Welcome back, health explorers, to the second thrilling episode of our "Inside Out: The Gut Health Revolution" podcast and blog series! πŸŽ™οΈβœ¨ In our first episode, we took a fascinating journey through the bustling city of your gut microbiome. Today, we're gearing up to meet your body's very own superhero team: the immune system! πŸ¦Έβ€β™€οΈπŸ¦Έβ€β™‚οΈ Buckle up, because we're about to dive deep into this complex and fascinating world that keeps you healthy every single day.

Introduction: Your Body's Defense Department 🏰

Imagine your body as a bustling medieval castle, constantly under threat from invading armies of pathogens - bacteria, viruses, fungi, and other microscopic troublemakers. Your immune system? Well, that's your castle's entire defense network - from the high walls and moat to the guards, archers, and even the secret tunnels and spy network. It's all working together to keep the bad guys out and maintain peace in the kingdom.

But it's more than just a static set of defenses. Your immune system is a dynamic, adaptable network of cells, tissues, and organs that work tirelessly to protect you from harm. It's constantly on alert, ready to spring into action at the first sign of trouble.

In this deep dive into the immune system, we'll explore:

  • The fascinating history of immunology πŸ“œ
  • The two main branches of your immune system: innate and adaptive immunity 🌳
  • The key players in your immune defense 🎭
  • How your immune system communicates and coordinates its responses πŸ“‘
  • The connection between your immune system and gut health πŸ”—
  • Lifestyle factors that can boost or hinder your immune function πŸ‹οΈβ€β™€οΈ
  • Common disorders of the immune system πŸš‘
  • Practical tips for supporting your immune health πŸ’ͺ

So, grab your imaginary suit of armor, and let's embark on a journey into the incredible world of your immune system. By the end of this episode, you'll have a new appreciation for the complex defense network operating within you every moment of every day!

A Journey Through Time: The Fascinating History of Immunology πŸ•°οΈ

Before we dive into the nitty-gritty of how your immune system works, let's take a moment to appreciate the rich history of immunology. This field has come a long way, with each discovery building upon the last to create our current understanding of this complex system.

The concept of immunity dates back to ancient times, with Greek historian Thucydides noting that survivors of a plague in Athens were immune to reinfection. Fast forward to the 18th and 19th centuries, and we see the birth of modern immunology. Scientists like Ilya Metchnikoff discovered phagocytosis, while Emil von Behring and Kitasato Shibasaburo uncovered antibodies.

The 20th century saw an explosion of knowledge in immunology, from Frank Macfarlane Burnet's clonal selection theory to the discovery of T-cell functions by Jacques Miller. More recent breakthroughs include the development of monoclonal antibodies and advances in cancer immunotherapy.

As we continue to unravel the complexities of the immune system, we build on centuries of scientific curiosity and discovery. And the best part? We're just getting started! The field of immunology continues to evolve, with new discoveries constantly reshaping our understanding of this remarkable system.

The Dynamic Duo: Innate and Adaptive Immunity πŸ¦Έβ€β™€οΈπŸ¦Έβ€β™‚οΈ

Your immune system is like a tag-team of two major partners: innate immunity and adaptive immunity. These two systems work together seamlessly to provide comprehensive protection against a wide array of threats. Let's meet our heroes!

Innate Immunity: The First Responders 🚨

Innate immunity is like the castle's outer defenses - always on duty, ready to tackle any intruder immediately. It's the part of your immune system you're born with, and it's your body's first line of defense against pathogens.

Physical Barriers 🧱

The first component of innate immunity is your physical barriers. These include:

  1. Skin: Your skin is like the castle walls, providing a tough, impenetrable barrier against most pathogens. It's not just a passive barrier, either. Your skin produces antimicrobial peptides that can kill bacteria, and its acidic pH makes it inhospitable for many microorganisms. This protective layer is intimately connected with your overall health, including the state of your gut microbiome, as explored in our gut-skin axis article.

  2. Mucous Membranes: These line your respiratory, digestive, and urogenital tracts. They secrete mucus, which traps pathogens and contains antimicrobial enzymes. The mucus layer is more than just sticky goo. It contains a variety of antimicrobial proteins such as defensins, cathelicidins, and histatins.

  3. Cilia: These tiny hair-like structures in your respiratory tract sweep debris and pathogens up and out of your lungs. Cilia work in conjunction with the mucus layer in a system called mucociliary clearance.

Chemical Barriers πŸ§ͺ

Next up are your chemical barriers. Think of these as the boiling oil that defenders pour on attackers. They include:

  1. Stomach Acid: With a pH as low as 1.5 to 3.5, your stomach acid can destroy many pathogens that enter through your mouth. This acidic environment is crucial for both digestion and immune defense, highlighting the intricate connection between gut health and immunity.

  2. Enzymes: Substances like lysozyme in your tears, saliva, and sweat can break down the cell walls of certain bacteria.

  3. Antimicrobial Proteins: Your body produces various proteins that can interfere with microbial growth or directly kill pathogens. One fascinating example is lactoferrin, found in milk and other bodily fluids.

Cellular Responders 🦠

The cellular components of innate immunity are like the guards who spot intruders and sound the alarm, then start fighting right away. Key players include:

  1. Neutrophils: These are usually the first immune cells to arrive at the site of an infection. They can engulf and destroy pathogens through a process called phagocytosis.

  2. Macrophages: These are the big eaters of the immune system. They not only destroy pathogens but also clean up cellular debris and signal other immune cells.

  3. Natural Killer (NK) Cells: These cells are specialized in detecting and destroying virus-infected cells or tumor cells.

  4. Dendritic Cells: These are the bridge between innate and adaptive immunity. They capture antigens from pathogens and present them to adaptive immune cells.

The innate immune system acts fast and doesn't discriminate. Any intruder gets the same treatment! However, it's not always enough to completely eliminate a threat, which is where our next superhero comes in.

