Immune System And Ulcerative Colitis

Understanding the immune system and ulcerative colitis

What is the immune system?

We are frequently exposed to microorganisms that live on our skin or mucous membranes or are breathed in or ingested. The organism's pathogenicity (the virulence factors at its disposal) and the effectiveness of the host defence mechanisms determine whether these organisms invade and cause illness. A network of lymphoid organs, cells, humoral factors, and cytokines interact to form the immune system.¹ The crucial role of the immune system in host defence is best emphasised when it malfunctions, with overactivity in allergy and autoimmune diseases and under-activity leading to severe infections and tumours of immunodeficiency. 

The speed and specificity of the reaction determine the two components of immunity. Although there is a lot of interaction between them in reality, they are referred to as innate and adaptive responses.¹ Physical, chemical, and microbiological barriers are occasionally included when "innate immunity" is used. Still, it is more frequently referred to as the immune system's components (neutrophils, monocytes, macrophages, complement, cytokines, and acute phase proteins) that offer immediate host defence.¹ The response's highly conserved character, evident in even the most basic species, attests to its significance in ensuring survival. The distinguishing feature of the immune systems of higher animals is adaptive immunity. T lymphocytes and B lymphocytes are involved in this response, which comprises antigen-specific responses. The adaptive reaction is precise but takes days or weeks to develop, in contrast to the innate response, which is quick but can occasionally harm healthy tissues due to its lack of specificity. A more robust and speedier reaction results after a repeat exposure because the adaptive response has memory, although this does not happen immediately.¹

What is ulcerative colitis

The two most common types of inflammatory bowel illness are ulcerative colitis and Crohn's disease.² Despite certain similarities, these types can be separated by variations in risk factors, clinical, endoscopic, and histological aspects, as well as genetic predisposition. Although the exact origin of inflammatory bowel disease is unknown, genetically predisposed people appear to have an abnormal mucosal immune response to commensal gut flora, which leads to intestinal inflammation.²

In ulcerative colitis, the inflammation usually only affects the mucosal surface. Although the illness spreads consistently proximally from the rectum to the whole colon, some people with proctitis or left-sided colitis may have an inflammatory patch in the caecum. The distribution of disorders, from proctitis to left-sided colitis or severe colitis, is stratified by the degree of intestinal involvement (pancolitis).²

Relationship between the immune system and ulcerative colitis

Studies have demonstrated that T-helper cells (Th) 2 cytokines such IL-13, IL-5, and IL-4 have a role in the pathogenesis of UC. NKT cells also contribute to the production of these Th2 cytokines. NKT cells are a distinct group of lymphocytes that express molecules from both natural killer (NK) cells and ordinary T cells. NKT cells are involved in tumour monitoring, immunological responses to infectious pathogens, autoimmune disease prevention, and the maintenance of self-tolerance. However, NKT cells and the cytokines they generate are also implicated in some immune responses that are harmful. For instance, IL-13 and IL-4 can cause epithelial cell tight junction disruption and airway hypersensitivity.³

Additionally, NKT cells operate in IBD both destructively and protectively. On the one hand, when NKT cells are activated with α-galactosylceramide (α-GalCer), they exhibit protective properties. NKT cells, on the other hand, contribute to a number of unfavourable inflammatory and immunological responses in the gut, such as the onset of oxazolone-induced colitis, by secreting IL-13. To influence tissues in vivo, NKT cells may also create a variety of cytokines. NKT cells have the ability to release Th2 cytokines throughout the development of UC, which causes inflammation and mucosal damage.^2 3

More on ulcerative colitis: causes, symptoms and treatment

Causes of ulcerative colitis

The highest incidence and prevalence rates of ulcerative colitis are seen in North America and northern Europe, ranging from nine to twenty cases per 100,000 person-years and prevalence rates from 156 to 291 cases per 100,000 persons. Eastern nations have the lowest rates. Environmental variables may have a significant role in the start of illness. The major onset peak for ulcerative colitis occurs between ages 15 and 30 years, and a second, less severe peak occurs between ages 50 and 70 years. According to studies, there is either no preference for sex.²

