Agranulocytes

Definition, Function, Production, Differences 


Definition:  What are Agranulocytes?

Agranulocytes, which include lymphocytes and monocytes, are a type of white blood cell that, unlike granulocytes, lack visible granules. As such, they have a clear cytoplasm that allows for better visibility of the nucleus.

Apart from lacking clearly visible granules, agranulocytes are also characterized by a single, large nucleus (not lobed). For this reason, they are also referred to as mononuclear leukocytes which differentiate them from multi-lobed granulocytes.

In the body, agranulocytes are involved in adaptive immunity (acquired immunity) and thus use immunological memory to act against invading pathogens. 

 

Some of the main functions of agranulocytes include:

 




Production of Agranulocytes

 

Like the other white blood cells, agranulocytes are produced through a process known as leukopoiesis. This process starts with the differentiation of the hemocytoblast (pluripotent hemopoietic stem cell).

Whereas monocytes are produced through the myeloid lineage, lymphocytes are produced through the lymphoid lineage. 


By CNX OpenStax [CC BY 4.0 (https://creativecommons.org/licenses/by/4.0)]By CNX OpenStax [CC BY 4.0 (https://creativecommons.org/licenses/by/4.0)]


Monocytes

During the production of monocytes, the hemocytoblasts first differentiate to produce myeloid stem cells. Under the influence of interleukins 3 and 5 as well as agranulocytic-colony stimulating factors (AG-CSF), the myeloid stem cells differentiate to form the monoblast which is committed to developing into a monocyte (committed progenitor cells).

Here, the monoblast further develops into a promonocyte which produces the monocyte.

 

* While granulocytes are also produced through the myeloid stem cell lineage, this is influenced by interleukins 3 and 5 as well as granulocytic stimulating factors.

 

Once they leave the circulation and enter into tissues, monocytes become macrophages that are described as "big eaters" in some books. Macrophages are known by a number of specific names depending on the type of tissue in which they reside. 


These include:

 

  • Microglia - Found in the central nervous system
  • Kupffer cells - Found in the liver 
  • Alveolar macrophages - Found in the lung
  • Osteoblasts - Found in the bone

 


Monocyte Characteristics


·       Monocytes make up between 2 and 8 percent of the total leukocyte count


·       Measuring between 12 and 20um in diameter, monocytes are the largest blood cells in the body 


·       Characterized by a horseshoe-shaped nucleus - However, the nucleus is not lobed


Lymphocytes

In the production of lymphocytes, the hemocytoblast first differentiates to produce the lymphoid stem cell. In turn, lymphoid stem cells differentiate under the influence of interleukins 3 and 5 as well as agranulocytic colony-stimulating factors to produce the lymphoblast.

Through specific proliferation and differentiation, the lymphoblast produces the prolymphocyte which in turn develops to produce a lymphocyte. Here, however, there are two types of lymphocytes (B and T lymphocytes). 

Being the mature lymphocyte, the B lymphocyte leaves the bone marrow and enters the bloodstream through the sinusoidal capillaries before reaching the lymphoid organs (secondary lymphoid organs like spleen, lymph nodes, etc where they mature further).

The T lymphocyte, on the other hand, is not functional and has to reach a lymphatic gland/organ (thymus) in order to mature. 

 

* The migration of T lymphocytes from the bone marrow to the thymus is influenced by several chemokines produced by the thymus including thymosin, thymotaxin, thymopoetin, and other thymic factors. 

 

* While lymphocytes and monocytes are produced through different lineages, their production is influenced by similar factors (IL-3, IL-5, and AG-CSF).


Lymphocyte Characteristics


·       Only blood cells produced by the lymphoid stem cells


·       Undergo reproduction in the lymphatic tissues (lymphocytes also undergo further maturation in the lymphatic tissue)


·       Make up between 20 and 30 percent of the total leukocyte count - This makes lymphocytes the second largest group of leukocytes in the blood


·       Based on size, lymphocytes are divided into three main groups: The largest cells measure between 14 and 17um in diameter, smaller cells measure between 6 and 9um in diameter  (characterized by a large nucleus), and relatively large cells measure between 10 and 14um in diameter (characterized by a smaller nucleus to cytoplasm ratio)


