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Immunology and disease
Immunology is not all about disease. Immunology is more about health, and in fact, our immune systems play intimate roles in all aspects of our physiology. Many events from ovulation to pregnancy involve various aspects of the immune system. We have shown that antimicrobial genes are also important for bull sperm function. We sometimes forget that health is our "default" setting. Fortunately most of us are healthy most of the time! But our immune system is potent, and tight regulation if critical to prevent issues arising.
Inflammation
Inflammation is usually viewed as an unwanted biological phenomenon. However healthy or physiological inflammation is intimately involved in many biological processes and is actually required for tissue repair and the restoration of homeostasis. The switch to pathological inflammation is what causes tissue pathology and can contribute to disease.
We have investigated the regulation of the proinflammatory cytokine IL-1B in cattle cells - both systemically (i.e. in peripheral blood cells) and locally (i.e. in epithelial and stromal cells).
It is now becoming increasingly apparent in diseases from obesity, to cancers and forms of dementia that an underlying low-grade but chronic level of inflammation contributes significantly to disease development, relapse and to pathology. It seems that multiple immune stressors acting locally combine to cause systemic inflammation that is difficult to control. We anticipate that applying this paradigm of an inflammatory threshold, above which dysregulation and pathology occurs to disease in livestock could be informative and useful.
We have investigated the regulation of the proinflammatory cytokine IL-1B in cattle cells - both systemically (i.e. in peripheral blood cells) and locally (i.e. in epithelial and stromal cells).
It is now becoming increasingly apparent in diseases from obesity, to cancers and forms of dementia that an underlying low-grade but chronic level of inflammation contributes significantly to disease development, relapse and to pathology. It seems that multiple immune stressors acting locally combine to cause systemic inflammation that is difficult to control. We anticipate that applying this paradigm of an inflammatory threshold, above which dysregulation and pathology occurs to disease in livestock could be informative and useful.
Epigenetics
Epigenetics refers to chemical switches on DNA and proteins which control access to DNA and as a result can shape the resulting immune response. The two main epigenetic mechanisms are methylation and acetylation. Some pathogens can hijack epigenetic machinery in the cell to silence DNA and benefit their survival - this is known as pathoepigenetics.
We have identified regions of DNA in T cells which are differentially methylated between cattle infected with TB and healthy controls. This contributes to our understanding of the regulation of the immune response and potentially identifies targets to improve disease diagnosis.
We have identified regions of DNA in T cells which are differentially methylated between cattle infected with TB and healthy controls. This contributes to our understanding of the regulation of the immune response and potentially identifies targets to improve disease diagnosis.
Immunometabolism
Fighting infections is an energy intensive process. In fact, changes in nutrient availability can determine the immune status of immune cells. Immunometabolism is the study of the interface between nutrients and the immune response. This area is of critical importance in livestock species where nutrients can be limited and this will have important knock on consequences for disease resistance.
The neutrophil
The neutrophil is the most abundant leukocyte in blood and critical to the innate immune system. They are referred to as polymorphonuclear neutrophils (PMNs) but are more commonly reflected in agriculture as increased somatic cell counts (SCC). SCC is used as a marker of sub-clinical mastitis and although viewed in a negative light (as high SCC milk is less valuable), these cells play a critical role in the defence against disease across all body sites.
When one considers the size and blood volume (8% body weight) of mature lactating Holstein cows, a potential pool of over 100 billion circulating mature PMN are circulating at any one time. Recent research is showing that these cells influence the activity of other cells around them and so are critical to the direction and efficiency of the immune response.
When one considers the size and blood volume (8% body weight) of mature lactating Holstein cows, a potential pool of over 100 billion circulating mature PMN are circulating at any one time. Recent research is showing that these cells influence the activity of other cells around them and so are critical to the direction and efficiency of the immune response.
The gamma delta T cell
The gd T cell is another immune cell, but one that links the innate immune system with the adaptive immune system. What that means is that it doesn't wait to be activated by other cells - it can directly respond to infection but it does also influence the activity of adaptive immune cells.
What is particularly interesting about these cells is that in most species (humans, mice), these cells represent <5% of the circulating lymphocytes, in cattle γδ T cells represent between 15 and 60%! the reasons behind this evolutionary difference remains incompletely understood but could hold a lot of potential to boost immunity in cattle.
What is particularly interesting about these cells is that in most species (humans, mice), these cells represent <5% of the circulating lymphocytes, in cattle γδ T cells represent between 15 and 60%! the reasons behind this evolutionary difference remains incompletely understood but could hold a lot of potential to boost immunity in cattle.
Innate Immune Training
Once thought to be limited to the adaptive immune system (as the basis of vaccination), the formation of memory is now known to occur in innate immune cells also. This memory is epigenetically regulated and allows the innate cell to respond more quickly when it re-encounters the pathogen. The induction of memory in innate cells is known as 'innate immune training' and interestingly is not pathogen-specific. As a result this technique can be used to provide broad (or heterologous) immunity to multiple pathogens.
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