Our immune system acts as the body's defense against infectious organisms and other invaders. With the immune response, the immune system attacks organisms and substances that invade body systems and cause disease.
We may think that immune responses are more of a cause. But it is actually an effect on the way we deal with our bodies. Sometimes, our immune system goes out of balance because of infections or stress. In this episode, get a bigger picture of how we could understand our immune system better so we would know how we could address some problems in the future.
Dr. Justin Marchegiani
In this episode, we cover:
2:07 TH1 & TH2 in Autoimmunity
5:16 Bacterial Infections, Food Allergies, and other causes
7:40 Immune Imbalances
13:09 Different Types of T helpers
20:40 Solutions to the Immune Imbalances
Dr. Justin Marchegiani: Hey guys, it's Dr. Justin Marchegiani. Welcome to today's podcast. Evan, how we doing today man?
Evan Brand: Hey man, happy Monday to you. It's coming up on July 4th so all of our US listeners are probably headed to the grocery store to go buy hopefully, grass-fed burgers for this week. I'm still here, can you hear me?
Dr. Justin Marchegiani: I hear you. Yep, you're good.
Evan Brand: Okay, perfect. Yeah, I said everybody's probably headed out to go buy hopefully grass-fed burgers for July 4th week.
Dr. Justin Marchegiani: I know, it's 4th of July coming up man. I got grass-fed burgers, trying to get some more pasture fed pork if I can, gonna do it up really good with some smoked ribs, good grass-fed burgers, gonna keep it real. Really excited man, how about you?
Evan Brand: I don't know what I'm gonna do. I don't even have a grill. I do so much cooking, but I do it usually all on my skillet, so I may need to borrow a grill to make a grass-fed burger.
Dr. Justin Marchegiani: Nice! Awesome. Well, I'm excited to hear. We talked about addressing a talk on the immune system, on TH1, TH2, kind of branch of the immune system, and this is kind of a heady topic just because the immune response is more of an effect, not necessarily a cause. So, a lot of people, they kind of look at like TH1, TH2 that they look at it on and they kind of like it's hard for them to wrap their head around it and they get so focused on the TH1 TH2 – the immune system stuff. But, that is more of an effect and we have the cause – maybe other infections or stress or that are pushing that immune system out of balance. It's kind of like you got two kids of different sizes, jumping on a seesaw. Well obviously, the bigger kid goes to the bottom and the ladder kick goes up. You could be sitting there so focused on why is that seesaw doing it, but it's like well you got a bigger kid going up against a smaller kid, like that he's not the seesaw right? So when we go over this topic, I just want everyone to look at it with eyes that are looking at the root cause. Like, what's the root cause and don't get overwhelmed with all of the extra details that we'll be addressing.
Evan Brand: Yeah, there's a lot of talk about TH1, TH2 in regards to autoimmunity. So, we were looking at all these studies and it gets really deep, really quick, but when we look at for example, Hashimoto's – which is a really common thyroid, autoimmune thyroid issue. That one is gonna be related to TH1 dominance and then also what were the others we found here.
Dr. Justin Marchegiani: Well, let's break it up for people. So, we have these various T-cells, okay. These T-cells can differentiate or mature into different kinds of T-cells. So, we have our thymus which is like, right here in this chest bone area, and we can make these various T-cells. And, they can differentiate the TH1, TH2, TH17, or these T regulatory cells. Okay. The big ones that we're going to focus on are TH1, TH2. So what influences these cells in what direction, they go in typically, they're going to be various inflammatory mediated compounds. So the ones that are gonna push TH1 are gonna be interfering — interferon, and then Tumor Necrosis Factor-Alpha. So just.. just kind of ignore the big stuff, just know that there's some inflammatory compounds that cause this T-cell response on the TH1. Now, TH1 is gonna be.. it's gonna be your Cytotoxic immune response. So think of T1, it’s like, this is your immediate reaction. This is like, “Hey we're going to war. This is the Special Forces, this is the Navy Seals, it's the Delta team, this is the Army Rangers”. These are the people that you want going into that territory first, right? They're the first responders. Now, the big things that can influence TH1 are gonna be various Interleukins and Cytokines, alright? Interleukins could be you know, Interleukin 6, it could be Interleukin 4, it can be interleukin 5, or 10, or 13. These are various Cytokines that are produced and they could be produced due to inflammation from whatever's happening in the environment. So TH1’s that part, or I'm sorry TH1 is going to be the TNF alpha, and the interferon. The TH2 is gonna be the other ones I just mentioned. That's the Interleukin 6, the 5, the 4, the 13, and the 10. So we have kind of backup TH1, Tumor Necrosis Factor Alpha, and then Interferon, TH2, are all gonna be the Interleukins and the Cytokine. So just kind of draw line in your head, TH1’s gonna be the Cytotoxic immediate immune response, TH2 will be the delayed immune response. Think of food allergens driving this. Think of anything that's more antibody based. These are people. These are the troops that are coming late to the show. These are the infantry that's coming. You know a couple of weeks after the Army Rangers and Navy Seals have done their Intel and done their initial strike. Does that make sense?