Adaptive Immunity: The Special Forces 🎯

If innate immunity is your castle's general defense, adaptive immunity is like having a team of special agents who can learn about specific intruders and remember them for next time. This system is unique to vertebrates and provides a targeted, specific response to pathogens.

Key players in adaptive immunity include:

T-cells 🧬

T-cells are like the commanders of your adaptive immune response. They come in several varieties:

  1. Helper T-cells (CD4+ cells): These coordinate the immune response by stimulating other immune cells.

  2. Cytotoxic T-cells (CD8+ cells): These are the trained killers that directly attack infected cells or tumor cells.

  3. Regulatory T-cells: These help prevent autoimmune responses by suppressing other T-cells.

  4. Memory T-cells: These stick around after an infection, ready to mount a quick response if the same pathogen returns.

The intricate dance between these different types of immunity forms the backbone of our body's defense system, a topic we delve into further in our comparison of innate and adaptive immunity.

B-cells 🧫

B-cells are your antibody factories. When activated, they transform into plasma cells that produce antibodies. Antibodies are like wanted posters that mark intruders for destruction. They can:

  1. Neutralize pathogens directly
  2. Mark pathogens for destruction by other immune cells
  3. Activate complement proteins that can punch holes in bacterial cell membranes

Like T-cells, some B-cells become memory cells, providing long-lasting immunity.

Adaptive immunity takes a bit longer to kick in, but it's super specific and has a great memory. Once it learns about a threat, it's ready for a rematch!

The Immune System's Secret Weapon: Inflammation πŸ”₯

Ever wondered why injured areas get red, swollen, and warm? That's inflammation - your immune system's way of calling for backup and creating a battleground. It's like your castle lighting signal fires and gathering troops in one area to fight off invaders.

Inflammation is a complex process involving various immune cells and chemical signals. While a little inflammation is good, too much can be a problem. It's like if your castle kept all its defenses on high alert all the time - exhausting and potentially damaging. Chronic inflammation is associated with numerous diseases, including arthritis, heart disease, and certain cancers.

Recent research has even linked chronic inflammation to neurodegenerative diseases like Alzheimer's and Parkinson's, highlighting the far-reaching effects of this process. This connection between inflammation and various health conditions underscores the importance of maintaining a balanced immune response, which brings us to our next topic...

The Gut-Immune Connection: A Dynamic Partnership 🀝

Remember our gut microbiome pals from the last episode? Turns out, they play a huge role in training your immune system! It's like your gut bugs are running a boot camp for immune cells, teaching them who's friend and who's foe.

The relationship between your immune system and your microbiome is complex and bidirectional:

  1. Microbiome Educates the Immune System: Exposure to diverse microbes early in life helps train the immune system to distinguish between harmful and harmless organisms.

  2. Immune System Shapes the Microbiome: Your immune system helps maintain a healthy balance of microbes, preventing any one species from overgrowing.

  3. Microbial Metabolites Influence Immunity: Some products of microbial metabolism can directly affect immune cell function. For example, short-chain fatty acids (SCFAs) produced by gut bacteria have been shown to promote the development of regulatory T cells, which help to maintain immune balance.

But it's a delicate balance. An out-of-whack microbiome can confuse your immune system, sometimes making it overreact (hello, allergies and autoimmune diseases) or under-react (making you more susceptible to infections).

Recent research has even suggested that the gut microbiome may influence immune responses in distant parts of the body, including the lungs and the brain. This has led to the concept of the gut-lung axis and the gut-brain axis, highlighting the far-reaching influence of our microbial partners. This fascinating interplay between our gut and our immune system is a cornerstone of our ongoing exploration of gut-immune connections.

Lifestyle Factors Affecting Immune Function πŸ‹οΈβ€β™€οΈ

Your immune system isn't just influenced by what's happening inside your body - your lifestyle choices play a big role too. Here are some key factors that can boost or hinder your immune function:

1. Nutrition 🍎

You are what you eat, and so is your immune system! A balanced diet rich in fruits, vegetables, whole grains, and lean proteins provides the nutrients your immune system needs to function optimally. Some key players include:

  • Vitamin C: Found in citrus fruits, berries, and leafy greens, vitamin C supports the production and function of immune cells. This powerful antioxidant plays a crucial role in both immune function and gut health.

  • Vitamin D: Often called the "sunshine vitamin," it plays a crucial role in modulating immune responses. Its importance, especially in countries with limited sunlight like Ireland, cannot be overstated, as we explore in our vitamin D deep dive.

  • Zinc: This mineral is essential for the development and function of immune cells. Its impact on both immunity and gut function makes it a key player in overall health, as discussed in our zinc overview.

  • Omega-3 Fatty Acids: These have anti-inflammatory properties and can help regulate immune function. Their role in supporting both gut and immune health is significant, as detailed in our omega-3 fatty acids article.

2. Sleep 😴

While you're catching Z's, your immune system is hard at work. During sleep, your body produces and releases cytokines, which help regulate immune responses. Aim for 7-9 hours of quality sleep per night to support your immune function. The intricate relationship between sleep and immunity is a fascinating area of study, with implications for both gut and overall health, as explored in our sleep and immunity article.

3. Exercise πŸƒβ€β™€οΈ

Regular moderate exercise is like a training camp for your immune cells. It can improve circulation of immune cells, reduce inflammation, and enhance overall immune function. However, intense, prolonged exercise can temporarily suppress immune function, so balance is key. Finding the right balance of exercise can have profound effects on both your gut health and immune system, a topic we delve into in our exercise and gut health guide.

4. Stress Management πŸ§˜β€β™€οΈ

Chronic stress is like kryptonite for your immune system. Stress hormones like cortisol can suppress immune function. Find ways to manage stress through meditation, regular exercise, or hobbies you enjoy. Effective stress management is crucial not only for mental well-being but also for maintaining a robust immune system and healthy gut, as we discuss in our stress management for gut health article.