Morphological characteristics of hematopoietic cells in a Wright’s stain, May-Giemsa stain/May-Grünwald-Giemsa stain by Jomegat assumed[CC BY-SA 3.0(http://creativecommons.org/licenses/by-sa/3.0/)]Morphological characteristics of hematopoietic cells in a Wright’s stain, May-Giemsa stain/May-Grünwald-Giemsa stain by Jomegat assumed[CC BY-SA 3.0(http://creativecommons.org/licenses/by-sa/3.0/)]


Functions


Monocyte


Once monocytes migrate and enter blood circulation, they may differentiate into macrophages or dendritic cells depending on the type of infection. Therefore, by looking at the different, general functions of these cells, it becomes possible to get a better understanding of monocyte functions. 



Macrophages


Following a microbial infection (e.g. bacterial), the innate immune system works to localize the infection through a process known as inflammation. This aims to keep the infection from spreading to other parts. Here, inflammation results in the dilation of the blood vessel thus bringing more blood to the area.

As monocytes leave circulation and enter into the affected tissue, they differentiate to form macrophages that typically reside in various body tissues. At the site of infection, the macrophages engulf the invading pathogens and destroy them through a process known as phagocytosis.

Once the pathogen has been engulfed (ingested), the macrophage forms a vacuole known as a phagosome that contains lysosomes, which contains proteolytic digestive enzymes, that act on the pathogen.

 

As digestion continues, macrophages, being antigen-presenting cells, start forming MHC class II complex (major histocompatibility complex molecules) which are then placed on its cell membrane.

In addition, the macrophage also places a small peptide (antigen) of the pathogen onto the MHC molecule. This allows for other immune cells (particularly T lymphocytes that carry CD4 glycoproteins) to identify and bind onto these antigens in order to initiate an immune response by releasing appropriate chemicals and activating B cells to action. 

 

Therefore, in addition to simply actively destroying pathogens through phagocytosis, macrophages also serve to stimulate other immune cells to action. For this reason, they are involved in both innate and adaptive immune systems. 


See more on Immunology


Dendritic Cells


As is the case with macrophages, dendritic cells are also differentiated monocytes in tissue. They, like macrophages, are also capable of phagocytosis. They primarily function as antigen-presenting cells and are thus commonly referred to as professional antigen-presenting cells.

For the most apart, dendritic cells are commonly found in areas of the body that are closer to the external environment. As such, they are more likely to be found on the skin and lungs among other tissues. 

In these areas, dendritic cells are well situated to interact with various pathogens invading the body. Here, they capture and phagocytose the pathogen which allows lysosomes to break them down. As with macrophages, a small peptide of the pathogen is then expressed on the MHC complex. 

Dendritic cells are also motile which is a great advantage given that they are able to migrate to various tissue such as the spleen where they present the antigen to other immune cells thus activating them to respond appropriately.

For this reason, dendritic cells have been shown to effectively work with T lymphocytes in the immune system thus protecting the body against invading microorganisms. 

 

* Monocytes are also described on CD14 and CD16 expression. 


Lymphocyte


B Lymphocytes


Produced as functional lymphocytes in the bone marrow, B cells (B lymphocytes) are involved in humoral immunity, also known as body fluid immunity.  As such, they produce and store antibodies in the event of re-infection. 

In the event of an infection, pathogens like bacteria ultimately release antigens that can be detected by receptors located on the surface of B cells.

The process may start with the engulfment of a pathogen by such immune cells as macrophages and dendritic cells that ultimately present the antigen to B cells. These antigens (which are basically peptide molecules) may float around the body and reach various tissues where they are detected. 

In the body, B cells have specific receptors that can identify and bind to given antigens (pathogen antigens) which cause the cell to undergo a process known as cell-mediated endocytosis.

Here, the cell membrane invaginates in order to engulf the antigen so that it can be acted upon by digestive enzymes. As the antigen is broken down, the cell also starts to form MHC class II which, along with molecules of the antigen (known as antigenic epitope), is placed on the cell membrane. 

Once the MHC class II complex is formed (which binds the antigenic epitope) on the surface of the B cells, interaction and binding with helper T cells (with  complementary T-cell receptors as well as CD4 glycoprotein) results in the production of chemicals known as lymphokines that influence the cloning of B cells.

This allows the newly produced B cells (Clones) to find and bind more antigens and also differentiate into plasma cells (produce antibodies that bind antigens) and memory B cells (which retain the memory of antigens allowing for the identification and destruction of the invading pathogen in the future).