Evan Brand: It does, yeah. So you mentioned the food allergies, and then if someone is TH2 dominant, now there's different causes of this right? Like you and I work a lot with the gut issues, so we're seeing a lot of bacterial infections, we see a lot of parasites, a lot of viral infections– it's not 100% crystal-clear, but, in general, we found most of the bacterial infections those are going to increase your TH1. And, if you're more TH2 dominant, these are more the food allergies, the people with histamine issues. Now, a lot of people I've noticed with Lyme and co-infections and mold, they also complain of tons of histamine issues. So it would make sense based on what we found in the literature, what we've seen clinically, which is if people with mold, Lyme, co-infections — these are the ones who report histamine intolerance where they have to go on a lower histamine diet and then we try to use things to stabilize the histamine reaction like herbal antihistamines, and sometimes these people are already put on antihistamines from their medical doctor or their allergist. But really that's an immune system problem that the drugs are not addressing.
Dr. Justin Marchegiani: 100%. So just kind of like, recap, TH1, kind of more immediate type of response. That's where you're seeing a lot of the nuclear factor, Kappa beta. That's where you're seeking to interfere on the TNF alpha, and the TH2, or all these various Cytokines and Interleukins, all right? TH2, they're making a lot more antibodies. It's making all those IgG. It could even be the IgE. The more anaphylactic ones, and these are kind of, they're making those long-term antibodies to help attack whatever is going on. So a lot of autoimmune conditions we may see TH2 response, and a lot of chronic ones like 5 Alger, and a lot of these issues we could see that chronic fatigue, a lot of asthma issues, hay fever — a lot of these long-term conditions that are hanging out a lot longer. We may see these TH2 things. Now, a couple — people couple articles, we've seen TH1 tends to be more intracellular parasites, smaller, smaller bugs. TH2 dominance can be pushed up by bigger bugs, or extracellular bugs — bugs that are hanging outside the red blood cells, outside the red blood cells, bigger bugs, you know they're bigger. They're not inside the blood cell. The smaller, more microscopic ones kind of like malaria, or Babesia, they're gonna be inside the red blood cell. Cryptosporidium is another one. That's gonna be more TH1 dominant. So smaller critters, TH1, slightly bigger critters and ones that hang out outside of the red blood cell TH2. So, when we kind of go over like the science stuff, like I'm just kind of drawing a line here, science stuff, okay, then we gotta focus on the root cause. So when we see there may be some immune imbalances, right. TH1, where you have more TH1 symptoms, or you have more TH2 symptoms, or whether we actually do a test to look at your TNF-alpha, or your Interferon, or whether we actually look at various Interleukin 2 Cytokines. We can look at this stuff, we can test it, which can give us a little bit of a window on what direction we should be pushing the immune system. Sometimes, we don't even have to push the immune system. We just work on the stressors, the infections, the food, and the gut and a lot of times that immune balance kind of just naturally goes back to where it wants to be, because the body wants to be in homeostasis. So we don't necessarily have to go and say, “Well, this mushroom supports TH1, therefore, I'm gonna give this mushroom”. We may just want to be focused on the actual infections or those stressors that could be affecting it, and then let homeostasis kind of naturally happen on its own.
