Contents

General Organisation

Factsheet & Roadmap

https://docs.google.com/spreadsheets/d/1qJv5ZDtQs7WxfUx_tDs-hjhOIvonsCIzQqA3YJGhyms/edit#gid=1239190165

Cloud

Drive: https://drive.google.com/folderview?id=0B73R6WMeqvwfRDk5VjBhbW5GLTg&usp=sharing (View Only link, edit link will be provided in private)


Week 4

Z3465531 (talk) 18:02, 24 March 2016 (AEDT) Hi everyone, I expected to have work on Good Friday, but it turns out that I do not and that I am available. If we need to meet at any time, I am available.

Z3465531 (talk) 15:41, 24 March 2016 (AEDT) Hi Everyone, I apologize again that I will not be able to meet tomorrow to discuss the outline. I am definitely available by phone or skype after 5 pm or perhaps for I could step away for 15 minutes during work if you shoot me a message. I have looked at the feedback for the other projects that were done in 2015, and I think we should be have an outline that looks something like the following:

z3329177 I'm in the main library till 6 i guess, if anyone can meet i would love to join.

Proposals for Structure

z5018866

1. Banner

2. Introduction

3. History

4. Add common structure and function

5. Types

5.a. Structure

5.b. Mechanisms and development

5.c. Functions and roles in the body

5.d. Clinical implications and diseases

6. Current research, future directions and do as conclusion

7. Glossary

8. References

In terms of dividing work I think we should do a type of t-cell each, making a glossary and doing references as we go along for our sub type. For the common structure and function and current research we can collaborate at the end Someone can do the intro and someone can do history whilst others can do the smaller subtypes of t cells

z3465531

1) Banner Heading (as in Group 1 2015)

2) Introduction (as in Group 1 2015, or with timeline graphic as in group 4 with internal referencing, or video as in group 5, careful with citing though) Be sure to cite textbook if used

3) History (Emphasizing research techniques)

4) Types of T Lymphocytes

5) Structure (as in Group 1 2015)

6) Function

7) Malfunction of T-lymphcyes – investigation of T-Lymphocyte malfunction as a causative agent of disease

8) Current Research – (Possibly switched in order with clinical significance, we’ll see how it feels, good example Group 5 2015 with collapsible tables) -

9) Clinical Significance (as in Group 3 2015)

10) Future Directions (Possibly unify this with the conclusion? Plenty of examples)

11) Conclusion (closing section)

12) Glossary (as in Group 1 2015)

13) References

What does everyone think?

z5105710

1)Titel Picture

2) Introduction

4) History (short! keep it on the history of discovery of structure and function, as this is a cell biology class)

3) Common Characteristics (Structure and function of T-Cells compared to other BC's, not too much as specific structure and function of each T-Cell type will be covered in Subsection and they are very different from each other)

Surface Proteins TCR ...

4) Development (Short, not too much immunology)


5) Types (focus on structure and function, Activation, mechanism of action, involved pathways etc.)


6) Clinical Significance (focus on cell biology pathways in the development of the disease)


7) Current research (Involved research centers, current theories related to cell biology of T-Cells etc.) Elaborate this section, he put emphasis on it on a) the lecture b) criticism to former projects

z3329177

I was looking at the structure, i will add a bit more,but the format could be roughly like this

1. General information (about t-cells, types etc.)

2. History (early and current researches, future expectations)

3. Cell structure

4. Function and mechanisms

5. Related diseases

6. Glossary

7. References


Division of Topics:

Helper - z3329177

Cytotoxic - z5018866

Memory - z3465531

Suppressor - z5105710

Natural killer

Mucosal associated invariant

Gamma delta T cells -

Suggestions for subtopic

z5105710: T Regulatory Cells: I

z3465531: T Regulatory Cells would be good. Red Blood Cell, Neutrophil, Eosinophil, Basophil, or Monocyte/Macrophage would be great because they always seem to be relevant to our studies. I'l be happy to go with whatever the group decides.

z5018866: I am more than happy to do T regulatory cells, as it would be great to do a topic that someone has a particular interest in. If there isn't enough on t reg cells alone we could maybe do T cells as a whole and z5105710 you could potentially focus on your interest of t reg cells.

z3329177: I'm happy with the topic, because there are many of articles about t-cells that we can access. For the T-Regulatory cells, i think that it is interesting topic, but i will need to learn more about it to be honest.

