Essay: TH1 vs. TH2 Response in Infection and/or Evasion

TH or T-helper cells are one of the biggest parts dealing with the immune system. TH1 and TH2 are a part of the immune system as lymphocytes better known as white blood cells. These two T-helper cells help the body to detect or recognize pathogens that the body is not used to seeing. In an article What is the Role of TH1 and TH2 in Autoimmune Disease, Trescott states, ‘In response to the recognition of foreign pathogens, they produce cytokines, which are hormonal messenger proteins that are responsible for the biological effects of the immune system’ (section 2, autoimmune-paleo.com). The two T-helper cells react differently in the immune system and are involved in different ways.
TH1 cells typically respond to a foreign pathogen first before anything else. A TH1 cell tends to be cell-mediated and acts upon certain bacteria and viruses causing an infection. TH2 cells typically respond to pathogens found in blood or body fluids. A TH2 cell tends to be humoral-mediated and acts upon allergens and bacteria. A TH1 cell tends to be pro-inflammatory meaning it can cause inflammation where as a TH2 cell tends to not to be inflammatory. The immune system manages to have an equal amount of TH1 cells and TH2 cells at the same time, depending on the wellness of the immune system.
The balance of TH1 and TH2 are not always there, which in that case will tend to cause some effects. In some cases the immune system can favor a TH1 pathway or vice versa and favor a TH2 pathway. After researching online a few conditions in regards to TH1 favoring could be Chron’s Disease, Psoriasis, Chronic viral infections and that is just mentioning a few. When TH2 is in favor some conditions that stand out are Asthma, Allergies, Inflammator Bowel Disease and the same thing with this, there tend to be many other conditions as well. Once I get into discussion of my research article it mentions that if one T-helper cell is favored or dominant it can suppress or inactivate the other helper cell. Depending on how badly or extremely one helper cell is favored could cause a worsening of disease or symptom. The article I chose somewhat goes into this topic of TH1 or TH2 dominance.
A couple animals tested (for example sheep and cattle) had Mycobacterium avim subspecies paratuberculosis or better known as MAP. This infects the intestines of these certain animals and is a chronic inflammatory disease, called Johne’s disease. From my article, Magombedze, Eda and Ganusov stated that, ‘Johne’s disease (JD), is a persistent and a slow progressing infection of ruminants such as cows and sheep, caused by slow replicating bacilli Mycobacterium avium subspecies paratuberculosis (MAP) infecting macrophages in the gut’ (pg. 1). As well found in humans MAP bacteria causes a disease called Chron’s disease, which are an inflammatory bowel disease. When MAP hits a late stage in the infected animals, the animal’s begin to shed bacilli which is in the animals feces and spread into the environment. Once the late stage happens the infection cycle is complete. There has been some research in trying to detect MAP in animals before the infection cycle is complete, but the MAP infection tends to be difficult to diagnose. Out of all the animals studied a few of the animals that were diagnosed early enough showed a cell-mediated, or as mentioned above TH1 response measured by IFN-??. The TH1 response only seemed to occur in the early stages of this infection since there were intracellular pathogens present. The IFN-?? was capable of killing off MAP with macrophages. When the animals studied hit later stages of the infection it then seemed to express more TH2 response. IgG1 antibodies measured this. These studies showed that the MAP infections in the host would switch from TH1 dominance in the early stage to a more TH2 dominant later stage. Through studies, it seemed that half the animals had a combined TH1 and TH2 response and only about eleven percent showed just a TH1 response. The reason behind this study is still not quite understood. TH1 effectors tend to come from a strong antigenic stimulation compared to the TH2 receptor coming from a weak antigenic stimulation. IL-12 and IFN-?? help in the regulation of TH1 whereas IL-4 helps regulate TH2. TH1 is a proinflammatory and it activates macrophages that kill intracellular bacteria. TH2 produce IL-4, IL-5, IL-6, IL-10, and IL-13, which direct B cells to produce MAP-specific antibodies. In immune response it is still unclear what causes the switch from TH1 to TH2. There were models used to try and understand when the switches occur and in the article it states, ‘Switch is driven by the accumulation of extracellular bacteria that in turn skew differentiation towards the TH2 response, and the switch is caused by exhaustion/suppression of TH1 response and concomitant rise of TH2 receptor’ (Magombedze, Eda and Ganuzov, pg 2).