Evan Brand: Yeah. I've got a test kit actually upstairs. I haven't run it yet. I didn't know if you know this, but diagnostic solutions actually has a Cytokine. It's sort of a pro-inflammatory, anti-inflammatory balance test that you can do. And I believe it's all based on serum, but I've got it upstairs. I haven't taken it yet, but I'll .. I'll put this in the chat for you. Other people won't see it, but in our chat I'll put it there. You can look at this sample report. It's pretty cool, so it looks at all like the pro-inflammatory Cytokine. So it's got like your Interleukin 18, which we know that ones tied in to Hashimoto's for example, and it gives you an expected reference range. TNF alpha is pro-inflammatory, it's got IL 6, it's got IL 7, IL 8 and then it goes into the anti-inflammatory, which is pretty cool. So the anti-inflammatory, they're kind of generalizing it here as putting proinflammatory TH1, anti-inflammatory TH2, so you can see here Interleukin 4, 5, 10, 13, 15s, on the anti-inflammatory category. Do you see that sample report?
Dr. Justin Marchegiani: Correct, that's pretty cool.
Evan Brand: So actually I should do it now. Doesn’t really change much though. See, that's the question with things like this right? Like we could spend days and days and days trying to get to the bottom of this and figure out, okay, you know, what are your T helper cells doing? Is your Cytokine balance off? But, if you don't have a foundation to go back on then you're really confused with this information. So I find that people may focus on a topic like this, but then they get lost in the science and they don't really know how to make an action step based on it.
Dr. Justin Marchegiani: 100%, right? So TH1, TH2, these things are gonna differentiate. They're gonna go ahead our T-cells, and they're gonna go one to two directions, for the most part TH1 TH2. And in that process where they differentiate, that's where all these Cytokines or Interleukins or TNF for all these inflammatory things happen. So think of a lot of the Cytostatic ions, or Interleukins, or TNF alpha or Nuclear Factor, Kappa beta or interference. Think of that as like the exhaust of the immune response. So you have these two vehicles driving in certain directions, and these Cytokines are gonna be the exhaust. So when we go and run a test like Evan talked about, with all these different Interleukins or Cytokines, it gives you a window of what cells are more active. Just like if you're trying to smell the exhaust to see, is that a diesel car, is that a race car, is that unleaded, you know, you can kind of tell a little bit by just on some of that fuel. It's the same thing here. And then that gives us more of a clinical window to say, well, how do we get to the root cause? Because we know things like gluten can easily throw off that immune response. We may be sitting here thinking about “Oh what kind of infections can we go after?”, but we may magically be able to support someone's immune balance just by stabilizing blood sugar. We know blood sugar can increase imbalances or fluctuations, and blood sugar could increase Interleukin 6. Interleukin 6 is gonna be a TH2 immune response. So we could jack up our TH2 immune system by just having big fluctuations in blood sugar or gluten sensitivity. Could be something that really increases that TH2 immune response. So, it may be something that's not that sexy. It's not like this crazy infection you have, it just could be some blood sugar stuff. It could be a gluten sensitivity thing. Also, we know low glutathione. Low glutathione is a big stress or two because glutathione is a natural kind of regulator of the TH1 TH2. So that's gonna have a major effect on our T regulatory cells. The T regulatory cells, they're kind of the governor that can come in there and kind of tip it and bring it back to balance. Right? So think of lower glutathione as a master balancer. Think of lower vitamin D as a massive master balancer. So if we have poor digestion and we're not breaking down proteins well, or we're like a vegan vegetarian, we're not getting enough good clean sulfur amino acids. Well this could be a stressor for our immune system or for not getting enough vitamin D. Whether supplementally and we're not getting outside, that could be a big stressor, because your vitamin D has a major effect on our T regulatory fat cells. And after your regulatory cells they just come in there and they help modulate imbalance the immune response. That makes sense? Am I-
Evan Brand: Yeah, no. I mean you're spot-on. I'm looking at the lab right in front of me. They're talking here about the different types of T helpers and they say right here: T regulatory, the normal role of it is to limit inflammatory responses, which is exactly what you said. The T regulatory is the balancing act, promoting what they call immune tolerance, and it says here if you have an issue or an imbalance, T regulatory cell problem, then that's when the autoimmune diseases come in, and that's when inflammatory bowel diseases come in.
