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Guide to Understanding Th1 and Th2 Cells

The Th1 Pathway

In this guide, we will explore the differences between TH1 and TH2 cells, their crucial roles in the immune system, and the contributions of cytokines and transcription factors to their differentiation. Furthermore, we will examine some common diseases associated with these cell types and possible treatment options, providing a comprehensive overview of T helper cell biology and its relevance to human health.

Key Takeaways

  1. T helper cells (TH1 and TH2) are integral in activating immune responses, with distinct functions.
  2. Cytokines play a crucial role in determining TH cell differentiation.
  3. Imbalances in TH cell subsets can lead to various diseases, and targeted therapies are emerging for treatment.
  4. TH17 cells represent another subset with roles in immune responses and disease pathogenesis.
 

What Are T Helper Cells?

T helper cells are a type of lymphocyte that play an important role in the immune system. They are responsible for activating other immune cells to fight off infection or disease. There are two main types of T helper cells, Th1 cells and Th2 cells, each with their own unique functions.

The main function of Th1 cells is to activate the cellular immune response. This involves recruiting macrophages and other effector cells to destroy infected or cancerous cells. The Th1 response is characterized by the production of Interferon gamma (IFNγ), a powerful cytokine that helps to activate macrophages and other immune cells.

The main function of Th2 cells is to activate the antibody-mediated immune response. This involves recruiting B cells to produce antibodies that can neutralize or destroy pathogens. The main function of Th2 cells is to produce Interleukin-13 (IL-13), a cytokine that helps to activate B cells and other immune cells.

The Role of Cytokines in T Helper Cells

Th cells are activated by cytokines, which are small proteins that act as messengers between cells. There are a number of different cytokines, each with its own role in the immune system. The Th cell response is triggered by a subset of cytokines called Th-cell-activating cytokines or TACs. These cytokines bind to specific receptors on the surface of T helper cells, triggering a cascade of events that leads to the activation and differentiation of these cells.

Cytokines play a major role in determining which type of Th cell will be produced. For example, the cytokine IL-12 is a Th-cell-activating cytokine that promotes the differentiation of Th cells into Th1 cells. On the other hand, the cytokine IL-21 is a Th-cell-inhibiting cytokine that inhibits the differentiation of Th cells into Th1 cells.

Th1 vs Th2 Cytokines

Th1 cytokines are a group of pro-inflammatory cytokines that promote the activation of macrophages and other effector cells. These cytokines include IFNγ, Tumor Necrosis Factor alpha (TNFα), and Interleukin-12 (IL-12). Th1 cytokines are involved in the immune response against intracellular pathogens such as viruses and intracellular bacteria. They activate macrophages to kill these pathogens and promote the development of cytotoxic T cells that can directly kill infected cells.

Th2 cytokines are a group of anti-inflammatory cytokines that inhibit the activation of macrophages and other effector cells. These cytokine include IL-21, IL-22, and transforming growth factor beta (TGFβ). Th2 cytokines are involved in the immune response against extracellular pathogens such as helminths and parasites. They promote the production of antibodies by B cells and activate eosinophils and other cells that can help to eliminate these pathogens.

Transcription Factors in T Helper Cell Differentiation

The signalling pathways involved in T helper cell differentiation are complex and not fully understood. However, it is known that a number of different transcription factors and cytokines are involved in this process. Transcription factors are proteins that bind to specific DNA sequences and regulate the expression of genes. Some of the transcription factors involved in Th cell differentiation include T-bet, GATA-binding protein-3 (GATA-3), and Forkhead box protein PIII (FoxpIII).

T-bet is a Th cell specific transcription factor that is required for the development of Th0 cells into effector Th cells. GATA-3 is a general lymphoid transcription factor that is required for both Th cell development and function. FoxpIII is a Th cell specific transcription factor that is required for the development of regulatory T cells. TCF-I is a transcription factor that binds to the promoter region of Th cell genes. TCF-I is activated by Wnt signals, which are signaling molecules that are involved in the development and differentiation of T cells.

STATs (signal transducers and activators of transcription) are a family of proteins that mediate the response to cytokines. There are four members of the STAT family, and each member is activated by a different subset of cytokines. For example, STAT-l is activated by Th1 cytokines like IFNγ, while STAT-IV is activated by Th2 cytokines like IL-21.

