THE OTHER CELLS

There are other cells that participate in the immune response besides the B and T lymphocytes. These cells are known as accessory cells.  They have many functions and play a central role in antigen presentation and elimination. The accessory cells,which are derived from the myeloid line, act both in the natural or innate immune response and in the adaptive immune response.

This group of cells is made up of:

We can differentiate two types of phagocytic cells: 

1. Monocytes-macrophages They are able to perform phagocytosis repeatedly, and along with dendritic cells and B lymphocytes belong to the antigen-presenting cells family (APC).

2. Granulocytes: neutrophils, basophils and esosinophils. These are fast phagocytic cells, but not able to perform phagocytosis  repeatedly. They do not present antigens (they do not express SLA II) 

Picture of macrophage surface using scanning electron microscopy. 

Monocytes-macrophages. They are large cells, with a diameter of around 15 mm, with a large cytoplasm and a single nucleus that can be spherical, ovoid or lobulated. A  very developed Golgi apparatus can be observed in their cytoplasm, as well as the  rough surface of the endoplasmic reticulum, mitochondria, and a large number of  lysosomes, which contain hydrolytic enzymes. This means that they have a great capability of producing and secreting proteins. 

They derive from the myeloid lineage. First, they undergo transformation into promonocytes in the bone marrow; then into monocytes, in periphery blood and finally into macrophages in the different organs.

Macrophage diagram.

Monocytes-macrophages,  together with dendritic cells and B lymphocytes, are the only porcine cells that express in their surface histocompatibility antigens SLA II. Thus, they are the only cells able to present antigens to helper T lymphocytes CD4+. This cellular family is known as Antigen- Presenting Cells (APC).  

Monoclonal antibodies are used nowadays to study and differentiate monocytes-macrophages. In the last Symposium about porcine immune system differentiation, in 1998, three monoclonal antibodies were defined for the study of porcine macrophages. They were called SWC (for Swine Workshop Cluster), plus a number. Thus, the most used Mab at the moment are: SWC1 and SWC9, which mainly differentiate monocytes and macrophages, and SWC 3 that react both with monocytes and with differentiated macrophages and granulocytes.

These markers have recently allowed us to come to know that monocytes are SCW1+SWC9-. When transformed to macrophages however, they become SWC1-SWC9+. Different studies in peripheral blood monocytes can be done by means of flow cytometry, while for tissue studies, histochemical techniques are performed (How are cells studied?) 

Macrophages Besides presenting a characteristic morphology depending on the organ where they are located, different types of activity, depending on their maturation level, their activation, and their specific localization.

Suspended cells, with monoclonal antibodies added , pass through a very thin tube, forming a single  line of cells. They are analyzed both by laser and light beams. First, the laser beam identifies labeled antibodies, and the light beam, measures cell size.

Macrophages have the function of phagocytosis and lysis of microorganisms and infected or tumor cells, acting both directly (natural or innate immunity) or through their Fc receptors for immunoglobulins or for  the complement. As antigen presenting cells, they participate in the acquired immunity, binding and processing antigens in order to present them to T lymphocytes. Finally, macrophages produce a large number of cytokines: interleukines 1, 2, 6, 12, interferon a and b, tumor necrosis factor-a (TNF-a) (Chapter 6). They also produce the complement elements as well as several enzymes (Chapter 7). 

Dendritic cells are also antigen presenting cells (APC) and, thus, have the natural capability of antigen uptake. They are located, just as macrophages, in tissues such as skin and mucosa (capture tissues) and in lymph nodes and spleen (presenting tissues). They are especially active in the skin, where they have the role of binding those antigens entering the body, taking them to the closest lymph node and then presenting them to lymphocytes T CD4+ . 

 Neutrophil or Polyimorphonuclear 

• Chemotaxis or attraction.
• Adherence and opsonization.
• Ingestion and vacuolization.
• Digestion or destruction.

A Macrophage phagocytizing two bacteria
Candida albicans.
© James A. Sullivan, Cells Alive!

Phagocytosis activation occurs by the liberation of chemotactic substances (chemotaxis). Tthe complement is activated when platelet factors are liberated or by means of other substances. Once the macrophage encounters a foreign particle, it binds to it neutralizing its negative charges (both are repelled). This phenomenon is  eased when the foreign particle is attached to immunoglobulins or the C3b fraction of the complement (Adherence). The ingestion  occurs by means of pseudopoda, which enclose the foreign particle, incorporating it  to the cytoplasm and forming a vacuole or  phagosome (Ingestion). Finally, the particle is digested by lysosomal enzymes (Destruction).

The  second most important granulocytes are the Eosinophils. They are so named because they incorporate acid histological stains, such as eosin. Eosinophils enter the spleen from the bone marrow when they are not completely mature, and then undergo maturation in this organ. Later, they  pass to blood and tissues. Their half live is very short, less than an hour. Their main role is also phagocytic, even though their granules do not contain lisozime.They do have large quantities of acid phosphatase and peroxidase. They are very effective against parasites.

In summary, even though granulocytes do not react in a specific way with antigens (recognition of antigens depends on innate reactions usually due to the receptors of the own pathogen or to complement activation) they play a main role in phagocytic and inflammatory processes, especially when these have an acute character. 

Their membrane receptors allow them to phagocyte opsonized particles.Thanks to their receptors for the Fc fraction of the immunoglobulins, they can act as effector cells in antibody depending cellular cytotoxicity  (ADCC)