Dr. Justin Marchegiani: And that's why when we like run a lot of organic acid test, we'll look at certain markers like sulfate, or we'll look at Pyro Glutamate, or Alpha Hydroxy Butyrate. We'll look at a lot of these organic acids that correlate to our glutathione precursors, because this is important. If we aren't able to have enough of these glutathione precursors, that could have a major effect on our immune system, right? That's that's really important. Also, for seeing just poor Hypo Methylation , right? If we're not getting adequate levels of B12 or Folate and we're HypoMethylating right, low levels of Methylation, we may see an increased amount of Homocysteine. We may see higher amounts of Methylmalonic Acid or Foramina Glutamate. Remember, Methylation is important because Methylation silences genes. So if we have these genes that are going to be like, let's say genes that are going to be predispose us to diseases or conditions, we want to be able to silence them. So having good Methylation with a lot of those nutrients is important to silencing those genes. So really really important that we have good Methylation, because that plays a huge role in all of us.
Evan Brand: So you can test this. I'm gonna do it just for fun because I've got the test kit. If you want to measure the immune system, it looks like, I mean we love diagnostic solutions for a lot of the other testing that we do with them. I've not run this yet, but this is the whole Cytokine assessment, which is all looking at the T helper cells. The TH1, TH2, T regulatory — I'm gonna do it and report back on, on what it shows because one thing it says here just back to the TH2 dominance thing quickly: If you're TH2 dominant, we talked about food allergy, seasonal allergies, you mentioned hay fever, and other things. It also says here chemical sensitivities — which I definitely have an increased chemical sensitivity problem. Since I got exposed to mold and possibly lyman Dorko infections from tick bites, that may be a driver of the sensitivity thing too. So what I'm curious to see is on a piece of paper, am I gonna show up really high with these TH2 ones they're talking here. Interleukin 4 or 5, 6, 10, 13. If so, there's the answer, but as we discussed it doesn't really change the protocol much. It's just it's good data, but I'm still gonna do the same things like do infrared sauna, and do charcoal and binders, and excess glutathione supplementation like you said and making sure I'm digesting.
Dr. Justin Marchegiani: Yeah, and we decided on doing this topic. It's an important topic as people are talking about it. But if you're coming into this, and you have health challenges and you're listening to this and you're feeling overwhelmed, don't worry about it. This, this is not the cause, this is the effect. It's important that you have a good functional medicine doc that they can look at the root cause but then maybe can take some of this data into account.
Evan Brand: Yeah.
Dr. Justin Marchegiani: So we're not gonna base our whole treatment plan off of it but it's just kind of a guide like a compass to, ‘hey am i moving in the right direction?’ Okay good excellent. I'm moving in the right direction. So it kind of gives you that confidence and ability. Also we were talking about low Methylation. Well, low methylation is also correlated with TH2 dominance. When we have that immune response, those antibody immune responses that are high, we tend to see low Methylation. So you see this a lot in allergies, asthma, autism is a big one, mucus, eczema, hives. You're gonna see it actually in chronic fatigue as well. So these are conditions we got to keep an eye on, but Methylation is very important. So we got to look at .. So when we run a lot of organic acid testing, we can get a window into some of these root cause stuff before it trickles down and affects the immune system. So I'm still a huge fan of the organic acid testing because it gives me a little bit more of a window to the root of what's happening versus the downstream Interleukin and Cytokines in and TNF-alpha and Interferon, which I think is more of a downstream trickle.
