Why are monocytes called antigen-presenting cells

Immunological basics - cells of the immune & complement system

Table of Contents


Image: “Simplified hematopoiesis” by Mikael Häggström. License: CC BY-SA 3.0


Overview of all cells of the immune system

Image: “This diagram shows the hematopoiesis as it occurs in humans” by A. Rad. License: CC BY-SA 3.0

The cells of the immune system come from pluripotent stem cells of the bone marrow and are differentiated in two ways:

  • Myeloid Differentiation Series
  • Lymphatic differentiation series

To the myeloid differentiation series include the following cells:

  • Polymorphonuclear granulocytes
    • Basophils
    • Neutrophils
    • Eosinophils
  • Mononuclear phagocytes
    • Monocytes
    • Macrophages
    • Antigen presenting cells e.g. Langerhans cells
  • Auxiliary cells
    • Mast cells
    • More antigen presenting cells
    • Platelets

Usually these cells proliferate in the bone marrow. From there, the living cells reach the periphery of the body via the bloodstream.

In the lymphatic differentiation series the following cells are distinguished:

  • B lymphocytes
  • T lymphocytes
  • Natural killer cells

After they have acquired immune competence, these cells settle in peripheral lymphatic organs, from where they can make a profile in the event of functional stimulation.

Numerous Proteins and Glycoproteins In addition to the cells of the immune system, they also play an important role in defense reactions. In the interstitial fluid and in the blood plasma (e.g. soluble antibodies) they exist partly free and bound as receptors on cell surfaces.

Polymorphonuclear granulocytes

Image: “Cells of the innate immune system” by The Immune System. License: Public Domain

One of the paracrine active cells is one basophils (in the blood) just like that Mast cells (in the connective tissue), which trigger the first steps of the inflammatory reaction when an antigen is detected. The granules of the basophils are usually made up of a cell nucleus consisting of 2 lobes. The cells of the basophils and mast cells correspond structurally and functionally in many respects, but their relationship has not been clarified.

The two cell types contain special inflammation mediators, among others. Leukotrine, Prostaglandins, histamine or Heparinthat are released when antigens (mostly foreign proteins) pass through the skin or mucous membrane. This is perceived by the two cells as soon as the foreign proteins are bound by immunoglobulin E to IGE receptors on the surface of the mast cells or basophilic granulocytes.

Neutrophils are very common in the blood and belong to the non-specific phagocytic cells. The cell nucleus consists of two to five lobes that are connected to one another by very fine strands of chromatin. The number of lobes also increases with age.

Under the influence of other inflammatory mediators, the neutrophils pass through the endothelium and migrate through the inflamed tissue. The granules of the neutrophils store proteases, myeloperoxidase and various phosphases as well as lysosym and lactoferrin, which binds free iron that the bacteria need for growth. The neutrophils prevent the bacteria from growing, kill them off and phagocytize they finally. In the end, they perish under obesity and leave a decay product of dead neutrophils and tissue remnants (pus).

Just like the neutrophils, the eosinophils stimulated by chemotactic factors to migrate through the endothelium. Eosinophil cells generally have a nucleus that consists of two lobes that are connected by a thick strand of chromatin.

The cells release basic protein, a substance that is cytotoxic and kills foreign cells and parasites. The main function, together with neutrophils and macrophages, is in the binding and phagocytosis of antigen-antibody complexes. The eosinophilic granulocytes also play an important role in allergic reactions, as they secrete a large number of cytokines.

Mononuclear phagocytes (monocytes)

Monocytes have a diameter of 12 to 20 microns and the nuclei are usually kidney and horseshoe shaped. The blood transports the monocytes to the tissues of the body, where they enlarge and close Macrophages differentiate. Through the chemotactic effect of the activated complement cascade and mast cells, monocytes are increasingly attracted to inflammation.

