Hematopoiesis (Part 3)

By Konstantina Bilali Panagiotidou - July 08, 2021

 

Megakaryopoiesis

Starting off, this procedure begins as it is expected, with the HCS, the multipotent self-renewing cells. HCS will produce a multipotent progenitor (MPP) which is a common progenitor for every cell in our body. This cell will differentiate into our common myeloid progenitor (CMP) which is produce by its turn another cell which is the progenitor of megakaryocytes and erythrocytes (MEP).  Basically, MEP is the cell that will give of either erythroblasts or megakaryocytes. The development of these two, depends on the signals, the factors, and the microenvironment. As a matter of fact, some important transcription factors that must exist in the surrounding in order for the Megakaryopoiesis to start being produced, are GATA-1 is crucial for the differentiation and the maturation of megakaryocytes, FOG-1 which interacts with GATA-1 and activates or deactivates it, GATA-2, Fii-1 , Pu.1 with its decrease being a key to the normal development of megakaryocytes  and RUNX1. The maturation and the final production of platelets take place in specific places in the bone marrow and with the interaction of other molecules and growth factors.

In order for the common myeloid progenitor to start developing towards the megakaryocytes, one important hormone must be present. This molecule is called thrombopoietin, it is produced in the liver and it regulates platelet production.

EMP cells will eventually differentiate into BFU cells and at that time, thrombopoietin is that one molecule that will get activated and help BFU cells differentiate into CFU. BFU and CFU cells are morphologically the same since both of them are immature cells of the bone marrow, however in cultivation, only the CFU cells are able to form colonies.  Eventually, the CFU cells will differentiate into promegakaryoblasts which will give off megakaryoblasts and these cells will mature into megakaryocytes.

Megakaryocyte has pseudopods and a specious cytoplasm. In addition, it is an excessively big cell, and its maturation happens in two stages: The first stage consists of the typical mitosis and in the second, there is the proliferation of the nucleus while the cytoplasm does not get divided (Polyploidy).  This results in a size increasement (by endomitosis).

The pseudopods the megakaryocyte has, will get detached from it , the nucleus will endure apoptosis and will get phagocytized by macrophages. At that time, the cell exists near the venus sinuses and then they will release the platelets in the blood circulation. Platelets have no nucleus, but they consist of vesicles such as lysosomes and alpha granules. 


https://www.sciencedirect.com/science/article/abs/pii/S0037196310000326


 Monocytes & Dendritic cells

Monocytes and dendritic cells are both considered to fall under the spectrum of myeloid cell line. They obviously share the MPP progenitor as all of them cells in our body, and also share the myeloid progenitor cell which will eventually differentiate into the granulocytes/macrophages progenitor (GMP). GMP cell will mature into monocytes/dendritic progenitor (MDG). One molecule which seems to separate which cells will be produced (monocytes or dendtritics) seem to be Ly6C+ cell. It is claimed that this cell appears both in the marrow and in the spleen and triggers the production of monocytes.

 

Monocytes

Monocytes are able to circulate in the blood for about 8 hours, increasing in size. After their enlargement, they migrate to different tissues and differentiate into macrophages. This differentiation process consists of the increment of their  organelles both in size and complexity and they also gain a high phagocytic capacity with the ability to produce higher levels of hydrolytic enzymes and a variety of soluble agents.

 

Dendritic cells

They have elongated cytoplasmic projections on their surface, and they are many different types of those cells.  Their main categories are: Langerhans cells, intracellular space cells, monocyte-derived dendrites, and plasma cell-derived dendrites. Each type of dendritic cells has different functions  of trapping the antigen in one area and presenting it in another place.

 

Lymphopoiesis

Lymphopoiesis is the creation of lymphocytes. These cells circulate all the time in the blood and in the lymph. As a matter of fact, the lymphatic system is one of the most important systems in our body because the lymph, originates from tissues and it slowly filters into the lymph node, piercing the cortex, paracortex and marrow, and gives phagocytes and dendritic cells the ability to trap bacteria or other antigens, which have been transferred by the lymph. If the same antigen invades again into our body, the lymph will immediately leave the lymph node while being filled with antibodies. The lymph that exists the lymph node, contains way more lymphocytes than the lymph that enter the lymph node. Lymphocytes are divided into three main categories: B cells, T cells and NK cells. Basically, those three cells have different molecules on their membranes surface.

T lymphocytes mature in the Thymus and during this procedure the T cell expresses on its membrane a molecule that binds antigens which is called T cell receptor (TCR). Those receptors are able to recognize antigens only when they have been connected with membrane proteins named Major Histocompatibility Complex (MHC) molecules and they are genetically diverse glycoproteins. After an antigen binds with MHC molecules, it will get recognized by some T cells, which will eventually start to multiply and differentiate into effector cells and T memory cells. It is important at this stage to distinguish, the three main different “subpopulation” of T cells: T helper cells, cytotoxic T cells and Regulatory T cells (Tregs).

T helper cells:  These cells contain a surface glycoprotein called CD4. After the presentation of an antigen connected with an MHC molecule the T helper cells are the ones starting to differentiate into the effector cells. Alternatively, the T helper cells can also differentiate into T memory cells which are responsible for the long-term immunity obtained against many pathogens.

Cytotoxic T cells:  The are part of the effector cells and  are recognized by their surface glycoprotein called CD8. Their utmost importance job is to monitor the body’s cells and kill the ones that present an antigen (always bonded with and MHC molecule I). For instance, such cells can be cells infected with a various, *cancer cells and a foreign tissue from a transplanted organ. 

Regulatory T cells:  They are identified by the presence of both CD4 and CD25 molecules in their cell membrane. However, Treg cells suppress immune responses, they basically are negative regulators of the immune system. It has been claimed that some members of the Treg cell subpopulation may be ancestors of the memory cells.

 

B lymphocytes mature in the bone marrow, and they compose and express some membranes molecules called antibodies or immunoglobulins (membrane bound immunoglobulins). These cells have receptors on their surface membrane called BCR and they are able to bind with antigens without the presence of MHC molecules.

 When a B lymphocyte cell interacts with an antigen for the first time, the cells start to get divided very quickly. It starts to differentiate into B effector cells which are called plasma cells and memory B cells. Memory B cells have a longer lifespan than B virgin cells and express the same membrane immunoglobulins as their parent cell. In addition, Plasma cells produce immunoglobulins in secretory form and have little or no membrane immunoglobulins. As a matter of fact, they are in the final stage of maturation and do not divide furthermore. However, they die within 1 or 2 weeks.

 

Nature killers (NK) cells are large granular lymphocytes and appear to have the ability of expressing cytotoxic activities against cancer cells and some virus infected cells. Nevertheless, it has been indicated that they do not contain receptors nor immunoglobulins. At the same time, an NK cell has receptors that allow the recognition of abnormalities, like the decrease of the expression of MHC class I molecules or the appearance of an unusual expression pattern of surface antigens, by some cancerous and virus-infected cells.

Some cancer cells express molecules that are foreign to our body. As a result, the immune system, triggers a respond by producing antibodies. These antibodies are called anti-cancerous (or anti-viral in case of virus-infected cells) antibodies that bind with the target cells. The NK cells, express a membrane receptor called CD16 which is designed for a specific region of the antibody molecule, and has the ability to bind to these antibodies  causing the destruction of target cells. This is known as Antibody-Dependent Cell-mediated Cytotoxicity (ADCC).



Sources :

Kuby immunology





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