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Asplenia

Functional Asplenia
Functional asplenia can occur when patients with metabolic or haematological disorders have their splenic tissue organisation altered. This can lead to results similar to those seen in patients who have undergone a splenectomy e.g. becoming infected with encapsulated bacteria such as Haemophilus influenzae, Streptococcus pneumoniae and Neisseria meningitidis. Patients who have some form of asplenia have an increased susceptibility to these encapsulated bacterial infections mainly because they lack IgM memory B cells and their non-adherence to polysaccharide vaccines. Furthermore there is a deficiency of other splenic cells e.g. splenic macrophages. This combined with the lack of B cells can provide an environment favourable for the development of bacterial infections.

Spleen section: red pulp

The red pulp also acts as a large reservoir for monocytes. These monocytes are found in clusters in the Billroth's cords (red pulp cords). The population of monocytes in this reservoir is greater than the total number of monocytes present in circulation. They can be rapidly mobilised to leave the spleen and assist in tackling ongoing infections.

Red Pulp Macrophages
Macrophages are highly diverse mononuclear phagocytes that are present throughout the body, including the spleen. Those located in the red pulp are known as red pulp macrophages (RPMs). They are necessary for maintaining blood homeostasis by performing phagocytosis upon injured and senescent erythrocytes and blood-borne particulates. Evidence suggests that RPMs are mainly produced during embryogenesis and are maintained during adult life.

Additionally, there are a number of cell-intrinsic and cell-extrinsic factors that regulate the development and survival of RPMs, these factors being: Spi-C, IRF8/4, heme oxygenase-1 and M-CSF.

RPM's are capable of inducing the differentiation of regulatory T cells by the expression of transforming growth factor-β. They can also secrete type-1 interferons during parasitic infections.

Blood in the arteries end in the Billroth's cords (red pulp cords). These cords are made up of fibroblasts and reticular fibres which form an open blood system without an endothelial lining, and it is within these cords that F4/80+ macrophages are found, which are associated with the reticular cells of these areas and are collectively known as red pulp macrophages. From the Billroth's cords, the blood passes into the venous sinuses of the red pulp, which are lined with discontinuous endothelium as well as stress fibres extending under the basal plasma membrane, parallel to the cellular axis. This arrangement of the stress fires combined with the parallel arrangement of the sinus endothelial cells forces the blood in the red pulp through slits that are formed by the stress fibres. However, this passage can become difficult for ageing red blood cells due to their less flexible membranes and therefore they get stuck in the cords and they will be subsequently phagocytosed by the red pulp macrophages. This process is known as erythrophagocytosis, which is important for the turnover of red blood cells and the recycling of iron, which is a major function of the red pulp macrophages and is made possible by this special structure of the red pulp.

The iron from the red blood cells is either released by the red pulp macrophages or they are stored in the erythrocyte itself in the form of ferritin. Also, the erythrocyte can store larger amounts of iron in the form of hemosiderin (an insoluble complex of partially degraded ferritin), and large deposits of this can be seen in the red pulp macrophages. The red pulp macrophages also obtain iron by scavenging a complex of haemoglobin (released from erythrocytes destroyed intravscularly throughout the body) and haptoglobin via. endocytosis through CD163. The iron stored in the splenic macrophages are released depending on the requirements from the bone marrow.

Splenectomy:

It has been found that the risk of acquiring sepsis is 10 to 20 times higher in a splenectomized patient compared to a non-splenectomized patient, which can result in death, especially in young children.[2]

Mild thrombocytosis may be observed after a splenectomy due to the lack of sequestering and destruction of platelets that would normally be carried out by the spleen. In addition, the splenectomy may result in in a slight increase in the production of platelets within the bone marrow. Normally, erythrocytes are stored and removed from the circulating blood by the spleen, including the removal of damaged erythrocytes. However, after a splenectomy the lack of presence of the spleen means this function cannot be carried out so damaged erythrocytes will continue to circulate in the blood and can release substances into the blood. If these damaged erythrocytes have a procoagulant activity then the substances they release can lead to the development of a procoagulant state and this can cause thromboembolic events e.g. pulmonary embolism, portal vein thrombosis and deep vein thrombosis.