Macrophages have the task, as the name suggests, to phagocytize and secrete factorsthat control the inflammatory response. They have a lifespan of days to months and are usually replaced by blood monocytes that follow. By Mitosis they are also increased in some organs so that they are then largely independent of the pool of blood monocytes.

Macrophages become stationary and migrating macrophages. The migrating macrophages comb through the tissue and gather at sources of infection or inflammation. Stationary macrophages remain in certain tissues that are organ-dependent.

E.g.:

  • Macrophages in the spleen
  • Alveolar macrophages in the lungs
  • Kupffer stellate cells in the liver

Phagocytosis

The phagocytosis process is a vital defense mechanism that helps protect the body from disease. Just Macrophages, basophils- and neutrophils have the ability of phagocytosis.

Macrophages can attach to foreign microorganisms and tumor cells via receptors and then phagocytize them. With the help of phagocytosis, macrophages eliminate invading microbes as well as billions of old, disused ones every day Erythrocytes. This process is made easier if the cell in question is already enveloped with proteins of the complement system or antibodies.

Not only do they fight inflammatory pathogens, they also produce numerous Cytokines (Growth factors). With the help of the cytokines, they can control inflammatory reactions and subsequent repair processes and make an important contribution to wound and inflammation healing.

Antigen presentation

The inflammatory response for the body could end with a successfully completed phagocytosis. However, to a specificimmunity To enable an antigen presentation is necessary. In order to bring about a faster immunity of foreign proteins or foreign cells in the future, information about the penetrated antigen is passed on to the responsible lymphocytes. This process is carried out by macrophages in particular, but also by other antigen-presenting cells.

Other antigen presenting cells

Langerhans cells, which are located in the stratum spinosum of the epidermis, are further antigen-presenting cells that are not only functionally related, but in some cases also with regard to their origin, are very closely related to the macrophages. They absorb antigens penetrating transepithelially and then migrate via the lymphatic system into the lymph nodes, where they become interdigitating cells that present their antigen fragments to the T lymphocytes.

Image: “White Blood Cells” from Blausen gallery 2014. License: CC BY 3.0

Auxiliary cells

Auxiliary cells belong neither to the mononuclear phagocytes, nor to the polymorphonuclear granulocytes, nor to lymphocytes. You are one heterogeneous group of cellsthat contribute to the innate or acquired immune response.

The following cell types are assigned to the auxiliary cells:

  • Mast cells
  • Cells that can present antigen after stimulation
  • Platelets

Mast cells are structurally and functionally identical to the basophilic granulocytes. They occur mainly in the connective tissue and release histamine in the course of inflammation or allergic reactions. They also have the ability to bind bacteria, incorporate them and ultimately kill them.

Antigen presenting cells (APC) are assigned to a special class of migration cells that process antigens and can present T cells as part of an immune response. APC include macrophages, B cells, and dendrites in skin, mucous membranes, and lymph nodes.

Platelets are cytoplasmic fragments in a cell membrane without a nucleus, which are found in the circulating blood and play an important role in coagulation. Furthermore, they can attract leukocytes and support an inflammatory reaction by releasing vasoactive substances and capillary permeability-increasing factors in the case of endothelial lesions.

Lymphocytes

Lymphocytes serve the specific inflammatory reaction, differentiate from a pluripotent stem cell of the red bone marrow and are divided into 2 groups:

  • B lymphocytes
  • T lymphocytes

Only after the fetal period and the first year of life, during a training phase in the primary lymphatic organs, do they learn their specific immune functions and immune skills.

B lymphocytes

The body has millions of different B lymphocytes that can respond to a specific antigen. As soon as a specific antigen is present in the spleen, lymph nodes or mucosa, they are activated. They then differentiate to Plasma cellsthat specific antibody secrete. So that the antibodies are "on the spot" quickly, they circulate in the lymph and blood to get to the Foreign antigen to get.