Evan Brand: I agree. Well, I just want to restate what you said a little differently, because it was interesting, which is that the Hypo Methylation is gonna affect and make you more TH2 dominant. And I would say, I mean you tell me if it's different with your clients, but I would say 50 plus percent of the people we’re working with, they come and say, “Hey I tested my genetics and I have Methylation issues and I am you know MTHFR with my genetics and I have one snip or two snips and I can't methyl ink properly.” And these are the same people who come to us with tons of food allergies, they feel like they can only eat limited food supply etc. I think this whole Methylation TH2 conversation is huge and I don't think we've ever talked about this before.
Dr. Justin Marchegiani: Yeah totally. And then again, typically bacterial and viral infections are gonna be more TH1 dominant, and that makes sense right? Because that's your natural killer cells. That's gonna be your helper cells. These are the guys that are coming out to the party first. So it makes sense if I get exposed to an acute virus or an acute bacterial that that TH1 immune response is really really important. And then also people that have a TH1 response that's really really high, they tend to make more Cortisol, right? So when you have chronically high Cortisol, you may actually see a decrease in that TH1 immune response. So this makes sense, right? Just think about it. If you have really low Cortisol, that's going to suppress your TH1 response, which may make it easier for you to get cold and get sick. So this is why we want really good TH1 immune response, and chronically low Cortisol could have an effect on that so it was a typical adrenal fatigue, or like, adrenal dysfunction type of imbalances could create a lower TH1 immune response and cause you to get sick more. So just getting your Cortisol levels supported, and then getting to the root cause of that. Could have a major effect on supporting your TH1.
Evan Brand: Yeah, which is why we test it. So you can look at doing urine, you can look at doing saliva. You mentioned the organic acids, that's a urine test. The saliva is what I use. I think you use mostly urine though now, don't you?
Dr. Justin Marchegiani: Yeah I've been doing more of the urine just because I get a window into the free and the total Cortisol. I still love the saliva, it's still great but it just it misses the total fraction which is nice to see.
Evan Brand: Mmm, okay. So you still have to get your foundational test. What we've talked about was kind of like a level like beyond what you typically need to do. This is like above and beyond the foundations. You and I don't really say when we're working with someone, “hey we're addressing your TH1 and TH2 imbalances”. Like, I don't think I've ever said that ever, maybe a couple times, but really what we're doing is we're fixing that as you mentioned the downstream effect. That's what this is. This is the downstream stuff we're dealing with, but we're fixing that indirectly by focusing on the root causes. So getting rid of the bacteria and viruses that are throwing the immune system the wrong way, getting rid of parasites that are shifting it the wrong way , lowering thyroid antibodies by healing the gut, replenishing vitamin D, replenishing glutathione, to move out toxins, and molds, and other things that are disrupting this balance so you have to do that.
Dr. Justin Marchegiani: Exactly. So think of like acute cortisol. Acute cortisol could actually bump up the TH1, could stimulate up a chronic cortisol. Chronic cortisol, chronic adrenal stimulation that eventually decreases the cortisol via getting the brain feedback loop dysregulated. That's called HPA access. This regulation that is going to actually weaken the immune system so just kind of think of it like this — there's chronic stress make your immune system weaker or stronger most people can wrap their head around the fact that it's gonna make it weaker. And then we're just talking about that mechanism. It's really gonna be dysregulation that TH1 immune response for sure.
Evan Brand: Yeah. Well said.
Dr. Justin Marchegiani: Anything else you want to address here today? I mean–
Evan Brand: So do we list out the major symptoms for TH1. I know I did it for TH2 right? That was gonna be nasal drip, mucus allergies, hay fever, hives, chronic fatigue, a lot of autism stuff think hypo methylation. A lot of allergy based stuff. And then we have the TH1 stuff it's more TH1 dominant. You're gonna see that graves Rogen's. You're gonna see lupus. You're gonna see I even think Hashimoto's is gonna be TH1, and anything else you want to say about the TH1 dominant conditions. Yeah, it seems like the TH1 problems are more autoimmune related, where TH2 or more I don't want to G over generalize, but TH – sounds more related to histamine allergy type.
