Difference between revisions of "Talk:2016 Group 7 Project"

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Tumour-associated eosinophilia: a review http://www.ncbi.nlm.nih.gov/pmc/articles/PMC494593/
 
Tumour-associated eosinophilia: a review http://www.ncbi.nlm.nih.gov/pmc/articles/PMC494593/
  
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==peer review==
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===3463953===
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colourful with short punchy paragraphs that are informative! here are some notes: - History is great, but only goes until 1879! Did nothing happen between then and now! - In terms of the paragraph structure of the Birth, Life and Death in the Body section, there is the number 3 (perhaps a footnote) in the 3rd paragraph that needs to be removed or converted to a footnote. There’s also some other spelling mistakes like in MBP section you’ve spelt asthema instead of asthma. Perhaps it’s worth just rereading over the whole thing to correct the little errors. - Add some text for the images, and I would recommend having the image title in bold. - Video did not play in Wikipedia, but it was spectacular to watch in youtube! - I would be interested in knowing if anytreatments are being developed specifically targetging eosinophils in eczema - The schematic representation of eosinophil trafficking image should be enlarged. Also to add a text box below the image refer to our first lab class. This should be done with all your images
  
  

Revision as of 11:02, 10 May 2016

2016 Projects: Group 1 | Group 2 | Group 3 | Group 4 | Group 5 | Group 6 | Group 7
Group Projects - Blood Cell Biology - Updated 21 April  
This year's main topic is Blood Cell Biology. Each group should discuss with group members the specific sub-topic that will be covered by their project.

Here is a list of some of the cell types (Structure and Function)

PuMed citations PuMed Central citations PuMed Central note
Note - that while full publications are available online at PuMed Central, not all these publications allow reuse. You should still always identify the copyright statement within the actual article that allows reuse. Many research labs that receive government grants are required to make their published research available on PMC, this does not mean that the publicly available copy content can be used in your projects.

Remember - No easily identifiable statement usually means that you cannot reuse.


Examples from Megakaryocyte references on PubMed Central

Embryology - content cannot be reused but a useful resource about cell development.

Histology - images these can be reused in your projects.

Group Assessment Criteria  

Group Assessment Criteria

  1. The key points relating to the topic that your group allocated are clearly described.
  2. The choice of content, headings and sub-headings, diagrams, tables, graphs show a good understanding of the topic area.
  3. Content is correctly cited and referenced.
  4. The wiki has an element of teaching at a peer level using the student's own innovative diagrams, tables or figures and/or using interesting examples or explanations.
  5. Evidence of significant research relating to basic and applied sciences that goes beyond the formal teaching activities.
  6. Relates the topic and content of the Wiki entry to learning aims of cell biology.
  7. Clearly reflects on editing/feedback from group peers and articulates how the Wiki could be improved (or not) based on peer comments/feedback. Demonstrates an ability to review own work when criticised in an open edited wiki format. Reflects on what was learned from the process of editing a peer's wiki.
  8. Evaluates own performance and that of group peers to give a rounded summary of this wiki process in terms of group effort and achievement.
  9. The content of the wiki should demonstrate to the reader that your group has researched adequately on this topic and covered the key areas necessary to inform your peers in their learning.
  10. Develops and edits the wiki entries in accordance with the above guidelines.

Group 7: User:Z5021060 | User:Z5016365 | User:Z5016784 | User:Z3414546 | User:Z3417773

Links from main page

Cytoskeleton:

Integrins are Mechanosensors That Modulate Human Eosinophil Activation http://www.ncbi.nlm.nih.gov/pubmed/26539194

http://www.ncbi.nlm.nih.gov/pubmed/26939881

Tumour-associated eosinophilia: a review http://www.ncbi.nlm.nih.gov/pmc/articles/PMC494593/

peer review

3463953

colourful with short punchy paragraphs that are informative! here are some notes: - History is great, but only goes until 1879! Did nothing happen between then and now! - In terms of the paragraph structure of the Birth, Life and Death in the Body section, there is the number 3 (perhaps a footnote) in the 3rd paragraph that needs to be removed or converted to a footnote. There’s also some other spelling mistakes like in MBP section you’ve spelt asthema instead of asthma. Perhaps it’s worth just rereading over the whole thing to correct the little errors. - Add some text for the images, and I would recommend having the image title in bold. - Video did not play in Wikipedia, but it was spectacular to watch in youtube! - I would be interested in knowing if anytreatments are being developed specifically targetging eosinophils in eczema - The schematic representation of eosinophil trafficking image should be enlarged. Also to add a text box below the image refer to our first lab class. This should be done with all your images