Activation, proliferation and differentiation of B cells

B cells are activated when the specific antigen is attached to them B cell receptors binds. Their response to processed antigens is much stronger than to unprocessed antigens that react in the lymph or interstitial fluid. The Processing takes place in the following steps:

  1. Antigen is taken up into the B cell
  2. Antigen is broken down into peptide fragments in the cell
  3. The peptides are bound to HLA-II molecules
  4. Antigen-HLA-II complex is transported to the plasma membrane of the B cell

T helper cells have the ability to recognize this antigen-HLA-II complex and a co-stimulatory signal to supply that is necessary for the proliferation and differentiation of B cells. T helper cells produce interleukins 4 and 6 in particular, which serve to proliferate B cells and differentiate into plasma cells and promote their antibody secretion.

Some of the active B cells enlarge, divide, and differentiate into one clone of antibody secreting plasma cells that release hundreds of millions of antibodies in a few days until they die. The antibodies reach the foreign antigen via the lymph, blood and intercellular fluid.

If an activated B-cell does not differentiate into a plasma cell, they remain as Memory B cells and can react faster when they come into contact with this antigen again.

Image: "Memory B cell response on first, and second infections of a virus." by Nreese22. License: CC BY-SA 4.0

T lymphocytes

The cellular immune response begins when a small number of T cells are activated by a specific antigen recognized by their receptor. Once a T cell is activated, it continues to proliferate and differentiate into one Effector cell clone and it comes to a population of identical cells. They have the ability to recognize the same antigen, are involved in the immune attack with the aim of eliminating the "intruder".

Activation, Proliferation and Differentiation

So-called T cell receptors (TCR) recognize and bind specific foreign antigen fragments, which are presented to you as an antigen-HLA complex. There are millions of different T cells in our body, each with its own unique TCR that recognizes a specific antigen-HLA complex.

Few T cells have matching T cell receptors when an antigen enters the body. For this reason, additional surface proteins of the T cells such as CD4 or CD8 proteins are necessary for antigen recognition, which interact with the HLA antigens and help with TCR-HLA binding. They are called Co-receptors designated.

The first signal of T cell activation is antigen recognition by a TCR together with the surface proteins. The activation of a T cell does not take place until it binds to a foreign antigen and a second signal as Co-stimulation receives. The second signal prevents immune responses from happening randomly. There are more than 20 co-stimulators that affect activated T cells in different ways.

Antigen binding to a receptor leads to a prolonged state of inactivity in T and B cells without additional co-stimulation, too Anergy called.

As soon as the T-cell receives the two signals, it is activated and begins to profile and differentiate itself. A clone, a population of identical cells, emerges that all recognize the same specific antigen.

The activation, proliferation and differentiation of T cells take place in the secondary lymphoid organs.

The T cells can be differentiated into the main classes:

  • T helper cells
    • Most T cells develop into T helper cells (CD4 T cells).
    • Inactive T helper cells recognize exogenous antigen related fragments HLA-II molecules on the surface of the antigen presenting cell (APC).
    • With the help of the CD4 molecule, the T helper cell and APC interact with each other, so that the co-stimulation and activation of the T helper cells occurs. T helper cells are also once again specialized in individual subgroups.
  • Cytotoxic cells
    • They recognize foreign antigens in connection with HLA-I molecules on the surface of e.g. a tumor cell.
    • After the antigen has been recognized, it is co-stimulated by interleukins 2 or other cytokines.
  • Memory cells
    • Cells that remain after the immune response is complete
    • In the event of renewed contact with the same foreign antigen, thousands of these cells are available and can trigger a faster reaction without the appearance of symptoms of the disease.

Image: “Clonal Selection and Expansion of T Lymphocytes” by OpenStax College. License: CC BY 3.0

Natural killer cells

In addition to the phagocytes, the natural killer cells stand in the way of the microorganisms once they have penetrated the skin or mucous membrane.

The natural killer cells (NK cells) make up about 5 - 10% of the lymphocytes in the blood and also come in spleen, Lymph nodes and the red one Bone marrow in front. They do not carry membrane molecules that specifically recognize B or T cells. They have the ability to kill various infected body cells and tumor cells, attacking any cell that carries abnormal proteins on the cell membrane.

The binding of NK cells to virus-infected target cells leads to the release of NK cell granules with their toxic substances. The protein Perforin is deposited e.g. in the cell membrane of the target cell and forms channels there to allow extracellular fluid to flow into the target cell until it bursts.

Granzyme, a protein-digesting enzyme, is released from other NK cell granules, which leads to apoptosis and self-destruction of the target cells. However, only the infected cells are destroyed, but not the microorganisms in the cells. The microorganisms are then taken up and removed by phagocytes.

Complement system

The complement system consists of over 30 proteinsproduced by the liver and found in blood plasma and tissues throughout the body. It will alsoDefense system called because the proteins destroy microorganisms by causing phagocytosis, cytolysis and inflammation.

With a C. most will Complement proteins numbered from C1 to C9 according to their discovery. They are in an inactive state until they are enzymatically cleaved into active fragments for activation. Thus, the active fragments are designated with the lowercase letters a and b, which carry out the destruction reaction.

E.g:

  • Inactive complement protein C3
  • Active complement protein C3a and C3b

Other complement proteins are called factor B, D and P (properdin).

The complement system is activated in a cascade-like manner, i.e. one reaction triggers another reaction which induces another. The effect is intensified with every further reaction.

Activation can take place in three different ways, but C3 is always activated. C3 can be activated in the following ways:

  • Classic activation path
    • This pathway begins with the binding of an antibody to an antigen and the antigen-antibody complex binds and activates C1. C3 is eventually activated, cleaved, and the C3 fragments initiate phagocytosis, cytolysis and inflammation.
  • Alternative activation path
    • The alternative activation path takes place without the involvement of antibodies.This path is initiated by the interaction of lipid-carbohydrate complexes on the surface of microorganisms with the complement factors B, D and P.
  • Lectin Activation Pathway
    • In the lectin activation pathway, microorganisms are digested by macrophages and factors are released that induce the production of lectins in the liver. The lectins bind to the surface of microorganisms and activate C3.

When the complement system is activated, the active C3 is broken down by proteins in the blood and on body cells and thus the destructive effect is stopped again very quickly and the damage to the body cells is limited.

Popular exam questions about the cells of the immune & complement system

The answers can be found below the source.

1. Which three cell types have the ability to phagocytose?

  1. Eosinophils, basophils and macrophages
  2. Eosinophils, neutrophils and macrophages
  3. Eosinophils, neutrophils and natural killer cells
  4. Basophils, macrophages and natural killer cells
  5. Neutrophils, mast cells and macrophages

2. Which active cell develops into a clone of antibody-producing plasma cells?

  1. Monocytes
  2. Platelets
  3. T lymphocytes
  4. B lymphocytes
  5. Eosinophils

3. Which answer about T lymphocytes is wrong?

  1. Antigen binding to a receptor leads to a prolonged state of inactivity (anergy) without additional co-stimulation.
  2. T cell receptors (TCR) recognize and bind specific foreign antigen fragments.
  3. Millions of different T cells with the same TCR are in our body, which recognizes a specific antigen-HLA complex.
  4. Co-receptors are often necessary for antigen recognition.
  5. A T cell is only activated when it binds to a foreign antigen and receives a second signal as co-stimulation.

 

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G.J. Tortora and B.H. Derrickson: Anatomy and Physiology - Wiley, VCH Verlag

Schieber, Schmidt and Zilles: Anatomy - Springer Verlag

Schünke, Schulte, Schumacher, Voll, Wesker: Head, Neck and Neuroanatomy - Prometheus, Thieme

Andreas Wöge: A scaphoid rides in the moonlight, 2nd edition, self-published in Bornheim

Answers to the exam questions: 1B, 2D, 3C

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