Reminders

- Do not cite a review article has having findings. "As reviewed by" is more appropriate terminology. (As in This reference (Biochemistry of tropoelastin. Vrhovski B, Weiss AS. Eur J Biochem. 1998 Nov 15;258(1):1-18. Review. No abstract available. PMID 9851686 ) is a good review article to introduce your topic. One key point is that it is a "review" not original research and should have been cited as such. For example "as reviewed in" or "see review". It is important to discriminate between original research articles and reviews in your writing., group 3 of 2015)

- At all times, remember: How is this sentence related to our topic/subtopic and what are the consequences thereof. Bspw Group 3 2015 made subsection of Vit. A deficiency but didn't explain what this had to do with their exact topic

- At least 1 image on the page should be a student drawn image (e.g flow diagram, power point slide of the cell structure).

- Remember to give all uploaded content an appropriate name.

- Any time that you see nomenclature in an article that is not the current nomenclature (eg. MSDS instead of SDS), that means the article is old and should not be used.

- Avoid add unnecessary detail explaining biological processes that not directly related to the topic (e.g. the description of translation in Group 1 2015)

- It might be a good idea to add "additional information" collapsible boxes (as in Group 3 2015)

Lab 3 Assessment

z3465531

1. Summary: Cathepsin B controls the persistence of memory CD8+ T lymphocytes, Byrne, S. M., et al. [1]

2. Summary: Expanded effector memory T-lymphocytes in DBA/2 mice do not inhibit the growth of SL2 tumours, Jursenaite, J., et al. [2]

3. Summary: Interleukin-22 is produced by invariant natural killer T lymphocytes during influenza A virus infection: potential role in protection against lung epithelial damages, Paget, C., et al. [3]

4. Summary: Microbial exposure during early life has persistent effects on natural killer T cell function, Olszak, T., et al. [4]

References

  1. <pubmed>22745374</pubmed>
  2. <pubmed>22773567</pubmed>
  3. <pubmed>22294696</pubmed>
  4. <pubmed>22442383</pubmed>

z5018866

1. Summary: Folate-mediated chitosan nanoparticles containing the IP-10 gene enhance melanoma-specific cytotoxic CD8+CD28+T Lymphocyte responses, He, J., “et. al.” [1]

In the study promising combination treatments for malignant melanomas are explored using adoptive immunotherapy with Cytotoxic T lymphocytes (CTL).

The study aimed to increase the CTL anti-tumor response by inducing melanoma TRP2-specific CD8+CD28+T cell in combination with folate-modified chitosan nanoparticles containing Interferon-y-inducible protein-10 (IP-10). IP-10 plays a role in chemotaxis particularly for CD8+ T cells towards the tumor [2][3]. The chitosan molecules where prepared with a IP-10 gene from a mouse and the TRP2-specific CD8+CD28+ T cells co-cultured with artificial antigen presenting cells, due to cost and efficiency. Affected mice were treated with one therapy, both or a saline control, with tumor size and survival times measured. Other immune cells were measured and TUNEL techniques used to determine proliferation and angiogenesis.

Overall the combination of the two therapies increased the anti-tumor response and hindered the advancement of the melanoma in vivo. Inhibiting growth and proliferation whilst promoting apoptosis of tumor cells leading to an extended survival time for the mice than either therapy alone. With the chitosan nanoparticles creating a chemotaxic by inducing IP-10 secretion, resulting in recruitment of CD8+ t cells in the tumor area angiogenesis and proliferation were reduced.

2. Summary: Delivery system of CpG oligodeoxynucleotides through eliciting and effective T cell immune response against melanoma in mice, Sun, W., “et. al.” [4]