5. Hydration πŸ’§

Staying well-hydrated helps your body eliminate toxins and waste materials that can make you susceptible to illness. It also helps your blood circulate, allowing immune cells to move freely throughout your body. Proper hydration is a cornerstone of both digestive wellness and immune function, as explored in our hydration and gut health guide.

When Things Go Haywire: Immune System Disorders πŸš‘

Sometimes, the immune system can get confused. It might start attacking things it shouldn't (that's autoimmune diseases) or overreact to harmless things (hello, allergies!). It's like if your castle guards started attacking innocent traders or freaking out over every tumbleweed.

Autoimmune Diseases 🎯

In autoimmune diseases, the immune system mistakenly attacks the body's own tissues. Examples include rheumatoid arthritis, type 1 diabetes, and multiple sclerosis. The connection between gut health and autoimmune conditions is an area of intense research, with growing evidence suggesting a strong link between the two, as we explore in our gut health and autoimmune conditions article.

Allergies 🀧

Allergies occur when the immune system overreacts to harmless substances (allergens) like pollen, certain foods, or pet dander. This overreaction can cause symptoms ranging from mild (sneezing, itching) to severe (anaphylaxis). Interestingly, emerging research suggests that gut health may play a role in both the development and management of allergies, a topic we discuss in our gut health and allergies guide.

Immunodeficiencies 😷

These disorders occur when one or more parts of the immune system don't function properly. They can be primary (present at birth) or secondary (acquired later in life).

Scientists are still figuring out why these immune dysfunctions happen, but it seems to be a mix of genetic and environmental factors. And yes, your gut microbiome might be playing a role here too!

Practical Tips for Supporting Your Immune Health πŸ’ͺ

Want to give your immune superheroes a boost? Here are some evidence-based tips:

  1. Eat a Rainbow 🌈: Different colored fruits and veggies have different nutrients that support immune function. It's like giving your immune cells a variety of super-powers!

  2. Get Moving πŸƒβ€β™‚οΈ: Aim for regular moderate exercise. Even a 30-minute walk most days of the week can make a difference.

  3. Prioritize Sleep 😴: Aim for 7-9 hours of quality sleep each night. Your immune system will thank you!

  4. Manage Stress πŸ§˜β€β™€οΈ: Find stress-reduction techniques that work for you, whether it's meditation, yoga, or simply spending time in nature.

  5. Stay Hydrated πŸ’§: Drink plenty of water throughout the day.

  6. Consider Probiotics 🦠: While more research is needed, some studies suggest that certain probiotic strains can enhance immune function. The role of beneficial bacteria in gut health and immunity is an exciting area of ongoing research, as we discuss in our probiotics for gut health article.

  7. Don't Smoke and Limit Alcohol 🚭🍷: Both smoking and excessive alcohol consumption can impair immune function.

  8. Practice Good Hygiene 🧼: Regular hand washing is one of the best ways to prevent the spread of infections.

  9. Laugh More πŸ˜‚: Believe it or not, laughter can boost immune function by reducing stress hormones and increasing antibody-producing cells.

  10. Spend Time in Nature 🌳: Exposure to nature has been shown to boost immune function and reduce stress.

Remember, supporting your immune system is a lifestyle, not a quick fix. Consistency is key!

Conclusion: Embracing Your Inner Defender πŸ›‘οΈ

Well, intrepid immune explorers, we've journeyed through the fascinating world of your body's defense system. From the bustling cellular cities of your innate immunity to the specialized forces of your adaptive immunity, we've uncovered the marvels of the immune system. Let's recap our adventure:

  1. Your immune system has a rich history of discovery, from ancient observations to cutting-edge modern research.
  2. It's a complex network of cells, tissues, and organs working together to protect you.
  3. It consists of two main branches: innate immunity (fast and general) and adaptive immunity (slower but specific).
  4. Inflammation is a key process in immune responses, but too much can be harmful.
  5. Your gut microbiome plays a crucial role in educating and modulating your immune system.
  6. Lifestyle factors like diet, sleep, exercise, and stress management significantly impact immune function.
  7. Sometimes the immune system can malfunction, leading to conditions like autoimmune diseases and allergies.
  8. There are many practical steps you can take to support your immune health.

As we close this second episode of "Inside Out: The Gut Health Revolution," I hope you're feeling inspired, informed, and ready to support your incredible immune system. Remember, every healthy choice you make is like giving your immune superheroes a power-up!

Stay tuned for our next episode, where we'll explore the fascinating gut-brain axis. Are you ready to discover how the bugs in your belly might be influencing your thoughts and emotions? Trust me, you won't want to miss this mind-blowing revelation about the hidden conductor of your bodily orchestra!

Until then, give your immune system a silent thank you for all its hard work. It's got your back, 24/7! πŸ™

Recommended Books for Further Reading πŸ“š

For those who want to dive deeper into the fascinating world of immunology, here are some excellent resources:

  1. "An Elegant Defense: The Extraordinary New Science of the Immune System" by Matt Richtel A captivating exploration of the immune system through personal stories and cutting-edge science.

  2. "The Beautiful Cure: The Revolution in Immunology and What It Means for Your Health" by Daniel M. Davis A compelling account of the latest breakthroughs in immunology and their implications for health and medicine.

  3. "How the Immune System Works" by Lauren Sompayrac A clear, concise introduction to immunology, perfect for those new to the subject.

  4. "Immunity: The Science of Staying Well" by Jenna Macciochi A practical guide to understanding and supporting your immune system through lifestyle choices.

  5. "The Compatibility Gene: How Our Bodies Fight Disease, Attract Others, and Define Our Selves" by Daniel M. Davis An intriguing look at the role of HLA genes in immunity, health, and even mate selection.