Assessment Discussion

Should we meet up and discuss how we are going to set out the entire project, or just write up a set up on here so we can add information I Did embryology last year, i dont know if yous want to use this as a guideline https://embryology.med.unsw.edu.au/embryology/index.php/2015_Group_Project_2


Maybe before lab 7 we should find more papers that have information on the subheadings that are empty and add the information that we found into the relevant subheadings and maybe the week after we can allocate subheadings to people to be responsible for making that section sound cohesive.


Before lab 5 please resummarise your 4 paper summaries in a form that can be put on the assessment page. Leave out all irrelevant information and add relevant info under the sub-headings. Thanks


Before lab 4 - Everyone find 1 Paper each on structure, function, History or Histamine interactions and 1 on a more specific topic that we can take the research project in the direction of, so that we have options to choose from after the midsem break. Cheers, Sam

Lab 4 Homework

Z5021060

Eosinophil Formation & Development

Eosinophils are created from the eosinophil lineage committed progenitors (EoP), CD34+ cells [1], [2]. They get produced in response to infections and diseases that cause an inflammatory responses which leads to an increase in amount of eosinophils present in the blood due to cytokine interleukin 5 (IL-5) [3], [4]. EoPs develop into its mature form via the influence of the regulatory molecules that control IL-5 [5], [6], [7]. The alteration of IL-5 levels affects the rate at which EoPs can mature but does not effect the ability of the bone marrow to produce CD34+ [8].

Surface Markers

Eosinophils migrating to different tissues in the body are part of its function[9]. Eosinophils that are part of the circulatory system remain inactive until they reach the tissue[10]. When eosinophils migrate to endothelial cells, interleukin (IL)-4 or IL-Beta encouragse further migration[10]. The rate of this process further increases if a chemoattractant is used[10]. In an experiment where a culture is used, the endothelial cells that were treated to prevent this chemotactic event lead to a decrease in the expression of CD68[10]. CD69 is an early marker and CD35 is a receptor[11]. Both of these are controlled by endothelial cells and thus their expression increased when the eosinophils migrated to the endothelial cells[11].

Activation & Apoptosis

Eosinophils are a type of leukocyte that has many functions in terms of inflammatory response: has a role in parasitic, bacterial and viral infection, allergies, tumours and injuries to tissues[12]. Therefore, maintaining a certain level of eosinophils via activation and programmed cell death is important for the immune system[13]. This is because eosinophils can regulate antigens, tissues and they can also encourage the inflammatory process via release of cytokines and lipid mediators[13]. In humans, eosinophil activation can be influenced by the increase in the CD69 protein activity and the decrease in CD62L activity[14]. On the other hand, eosinophil apoptosis can also be influenced by NK which could be seen as the rate of apoptosis was higher in the culture that was incubated with Natural Killer cells[14].

Eosinophils in Parasitic Infections

Eosinophils can often be seen during allergic reactions and in parasitic diseases [15]. This can be investigated by looking at granules granule proteins of eosinophils. During parasitic infection, the granules such as eosinophil peroxides (EPO) and major basic protein-1 (MBP-1) eosinophil-derived neurotoxin and eosinophil catatonic protein can deposit its contents onto the helminth to kill it [16]. Thus eosinophils are needed for eliminating the the parasite as without it, the parasite would be able to survive in the body for a longer period of time [15].

Lab 3 Assessment

z5021060

Paper 1

Eosinophils migrating to different tissues in the body are part of its function[9]. Eosinophils that are part of the circulatory system remain inactive until they reach the tissue[10]. The article looks at what occurs in terms of the surface markers and release of leukotriene C4 when eosinophils reach these endothelial cells[10]. It was found that when eosinophils migrated to the endothelial cell, interleukin (IL)-4 or IL-Beta would encourage further migration. The rate of this process further increased if a chemoattractant was used. In the culture, the endothelial cells that were treated to prevent this chemotactic event would lead to a decrease in the expression of CD68. CD69 is an early marker and CD35 is a receptor[11]. Both of these are controlled by endothelial cells and thus their expression increased when the eosinophils migrated to the endothelial cells[11].