Marginal Zone:

Marginal Zone Macrophages
Within the marginal zone there exists two types of macrophages that are unique to this area: the marginal zone macrophages and the marginal metallophilic macrophages. These two macrophage sub-types are characterized by the expression of SIGN-R1 on the marginal zone macrophages and CD169 (siglec-1, sialoadhesin) on the marginal metallophilic macrophages.

In addition to the marginal zone B-cells that normally reside there, a number of other cell types that are present in the blood pass through the marginal zone e.g. lymphocytes and granulocytes. In addition, a large number of dendritic cells are thought to reside temporarily in the marginal zone before migrating into the white pulp following stimulation and antigen uptake, as well as a large number of lymphocytes remaining in the marginal zone for a period of time during the process of transmigration into the white pulp. It can be assumed that both these cells wills interact with the marginal zone macrophages.

Recent studies have shown that the marginal zone macrophages possess both important innate functions, as well as being able to promote adaptive immune responses, so these macrophages can bridge the innate and adaptive immunity.

The marginal zone macrophages have a variety of functions, one of which is the phagocytosis of blood-borne pathogens. Because of the anatomy of the marginal zone, the blood within it slows down and therefore the pathogens present in the systemic circulation are phagocytosed by both marginal zone macrophages. It should be noted that there is limited data regarding the specific roles of these two macrophage subsets in the uptake and eradication of pathogens. However there is evidence and reports that show there is a specific involvement of the various pathogen receptors on the marginal zone macrophages in recognising and eliminating certain pathogens, especially encapsulated bacteria. For example, the C-type lectin SIGN-R1 receptor (present on the marginal zone macrophages), mediates the recognition of pneumococcal saccharides and is necessary for Streptococcus pneumoniae clearance.

Furthermore, both types of marginal zone macrophages in the clearance and degradation of viruses e.g. cowpox virus and adenovirus serotype 5. Evidence has shown that the clearance of lymphocitic choriomeningitis virus by marginal zone macrophages is crucial to prevent the spreading of viral infections to peripheral organs.

White pulp:

exists between the white pulp and red pulp.

Macrophages in the White Pulp
The T cell zone, periarteriolar sheath and B cell follicles contain discrete macrophage populations, however not much is known about these macrophage populations in terms of their origin and life span. These macrophages are not unique to the spleen but instead make up an integral part of the lymphoid parts of all secondary lymphoid organs.

In the B cell follicles, the macrophages are important in clearing the apoptotic B cells that occur during the germinal centre reaction in the process of somatic hypermutation and isotype switching. B cells that cannot form their appropriate receptors will die of apoptosis and are subsequently cleared by the macrophages in the germinal centre. During intensive germinal centre reactions, this process is obvious due to the presence of the large macrophages in the germinal centre, known as tingible body macrophages (they're named this because their 'tingible bodies' represent condensed apoptotic nuclei. In order for the apoptotic cells to be be taken up by macrophages, it is important that phosphatidyl serine is expressed on the outer surface of the apoptotic cells, which is recognised by multiple receptors. The tingible body macrophages express: tyrosine kinase Mer, the milk fat globule epidermal growth factor 8 and Tim-4, all of which supports the engulfment of the apoptotic cells into the macrophages.

Macrophages are also present in the T cell area of the white pulp but their role is less well understood. This population of macrophages can be found in all the other T cell zones of the secondary lymphoid organs. It is possible that these macrophages are descendants of patrolling monocytes that entered the white pulp from the blood. Due to them being positioned alongside T cells, it is suggested that these macrophages have a role in antigen presentation or the removal of dying lymphocytes.