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Hello, I am a current intern at Nationwide Children's Hospital in Columbus Ohio and I am having some trouble with teaching myself some cell signaling pathways for microbial pathogenesis. I taught myself the three complement pathways to destroy pathogens through the use of C5bC78 added to around 10-16 C9s to make a MAC, but I am trying to teach myself the toll-like receptor pathways and others like that. I am very much a visual learner but these pictures that I am getting online are too complex for me to decipher. Also, the videos online that I am finding are too simple and I need to go more into depth. I have a presentation of what I did in the lab for the past few months coming up on August 10th and I need to be as well prepared as I can be because a scholarship is on the line that I am competing with other students for and it is vital that I am well prepared to be as versed as I can be in the topic of microbial pathogenesis and immunology. Are there any sites or books that you would recommend me looking for? I would really like help here! Thanks so much.

Answer 1:

Perhaps it would be useful to step back a little and think about the major pathways that have been identified that play roles in immunity to pathogens. First innate immunity, which is the rapidly responding arm of the immune system that includes TLRs (Toll-like Receptors) and interferon response pathways. In a nutshell, our immune cells have developed specific receptors for components of bacteria such as flagella and cell envelope components, and components of viruses including double stranded RNAs. Once these components are bound, signals are sent to the immune cell and various pathways that kill or tie up bacteria and viruses, or kill cells harboring intracellular pathogens, are activated.

Second: acquired immunity, which takes more time and generates highly specific antibodies (humoral response) and T cell receptors (cellular response) that can recognize antigens on target cells. Humoral immunity is very useful against pathogens that cannot enter our cells- for example antibodies and complement can poke holes in the pathogen, antibodies to components like capsules that allow bacteria to "slip" out of the grasp of white blood cells/macrophages can "opsonize" them, which allows them to be recognized and engulfed by immune cells. However, intracellular pathogens can escape the humoral system. You might ask how this is possible since you would think the pathogen would need to pop out of the host cell to gain entrance to a neighboring cell- but, many pathogens have developed ways to travel from cell to cell without ever having to leave the cell and be exposed to antibodies or complement in the blood. (Examples are Listeria, Shigella, Burkholderia).

The complement system is involved in both innate immunity and acquired immunity. The classical complement pathway requires antigen antibody complexes for activation and eventual killing of pathogens, whereas the alternative pathway works without antibodies, involving C3b, which can bind directly to pathogens and initiate an activation pathway.

I enclose a couple of papers focused on innate immunity, which seems to be the focus of your research?

immunityto bacteria
toll-likereceptors

For a general textbook, this URL may be useful- search chapters on innate and acquired immunity-

textbookof bacteriology
Cheers,

Answer 2:

Great question! I have two recommendations for you. First, check out Todar's Online Textbook of Bacteriology mentioned in the answer above.

We use this free on-line textbook to teach Bacterial Pathogenesis, and it is fantastic! I think you will find the answers to most of your questions there by going to the "Table of Contents" and looking under the heading of "Bacterial Relationships with Animals". There are two fantastic chapters on Immune Defense against Microbial Pathogens! Second, you can also try the textbook "Bacterial Pathogenesis: A Molecular Approach" by Salyers and Whitt. I would recommend either the 2nd or 3rd edition. This textbook also has a thorough description of immune defenses against microbes. These are the two textbooks we use to teach Bacterial Pathogenesis here at UCSB, and I am sure you will find what you are looking for.



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