Happy reading, immune system enthusiasts! πŸ€“

References

  1. Retief, F. P., & Cilliers, L. (1998). The epidemic of Athens, 430-426 BC. South African Medical Journal, 88(1), 50-53. https://pubmed.ncbi.nlm.nih.gov/9539938/

  2. Modanlou, H. D. (2011). A tribute to Zakariya Razi (865 - 925 AD), an Iranian pioneer scholar. Archives of Iranian Medicine, 14(5), 370-372. https://pubmed.ncbi.nlm.nih.gov/21888458/

  3. Riedel, S. (2005). Edward Jenner and the history of smallpox and vaccination. Proceedings (Baylor University. Medical Center), 18(1), 21-25. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1200696/

  4. Gordon, S. (2016). Phagocytosis: An Immunobiologic Process. Immunity, 44(3), 463-475. https://www.sciencedirect.com/science/article/pii/S1074761316300693

  5. Kaufmann, S. H. (2017). Remembering Emil von Behring: from Tetanus Treatment to Antibody Cooperation with Phagocytes. mBio, 8(1), e00117-17. https://mbio.asm.org/content/8/1/e00117-17

  6. Burnet, F. M. (1959). The Clonal Selection Theory of Acquired Immunity. Cambridge University Press. https://www.cambridge.org/core/books/clonal-selection-theory-of-acquired-immunity/9F9BA471A03A29A4AE9CE8BA75DC1784

  7. Miller, J. F. (2011). The golden anniversary of the thymus. Nature Reviews Immunology, 11(7), 489-495. https://www.nature.com/articles/nri2993

  8. Doherty, P. C., & Zinkernagel, R. M. (1975). A biological role for the major histocompatibility antigens. The Lancet, 305(7922), 1406-1409. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(75)92610-0/fulltext

  9. KΓΆhler, G., & Milstein, C. (1975). Continuous cultures of fused cells secreting antibody of predefined specificity. Nature, 256(5517), 495-497. https://www.nature.com/articles/256495a0

  10. Beutler, B. (2009). Microbe sensing, positive feedback loops, and the pathogenesis of inflammatory diseases. Immunological Reviews, 227(1), 248-263. https://onlinelibrary.wiley.com/doi/full/10.1111/j.1600-065X.2008.00733.x

  11. June, C. H., O'Connor, R. S., Kawalekar, O. U., Ghassemi, S., & Milone, M. C. (2018). CAR T cell immunotherapy for human cancer. Science, 359(6382), 1361-1365. https://science.sciencemag.org/content/359/6382/1361

  12. Gallo, R. L., & Hooper, L. V. (2012). Epithelial antimicrobial defence of the skin and intestine. Nature Reviews Immunology, 12(7), 503-516. https://www.nature.com/articles/nri3228

  13. Romani, N., Clausen, B. E., & Stoitzner, P. (2010). Langerhans cells and more: langerin-expressing dendritic cell subsets in the skin. Immunological Reviews, 234(1), 120-141. https://onlinelibrary.wiley.com/doi/full/10.1111/j.0105-2896.2009.00886.x

  14. Hansson, G. C. (2012). Role of mucus layers in gut infection and inflammation. Current Opinion in Microbiology, 15(1), 57-62. https://www.sciencedirect.com/science/article/pii/S1369527411002001

  15. Bustamante-Marin, X. M., & Ostrowski, L. E. (2017). Cilia and Mucociliary Clearance. Cold Spring Harbor Perspectives in Biology, 9(4), a028241. https://cshperspectives.cshlp.org/content/9/4/a028241

  16. Martinsen, T. C., Bergh, K., & Waldum, H. L. (2005). Gastric juice: a barrier against infectious diseases. Basic & Clinical Pharmacology & Toxicology, 96(2), 94-102. https://onlinelibrary.wiley.com/doi/full/10.1111/j.1742-7843.2005.pto960202.x

  17. Callewaert, L., & Michiels, C. W. (2010). Lysozymes in the animal kingdom. Journal of Biosciences, 35(1), 127-160. https://link.springer.com/article/10.1007/s12038-010-0015-5

  18. Ward, P. P., Paz, E., & Conneely, O. M. (2005). Multifunctional roles of lactoferrin: a critical overview. Cellular and Molecular Life Sciences, 62(22), 2540. https://link.springer.com/article/10.1007/s00018-005-5369-8

  19. Kolaczkowska, E., & Kubes, P. (2013). Neutrophil recruitment and function in health and inflammation. Nature Reviews Immunology, 13(3), 159-175. https://www.nature.com/articles/nri3399

  20. Brinkmann, V., Reichard, U., Goosmann, C., Fauler, B., Uhlemann, Y., Weiss, D. S., ... & Zychlinsky, A. (2004). Neutrophil extracellular traps kill bacteria. Science, 303(5663), 1532-1535. https://science.sciencemag.org/content/303/5663/1532

  21. Mosser, D. M., & Edwards, J. P. (2008). Exploring the full spectrum of macrophage activation. Nature Reviews Immunology, 8(12), 958-969. https://www.nature.com/articles/nri2448

  22. Vivier, E., Tomasello, E., Baratin, M., Walzer, T., & Ugolini, S. (2008). Functions of natural killer cells. Nature Immunology, 9(5), 503-510. https://www.nature.com/articles/ni1582

  23. Banchereau, J., & Steinman, R. M. (1998). Dendritic cells and the control of immunity. Nature, 392(6673), 245-252. https://www.nature.com/articles/32588

  24. Zhu, J., & Paul, W. E. (2008). CD4 T cells: fates, functions, and faults. Blood, 112(5), 1557-1569. https://ashpublications.org/blood/article/112/5/1557/25580/CD4-T-cells-fates-functions-and-faults

  25. Zhang, N., & Bevan, M. J. (2011). CD8+ T cells: foot soldiers of the immune system. Immunity, 35(2), 161-168. https://www.sciencedirect.com/science/article/pii/S1074761311003141

  26. Sakaguchi, S., Yamaguchi, T., Nomura, T., & Ono, M. (2008). Regulatory T cells and immune tolerance. Cell, 133(5), 775-787. https://www.sciencedirect.com/science/article/pii/S0092867408005843

