Phagocytosis is the process by which particulate material is endocytosed (“eaten”) by a cell (From Greek phagein, to eat.). The process of phagocytosis is one of the many different ways our immune cells fight infections. Macrophages and neutrophils are cells of the immune system that use phagocytosis to bind and ingest invading microorganisms. Phagocytosis is a complex mechanism that requires for the cells to rearrange its inner cell bits to surround and engulf the target.

 

Macrophage engulfing bacteria animation              Neutrophil, a leukocyte phagocytoses bacteria

 

Below is a playful animation I created showing a macrophage chasing bacteria to ultimately phagocytose them.

 

 

Here is a video of an actual cell under the microscope chasing a bacteria to engulf it. This cell shown is a neutrophil, which are the first cells to get to the site of infection and are ferocious eaters that rapidly engulf invaders.
 

You can learn more information about phagocytosis here:

The granulocytes are so called because they have densely granules in their cytoplasm; they are also called polymorphonuclear leukocytes because of their lobulated nuclei. There are three types of granulocytes:

  • Neutrophils can perform phagocytosis and are the most abundant type of granulocytes and the most abundant type of white blood cells overall in most mammals.
  • Eosinophils make up about 1–6% of white blood cells and play a role in defence against parasitic infections.
  • Basophils are the least common of the granulocytes, they can perform phagocytosis, produce histamine and serotonin and these cells play a role in immune regulation and allergic responses.

Let us explore more details about these cells.

 

Cartoon of granulocytes, basophil, eosinophil and neutrophil

Neutrophils

These cells are typically the first leukocytes to be recruited to an inflammatory site and are capable of eliminating pathogens by multiple mechanisms.

Super powers include:

  • Phagocytosis
  • Degranulation
  • Release of neutrophil extracellular traps (NETs)

cartoon of a neutrophil granulocyte cell

 The picture of the blood smear above was taken from The Histology Guide. You can see the neutrophil has a single but multilobed nucleus stained in a pink color. The multilobed nuclei can have between 2 and 5 lobes.

Neutrophils are an important first line of defence and part of the innate immune system. They are crucial players in the response against fungal infection. The localization of neutrophils to the site of inflammation is important for clearance of the infection. Even though they play a big role in the innate immune response neutrophils can also regulate adaptive immune responses by releasing arginasea 1 and suppressing T cell proliferation and activity. Neutrophils can also act as antigen-presenting cells (APCs).

Eosinophils

Eosinophils contribute to the pathogenesis of different diseases, including asthma and primary hypereosinophilic syndromes. They are activated and recruited into tissues in response to inflammatory stimuli.

Super powers include:

cartoon of an immune cell called eosinophil

The picture of the blood smear above was taken from The Histology Guide and shows an eosinophil with a two lobed nucleus. Eosinophils have large acidophilic specific granules that are stained bright red, or reddish-purple.

Eosinophils play a role in host defence against parasites such as helminths and can elicit a profound TH2-type cytokine-mediated pathology. In the gif below mouse eosinophils are migrating toward a C. elegans dauer larva, a parasite.

Basophils

Like eosinophils, basophils play a role in both parasitic infections and allergies. Basophils have protein receptors on their cell surface that bind IgE, an immunoglobulin involved in parasite defense and allergy.

Super powers include:

  • Degranulation
  • Production of heparin, which prevents blood from clotting too quickly and histamine, which promotes blood flow to tissues
  • Fighting ectoparasite infection, e.g., ticks

cartoon of immune cell called basophil

The picture of the blood smear above was taken from The Histology Guide and shows a a basophil with granules stained in deep blue. The contents of the granules include heparin, histamine and serotonin.

A review by Nature Immunology goes in more detail about the various roles basophils. Superpowers:

  • Initiating of chronic allergy
  • IgG-mediated anaphylaxis
  • Driving TH2-cell differentiation

Mast Cells

Where do Mast Cells fit in?

Just like granulocytes, mast cells have prominent dense granules in their cytoplasm and the contents of these granules include histamine, heparin and proteases. Event hough mast cells look morphologically very similar to basophils and both express CD34, mast cells have a different bone marrow precursors. Below is a diagram from Nature Reviews Immunology 12, 253-268 (April 2012), showing the development of neutrophils, eosinophils, basophils and mast cells and how they originate from different precursors.

Unlike basophils, masts cell circulate in an immature form, maturing only in tissue sites where they are resident. They are long-lived cells, able to survive for months or years. At the earliest stages of infection, mast cells are important for communicating the presence of a pathogen to many cell types located nearby. Mast cells are well known to have a role in allergy and anaphylaxis, but are also found to be involved in wound healing, angiogenesis and immune tolerance.