<pubmed>12797482</pubmed>

Paper 2

Eosinophils can often be seen during allergic reactions and in parasitic diseases [15]. This can be investigated by looking at granules granule proteins of eosinophils. During parasitic infection, the granules such as eosinophil peroxides (EPO) and major basic protein-1 (MBP-1) eosinophil-derived neurotoxin and eosinophil catatonic protein can deposit its contents onto the helminth to kill it [16]. Thus the article looks at the presence or absence of these proteins to see its effects on parasitic disease.The article looks at the parasite Brugia malayi microfilariae for the investigation. It was found that eosinophils were needed for eliminating the microfilariae during primary infection as its absence would allow for the microfilariae to survive in the body for a longer period of time [15]. The absence of EPO lead to the increase in levels of Immunoglobin E (IgE) which meant that eosinophils have a role in the controlling the levels of IgE [15]. The article also states that eosinophils can have both a positive and negative effect as the removal of MBP-1 lead to increased mucus production by goblet cell[15]s but the physiology of the respiratory system did not change with its absence [17].

<pubmed>24626328</pubmed>

Paper 3

Eosinophils are a type of leukocyte that has many functions in terms of inflammatory response: has a role in parasitic, bacterial and viral infection, allergies, tumours and injuries to tissues[12]. Therefore, maintaining a certain level of eosinophils via activation and programmed cell death is important for the immune system, as eosinophils can regulate antigens, tissues, as they can also encourage the inflammatory process via release of cytokines and lipid mediators[13]. This article further studies the regulation activation and apoptosis of eosinophils via the influence of Natural Killer (NK) cells. In humans, eosinophil activation can be influenced by the increase in the CD69 protein activity and the decrease in CD62L activity. On the other hand, eosinophil apoptosis can also be influenced by NK which could be seen as the rate of apoptosis was higher in the culture that was incubated with NK cells.

<pubmed>24727794</pubmed>

Paper 4

EoP count in eosinophila patients[6]

Eosinophils are created from the eosinophil lineage committed progenitors (EoP), CD34+ cells [1], [2]. They get produced in response to infections and diseases that cause an inflammatory responses which leads to an increase in amount of eosinophils present in the blood due to cytokine interleukin 5 (IL-5) [3], [4]. EoPs develop into its mature form via the influence of the regulatory molecules that control IL-5 [5], [6], [7]. The alteration of IL-5 levels affects the rate at which EoPs can mature but does not effect the ability of the bone marrow to produce CD34+ [8].

z3414546

Eosinophilic Inflammation in Allergic Asthma

<pubmed> PMC3627984</pubmed>

This paper broadly explores the molecular events that lead to eosinophil recruitment in allergic asthma and their participation in airway hyper responsiveness and remodelling. It also provides a good overview of the immune response (and pathogenesis) upon allergen challenge, hence would be a suitable source of information for the sub-section concerning the role of eosinophils in disease [18].

Evidence suggests that Phosphatidylinositol 3-kinase (PI3K) regulates the adhesion, distribution and morphologic changes in eosinophils. Whilst certain Leukotrienes (e.g. leukotriene B4 (LTB4)) promote the trafficking and recruitment of eosinophils to inflamed tissues and ensure their survival once there. According to the research, inhaled allergens activate mast cells and Th2 CD4+ lymphocytes to produce cytokines IL-13, IL-4, IL-5 and TNF-α[18][19]. These stimulate epithelial cells, smooth muscle cells and fibroblasts to produce eotaxin. IL-5 regulates migration of eosinophils out of bone marrow, eotaxin directs their movement to lung tissue through blood vessels (via CC chemokine receptors CCR3) [18][20]. Eosinophils then release granule proteins (e.g. eosinophil cationic protein and major basic protein) as well as other molecules such as leukotrienes and metalloproteinases. These are cytotoxic and induce further immune responses that lead to airway hyper-responsiveness and remodelling [18][21].

Research has also demonstrated that some leukotrienes are bronchoconstrictors and have been known to prolong the migration of eosinophils to the airways in allergic asthma [22]. It has further been revealed that eosinophil recruitment occurs in the lung parenchyma as well. Lastly, whilst eosinophils play a major role in the pathogenesis of asthma, research shows they also play a crucial role in lung defence, through the direct regulation of T-cell activities [18][23].