  27. Farber, D. L., Yudanin, N. A., & Restifo, N. P. (2014). Human memory T cells: generation, compartmentalization and homeostasis. Nature Reviews Immunology, 14(1), 24-35. https://www.nature.com/articles/nri3567

  28. Sallusto, F., Geginat, J., & Lanzavecchia, A. (2004). Central memory and effector memory T cell subsets: function, generation, and maintenance. Annual Review of Immunology, 22, 745-763. https://www.annualreviews.org/doi/full/10.1146/annurev.immunol.22.012703.104702

  29. LeBien, T. W., & Tedder, T. F. (2008). B lymphocytes: how they develop and function. Blood, 112(5), 1570-1580. https://ashpublications.org/blood/article/112/5/1570/25582/B-lymphocytes-how-they-develop-and-function

  30. Teng, G., & Papavasiliou, F. N. (2007). Immunoglobulin somatic hypermutation. Annual Review of Genetics, 41, 107-120. https://www.annualreviews.org/doi/full/10.1146/annurev.genet.41.110306.130340

  31. Medzhitov, R. (2008). Origin and physiological roles of inflammation. Nature, 454(7203), 428-435. https://www.nature.com/articles/nature07201

  32. Turner, M. D., Nedjai, B., Hurst, T., & Pennington, D. J. (2014). Cytokines and chemokines: At the crossroads of cell signalling and inflammatory disease. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research, 1843(11), 2563-2582. https://www.sciencedirect.com/science/article/pii/S0167488914001967

  33. Griffith, J. W., Sokol, C. L., & Luster, A. D. (2014). Chemokines and chemokine receptors: positioning cells for host defense and immunity. Annual Review of Immunology, 32, 659-702. https://www.annualreviews.org/doi/full/10.1146/annurev-immunol-032713-120145

  34. Ricciotti, E., & FitzGerald, G. A. (2011). Prostaglandins and inflammation. Arteriosclerosis, Thrombosis, and Vascular Biology, 31(5), 986-1000. https://www.ahajournals.org/doi/full/10.1161/ATVBAHA.110.207449

  35. Jutel, M., Akdis, M., & Akdis, C. A. (2009). Histamine, histamine receptors and their role in immune pathology. Clinical & Experimental Allergy, 39(12), 1786-1800. https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2222.2009.03374.x

  36. Furman, D., Campisi, J., Verdin, E., Carrera-Bastos, P., Targ, S., Franceschi, C., ... & Slavich, G. M. (2019). Chronic inflammation in the etiology of disease across the life span. Nature Medicine, 25(12), 1822-1832. https://www.nature.com/articles/s41591-019-0675-0

  37. Heneka, M. T., Kummer, M. P., & Latz, E. (2014). Innate immune activation in neurodegenerative disease. Nature Reviews Immunology, 14(7), 463-477. https://www.nature.com/articles/nri3705

  38. Belkaid, Y., & Hand, T. W. (2014). Role of the microbiota in immunity and inflammation. Cell, 157(1), 121-141. https://www.sciencedirect.com/science/article/pii/S0092867414003456

  39. Gensollen, T., Iyer, S. S., Kasper, D. L., & Blumberg, R. S. (2016). How colonization by microbiota in early life shapes the immune system. Science, 352(6285), 539-544. https://science.sciencemag.org/content/352/6285/539

  40. Hooper, L. V., Littman, D. R., & Macpherson, A. J. (2012). Interactions between the microbiota and the immune system. Science, 336(6086), 1268-1273. https://science.sciencemag.org/content/336/6086/1268

  41. Macpherson, A. J., & Uhr, T. (2004). Induction of protective IgA by intestinal dendritic cells carrying commensal bacteria. Science, 303(5664), 1662-1665. https://science.sciencemag.org/content/303/5664/1662

  42. Schirmer, M., Smeekens, S. P., Vlamakis, H., Jaeger, M., Oosting, M., Franzosa, E. A., ... & Xavier, R. J. (2016). Linking the human gut microbiome to inflammatory cytokine production capacity. Cell, 167(4), 1125-1136. https://www.sciencedirect.com/science/article/pii/S009286741631473X

  43. Smith, P. M., Howitt, M. R., Panikov, N., Michaud, M., Gallini, C. A., Bohlooly-Y, M., ... & Garrett, W. S. (2013). The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science, 341(6145), 569-573. https://science.sciencemag.org/content/341/6145/569

  44. Budden, K. F., Gellatly, S. L., Wood, D. L., Cooper, M. A., Morrison, M., Hugenholtz, P., & Hansbro, P. M. (2017). Emerging pathogenic links between microbiota and the gut–lung axis. Nature Reviews Microbiology, 15(1), 55-63. https://www.nature.com/articles/nrmicro.2016.142

  45. Cryan, J. F., O'Riordan, K. J., Cowan, C. S., Sandhu, K. V., Bastiaanssen, T. F., Boehme, M., ... & Dinan, T. G. (2019). The microbiota-gut-brain axis. Physiological Reviews, 99(4), 1877-2013. https://journals.physiology.org/doi/full/10.1152/physrev.00018.2018

  46. Carr, A. C., & Maggini, S. (2017). Vitamin C and immune function. Nutrients, 9(11), 1211. https://www.mdpi.com/2072-6643/9/11/1211

  47. Wintergerst, E. S., Maggini, S., & Hornig, D. H. (2006). Immune-enhancing role of vitamin C and zinc and effect on clinical conditions. Annals of Nutrition and Metabolism, 50(2), 85-94. https://www.karger.com/Article/Abstract/90495

  48. Aranow, C. (2011). Vitamin D and the immune system. Journal of Investigative Medicine, 59(6), 881-886. https://jim.bmj.com/content/59/6/881

  49. Prietl, B., Treiber, G., Pieber, T. R., & Amrein, K. (2013). Vitamin D and immune function. Nutrients, 5(7), 2502-2521. https://www.mdpi.com/2072-6643/5/7/2502