Mast cells express a high-affinity receptor (FcεRI) for the Fc region of IgE, the least-abundant member of the antibodies and as a result mast cells are coated with IgE. When they encounter the antigen specific for the antibody mast cells are stimulated to release the contents of their granules (process known as degranulation) which is what causes the symptoms of allergy.

cartoon of a mast cell immune type

One of the chemicals mast cells release is histamine. Histamine is responsible for dilation of post-capillary venules, increase in blood vessel permeability which then leads to swelling and redness. 

 

Resources

References

The Histology Guide: White blood cells
Newly discovered roles for basophils: a neglected minority gains new respect. Nature Reviews Immunology 9, 9-13 (January 2009).
Neutrophil recruitment and function in health and inflammation. Nature Reviews Immunology 9, 9-13 (January 2009)
Eosinophils: changing perspectives in health and disease. Nature Reviews Immunology 13, 9-22 (January 2013).

Coordinated regulation of myeloid cells by tumours. Nature Reviews Immunology 12, 253-268 (April 2012)

Immunobiology: The Immune System in Health and Disease. 5th edition. Janeway CA Jr, Travers P, Walport M, et al. New York: Garland Science; 2001.

This video shows how dendritic cells growing in culture are transfected with a plasmid containing a gene for the Green fluorescent protein (GFP).

 

Transfection is the process of deliberately introducing nucleic acids into eukaryotic cells. Various methods can be used to transfect. Electroporation, shown in this video, is a technique by which an externally applied electrical field applied to the cells makes the plasma membrane of a cell temporarily porous so that molecules such as DNA can pass freely through it.

Once the DNA is inside the cells the genes in this DNA molecule can be “read” by the cell machinery and made into proteins. In this example the molecule DNA entered the cell has information to produce the green fluorescent protein GFP. Therefore the cells that have taken in the DNA can now make GFP and glow green.

This video is inspired in the DC transfection I was doing while I was in graduate school. The results using transfected DCs  are published in Figure 5.f in the paper A CD74-dependent MHC class I endolysosomal cross-presentation pathway.

Dendritic cell transfected and expressing green fluorescent protein

Below are some links with more information on the topics discussed in this post.

 

 

This animation is a cartoon depicting a macrophage chasing bacteria to ultimately phagocytose them.

 

 

Macrophages are white blood cells. One of their main roles is to engulf and then digest pathogens such as bacteria. This process is known as PHAGOCYTOSIS. It is a complex mechanism that requires for the macrophage to rearrange its inner cell bits to surround and engulf the target.
 

macrophage jumping to engulf bacteria cartoon
 

The word macrophage comes from the word macros “large” and phagein “eat”. Macrophages are big cells that eat. The function of these cells is to phagocytose (engulf and then digest) cellular debris and also pathogens such as bacteria. 

 

Dendritic cells are named after their branched projections called dendrites. These cells are the sentinels of the immune system and are always testing their surroundings in case they see any danger.

 

Dendritic Cell Cartoon Immunology

Below is a links with more information on dendritic cells.

The lymphocytes are a class of white blood cells considered to be part of the adaptive immune system. There are two major classes of lymphocytes:

Lymphocytes have evolved to provide a more versatile means of defense. These cells display on their cell surface receptors that recognize specific antigens. When activated, the cell enlarges to form a lymphoblast and then proliferates and differentiates into an antigen-specific effector cell.

 

cartoon of lymphocytes T cells CD4, CD8, Treg and B cells

T cells are named after the organ they develop in, the Thymus.

T cells are divided in different subsets and types depending on the receptors they express on the surface as well as their gene expression and function.

T helper cells, also known as CD4+ T Cells, organize and “help” to alert other cells to coordinate the immune system to clear pathogens (the bad guys). CD4 T cells are divided into various subsets such as T h1, Th2, Th17. Another subset of CD4 T cells includes regulatory T cells also known as suppressor T cells, which are shown in the cartoon above as the police CD4 T cells. Regulatory T cells (T regs) act like suppressor cells that control the immune system and promote tolerance. These cells make sure the immune response doesn’t get out of hand and I therefore think of them as little police officers controlling and ensuring there is order.

CD4 T cell Lymphocyte Cartoon Super hero

Cytotoxic T cells (CTLs), also known as Killer T cells,  are a special type of T cells with the ability to kill other cells. Usually they kill cells that have been infected with a virus. This way the virus can no longer use these cells for replicating inside of them. CTLs secrete cytotoxins to kill the other cells and are therefore called “cytotoxic” T cells.

 

CD8 CTL Killer T Cell Cartoon

 

B cells develop in the bone marrow and are therefore called B cells. These cells are responsible for producing antibodies. The antibodies produced by B cells circulate around our body and bind to specific viruses or bacteria to neutralize them and help get them killed by other cells of the immune system.
B cell Cartoon antibodies white background

 

References:

Immunobiology, 5th edition. The Immune System in Health and Disease
Authors: Charles A Janeway, Jr, Paul Travers, Mark Walport, and Mark J Shlomchik.