Dr. Justin Marchegiani: Histamine allergy kind of thing so our Hashimoto's a lot of irritable bowel conditions. T3, lower T3 conversion issues, TH1 MS. I think MS may actually be TH2. I think lupus may have a TH2 connection. So with the research like nothing's 100% right, there are some nuance to it. Vitiligo autoimmune condition affecting the skin, that's in the B TH1, Lyme can be TH1, but chronic Lyme can potentially switch the TH2 so there's a couple of variations with that. Also, this is really cool and this is part of why I utilize pregnenolone in a lot of my patients. A lot of my adrenal patients. It's because a lot of these autoimmune conditions that are TH1 dominant, they tend to have lower pregnenolone. And it makes sense because the more you're pregnenolone drops, the more your immune system tends to be dysregulated, right? So the more that TH1 tends to be up that can deplete your pregnenolone, and then the longer that TH1 is up, eventually that immune response can drop too. So you could still be TH1 dominant, but the immune system starts to get weaker and weaker and weaker. It's kind of like estrogen dominance. You can be a sturgeon dominant while still having low estrogen. Right? I see it all the time. So it's that it's all about the balance. And we know the adrenals interplay here significantly, we know gluten and gut barrier function interplay, and we know infections interplay, so if all this stuff isn't making sense just focus on the root cause and then the immune imbalances should just take care of itself naturally.
Evan Brand: That's amazing. So the pregnenolone you know that's considered kind of the master right? So when you throw in pregnenolone, you're saying you're allowing the body to go and generate whatever other hormones it needs to from just giving pregnenolone.
Dr. Justin Marchegiani: Exactly. And again if your people are listening to this, … owns like an adrenal precursor. That's like can make about 27 different adrenal hormones you want to remember though. You want to have your levels tested, and you want to do it the right way. So work with a practitioner on that and make sure you're getting to the root cause. It's easy for someone to listen to this and say well I'm gonna just take pregnenolone, but you may ignore how you got here right? So yeah, pregnenolone taking with the eye to getting all the other root cause, things under control that's the best functional medicine perspective to address it.
Evan Brand: Beautiful. Well, reach out to Justin if you need help with this stuff. We know we got a little .. a little as you called it heady, a little complex, with this stuff. It can't get complex but at the end of the day you just have to address the root causes but how do you do that? Well you have to find them first, and so that's why we do comprehensive testing depending on what the symptoms are we may look at different things like stool, urine, saliva, blood, depending on what's going on. And someone promises or sells you a silver bullet to fix your chronic health issues, they're wrong. I would run away. There is no silver bullet, all these people they say, ‘Oh everything is Lyme disease’. Or ‘everything is Epstein-barr virus’, or ‘everything is this’. Know nothing is nothing, it’s that simple. It's always multiple layers or different pieces of the puzzle. I mean I've been working on myself with herbs and gut and adrenals and immune, and all sorts of stuff for 10 years and I'm still in the game. I'm still going so it you got to just keep peeling back these layers.
Dr. Justin Marchegiani: And we'll put some of the references here in the articles that you guys can take a look at some of the references if you want to digest it slower. We'll put some pictures here as well, and I'm gonna do a little summary video that'll be shorter with a little bit of drawings and stuff to help kind of guide you through the understanding of what's happening. So if it's too much for anyone or you're feeling overwhelmed, don't worry, we'll try to break it down, we'll put some pictures, some images, some references, and just kind of have a mind to focusing on the root cause.
Evan Brand: Yep. If you want to reach out to Justin, he can help you around the world. justinhealth.com — just go there, and you can find the appointments and you can book yourself on his calendar. My website’s evanbrand.com. We really look forward to helping you address whatever concerns you have. There's a whole list of different symptoms, conditions, etc on our website, so you can look through that and see if we are compatible with each other.
Dr. Justin Marchegiani: And make sure you subscribe to the YouTube channel so you can get some of these summary videos after the fact, if you guys are enjoying it. justinhealth.com / (slash) Youtube and evanbrand.com /(slash) Youtube as well. Evan, hey man, it's been great. You have a phenomenal 4th of July. If we don't connect till after that point. And today was great man, really appreciate it.
Evan Brand: You too. Take care have a good one.
Dr. Justin Marchegiani: Evan take care. Bye bye.
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