  50. Prasad, A. S. (2008). Zinc in human health: effect of zinc on immune cells. Molecular Medicine, 14(5), 353-357. https://molmed.biomedcentral.com/articles/10.2119/2008-00033.Prasad

  51. Shankar, A. H., & Prasad, A. S. (1998). Zinc and immune function: the biological basis of altered resistance to infection. The American Journal of Clinical Nutrition, 68(2), 447S-463S. https://academic.oup.com/ajcn/article/68/2/447S/4648668

  52. Calder, P. C. (2013). Omega‐3 polyunsaturated fatty acids and inflammatory processes: nutrition or pharmacology?. British Journal of Clinical Pharmacology, 75(3), 645-662. https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2125.2012.04374.x

  53. Serhan, C. N., & Levy, B. D. (2018). Resolvins in inflammation: emergence of the pro-resolving superfamily of mediators. The Journal of Clinical Investigation, 128(7), 2657-2669. https://www.jci.org/articles/view/97943

  54. Besedovsky, L., Lange, T., & Born, J. (2012). Sleep and immune function. PflΓΌgers Archiv-European Journal of Physiology, 463(1), 121-137. https://link.springer.com/article/10.1007/s00424-011-1044-0

  55. Irwin, M. R. (2015). Why sleep is important for health: a psychoneuroimmunology perspective. Annual Review of Psychology, 66, 143-172. https://www.annualreviews.org/doi/full/10.1146/annurev-psych-010213-115205

  56. Nieman, D. C., & Wentz, L. M. (2019). The compelling link between physical activity and the body's defense system. Journal of Sport and Health Science, 8(3), 201-217. https://www.sciencedirect.com/science/article/pii/S2095254618301005

  57. Simpson, R. J., Kunz, H., Agha, N., & Graff, R. (2015). Exercise and the regulation of immune functions. Progress in Molecular Biology and Translational Science, 135, 355-380. https://www.sciencedirect.com/science/article/pii/S1877117315001714

  58. Walsh, N. P., Gleeson, M., Shephard, R. J., Gleeson, M., Woods, J. A., Bishop, N. C., ... & Simon, P. (2011). Position statement part one: immune function and exercise. Exercise Immunology Review, 17, 6-63. https://pubmed.ncbi.nlm.nih.gov/21446352/

  59. Segerstrom, S. C., & Miller, G. E. (2004). Psychological stress and the human immune system: a meta-analytic study of 30 years of inquiry. Psychological Bulletin, 130(4), 601. https://psycnet.apa.org/doiLanding?doi=10.1037%2F0033-2909.130.4.601

  60. Dhabhar, F. S. (2014). Effects of stress on immune function: the good, the bad, and the beautiful. Immunologic Research, 58(2), 193-210. https://link.springer.com/article/10.1007/s12026-014-8517-0

  61. Keller, A., Litzelman, K., Wisk, L. E., Maddox, T., Cheng, E. R., Creswell, P. D., & Witt, W. P. (2012). Does the perception that stress affects health matter? The association with health and mortality. Health Psychology, 31(5), 677. https://psycnet.apa.org/doiLanding?doi=10.1037%2Fa0026743

  62. Popkin, B. M., D'Anci, K. E., & Rosenberg, I. H. (2010). Water, hydration, and health. Nutrition Reviews, 68(8), 439-458. https://academic.oup.com/nutritionreviews/article/68/8/439/1841926

  63. JΓ©quier, E., & Constant, F. (2010). Water as an essential nutrient: the physiological basis of hydration. European Journal of Clinical Nutrition, 64(2), 115-123. https://www.nature.com/articles/ejcn2009111

  64. Wang, L., Wang, F. S., & Gershwin, M. E. (2015). Human autoimmune diseases: a comprehensive update. Journal of Internal Medicine, 278(4), 369-395. https://onlinelibrary.wiley.com/doi/full/10.1111/joim.12395

  65. Rosenblum, M. D., Remedios, K. A., & Abbas, A. K. (2015). Mechanisms of human autoimmunity. The Journal of Clinical Investigation, 125(6), 2228-2233. https://www.jci.org/articles/view/78088

  66. Cusick, M. F., Libbey, J. E., & Fujinami, R. S. (2012). Molecular mimicry as a mechanism of autoimmune disease. Clinical Reviews in Allergy & Immunology, 42(1), 102-111. https://link.springer.com/article/10.1007/s12016-011-8294-7

  67. Vanderlugt, C. L., & Miller, S. D. (2002). Epitope spreading in immune-mediated diseases: implications for immunotherapy. Nature Reviews Immunology, 2(2), 85-95. https://www.nature.com/articles/nri724

  68. Fujinami, R. S., von Herrath, M. G., Christen, U., & Whitton, J. L. (2006). Molecular mimicry, bystander activation, or viral persistence: infections and autoimmune disease. Clinical Microbiology Reviews, 19(1), 80-94. https://cmr.asm.org/content/19/1/80

  69. Galli, S. J., Tsai, M., & Piliponsky, A. M. (2008). The development of allergic inflammation. Nature, 454(7203), 445-454. https://www.nature.com/articles/nature07204

  70. Gould, H. J., & Sutton, B. J. (2008). IgE in allergy and asthma today. Nature Reviews Immunology, 8(3), 205-217. https://www.nature.com/articles/nri2273

  71. Strachan, D. P. (1989). Hay fever, hygiene, and household size. BMJ, 299(6710), 1259-1260. https://www.bmj.com/content/299/6710/1259

  72. Cunningham-Rundles, C., & Ponda, P. P. (2005). Molecular defects in T-and B-cell primary immunodeficiency diseases. Nature Reviews Immunology, 5(11), 880-892. https://www.nature.com/articles/nri1713

  73. Fischer, A. (2015). Recent advances in understanding the pathophysiology of primary T cell immunodeficiencies. Trends in Molecular Medicine, 21(7), 408-416. https://www.sciencedirect.com/science/article/pii/S1471491415000854