The early history of the eosinophil

<pubmed>25544991</pubmed> This paper is particularly useful for the subsection on the history of the eosinophil as it presents a comprehensive timeline and findings regarding morphology, formation, function and fate of the eosinophil as well as important events that contributed to these discoveries. According Kay 2015 eosinophils where first identified and named by Paul Ehrlich during the 1870s due to the development of specific staining techniques for blood films. The most significant stain utilised was Eosin, a synthetic red dye discovered by Heinrich Caro, 1874. Eosin stains basic proteins due to its acidic properties and eosinophil granules possess a particularly high affinity for it. Kay 2015 stated that Ehrlich was able to describe the features of eosinophils in great detail as a result of this essential stain, for example alpha granules appeared spherical or as short rods with round ends. He also observed beta-granules in eosinophils derived from the bone marrow, most likely immature alpha granules. He further identified inconsistencies in the number of nuclear lobes and granules from one cell to another[24].

Ehrlich documented the distribution of eosinophils in tissues and their formation in bone marrow. According Kay 2015, Ehrlich accurately recognised that granules possessed secretory components and that eosinophils were somewhat responsible for the reactions seen in asthma, helminth infections and certain skin diseases. Kay 2015 highlights that there were many others that observed this cell before Ehrlich, Thomas Wharton Jones first noted granulated cells in human and animal blood specimens in 1846. Julius Vogel observed eosinophils in inflammatory exudates, whilst Max Johann Sigismund Schultze first observed the movements and phagocytic nature of these cells[24].


Eosinophil granules function extracellularly as receptor-mediated secretory organelles

<pubmed>19017810</pubmed> This paper is appropriate for the subsection on eosinophil function, it highlights a rather specific function of their intracellular components as opposed to the generalized function of the cell as a whole. The article particularly focuses on eosinophil granules and granule protein release extracellularly and further provides a perspective on the mechanisms that drive this protein release and how this process may contribute to the severity of an inflammatory response (during eosinophil associated disease)[25].

Neves et al. observed that granules of eosinophils express receptors for cytokines and G protein coupled receptors (CCR3) for chemokines. They found that these receptors are located on the surface membranes of granules, and respond to external cytokines and chemokines by activating a signal-transduction pathway within granules. They also highlight that IFN-γ (cytokine) and eotaxin (chemokine) are responsible for stimulating the secretion of cationic proteins, enzymes and cytokines originating from granules[25].

Neves et al. suggest that this extracellular secretion process is regulated by the ability of granules to function as individual secretory vessels outside of eosinophils (in diseased tissue sites). This is how they may contribute to inflammation mediated by eosinophils and immunoregulation/immunomodulation[25].


IgE, Mast Cells, Basophils, and Eosinophils

<pubmed>20176269</pubmed> This article is relevant for the subsection on structure, the information in this article was derived from a broad range of investigations. It provides an overview of the major morphological features specific to eosinophils, with particular focus on granules, cytoplasmic components and surface markers. Stone et al. state that eosinophils possess a large bi-lobed nucleus, containing highly condensed chromatin within. Another specific feature that Stone et al. highlights are granules, there are two major types. Specific granules contain cationic proteins such as major basic protein, eosinophil peroxidase, eosinophil cationic protein and eosinophil-derived neurotoxin. These proteins give eosinophils their distinct staining property. Primary granules on the other hand, possess Charcot-Leyden crystal proteins [26][27]. Stone et al. also draw attention to lipid bodies that reside in the cytoplasm (not membrane bound) which contain eicosanoid synthetic enzymes and from rapidly after eosinophil activation[26][27].