A modified atypical Th2 response, which results in mucosal hyper-responsiveness to commensal bacteria in genetically susceptible hosts, is the significant aberration generating inflammation in ulcerative colitis. Therefore, developing innovative therapeutic approaches depends on expanding knowledge of illness pathogenesis.^2 4

Symptoms of ulcerative colitis

Bloody stool, diarrhoea, and stomach discomfort are the most common symptoms of ulcerative colitis.^2 4 Symptoms may appear suddenly or gradually. Anaemia, thrombocytosis (high platelet count), or hypoalbuminemia could be signs of inflammatory bowel illness. However, ulcerative colitis patients often do not have these abnormalities. Erythrocyte sedimentation rate and C-reactive protein levels are insensitive for identifying ulcerative colitis and shouldn't be used to rule out inflammatory bowel disease. Less than half of ulcerative colitis patients had aberrant results on these tests at the time of diagnosis. Using an endoscopic biopsy, the diagnosis is established.^2 4

Crohn's disease and infectious colitis brought on by bacterial, viral, or parasitic pathogens are included in the differential diagnosis for ulcerative colitis. In contrast to Crohn's disease patients, those with ulcerative colitis may have patches of normal mucosa between areas of illness. Additionally, microscopic colitis must be separated from ulcerative colitis, a common cause of non-bloody diarrhoea, tummy aches, and weight loss in adults.² Endoscopic biopsy is used to detect microscopic colitis. Bacterial stool cultures should be done on patients who may have ulcerative colitis. Testing for the Clostridium difficile toxin should be done on those who have recently used antibiotics. Further tests to exclude infectious aetiologies may be carried out depending on the patient's past.²

Treatment for ulcerative colitis

The first step in management would always be to induce remission unless symptoms have worsened or remission has not been achieved in 4 weeks.⁵

A moderate initial presentation would suggest topical aminosalicylate as the first line of therapy for mild to moderate UC. Consider adding oral prednisolone if remission is not obtained in 4 weeks. Consider adding oral tacrolimus if the symptoms do not improve after two to four weeks or if they get worse.⁵

The first-step for acute and severe cases should include IV corticosteroids. Then, if there is no improvement, add IV ciclosporins (or Infiximab if contraindicated) or surgery.² 

By relieving the patient's body of the strain of the inflamed colon, emergency and urgent surgery aim to restore the patient's health. A subtotal colectomy (Removal of a part of or the whole large intestine ⁶) with a temporary ileostomy and no rectal stump removal is the primary surgery in these cases. Due to the significant risk of pelvic bleeding, infections, and damage to pelvic nerves, the construction of the pouch should be avoided in acute situations. After the patient fully recovers, a restorative procedure can be performed with a lower risk of problems, including forming the ileal-pouch anal anastomosis (IPAA), which is the elimination of waste generally after removal of your entire large intestine, and ileostomy closure.^2 5 6

Summary

The immune system comprises of a network of lymphoid organs, cells, humoral factors, and cytokines interactions. Malfunctions can be of varying degreesdegress with overactivity in allergy and autoimmune diseases and under-activity leading to severe infections and tumours of immunodeficiency. 

Ulcerative colitis usually only affects the mucosal surface of the colon, with continuous inflammation observed in the distal colon and rectum. A modified atypical Th2 response, which results in mucosal hyper-responsiveness to commensal bacteria in genetically susceptible hosts, is a significant cause of ulcerative colitis, and common symptoms include bloody stool, diarrhoea, and stomach discomfort.

The first step in management would always be to induce remission unless symptoms have worsened or remission has not been achieved in 4 weeks. A moderate initial presentation would suggest topical aminosalicylate as the first line of therapy for mild to moderate UC. The first-step for acute and severe cases should include IV corticosteroids. Then, if there is no improvement, add IV ciclosporins (or Infiximab if contraindicated) or surgery.