  74. Vatanen, T., Franzosa, E. A., Schwager, R., Tripathi, S., Arthur, T. D., Vehik, K., ... & Xavier, R. J. (2018). The human gut microbiome in early-onset type 1 diabetes from the TEDDY study. Nature, 562(7728), 589-594. https://www.nature.com/articles/s41586-018-0620-2

  75. Liu, R. H. (2013). Health-promoting components of fruits and vegetables in the diet. Advances in Nutrition, 4(3), 384S-392S. https://academic.oup.com/advances/article/4/3/384S/4591619

  76. Piercy, K. L., Troiano, R. P., Ballard, R. M., Carlson, S. A., Fulton, J. E., Galuska, D. A., ... & Olson, R. D. (2018). The physical activity guidelines for Americans. Jama, 320(19), 2020-2028. https://jamanetwork.com/journals/jama/article-abstract/2712935

  77. Hirshkowitz, M., Whiton, K., Albert, S. M., Alessi, C., Bruni, O., DonCarlos, L., ... & Neubauer, D. N. (2015). National Sleep Foundation's sleep time duration recommendations: methodology and results summary. Sleep Health, 1(1), 40-43. https://www.sciencedirect.com/science/article/pii/S2352721815000157

  78. Black, D. S., & Slavich, G. M. (2016). Mindfulness meditation and the immune system: a systematic review of randomized controlled trials. Annals of the New York Academy of Sciences, 1373(1), 13-24. https://nyaspubs.onlinelibrary.wiley.com/doi/full/10.1111/nyas.12998

  79. Institute of Medicine. (2005). Dietary Reference Intakes for Water, Potassium, Sodium, Chloride, and Sulfate. Washington, DC: The National Academies Press. https://www.nap.edu/catalog/10925/dietary-reference-intakes-for-water-potassium-sodium-chloride-and-sulfate

  80. Yan, F., & Polk, D. B. (2011). Probiotics and immune health. Current Opinion in Gastroenterology, 27(6), 496. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4006993/

  81. Hill, C., Guarner, F., Reid, G., Gibson, G. R., Merenstein, D. J., Pot, B., ... & Sanders, M. E. (2014). Expert consensus document: The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nature Reviews Gastroenterology & Hepatology, 11(8), 506-514. https://www.nature.com/articles/nrgastro.2014.66

  82. U.S. Department of Health and Human Services and U.S. Department of Agriculture. 2015–2020 Dietary Guidelines for Americans. 8th Edition. December 2015. https://health.gov/our-work/food-nutrition/previous-dietary-guidelines/2015

  83. Centers for Disease Control and Prevention. (2020). When and How to Wash Your Hands. https://www.cdc.gov/handwashing/when-how-handwashing.html

  84. Bennett, M. P., Zeller, J. M., Rosenberg, L., & McCann, J. (2003). The effect of mirthful laughter on stress and natural killer cell activity. Alternative Therapies in Health and Medicine, 9(2), 38-45. https://pubmed.ncbi.nlm.nih.gov/12652882/

  85. Berk, L. S., Felten, D. L., Tan, S. A., Bittman, B. B., & Westengard, J. (2001). Modulation of neuroimmune parameters during the eustress of humor-associated mirthful laughter. Alternative Therapies in Health and Medicine, 7(2), 62-76. https://pubmed.ncbi.nlm.nih.gov/11251731/

  86. Li, Q. (2010). Effect of forest bathing trips on human immune function. Environmental Health and Preventive Medicine, 15(1), 9-17. https://link.springer.com/article/10.1007/s12199-008-0068-3

  87. Romagnani, S. (2000). T-cell subsets (Th1 versus Th2). Annals of Allergy, Asthma & Immunology, 85(1), 9-18. https://www.annallergy.org/article/S1081-1206(10)62426-X/fulltext

  88. Iwasaki, A., & Medzhitov, R. (2015). Control of adaptive immunity by the innate immune system. Nature Immunology, 16(4), 343-353. https://www.nature.com/articles/ni.3123

  89. Schroeder Jr, H. W., & Cavacini, L. (2010). Structure and function of immunoglobulins. Journal of Allergy and Clinical Immunology, 125(2), S41-S52. https://www.jacionline.org/article/S0091-6749(09)01470-5/fulltext

  90. Chaplin, D. D. (2010). Overview of the immune response. Journal of Allergy and Clinical Immunology, 125(2), S3-S23. https://www.jacionline.org/article/S0091-6749(09)01459-6/fulltext

  91. Netea, M. G., Joosten, L. A., Latz, E., Mills, K. H., Natoli, G., Stunnenberg, H. G., ... & Xavier, R. J. (2016). Trained immunity: a program of innate immune memory in health and disease. Science, 352(6284), aaf1098. https://science.sciencemag.org/content/352/6284/aaf1098

  92. Chen, L., & Flies, D. B. (2013). Molecular mechanisms of T cell co-stimulation and co-inhibition. Nature Reviews Immunology, 13(4), 227-242. https://www.nature.com/articles/nri3405

  93. Raker, V. K., Domogalla, M. P., & Steinbrink, K. (2015). Tolerogenic dendritic cells for regulatory T cell induction in man. Frontiers in Immunology, 6, 569. https://www.frontiersin.org/articles/10.3389/fimmu.2015.00569/full

  94. Marrack, P., McKee, A. S., & Munks, M. W. (2009). Towards an understanding of the adjuvant action of aluminium. Nature Reviews Immunology, 9(4), 287-293. https://www.nature.com/articles/nri2510

  95. Mackay, I. R., & Rose, N. R. (2001). Autoimmunity and lymphoma: tribulations of B cells. Nature Immunology, 2(9), 793-795. https://www.nature.com/articles/ni0901-793

