Hey

Hey I definitely agree there was some confusion.

I thought it was talking about a general immune response to bacterial pathogens. And other than the last question, the questions seemed pretty general (but I looked at the other case studies and they all ask the same questions so I guess we now know what to say.)

What other roles do you have outlined?

Waldo

Hey guys,

So I thought I had uploaded my answer but it seems I did something wrong (still trying to figure out how to use this thing). If it wasn't for Alysha's connect message I wouldn't have seen this and realized that my answer was the missing one so thanks Alysha :). Can we figure out how we are going to divide up the tasks for the group project. We really should get on it as soon as possible. I would expect that since this is a case study, we were meant to focus on the specific bacteria, unless I'm missing something?

Cheers, Atif

Because everyone seems rushed do guys want to use a simpler format such as this wiki to present our answer?

Looking for everyone's responses I think we should make a table highlighting some of the stuff for the innate response with citations from the textbook

Then make a table for the adaptive response and how the bacteria may try to evade these responses cause there seems to be quite a bit of recent literature on that.

Have a separate table or response for induced damage from the immune system

And perhaps the last question, bring in some recent statistics about immunization rates, and pertussis, its re-emergence.

Thoughts?

If you like, I can put together a prezi or powerpoint for the case once we have a fully referenced consensus on an answer, as well as illustrations? Walden, would you and Alysha like to take the lead on compiling the information and referencing it? Armaan could then help design (or source) illustrations and I could edit the whole thing and compile a presentation, perhaps even add in some audio for explanations?

Yes will do!

Thanks Walden! I am still waiting for Alysha and Armaan to respond.

I requested some feedback on my response from Dr. Kelly- I encourage you guys to do the same since her insight very useful. Here is her reponse:

"There are two areas for improvement: (i) you could broaden the discussion to include other potential pathogens, e.g. Streptococcus and Heamophilus; and (ii) be sure to include mechanistic details along with mention of the molecules involved in bacterial pathogenicity and the host response For instance, you mention that “Peptides such as defensins which can damage the cell membrane” – how do defensins act to damage the cell membrane; “NK Cell Activation- IL-12 mediates the activation of NK (natural killer) cells which are capable of killing/destroying bacteria” – how do NK cells kill or destroy the bacteria?; “Cytokine expression is shifted towards regulatory cytokines instead of pro-inflammatory cytokines (Higgins et al. 2003)” – what in the stimulus for this shift?."

Hey Everyone,

For some reason this discussion board just updated for me so I have been sitting here thinking no one had responded to me. I will quickly look over the replies and get back ASAP.

Thanks, Alysha

Okay, so I think our first step is to figure out what pathogens we want to do. From looking at other group responses B. pertussis (of course), S. pneumoniae, H. influenzae, and M. tuberculosis seem to be them. For the first question I think we should focus on the immune response in the respiratory system (meaning talking about mucociliary system and alveolar macrophages) while adding specific immune response mechanisms for each bacteria. They generally use the same mechanism such as PAMP activating PRR and what not. Its just figuring out the best way to present the info. I like the tables Armaan had created.

Quickly adapted from Armaan. What does everyone think?

Pathogen	Cytokines & Chemokines	Function
B. pertussis, S. pneumoniae	TNF-a (Tumor Necrosis Factor- Alpha)	Involved in: Cell proliferation Cell differentiation Coagulation Apoptosis Lipid Metabolism (NIH, 2015)
B. pertussis, S. pneumoniae	Interleukin-1, 6, 12, & 23	Increase: Fever Vessel Permeability Phagocytotic Cells

I think it's good but we could expand on the function section, as Atif mentioned from Dr. Kelly we may need more of a mechanistic explanation for our answer.

Yeah I figured this could be a nice way to show it in a simple manner while keeping paragraphs with a thorough description. We need to figure out what pathogens to do and start sourcing the information if we don't have it. I think everyone should help with this first question since it is the most complex. The other questions aren't too complicated just would be nice to have some illustrations if possible for them.

I'm compiling our responses for the first part right now. I can post my part tomorrow night. Is that enough time?

What pathogens are you including? From the look of the other groups and what Dr. Kelly said to Atif we may want to add H. influenzae and maybe take about M. pneumoniae since I don't recall any other group looking at this. If so I could source H. influenzae and provide a paragraph for you to add to what you are putting together.

M. tuberculosis, S. pneumoniae, H. influenzae, B. pertussis? Are these sufficient?

I think that would be good. We can re-evaluate M. tub. I am not the fence about that one since I don't think it would present like that but maybe something we can decide later as a group. I will source H. influenzae and have something to you tomorrow evening.

Just for clarification, you want me to follow the template of the table shown above?

And have paragraph for the functions of the just chemokines in response to the pathogen, or also include paragraph about the pathogen as well?

Hey Everyone,

I want to apologize for such a delayed response. I focused my response on one particular pathogen, however, I feel that it was a wrong doing on my behalf.

I was wondering what approach we are taking to presenting our answers. I understand that we are taking a more general approach and incorporating more pathogens, however, what area should I focus on.

I just want to ensure I have a particular direction prior to starting my portion of the work. Additionally, I am more than happy to help with formatting, etc.

