WRU Division Four South East

The Welsh Rugby Union Division Four South East is a rugby union league in Wales. There are 12 clubs in the WRU Division Three South East. During the course of a season each club plays the others twice, once at their home ground and once at that of their opponents for a total of 22 games for each club, with a total of 132 games in each season. Teams receive four points for a win and two point for a draw, additional bonus win is awarded to either team if they score four tries or more in a single match. No points are awarded for a loss though the losing team can gain a bonus point for finishing the match within seven points of the winning team. Teams are ranked by total points the number of tries scored and points difference. At the end of each season, the club with the most points is crowned as champion. If points are equal the tries scored points difference determines the winner; the team, declared champion at the end of the season is eligible for promotion to the WRU Division Three South East.

The two lowest placed teams are relegated to the WRU Division Five South East. In 2008 the Welsh Rugby Union announced a new sponsorship deal for the club rugby leagues with SWALEC valued at £1 million; the initial three year sponsorship was extended at the end of the 2010/11 season, making SWALEC the league sponsors until 2015. The leagues sponsored are the WRU Divisions one through to seven. Lloyds TSB Asda SWALEC Abercwmboi RFC Barry RFC Bridgend Sports RFC Llandaff North RFC Llandaff RFC Llantwit Major RFC Nantymoel RFC Penygraig RFC Pontyclun RFC Pontycymmer RFC Porth Harlequins RFC Wattstown RFC Abercwmboi RFC Barry RFC Cardiff HSOB RFC Llandaff RFC Llantwit Major RFC Nantymoel RFC Pontyclun RFC Porth Harlequins RFC Rhiwbina RFC St. Joseph's RFC Tonyrefail RFC Treherbert RFC Abercwmboi RFC Cardiff HSOB RFC Dowlais RFC Ferndale RFC Llantwit Major RFC Nantymoel RFC Pontyclun RFC Pontycymmer RFC Porth Harlequins RFC Rhiwbina RFC Taffs Well RFC Tonyrefail RFC Abercwmboi RFC Cardiff HSOB RFC Cefn Coed RFC Dowlais RFC Ferndale RFC Heol y Cyw RFC Llantwit Major RFC Pentyrch RFC Porth Harlequins RFC Senghenydd RFC Taffs Well RFC Tonyrefail RFC Abercwmboi RFC Aberdare RFC Barry RFC Cardiff HSOB RFC Cefn Coed RFC Cilfynydd RFC Dowlais RFC Ferndale RFC Llantwit Major RFC Llandaff North RFC Pentyrch RFC Taffs Well RFC

Immunoglobulin E

Immunoglobulin E is a type of antibody that has only been found in mammals. IgE is synthesised by plasma cells. Monomers of IgE consist of two heavy chains and two light chains, with the ε chain containing 4 Ig-like constant domains. IgE's main function is immunity to parasites such as helminths like Schistosoma mansoni, Trichinella spiralis, Fasciola hepatica. IgE is utilized during immune defense against certain protozoan parasites such as Plasmodium falciparum. IgE has an essential role in type I hypersensitivity, which manifests in various allergic diseases, such as allergic asthma, most types of sinusitis, allergic rhinitis, food allergies, specific types of chronic urticaria and atopic dermatitis. IgE plays a pivotal role in responses to allergens, such as: anaphylactic drugs, bee stings, antigen preparations used in desensitization immunotherapy. Although IgE is the least abundant isotype—blood serum IgE levels in a normal individual are only 0.05% of the Ig concentration, compared to 75% for the IgGs at 10 mg/ml, which are the isotypes responsible for most of the classical adaptive immune response—it is capable of triggering the most powerful inflammatory reactions.

IgE was discovered in 1966 and 1967 by two independent groups: Kimishige Ishizaka and his wife Teruko Ishizaka at the Children's Asthma Research Institute and Hospital in Denver, by S. G. O Johansson and Hans Bennich in Sweden, their joint paper was published in April 1969. IgE primes the IgE-mediated allergic response by binding to Fc receptors found on the surface of mast cells and basophils. Fc receptors are found on eosinophils, monocytes and platelets in humans. There are two types of Fcε receptors: FcεRI, the high-affinity IgE receptor FcεRII known as CD23, the low-affinity IgE receptorIgE can upregulate the expression of both types of Fcε receptors. FcεRI is expressed on mast cells and the antigen-presenting dendritic cells in both mice and humans. Binding of antigens to IgE bound by the FcεRI on mast cells causes cross-linking of the bound IgE and the aggregation of the underlying FcεRI, leading to degranulation and the secretion of several types of type 2 cytokines like IL-3 and Stem Cell Factor which both help the mast cells survive and accumulate in tissue, IL-4, IL-5 and IL-13 as well as IL-33 which in turn activate group 2-innate lymphoid cells.

Basophils, which share a common haemopoietic progenitor with mast cells, upon the cross-linking of their surface bound IgE by antigens release type 2 cytokines like interleukin-4 and interleukin-13 and other inflammatory mediators. The low-affinity receptor is always expressed on B cells. There has been an accumulating evidence in the past decade on the physiological role of IgE: this isotype has co-evolved with basophils and mast cells in the defence against parasites like helminths but may be effective in bacterial infections. Epidemiological research shows that IgE level is increased when infected by Schistosoma mansoni, Necator americanus, nematodes in humans, it is most beneficial in removal of hookworms from the lung. Although it is not yet well understood, IgE may play an important role in the immune system's recognition of cancer, in which the stimulation of a strong cytotoxic response against cells displaying only small amounts of early cancer markers would be beneficial. If this were the case, anti-IgE treatments such as omalizumab might have some undesirable side effects.

However, a recent study, performed based on pooled analysis using comprehensive data from 67 phase I to IV clinical trials of omalizumab in various indications, concluded that a causal relationship between omalizumab therapy and malignancy is unlikely. Atopic individuals can have up to ten times the normal level of IgE in their blood. However, this may not be a requirement for symptoms to occur as has been seen in asthmatics with normal IgE levels in their blood—recent research has shown that IgE production can occur locally in the nasal mucosa. IgE that can recognise an allergen has a unique long-lived interaction with its high-affinity receptor FcεRI so that basophils and mast cells, capable of mediating inflammatory reactions, become "primed", ready to release chemicals like histamine and certain interleukins; these chemicals cause many of the symptoms we associate with allergy, such as airway constriction in asthma, local inflammation in eczema, increased mucus secretion in allergic rhinitis, increased vascular permeability, it is presumed, to allow other immune cells to gain access to tissues, but which can lead to a fatal drop in blood pressure as in anaphylaxis.

IgE is known to be elevated in various autoimmune disorders such as Lupus, Rheumatoid Arthritis & psoriasis, is theorized to be of pathogenetic importance in RA and SLE by eliciting a hypersensitivity reaction. Regulation of IgE levels through control of B cell differentiation to antibody-secreting plasma cells is thought to involve the "low-affinity" receptor FcεRII, or CD23. CD23 may allow facilitated antigen presentation, an IgE-dependent mechanism whereby B cells expressing CD23 are able to present allergen to specific T helper cells, causing the perpetuation of a Th2 response, one of the hallmarks o