Stone et al. specifies many of the cell surface markers present on eosinophils, some of these include cytokine receptors (IL-3R, IL-5R, GM-CSF) which promote their development, Immunoglobulin receptors (IgA, IgG); complement receptors (CR3, CD88) as well as receptors for chemokines (CCR1 and CCR3) and many other receptor molecules [27][28].

z5016784

Role of Eosinophils In Disease

Viral infection - Eosinophil granule proteins are known for their ribonuclease activity and have been shown to degrade single stranded RNA containing viruses. It has recently been shown that viruses such as parainfluenza virus, respiratory syncytial virus, or rhinovirus induce the release of EPO by eosinophils when co-incubated in the presence of antigen-presenting cells and T cells . Eosinophils may also have a protective role in other infections, especially against RNA viruses such as respiratory syncytial virus and pneumonia virus of mice (PVM)

Fungal infection - Recent investigation has focused on the role of eosinophils in fungal infections. Eosinophils release their cytotoxic granule proteins into the extracellular milieu and onto the surface of fungal organisms in order to kill fungi in a contact-dependent manner. However eosinophils do not react with chitin, a fungal cell wall component.

Bacterial infection - Eosinophils rapidly release mitochondrial DNA in response to exposure to bacteria, C5a or CCR3 ligands. The traps contain the granule protein ECP and MBP, and display antimicrobial activity. In the extracellular space, the mitochondrial DNA and the granule proteins form extracellular structures that bind and kill bacteria both in vitro and under inflammatory conditions in vivo. After cecal ligation and puncture, IL5-transgenic but not wild-type mice show intestinal eosinophil infiltration and extracellular DNA deposition in association with protection against microbial sepsis. This data suggests a previously undescribed mechanism of eosinophil-mediated innate immune responses that might be crucial for maintaining the intestinal barrier function after inflammation-associated epithelial cell damage, preventing the host from uncontrolled invasion of bacteria .

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4109275/

http://www.ncbi.nlm.nih.gov/pmc/?term=22475285[PMID]&report=imagesdocsum

http://www.ncbi.nlm.nih.gov/pmc/?term=19231593[PMID]&report=imagesdocsum

Targeting Eosinophils in Allergy, Inflammation and Beyond

Eosinophils can regulate local immune and inflammatory responses, and their accumulation in the blood and tissue is associated with several inflammatory and infectious diseases. As such, therapies aimed at eosinophils may help control diverse diseases, including disorders such as asthma and allergy, and also diseases that are not primarily associated with eosinophils such as autoimmunity and malignancy. Recently, eosinophil-targeted therapeutic agents aimed at blocking specific steps involved in eosinophil development, migration and activation have entered clinical testing and have produced encouraging results and insights into the role of eosinophils.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3822762/

Eosinophila

Different stages and ways to treat it

References

  1. 1.0 1.1 <pubmed>11884474</pubmed>
  2. 2.0 2.1 <pubmed>9366561</pubmed>
  3. 3.0 3.1 <pubmed>11034415</pubmed>
  4. 4.0 4.1 <pubmed>19264686</pubmed>
  5. 5.0 5.1 <pubmed>15955840</pubmed>
  6. 6.0 6.1 6.2 <pubmed>19114669</pubmed>
  7. 7.0 7.1 <pubmed>18802108</pubmed>
  8. 8.0 8.1 <pubmed>12704348</pubmed>
  9. 9.0 9.1 <pubmed>8871054</pubmed>
  10. 10.0 10.1 10.2 10.3 10.4 10.5 <pubmed>8648134</pubmed>
  11. 11.0 11.1 11.2 11.3 <pubmed>12797482</pubmed>
  12. 12.0 12.1 <pubmed>1596561</pubmed>
  13. 13.0 13.1 13.2 <pubmed>18384431</pubmed>
  14. 14.0 14.1 <pubmed>24727794</pubmed>
  15. 15.0 15.1 15.2 15.3 15.4 15.5 <pubmed>24626328</pubmed>
  16. 16.0 16.1 <pubmed>2324497</pubmed>
  17. <pubmed>16982928</pubmed>
  18. 18.0 18.1 18.2 18.3 18.4 <pubmed> PMC3627984</pubmed>
  19. <pubmed> 14561170</pubmed>
  20. <pubmed>21828027</pubmed>
  21. <pubmed>17364144</pubmed>
  22. <pubmed>10673230</pubmed>
  23. <pubmed>22936660</pubmed>
  24. 24.0 24.1 <pubmed>25544991</pubmed>
  25. 25.0 25.1 25.2 <pubmed>19017810</pubmed>
  26. 26.0 26.1 <pubmed>1657792</pubmed>
  27. 27.0 27.1 27.2 <pubmed>20176269</pubmed>
  28. <pubmed>17337299</pubmed>