Through the addition of a C-class CpG ODN-685 (oligodeoxynucleotides) the study aims to explore the effects on anti-tumor activity in melanoma inoculated mice as well as prophylactically in healthy mice to ultimately improve the immunogenicity of the whole tumor cell lysate developed as a vaccine for tumors, whilst. The CpG ODNs are involved in stimulating the early immune responses with T cell activation occurring during their transport to the immune system. There were two groups of study, prophylactic – which were given tumor cell lysate, CpG ODN, tumor cell lysate plus CpG ODN or PBS as control. At a later stage were given tumor cells. The other therapeutic group was inoculated with melanoma tumor cells and then received a treatment. Tumors were either inoculated in hind leg or peritoneum of mice. Subcutaneous and intraperitoneal melanoma affected mice did not respond to tumor lysate or CpG ODN but when combined an immune response was triggered. This led to longer survival time and prevented tumor spread to through the abdominal cavity. Upon analysis of splenocytes the lysate only group displayed anti-tumor effects whilst the CpG ODN alone did not however, when used in conjunction an enhanced response was displayed. Suggesting assistance from CpG ODN in stimulating a cytotoxic immune response. CD4+ / CD8+ T cells increased significantly after tumor inoculation signifying their involvement in immune response and when CpG ODNs where combine with tumor lysate a strong specific Cytotoxic T lymphocyte response was generated. It was concluded that CpG ODN-685 could be effective in increasing immunogenicity of tumor vaccines against melanoma.

3. Summary: Spinal cord T-cell infiltration in the rate spread nerve injury model: a time course study, Gattlen, C., “et. al.” [5]

Infiltration of the spinal cord by T-cells after SCI [5]

In this study Gattlen et. al. explored the immune response following a spared nerve injury (SNI) [6] in mice, in particular microglia, T-lymphocytes and cytotoxic T-lymphocytes responses. The study looks at the relation between different immune cell types and their role in pain and chronic pain. Levels of microglia (Iba1), T-lymphocyte (CD2) and cytotoxic T-lymphocyte (CD8) were measured through various techniques such as measuring gene expression and immunofluorescence.

Microglial reactivity gene expression was unregulated for a prolong period, whilst microglial proliferation measured through immunofluorescence was only increased sharply on day 2. Inflammatory genes were regulated following the SNI with pro-inflammatory factors such as interleukins being increased soon after injury and typical anti-inflammatory factors began to increase at a later stage. Following the SNI CD2 and CD8 cells were counted in the dorsal horn to detect T-cell infiltration into the spinal cord however, a significant difference was not found. This is comparable to a spinal cord injury where T-cell infiltration is displayed.

The increase of anti-inflammatory factors could be a factor in the resolution of the inflammation [7]. Increased excitability in the lamina neurons of the spinal cord has been linked to the increased presence of Pro-inflammatory factors [8]. From this the study concluded that further study should focus on the transition from pro- to anti- inflammatory phases of the microglial cells.

4. Summary: Eliciting cytotoxic T lymphocytes against human laryngeal cancer-derived antigens” evaluation of dendritic cells pulsed with a heat-treated tumour lysate and other antigen loading strategies for dendritic cell based vaccination, Wei, F., “et. al.” [9]

With the goal of improving the antitumor immunity though optimizing antigen loading of current dendritic cell (DC) vaccinations, Wei et. al. explore the value of various dendritic cell vaccinations comprised of whole tumor cells or their derivatives. Through antigen loading DCs tumor-associated antigen (TAA) specific t-cells and cytokine production can be induced. DCs pulsed with tumor cell supernatant (DC-TCS), whole-cell tumor stressed lysate (DC-TSL) and irradiated tumor cells (DC-ITC) where the three different types. It was found that DC-TSL induced strongest responses for TAA-specific T-cells, Th1 cytokine production, and cytotoxic T lymphocyte activity. Making it the most efficient of the three tested for laryngeal squamous cell carcinoma. DC-TCS and ITC inhibited T cell activation however, had limited capacity for CTL activity.

DCs have a potent antigen presenting capacity, which are taken advantage of in the vaccines that have shown promising clinical results [10]. However, a percentage of patients remain insensitive to the therapy, where further research can develop the immunogenicity of these current vaccinations.

References

  1. <pubmed>27022421</pubmed>
  2. <pubmed>18723067</pubmed>
  3. <pubmed>21802343</pubmed>
  4. <pubmed>26918036</pubmed>
  5. 5.0 5.1 <pubmed>27005622 </pubmed> Cite error: Invalid <ref> tag; name "PMID27005622" defined multiple times with different content
  6. <pubmed>19923276</pubmed>
  7. <pubmed>10767254</pubmed>
  8. <pubmed>18480275 </pubmed>
  9. <pubmed>26795730</pubmed>
  10. <pubmed>12633662</pubmed>

z5105710

1. T lymphocytes need less than 3 min to discriminate between peptide MHCs with similar TCR-binding parameters, Brodovitch, A., et al. [1]

Summary

Brodovitch et al. investigated the kinetics of the interaction between MHCs and TCRs. MHC and TCR interaction plays a crucial role in the foundation of "immunological synapses" and discrimination of self and non-self. 1G4 TCR carrying human T-Lymphocytes are dropped on a surface functionalized with various different types, formes (diamonds, squares, crosses) and amounts of pMHCs. To determine the time necessary to differentiate between the distinguished pMHC types, interference reflection microscopy (IRM) was used to quantify the spreading area in real time. The results indicate, that the differentiation process is completed already after 2 minutes, a reflection of how fast our immune system is able to process attacks on our system.

