk and, once they have been ingested by an infant, can be transported into the blood, where they confer immunity.

IgM

Immunoglobulin M is the first class of immunoglobulin made by B cells as they mature, and it is the form most commonly present as the antigen receptor on the B-cell surface. When IgM is secreted from the cells, five of the basic Y-shaped units become joined together to make a large pentamer molecule with 10 antigen-binding sites. This large antibody molecule is particularly effective at attaching to antigenic determinants present on the outer coats of bacteria. When this IgM attachment occurs, it causes microorganisms to agglutinate, or clump together.

IgE

Immunoglobulin E is made by a small proportion of B cells and is present in the blood in low concentrations. Each molecule of IgE consists of one four-chain unit and so has two antigen-binding sites, like the IgG molecule; however, each of its H chains has an extra constant domain (CH4), which confers on IgE the special property of binding to the surface of basophils and mast cells. When antigens bind to these attached IgE molecules, the cell is stimulated to release chemicals, such as histamines, that are involved in allergic reactions. IgE antibodies also help protect against parasitic infections.

IgD

Immunoglobulin D molecules are present on the surface of most, but not all, B cells early in their development, but little IgD is ever released into the circulation. It is not clear what function IgD performs, though it may play a role in determining whether antigens activate the B cells.

T cells (T lymphocytes)

Unlike B cells, T cells do not recognize freely circulating antigens. Rather, their surface has specialized receptors (so-called antibody-like receptors) that recognize fragments of antigens on the surface of infected or cancer cells. T cells participate in immune defense in two main ways: some direct and regulate the immune response; others attack directly infected or cancer cells.

T helper lymphocytes (Th cells) coordinate immune responses by communicating with other cells. Some stimulate nearby B cells to produce antibodies, others call on phagocytes, and others activate other T cells.

Tc cells

Cytotoxic T lymphocytes, also called Tc cells or Tc lymphocytes (Cytotoxic T Lymphocytes - CTLs), perform various tasks. These cells directly attack other cells that carry certain foreign or abnormal molecules on their surface. Cytotoxic T cells are particularly useful in defense against viruses because viruses are often hidden from other elements of the immune system because viruses often multiply inside infected cells. These cells can detect even small fragments of the virus protruding through the cell membrane of a virus-infected cell and attack it to destroy it.

In most cases, T cells can only recognize an antigen if it is carried on the cell surface by its own MHC molecules (major histocompatibility complex). MCH molecules are proteins recognized by T cells when they distinguish between self and foreign. Own MHC molecules create a recognizable scaffold for presenting foreign antigens to T cells.

Although MHC molecules are needed by Tc cells to attack foreign invaders, they pose problems in the case of organ transplantation. Each cell of the body has MHC proteins on its surface, and each person has his or her own set of these proteins. If a Tc lymphocyte recognizes "foreign" MHC molecules on the surface of a cell, which happens in transplants, it will begin to destroy it. Therefore, it is necessary to select organ donors with the set of MH molecules (major histocompatibility complex) that is most similar to the recipient's set. Otherwise, Tc lymphocytes will probably attack the transplanted organ and lead to its rejection.

NK cells

NK cells, or natural killer cells, are another type of white blood cells of the lymphocyte class. Like cytotoxic T cells (LTc), NK cells are armed with granules filled with powerful chemicals. However, while killer cytotoxic T cells look for antigen fragments attached to molecules of "their" MHC, NK cells recognize cells that do not have molecules of "their" MHC. Therefore, NK cells have the ability to attack various types of foreign cells.

Both types of killer cells kill through contact. Assassins attach themselves to their target, turn their weapons on him and trigger a deadly chemical explosion.

Phagocytes and their relatives

Phagocytes are large white cells that can devour and digest microbes and other foreign particles. Monocytes are phagocytes that circulate in the blood. When monocytes enter the tissues, they transform into macrophages.

Specialized types of macrophages are found in many organs: lungs, kidneys, brain and liver. Macrophages perform many functions. Like cleaners, they free the body of used cells and other debris (garbage). They display pieces of foreign antigens so as to attract the attention of the appropriate lymphocytes. They project out an incredible multitude of powerful chemical signals, known as monokines, that are important for the immune response.

Another type of immune system cells are granulocytes. They contain granules filled with powerful chemicals that allow granulocytes to destroy microorganisms. Some of these substances, such as histamine, are also involved in the processes of inflammation and allergy.

One of the granulocytes, the neutrophil, is also a phagocyte; it uses previously stored chemicals to break down and digest microbes. Eosinophils and basophils are other granulocytes that release chemicals from their granules, spraying them onto nearby microbes and harmful cells.

Mast cells are the twins of basophils, except that they are not blood cells. They are found in the tissues: lungs, skin, tongue, mucous membrane lining the nasal cavity and the digestive tract, where they are responsible for allergy symptoms.

A related structure is platelets. These are cell fragments that also contain granules. The function of platelets related to blood cell aggregation, coagulation and wound healing also includes immune activation.

Cytokines

Cytokines are proteins that function as chemical messengers in your immune system. Your immune system is a network with several parts that work together to protect your body from threats, like germs that can make you sick. It contains immune cells that fight invading pathogens (like viruses and bacteria), allergens and other harmful substances that enter your body. Cytokines signal those immune cells to fight the invaders. Even when there’s no threat, cytokines send signals to other cells that keep your immune system functioning.

