Friend or foe? – A walk through autoimmunity

The immune system- An overview of fighting a bacterial infection

Don’t jeopardise your health, immunise!

Ever wondered how taking a vaccine prevents us from getting sick?

No more needles! The revolutionary nano-patch vaccine

What is your blood type? ABO and Rh explained with doughnuts and sprinkles!

Done with the white, bring on the red! What is blood?

 

Ever wondered what our blood consists of? Here is a very nice and thorough illustration:

Mouse models for Sjögren’s syndrome- why mice?

Various animal models have been developed throughout the years for Sjögren’s syndrome, which elicit both spontaneous and experimentally induced disease development. The use of such animal models makes it possible to study different stages of disease development in a controlled environment, in addition to testing different therapeutic approaches. Mouse strains that naturally develop an immune condition resembling SS were first described in the late 1960s. Ideally, a model for SS should display the common symptoms of ocular and oral dryness, in addition to chronic inflammation in the lachrymal and salivary glands, and systemic immunological features that resemble the human form of the disease, such as antinuclear antibodies, autoantibodies and hypergammaglobulinemia.

Some of the best characterised animal models for studying Sjögren’s syndrome include the Murphy Roth’s Large (MRL/lpr) and the Non-obese Diabetic (NOD) mouse. To date, the NOD mouse is one of the most used and thus best described out of these models. However, the NOD model has also been applied to study insulin dependent diabetes mellitus. Nonetheless, due to the loss of secretory function alongside lymphocytic infiltration in its exocrine glands this model has also been widely used for studying Sjögren’s syndrome-like disease development. As the NOD mouse also develops diabetes, this model seems more appropriate for studying the secondary rather than primary form of Sjögren’s syndrome. To overcome this predicament another congenic NOD strain has been developed, namely the NOD.B10.H2b mouse. Here the NOD MHC I-Ag7 locus has been replaced with the non-diabetogenic MHC I-Ab locus of C57BL/10 mice. Hence, due to the lack of the diabetogenic locus this novel NOD.B10.H2b strain does not develop diabetes. Moreover, the NOD.B10.H2b mouse also exhibits all the immunopathological manifestations of the human form of primary Sjögren’s syndrome such as loss of secretory function, histological features with lymphocytic infiltration of exocrine glands (lacrimal and salivary glands), the presence of hypergammaglobulinaemia and the production of antinuclear autoantibodies. However, in contrast to human primary Sjögren’s syndrome, in NOD.B10.H2b mice anti-Ro/SSA and anti-La/SSB autoantibodies have not been detected, and there seems to be an equal distribution of disease development amongst both males and females.

Taking all the aforementioned features into account the different mouse models described have their strengths and limitations, yet nonetheless represent solid starting points for unraveling different aspects of disease development and pathogenesis.

The swine flue… Pigs are protesting!

Attchuuuuuu! Oh no it’s the flue!

The 1918 influenza pandemic

Circulating B cells and salivary gland involvement in the pathogenesis of Sjögren’s syndrome

Circulating B cells

Many features of primary Sjögren’s syndrome (pSS) underline the important role of B cells in disease pathogenesis. For instance, patients with pSS produce high levels of circulating autoantibodies that target the self-antigens SSA (Ro52 and Ro60) and SSB (La48). This is observed in approximately 70% of the patients, and it has recently been shown that autoantibodies could be detected in the patients long before symptom onset (as early as 18 years!). Other autoantibodies include rheumatoid factor (RF), anti-nuclear antibodies (ANA), and anti-muscarinic acetylcholine M3 receptor antibodies. In addition to this, B cell hyperactivity in pSS may also result in hypergammaglobulinaemia, with increased levels of IgG in patient sera. Interestingly, patients with pSS show a characteristic alteration in their circulating peripheral B cell subsets, where decreased frequencies of CD27+ memory B cells are observed in combination with increased levels of naïve B cells and plasma cells. Moreover, an increase in the CD5+ B cell population has also been described. Nonetheless, whether B cell activation is a primary cause or a secondary effect in SS remains unclear.

 

Salivary gland involvement

Focal chronic inflammation within the salivary gland of pSS patients is usually the result of infiltration and accumulation of mononuclear cells such as B cells, T cells, short- and long-lived plasma cells, macrophages and dendritic cells. These infiltrating cells are in some cases able to organise themselves into B and T cell areas (zones) where the infiltrating B cells in the salivary gland tissue constitute approximately 20% of the total mononuclear cell infiltration. This could in turn result in the formation of tertiary lymphoid structures, referred to as ectopic germinal centre-like structures, at the site of inflammation. Structurally, these ectopic germinal centres in the salivary gland appear similar to the conventional germinal centres observed in secondary lymphoid organs, but whether there is a functional similarity between the two still requires further studies.

 

Lower labial minor salivary gland of a pSS patient. A haematoxylin and eosin (H&E) stained section of the minor salivary gland showing focal mononuclear cell infiltrates of >50 cells/mm2 indicated with arrow. This patient has a focus score value of 1.

 

Double immunohistochemical staining of CD20 (red) and CD27 (brown) was carried out on paraffin-embedded salivary gland tissue from 10 pSS patients to distinguish CD20+/CD27+ memory B cells, and identify the CD20+ glandular B cell zones (BCZ) (red). Low number of double- positive memory B cells expressing both CD27 (brown) and CD20 (red) was observed at site of inflammation. Other naive B cells that are single-positive for CD20 and are infiltrating the BCZ are also detected (red).

 

For further reading: