Introduction. Innate immunity has a major role in the initial prevention of infections. However, it can cause autoimmune type 1 diabetes when it fails to differentiate between self and non-self cells.

Discussion. The TLRs recognize the foreign antigens and then activates the immune system. It’s important to do so because the recognition helps prevent infection before they cause diseases. Sometimes, they recognize self cells as foreign leading to their destruction, depleting the body’s capacity to secrete insulin. There are models supporting autoimmunity as the cause of T1D. The ? cells expose HLA class I antigens from the triggers like viruses. That attracts the cytotoxic CD8+ T cells that destroy them. Evidence has shown that IL-1?, TNF-? and INF-? are toxic to the ? cells, resulting in the destruction, hence their depletion. Destruction of the cells impairs the body of its insulin-secreting function. In turn, glucose regulation becomes a problem, hence diabetes.

Introduction

The chief role of the immune system is to prevent the human body from infections, some of which arise from pathogenic organisms. It comprised of the innate and acquired immune system components. In the body, the innate type provides the initial protection against any pathogen. Prevention is aided by the body’s ability to recognize pathogen-associated molecular patterns [PAMPs] (Mogensen 2009, p. 241). This component of the immune system doesn’t develop the memory to infections like the adaptive immune system. However, the innate immunity is behind the cause of autoimmune diseases (Kim and Lee 2009, p. 33). In causing this, the innate immunity fails to distinguish between self from non-self tissues. In this case, we shall discuss the contribution of this type of the immune system to the pathology of type 1 diabetes (T1D). In this autoimmune disease, the pancreatic ? beta cells are destroyed by the body’s immunity, resulting in insulin insufficiency, hence the disease (Atkinson and Eisenbarth 2001, p. 226). The most common clinical manifestations of the disease are polyuria, polyphagia, and polydipsia.

Discussion

Inflammatory Response

Innate immunity involves the pattern recognition receptors (PRRs), which are secreted throughout the tissues and on the surface of cells. They include the Toll-like receptors (TLRs), retinoic acid-inducible gene-I-like helicases and nucleotide oligomerization domain-like receptors (NLRs) that recognize pathogens through PAMPs (Medzhitov and Janeway 1997, p. 243-4). On binding of the PAMPs to PRR, there are various defense mechanisms that follow, including the release of cytokines and chemokines resulting in inflammation (Eizirik, Colli & Ortis 2009). In normal cases, the inflammatory system targets pathogens, but in this disease, inflammation is defective (Si-Tahar, Touqui and Chignard 2009). It targets the ? cells of the pancreas. That results in insulitis (inflammation of the pancreatic islets).

During insulitis, several immune cells are recruited, which include the CD8⁺ cytotoxic cells and macrophages. According to Willcox et al., (2009), the two types of cells result in an early loss of the ? cells of the pancreas. On the same line, the CD20⁺ cells play a great role in the latter stages of the inflammatory process. According to In’t Veld (2012), insulitis consists of the accumulation of lymphocytes, macrophages in the peri-islets or intra-islets. Among the cells are the CD3+CD8+ lymphocytes of the T-helper type and CD3+CD4+ B-lymphocytes among others. The process of inflammation may happen slowly over a given period before all the involved cells are affected.

In general, genetic alleles and environmental triggers make an individual vulnerable to developing the disease. The ? cells in the pancreas up-regulate the ? interferon (IFN-?) and then the MHC class I. That exposes the cells to attack by the lethal autoreactive CD8 T cells. The beta cell-cell antigens get picked by the antigen presenting cells, which transfer them to the lymph nodes draining the pancreas (Mogensen 2009). Meanwhile, the CD8+ proliferate, migrating into the pancreas. After that, IFN-?, perforin, and IFN-? starts affecting the beta-cells by inducing their death. The process complicates further, by more recruitment of the CD4 and CD8 T cells resulting in the complete depletion of the insulin-secreting cells.

Toll-like receptors

The Toll-like receptors (TLRs) contributes to the innate immune response (Mogensen 2009). TLRs are a group of PRRs. They are the TLRs that recognize the foreign antigens before signaling the immune response by activating it (Wong et al., 2008, p. 147). The proteins play a chief role in the prevention of diseases due to their noble function of detecting pathogens and enabling the activation of the innate immune system. With that in place, the immune system can fight the pathogen before it causes disease manifestation (Takeda et al., 2001, p. 737). In autoimmune cases like T1D, they recognize the insulin-secreting cells as unwanted to the body. Once this happens, the innate immunity gets activated, hence the inflammation response resulting in the destruction of the cells.

Study Models

There are many important models that try to explain how the insulin-secreting cells are affected by autoimmunity. Unfortunately, none of these models exist at a human level. The ? cells have HLA class I antigens on their surface (Zipris 2009, p. 14). The HLAs are from major autoantigens or triggers in the environment like viruses. Viruses like rubella, cytomegalovirus, and mumps are some of the triggers of the inflammatory process (Honeyman 2005, p. 617). Upon the recognition, the cytotoxic CD8+ T cells swing into action by destroying them (Honeyman 2005, p. 718). What the models are unclear about is whether the infiltrating inflammatory cells express cytokines, which lead to either cellular cytotoxicity or formation of autoantibodies or both. The IL-1?, TNF-? and INF-?, are toxic to the islet cells of the human pancreas.That explain why these inflammatory molecules can be behind the death of the insulin-secreting cells during insulitis. On the same line, there is an alternative approach, which is less convincing. It involves the measurement of immunoglobulin isotypes (Wentworth, Fourlanos and Harrison 2009). The isotypes are surrogate markers for the identification of T helper-2 and T helper 1 cell responses. Through the studies, autoantibodies to GAD65 and IA-2 are of the Isotype of the IgG1. The argument is that the Th1-type response in autoimmune T1D.

Consequence of the Autoimmune Process

The insulin ? insulin-secreting cells in the pancreas get damaged by the immune system due to failure to recognize them as self-cells (Atkinson and Eisenbarth 2001). Once it is done, the body cannot produce insulin on its own. For this reason, the glucose levels can keep rising as the hormone responsible for lowering the sugars will be missing. In addition, the glucose cannot enter the cells, resulting in the burning of fats in order to provide energy. That explains why individuals with the disease experience hyperglycemia yet their bodies are burning fat for energy.

Conclusion

The human body has the immune system whose role is to protect the body against infections of any kind. The immune system comprises of the innate and acquired immunity. It is the innate immunity that brings autoimmune activity in the ? cells of the pancreas when there is a failure to recognize between self from non-self cells. This results in insulitis, which leads to the death of the insulin-secreting cells. There are several models that describe how the autoimmune process occurs. However, the models are from animal studies since there has been no one from humans. Once the islet cells die, insulin secretion diminishes, resulting in T1D.

References

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