  96. Ramos, G. C., van den Berg, A., Nunes-Silva, V., Weirather, J., Peters, L., Burkard, M., ... & Frantz, S. (2017). Myocardial aging as a T-cell–mediated phenomenon. Proceedings of the National Academy of Sciences, 114(12), E2420-E2429. https://www.pnas.org/content/114/12/E2420

  97. Hammad, H., & Lambrecht, B. N. (2015). Barrier epithelial cells and the control of type 2 immunity. Immunity, 43(1), 29-40. https://www.sciencedirect.com/science/article/pii/S1074761315002642

  98. Matzinger, P. (2002). The danger model: a renewed sense of self. Science, 296(5566), 301-305. https://science.sciencemag.org/content/296/5566/301

  99. Korn, T., Bettelli, E., Oukka, M., & Kuchroo, V. K. (2009). IL-17 and Th17 Cells. Annual Review of Immunology, 27, 485-517. https://www.annualreviews.org/doi/full/10.1146/annurev.immunol.021908.132710

  100. Mantovani, A., Cassatella, M. A., Costantini, C., & Jaillon, S. (2011). Neutrophils in the activation and regulation of innate and adaptive immunity. Nature Reviews Immunology, 11(8), 519-531. https://www.nature.com/articles/nri3024

  101. Schreiber, R. D., Old, L. J., & Smyth, M. J. (2011). Cancer immunoediting: integrating immunity's roles in cancer suppression and promotion. Science, 331(6024), 1565-1570. https://science.sciencemag.org/content/331/6024/1565

  102. Galli, S. J., Borregaard, N., & Wynn, T. A. (2011). Phenotypic and functional plasticity of cells of innate immunity: macrophages, mast cells and neutrophils. Nature Immunology, 12(11), 1035-1044. https://www.nature.com/articles/ni.2109

  103. Takeuchi, O., & Akira, S. (2010). Pattern recognition receptors and inflammation. Cell, 140(6), 805-820. https://www.sciencedirect.com/science/article/pii/S0092867410000231

  104. Victora, G. D., & Nussenzweig, M. C. (2012). Germinal centers. Annual Review of Immunology, 30, 429-457. https://www.annualreviews.org/doi/full/10.1146/annurev-immunol-020711-075032

  105. Gause, W. C., Wynn, T. A., & Allen, J. E. (2013). Type 2 immunity and wound healing: evolutionary refinement of adaptive immunity by helminths. Nature Reviews Immunology, 13(8), 607-614. https://www.nature.com/articles/nri3476

  106. Roche, P. A., & Furuta, K. (2015). The ins and outs of MHC class II-mediated antigen processing and presentation. Nature Reviews Immunology, 15(4), 203-216. https://www.nature.com/articles/nri3818

  107. Theofilopoulos, A. N., Kono, D. H., & Baccala, R. (2017). The multiple pathways to autoimmunity. Nature Immunology, 18(7), 716-724. https://www.nature.com/articles/ni.3731

  108. Akira, S., Uematsu, S., & Takeuchi, O. (2006). Pathogen recognition and innate immunity. Cell, 124(4), 783-801. https://www.sciencedirect.com/science/article/pii/S0092867406001905

  109. Crotty, S. (2014). T follicular helper cell differentiation, function, and roles in disease. Immunity, 41(4), 529-542. https://www.sciencedirect.com/science/article/pii/S1074761314003422

  110. Kumar, B. V., Connors, T. J., & Farber, D. L. (2018). Human T cell development, localization, and function throughout life. Immunity, 48(2), 202-213. https://www.sciencedirect.com/science/article/pii/S1074761318300153

  111. Rothenberg, E. V. (2014). Transcriptional control of early T and B cell developmental choices. Annual Review of Immunology, 32, 283-321. https://www.annualreviews.org/doi/full/10.1146/annurev-immunol-032712-100024

  112. Tangye, S. G., Ma, C. S., Brink, R., & Deenick, E. K. (2013). The good, the bad and the uglyβ€”TFH cells in human health and disease. Nature Reviews Immunology, 13(6), 412-426. https://www.nature.com/articles/nri3447

  113. Paust, S., & von Andrian, U. H. (2011). Natural killer cell memory. Nature Immunology, 12(6), 500-508. https://www.nature.com/articles/ni.2032

  114. Nutt, S. L., Hodgkin, P. D., Tarlinton, D. M., & Corcoran, L. M. (2015). The generation of antibody-secreting plasma cells. Nature Reviews Immunology, 15(3), 160-171. https://www.nature.com/articles/nri3795

  115. Bousso, P., & Moreau, H. D. (2012). Functional immunoimaging: the revolution continues. Nature Reviews Immunology, 12(12), 858-864. https://www.nature.com/articles/nri3342

  116. Gasteiger, G., & Rudensky, A. Y. (2014). Interactions between innate and adaptive lymphocytes. Nature Reviews Immunology, 14(9), 631-639. https://www.nature.com/articles/nri3726

  117. Zehn, D., King, C., Bevan, M. J., & Palmer, E. (2012). TCR signaling requirements for activating T cells and for generating memory. Cellular and Molecular Life Sciences, 69(10), 1565-1575. https://link.springer.com/article/10.1007/s00018-012-0965-x

  118. Olson, J. A., McDonald-Hyman, C., Jameson, S. C., & Hamilton, S. E. (2013). Effector-like CD8+ T cells in the memory population mediate potent protective immunity. Immunity, 38(6), 1250-1260. https://www.sciencedirect.com/science/article/pii/S1074761313002306

  119. Jiang, S., & Dong, C. (2013). A complex issue on CD4+ T-cell subsets. Immunological Reviews, 252(1), 5-11. https://onlinelibrary.wiley.com/doi/full/10.1111/imr.12041

  120. Eberl, G., Colonna, M., Di Santo, J. P., & McKenzie, A. N. (2015). Innate lymphoid cells: a new paradigm in immunology. Science, 348(6237), aaa6566. https://science.sciencemag.org/content/348/6237/aaa6566