2. The direction of migration of T-lymphocytes under flow depends upon which adhesion receptors are engaged, Dominiquez, GA., et al. [2]

Summary

The movement of leukocytes within vascular environments has given invaluable insight in the progression of auto-immune diseases such as multiple sklerose. The effort of basic research has been promptly rewarded by the discovery of one of the most effective treatments against MS, a monoclonal antibody called Natalizumab, which opts against the delocalisation of lymphocytes from the blood stream into nervous tissue[3]. In the light of such discoveries, further emphasis has been placed on the research of Lymphocyte movement. This paper tried to observe the interaction between lymphocyte function-associated antigen-1 (LFA-1; αLβ2), very late antigen-4 (VLA-4; α4β1) and their ligands, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), cell adhesion molecules expressed on the vascular endothelial lining. VCAM and ICAM was printed on a silicone polymer (PDSM) to inquire, whether ligand type and engagement strenght would influence the migration direction. It was found that direction and cell polarity are well influenced by ligand type and engagement strenght.

3. Broad T-cell receptor repertoire in T-lymphocytes derived from human induced pluripotent stem cells, Chang, CW., et al.[4]

Summary

Induced pluripotent stem cells (iPSC) are one of the biggest promises nowadays. The standard approach, also used in this paper, is viral transfection with Oct3/4, Sox2, c-Myc, and Klf4 [5]. These are the four transcription factors with the power to push cells back to the initial steps of their development. The therapeutic options for iPS are mind-boggling, from Leukemia to Multiple Sclerosis, an uncountable number of diseases is a direct consequence of a malfunctioning immune system. Chang et al. achieved for the first time to induce pluripotent human T-Lymphocytes with expression of various different T Cell Receptors (TCRs). The number of TCRs decreases with the advancing T-Cell development, an increase of incorporation of different TCRs thus signals dedifferentiation. The observed iPSC showed normal patterns of differentiation, as shown in subsequent expression of CD7 and CD3. Furthermore, cytokine signaling strongly resembled natural patterns. The importance of the findings in this paper are emphasized if one takes into account one of the major difficulties with iPSC: directed differentiation. Current approaches focus on mimicking the natural cell environment and copy it from in-vivo to in-vitro, an approach which has been successfully applied by the authors of this paper.

4. Restrictions to HIV-1 replication in resting CD4+ T lymphocytes, Pan, X., et al.[6], a review

Summary

Schematic model of HIV-1 replication and restrictions thereof in activated and resting CD4+ T lymphocytes[6]

Inarguably one of the most important Type of T-Cells are Cells expressing a CD4 surface glycoprotein (not in the Paper, but on a side note: In the range of T-Lymphocytes, CD4 is mainly expressed by T-Helper cells, but also found on other Leukocytes, such as NK-Cells[7]). As reviewed in the paper, besides physiological functions, T-Helper Cells also serve as the main host for HIV1, but only as long as they are in a active state. Active T-Helper Cells primarily reside in lympnodes and replicate not only its own, but also the viral genome. As CD4+ T-Lymphocytes become inactive, a actin structure forms around the cell nucleus and the cell becomes insusceptible for HIV invasion. The review states the cell restriction factor SAMHD1, a deoxynucleoside triphosphate triphosphohydrolase, a key player in inactive CD4+ Cell defense against reverse transcriptase and insertion of viral genom into nuclear DNA.

References

  1. <pubmed>25782169</pubmed>
  2. <pubmed>25674729</pubmed>
  3. <pubmed>16510744</pubmed>
  4. <pubmed>PMC4020825</pubmed>
  5. <pubmed>16904174</pubmed>
  6. 6.0 6.1 <pubmed>PMC3698640</pubmed>
  7. <pubmed>16951326</pubmed>


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 6: User:Z5018866 | User:Z3329177 | User:Z3465531 | User:Z5105710