Thanks :)

To reiterate what Alysha had said, it is easiest to use paragraphs and tables within wiki for formatting purposes. It's a simple and effective way of presenting our information.

Hum not exactly sure what you are saying Walden. Maybe look at how I formatted all the pathogens into that section. Also I think we should do a table similar to what I posted just to break up the text. Something simple and informative.
Something I know we are lacking that Armaan if you don't mind doing is the damage that occurs to the host from the host immune response. The responses we have a pretty broad and maybe see if we can supplement it by finding exact examples like I had said
"For example, M. pneumoniae infection causes the release of pro-inflammatory cytokines possibly directly causing or contributing to the development of chronic pulmonary diseases such as bronchial asthma."
However, we aren't doing this bacteria anymore. I had written this before I found out we weren't to do it specific on B. pertussis

"B. pertussis virulence factors have been implicated in causing damage as a result of the immune response. PT elicits extensive production of inflammatory genes(Connelly, Sun, & Carbonetti, 2012). This upregulation in inflammatory products increases the risk of damage to the airway and lungs(Connelly et al., 2012). Furthermore, studies indicate PT increases the duration of inflammatory response further contributing to the risk of damage to the host(Connelly et al., 2012). CyaA increases Th17 response which when exacerbated can result in substantial lung inflammation and damage(Fedele et al., 2010)."

However, we don't have anything on the other pathogens S.pneumoniae and M.tub so it would be nice to have that assuming there is literature on it.
What do you think?

Ok I think get it haha.

I'll post what I have tomorrow night

Hey Alysha,

I will look for some literature on damage ensued to the host, however, I feel that there is very little information for this component of the question. I struggled to find data pertaining to damage caused by an immune response to B. pertussis.

I'll try to find some info for H. pneumoniae and H. influenzae. Are we still doing M. tuberculosis?

I'll post what I can find tomorrow and I will format it directly into the wiki page.

Anything else I should focus on?

Hey Everyone,

I am going to create a structural framework for our answers in the wiki. I rather start this now than do it all at once.

Perhaps, you all can put the information you have compiled under the subheadings?

Sounds good.

For the immune response damage pertaining B. pertussis, there was some literature of it being an intracellular pathogen within the macrophages as it hid from antibodies, I think there was some literature discussing on how macrophages were activated to secrete proteases and superoxides causing oxidative damage to the surrounding epithelial tissue in the lungs (http://iai.asm.org/content/68/5/2819.short) , or how the leukocytosis caused pulmonary hypertension which disrupted gas exchange (http://cid.oxfordjournals.org/content/47/3/328.short)

Again I don't know if we should lump the pathogens into a similar category for this, as the damage usually comes from these methods

Yes completely understandable it took a lot of rewording the search text to find literature (or just papers that had a little sentence on it). I assume you mean S. pneum. If possible look into all three (S. pneum, M. tub, H. influ) I think we are good on B. pertussis. Let me know how the search goes and I don't mind helping.

If that search seems futile if you want to work on Bacterial evasions. See papers below.

Anti-immunology: evasion of the host immune system by bacterial and viral pathogens.Finlay, B Brett McFadden, Grant, 2006
"Modulators on Bacterial Surfaces Bacterial surfaces are complex structures which, from the host's viewpoint, present many diverse antigenic targets. A major difficulty for bacterial pathogens is hiding this complex surface of proteins and carbohydrates from immune surveillance and TLR recognition yet exposing key molecules such as adhesins and invasins. A common mechanism of masking bacterial surfaces is to express a carbohydrate capsule. This mechanism is used by most extracellular bacterial pathogens that circulate systemically within the body. For example, the pneumococcus (Streptococcus pneumoniae) relies extensively on its capsule to prevent antibody and complement deposition on its surface, thereby avoiding opsonization and phagocytic clearance. Similarly, bacteria that cause meningitis (Haemophilus influenzae, Escherchia coli K1, and Neisseria meningitidis) rely extensively on capsules to promote their extracellular lifestyle within the host by preventing antibody and complement deposition and insertion. Pathogens expressing surface capsules also often have filamentous adhesins (fimbriae and pili) that protrude through the capsular surface, enabling the adhesins to bind to host receptors yet keeping the bacterial surface hidden."
Evasion of host recognition by phase variation in Haemophilus influenzae. Clark, SE, 2013

Based on what Dr. Kelly said to me, we should be focusing on B pertussis, S.Pneumoniae, H. influenzae. Throw all other bacteria out, especially tuberculosis which is miles away from this case definition. Please remember to take her suggestions in the context of my answer to the questions, since her comments point out what is missing only in mine. If you look at my organization of the the immune response question, I gave a general overview off adaptive and innate immunity (defensin and NK need to be expanded), followed by a small section of the responses specific to B. pertussis. I feel writing a small section for the other two pathogens should be sufficient and more organized, allowing the reader to compare the 3 bacteria. I'm willing to write up on H. influenzae. Can someone do S.pneumoniae?

We need to expand on the mechanism aspects of host evasion, which two of you will take the lead on that?

Can we aim to have all research and writing done by noon Friday, leaving enough time for illustrations and formatting? Let's just present on the wiki page or in a word document converted to PDF (easy to format, download and print/save if needed). Let's aim to complete everything by noon Saturday.