In the models extracellular bacteria started the infections. The site of infection was supplied macrophages by the progenitor monocytes. When the macrophages reached the infected site they would burst and release more bacteria in the extracellular environment. TH1 cells responded and would begin removing the infected macrophages from the infected area. In the same process the CD4 T cells would begin activating non-infected macrophages to help kill the intracellular bacteria. After studying, it seemed that the MAP-specific antibodies or TH2 response was ineffective during the time of infection. The TH1 responses are created by intracellular pathogens, for instance viruses and TH2 responses are created with extracellular bacteria.
The results showed that there was a good generation of TH1 response. In their model behavior Magombedze, Eda and Ganuzov state, ‘Due to high infectivity of free bacteria and a large population of resident macrophages, many macrophages become infected and very few extracellular bacteria exist. The large population of infected macrophages leads to the generation of a TH1 response, which however, lacks the ability to eliminate the infection’ (pg. 5). The TH1 response is unable to eliminate the infection because the already infected macrophages keep producing new bacteria, which will keep contaminating the new macrophages coming in. Since the TH1 response cannot clear the extracellular bacteria, it begins to pile up over time. Once so much builds up over time, it will begin to suppress the TH1 response. The TH1 response will still remain dominant in this case, although it will begin to be suppressed. It remains dominant because it runs off of infected macrophages, while free bacteria run TH2. When you increase the death rate of extracellular bacteria, it eliminates the TH1 and TH2 switch causing TH1 to remain dominant. When the bacteria remain constant with macrophages, it never gives TH2 the chance to outgrow the initially dominant TH1 response.
The main test of this article was switch time between TH1 and TH2 when infected. When the host was dosed with a large amount of bacteria the switch tended to happen much faster. The only problem was the dose increase had to be very large for it to be noticeable. When they increased the dose size the macrophages were infected much faster, causing a faster TH1 response. Once the macrophages begin to get infected, there begins to be a rapid growth of bacterial population, which pushes an early TH2 response and a faster switch between the two responses.
This study showed a number of results that had happened with infection and the switch of TH1 responses to TH2 responses. When the host was diagnosed with infection, the infection was then being eliminated. This scenario dealt mainly with a TH1 response. The TH1 response is dominant and with the elimination of infection, it was the only response shown. A slower switch, but still a switch occurred in the infection latency. With this infection both a TH1 response and TH2 response occurred, but the TH1 response was still on top of the TH2 response. When extracellular bacteria were not removed quickly and the bacteria began to build up the stimulation showed a TH1/TH2 switch, which was due to the long-lived extracellular bacteria. In the article, they stated, ‘The last experiment showed that the TH1 and TH2 switch were a result of disease progression rather than a disease cause’ (pg 7). The study showed that inhibition of either effector TH1 or TH2 did not influence a switch. The switch came directly from the accumulation of extracellular bacteria.
In the Johne’s disease the study indicated that the timing of the switch could occur with bacteria dose size, the amount of time the extracellular bacteria build up and the TH1 exhaustion.
References
Magombedze, Gesham, Shigetoshi Eda, and Vitaly V. Ganuzov. “Competition for Antigen between Th1 and Th2 Responses Determines the Timing of the Immune Response Switch during Mycobacterium Avium Subspecies Paratuberulosis Infection in Ruminants.” PLOS/Computational Biology. N.p., Jan. 2014. Web. 09 Apr. 2015. .
Trescott, Mickey. “What Is the Role of Th1 and Th2 in Autoimmune Disease?” Autoimmune Paleo. N.p., 21 Jan. 2013. Web. 15 Apr. 2015. .