The components of the immune system communicate with each other by exchanging chemical messengers called cytokines. These proteins are secreted by cells and act on other cells to coordinate an appropriate immune response. Cytokines include a diverse range of interleukins, interferons, and growth factors. Some cytokines are types of chemical switches that turn certain types of immune cells on or off.

Different types of cytokines

Cytokines include different types of proteins that tell immune cells where to go and what to do to keep your immune system functioning correctly.

  • Chemokines direct immune cells toward places in your body where they can fight infection.
  • Interferons signal cells to put up their defenses against viruses invading your body. In this way, interferons “interfere” in the process that allows viruses to replicate, or make more viruses once they’ve invaded a healthy cell.
  • Interleukins get their name from “inter” which means between and “leukocyte,” which is another name for a white blood cell. Originally, scientists thought that leukocytes alone released interleukins and only relayed messages to other leukocytes. But now we know that cells other than leukocytes release these proteins. Also, interleukins can relay messages between cells that aren’t leukocytes.
  • Tumor necrosis factor (TNF) helps regulate inflammation in your body. TNF also signals to immune cells that kill tumor cells.
  • Colony-stimulating factors CSF signals hematopoietic stem cells to develop into specific cell types. Hematopoietic stem cells (HSC) are precursor cells that give rise to all blood cell types: white blood cells, red blood cells and platelets. These changes take place during a process called hematopoiesis. For example, granulocyte-colony stimulating factor (G-CSF) signals an HSC to become a white blood cell called a neutrophil. Neutrophils help fight infection.
Some cytokines get their names from the type of cell that makes them, including:
  • Lymphokines – produced by lymphocytes, a type of white blood cell.
  • Monokines – produced by monocytes, a type of white blood cell.

One of the cytokines, interleukin 2 (IL-2), triggers the production of T cells by the immune system. The immune-stimulating properties of IL-2 have traditionally made it hopeful in the treatment of a number of diseases. Clinical trials are underway testing their benefits in other diseases such as cancer, hepatitis C, HIV infection and AIDS. Other cytokines are also being investigated for their potential therapeutic benefits and clinical applications.

Other cytokines chemically attract particular types of cells. These so-called chemokines are released by cells at the site of damage (injury) or infection and call other immune cells to the site to help repair the damage and fight off invaders. Chemokines often play a key role in inflammation and are promising targets for new drugs that regulate the immune response.

The complemment system

The complement system contains approximately 25 proteins that work together to "complement" the action of antibodies in destroying bacteria. Complement also supports the body's release from antigen-antibody complexes. Complement proteins, which cause blood vessels to dilate and cause their permeability, are involved in the development of redness, swelling, pain, increase in temperature and loss of function that characterize the inflammatory response.

Complement proteins circulate in the blood in an inactive form. When the first complement protein is activated – typically by an antibody that locks with an antigen – a domino effect is triggered. Each component (takes) contributes to a precise chain of steps known as the complement cascade. The end product is a cylinder that sticks into the cell wall, creating a hole (hole) in it. Fluids and particles flow in and out through it into the cell, which swells (buzzes) and bursts. Other components of the complement system make bacteria susceptible to phagocytosis and/or attract other cells to the region.

Structure of the Immune System

The immune system is a very complex structure consisting of cells, tissues and organs that work together to protect (defend) our body against "foreign" invaders . . .

How the Immune System Works?

It is one of nature's most fascinating inventions. It easily protects us against billions of bacteria, viruses and pathogens. We don't realize that the immune system . . .

Immunodeficiencies

Immunodeficiencies are disorders of the immune system that are characterized by a reduced or lack of ability to . . .

Maintain Healthy Immune System

If we are not dealing with an immune system disease, it is usually enough to use a few simple . . .

News

The European Medicines Agency (EMA) has approved gene therapy for the treatment of severe combined immunodeficiency due to adesine deaminase deficiency (ADA-SCID), which is the result of a genetic mutation - reports New Scientist. You can read about gene therapy, what it is and its prospects, on the website News Medical Life Sciencies

17.01.2024

Source: Memorial Sloan Kettering Cancer Center Library / LibGuides / COVID Impacts / Immune Dysfunction

Detailed information and resources on the long-term health consequences of COVID-19 infection and the broad social impacts of the COVID-19 pandemic.

One of the most concerning long-term effects of COVID-19 is the dysregulation and dysfunction of the immune system.

08.08.2023

Source: Nutrients Authors: van Steenwijk H, Bast, A and de Boer A.

Beta-glucans derived from mushrooms are bioactive long-chain polysaccharide compounds, insoluble in water and with immunomodulatory properties. Knowledge of the action and functions of beta-glucans, which have been used in traditional medicine for centuries, is developing thanks to modern immunological and biotechnological methods.

04.08.2023

Source: Oncology Reports; Authors: Hiromi Okuyama Akira Tominaga, z Laboratory of Immunology, Faculty of Pharmacy, Osaka Ohtani University, Tondabayashi, Osaka 584-8540, Japan

Spirulina lipopolysaccharides inhibit tumor growth in a Toll-like receptor 4-dependent manner by altering the cytokine milieu from interleukin-17/interleukin-23 to interferon-γ