Cell Traffic

  The cells involved in the immune response are organised into tissues and organs in order to perform their functions most effectively. These structures are collectively referred to as the lymphoid system.

   The primary lymphoid organs are the bone marrow and the thymus.

   The secondary lymphoid organs include the spleen, the lymph nodes, which are distributed at various places around the body, and the mucosa-associated tissues including the Peyer's patches of the gut, the tissues around the bronchus, and the tonsils and adenoids, known as Waldeyer's ring.

    These organs and tissues are connected together by the lymphatic network, and the cells belonging to the immune system migrate from the blood to the tissues and then back to the blood again via the lymphatic network. The lymphoid organs guard against infections in the particular regions of the body where they are situated, while the cells which move around the network are patrolling between these guard posts.

    The principal cells are; lymphocytes, neutrophils, macrophages, and dendritic cells, all of which originate in the bone marrow.

    The lymphocytes consist of B and T cells. T-cells emerge from the bone marrow and travel to the thymus where they are educated and mature into functional cells, acquiring their receptors for specific antigens. This is the means by which the different lymphocytes are committed to recognising different antigens.

   They then go through a process of selection which ensures tolerance of self-antigens, those which are the normal constituents of our body, and the capacity to recognise and react to non-self antigens. The identification of appropriate antigens occurs by means of special recognition molecules on their surface, which are called T-cell receptors.

    From the thymus they travel through the blood stream to the various secondary lymphoid tissues, such as the lymph nodes, the Peyer's patches on the gut, or the spleen. They then circulate through the lymphatics back into the blood stream.

    B-cells develop in the bone marrow. They do not pass through the thymus, but move directly to the lymph nodes and the spleen through the blood stream, and circulate around the lymphatic network. The antibody on each antigen-reactive B-cell is specific for one antigen only.

So, although T and B-cells are different in their origins, each has a repertoire of specificities from which particular members can be selected to respond specifically to individual antigens. They will continue to circulate between secondary lymphoid tissues until they encounter an antigen which the lymphocyte receptor can recognise, or they die.



    The next group is thu neetrophils. These originate in the bone marrow and travel through the blood stream, but unlike the lymphocytes they do not recirculate. Instead they make a one way journey to the tissues, particularly areas of infection. If they find any foreign material, they will phagocytose it and destroy it internally before they eventually die.

Neutrophils tend to migrate into the inflammatory sites but some will go to all tissues except the brain.

     Macrophages fall into two categories, fixed and mobile. Fixed macrophages move from the bone marrow to their own secondary lymphoid tissue and remain there. The fixed macrophages also go to non-lymphoid tissue.

Mobile macrophages travel from the bone marrow through the blood stream and back to the local lymph nodes through the lymphatic network. Their main role is to destroy the antigens by phagocytosing them.

     Dendritc cells are antigen presenting cells. These travel from the bone marrow to fixed areas in the lymph nodes, the spleen and tissues. Their job is to trap antigens circulating in the lymph and blood and present it to the resident lymphocytes.

They can also take up antigens from non-lymphoid tissue, migrate to lymphoid tissues and then present the antigens to lymphocytes which are able to bind to them via suitable receptors on their surfaces.

    The lymph node is part of the network which filters antigens from the interstitial tissue fluid and lymph during its passage from the periphery to the thoracic duct. They are kidney shaped and have an indentation called the hilus where blood vessels enter and leave the node.

Within the node are various B-cell areas in the germinal centres in the cortex. Around these, in the paracortex are the T-cell areas. The medulla contains both T and B-cells.

   In the paracortex there is a pattern of blood vessels which are called the high endothelial venules. The lymphocytes will come into the lymph node through the blood stream. They will then migrate out across the high endothelial venule to the B-cell and T-cell areas.

    Because the lymph nodes run in chains, lymphocytes can also come in from other lymph nodes via the afferent lymphatics. They pass out through the efferent lymphatic.

    Recirculating macrophages pass in through the afferent lymphatics and will tend to go straight to the cortex, then the medulla and then out through the efferent lymphatic.

     Dendritic cells will come in through the tissue, entering through the afferent lymphatics and will go to the T-cell areas. If an antigen comes into the node, either presented by a macrophage or dendritic cell, an immune response takes place with proliferation and activation of responding cells.

The lymphocytes will then come out of the lymph nodes and go to the area of infection as effector cells or as memory cells to other lymphoid tissues.

    The spleen is organised into areas of red pulp, that surround the white pulp which encases small arterioles. The white matter contains the lymphocytes, the B-cell areas and T-cell areas.

    The lymphocytes come in through the blood vessels and distribute themselves into the areas of white pulp or the periarteriolar lymphatic sheath. Antigens from the blood are also trapped in the spleen. The cells leave by crossing the marginal zone bridging channels.

    Cells entering into the Peyer's patches do so through the high endothelial venules - HEV's. Lymphocytes drain out through lymphatics to the local lymph nodes. Antigen comes from the lumen of the gut.

A group of special cells across the top of the patch, called M-cells, take antigen from the gut and transport it across into the area where the lymphocytes can recognise it. If an immune response takes place, these lymphocytes will migrate to the infected area of mocosa.