T Lymphocytes


Unlike B cells (B lymphocytes), T cells released from the bone marrow are not functional/active. As such, they move to the thymus where they undergo further development and maturation. At this point, they are described as naive given that they are not yet activated. 

 

* In the immune system, T lymphocytes have both effector and regulatory functions.





Types of T Cells


Helper T Cells


As already mentioned, helper T cells are activated when they interact with antigen-presenting cells such as dendritic cells. On their surface, Helper T cells have T cell receptors that bind to specific MHC class II complex located on the antigen-presenting cells thus resulting in their activation.

As with the B cells, this activation resulting in the cloning of helper T cells to form many clones of themselves that are involved in immune response. On the other hand, helper T cells also produce memory T cells that retain memory of the antigen (and thus the specific pathogen).

Whereas memory T cells produced last longer in order to identify the pathogen in the future, the effector helper T cells (clones) release cytokines that stimulate increased production of other immune cells (e.g. macrophages and killer T cells) to respond to the invading pathogen.  

 

* Cytokines released by effector T cells also play an important role in promoting the maturation of B cells into plasma and memory B cells. 


Cytotoxic T Cells (Killer T Cells)


In the body, cytotoxic cells are primarily involved in the destruction/lysis of cancerous or infected cells (e.g. virus-infected cells). 

Unlike antigen presenting cells (which contain MHC class II), all cells in the body (nucleated cell) carry MHC class I complex on their surface. In cases where a cell is damaged, as is the case with cancer cells, abnormal proteins from the cells are presented on the MHC class I complex on their surface.

This also occurs in cases where a cell is infected by a virus. Here, viral proteins are also presented on the MHC class I complex. These proteins are then identified by specific receptors located on the cytotoxic T cells which result in binding.

In turn, this results in the activation of cytotoxic T cells followed by differentiation of the cells into effector cytotoxic T cells and memory cytotoxic T cells. Here, the effector cells may then destroy the infected/damaged cells by releasing perforins (which perforate the damaged/infected cell thus destroying it) or produce proteins known as granzymes that promote cell destruction. 

 

* Natural killer cells are examples of cytotoxic T cells.


Agranulocytes Vs Granulocytes

Granulocytes and agranulocytes are white blood cells that play an important role in body immunity. While they both serve the same functions in animals and human beings, there are a number of differences between the two based on presence and absence of cytoplasmic granules, shape of the nucleus, types of immune cells and origin among others. 

One of the main notable differences between granulocytes and agranulocytes is the fact that while granulocytes contain clearly visible granules, they are not readily visible/obvious in agranulocytes.

The other obvious difference between the two is that while granulocytes are polymorphonucleate, agranulocytes and mononuclear leukocytes.

Whereas granulocytes are characterized by a lobed nucleus (a nucleus with two or more lobes), agranulocytes contain a single, large nucleus. For lymphocytes (agranulocytes), in particular, the nucleus is significantly large leaving very little space for the eosinophilic cytoplasm. 


In blood, granulocytes, which consist of eosinophils, neutrophils make up the majority of white blood cells (65 percent) while agranulocytes (monocytes and lymphocytes) only make up about 35 percent of the total leukocytes. While they all originate from the bone marrow, some of the agranulocytes (T cells) mature and develop further in the lymphoid organs.

While granulocytes are largely involved in innate immunity, agranulocytes are mostly involved in adaptive immunity. However, both can be indirectly involved either immune systems. 


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References


J Prinyakupt. (2015). Segmentation of white blood cells and comparison of cell morphology by linear and naïve Bayes classifiers. ncbi. 

 

Karen Raymaakers. (2019). How Monocytes Function in the Body. 

 

Lakna Panawala. (2017). Main Difference – Granulocytes vs Agranulocytes Stunning images of cells AAT Bioquest Discover how scientists use immunofluorescence to capture beautiful cell images! ResearchGate. 

 

Stephen Chiu and Ankit Bharat. (2017). Role of monocytes and macrophages in regulating immune response following lung transplantation. ncbi. 

 

 

 

Links

 

https://microbiologyinfo.com/blood-cells-types-functions/

https://www.mabtech.com/knowledge-center/applied-research/monocytes-and-macrophages



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