The Th1 Pathway

The TH1 pathway is a subset of the T helper cell immune response that is activated in response to intracellular pathogens, such as viruses and intracellular bacteria. When activated, naive CD4+ T cells differentiate into TH1 cells and produce cytokines such as interferon-gamma (IFN-γ), interleukin-2 (IL-2), and tumor necrosis factor-alpha (TNF-α). These cytokines activate macrophages and enhance their ability to kill intracellular pathogens. In addition, TH1 cells can also stimulate the development of cytotoxic T cells, which can directly kill infected cells. Overall, the TH1 pathway plays an important role in the immune response against intracellular pathogens and is crucial for controlling infections caused by these types of pathogens.

TH1 Cell Markers

TH1 cells express a unique set of cell surface markers, intracellular markers, and secreted factors that help to identify and regulate their activity. Examples of TH1 cell surface markers include CCR1, CCR5, and CXCR3, which are involved in cell migration and recruitment to sites of infection. TH1 intracellular markers such as T-bet and STAT1 are transcription factors that regulate the expression of TH1-specific genes, while STAT4 is involved in the differentiation of TH1 cells from naive CD4+ T cells. Secreted factors produced by TH1 cells include IFN-gamma, IL-2, and TNF-alpha, which activate macrophages and enhance their ability to kill intracellular pathogens. Additionally, TNF-beta is also produced by TH1 cells and is involved in the regulation of immune cell proliferation and differentiation. Overall, the expression of these markers and factors help to distinguish and regulate TH1 cells in the immune response against intracellular pathogens.

Cell Surface Intracellular Secreted Factors

CCR1

STAT1

IFN Gamma

CCR5

STAT4

IL-2

CD3

T-bet

TNF Alpha

CD4

TNF Beta

CD8

CD14

CD19

CXCR3

IFN Gamma R1

IFN Gamma R2

IL-12 R Beta

IL-18 R Alpha

IL-27 R Alpha

Table 1: List of Th1 Cell Markers

Th1 and Th2 Diseases

There are a number of diseases that can be attributed to differences in T helper cell function. Th1 diseases are characterized by a strong Th1 response, while Th2 diseases are characterized by a weak or absent Th1 response. Th1 cytokines like IFNγ and TNFα promote inflammation, while Th2 cytokines like IL-21 and IL-22 inhibit inflammation.

Th1 Diseases

  • Asthma is a chronic lung disease that is characterized by airway obstruction and inflammation. Asthma is a Th1 disease, and the Th1 cytokines IFNγ and TNFα play a key role in the development of this disease.
  • Rheumatoid arthritis and Multiple sclerosis are both chronic inflammatory diseases that are caused by autoimmune reactions to joint tissue and myelin respectively. This autoimmune reaction is mediated by Th1 cytokines like IFNγ and TNFα.

Th2 Diseases

  • Allergies are a type of hypersensitivity reaction that is mediated by Th2 cytokines such as IL-21 and IL-22. Allergies can cause a range of symptoms, from mild (rash, hives, itching) to severe (anaphylaxis).
  • Eczema is a chronic skin condition that is characterized by dry, itchy skin. Eczema is a Th2 disease, and the Th2 cytokines IL-21 and IL-22 play a key role in the development of this condition.
  • Psoriasis is a chronic skin condition that is characterized by red, scaly patches on the skin. Psoriasis is thought to be caused by an autoimmune reaction to skin cells. This autoimmune reaction is mediated by Th2 cytokines like IL-21 and IL-22.

Th1 and Th2 Cytokines in Autoimmune Diseases

The main goal of treatment for autoimmune diseases is to reduce inflammation and prevent tissue damage. In some cases, this can be done with corticosteroids or other immunosuppressive drugs. However, these treatments often have side effects and can only provide temporary relief.

Recent advances in our understanding of Th cell differentiation have led to the development of targeted therapies that specifically target Th cells. These therapies seek to modulate the activity of specific cytokines that are involved in the development of autoimmune diseases. For example, therapies targeting IL-12 and IL-23 are currently being developed for the treatment of psoriasis and Crohn's disease. Similarly, therapies targeting IFNγ are being developed for the of rheumatoid arthritis, multiple sclerosis, and eczema.

TH1 vs TH2 vs TH17

While TH1 and TH2 cells are two well-characterized subsets of T helper cells, there are other T helper cell subsets that have been identified and studied in the context of various immune responses and diseases. One such subset is TH17 cells, which produce pro-inflammatory cytokines such as IL-17A, IL-17F, and IL-22, and are involved in the defense against extracellular bacteria and fungi.TH17 cells also play a role in the development of autoimmune diseases, such as multiple sclerosis and psoriasis.

The balance between TH17 and TH1/TH2 cells is important for maintaining immune homeostasis, and imbalances in TH17 cells have been implicated in various immune-related disorders. While TH1 and TH2 cells are primarily involved in the defense against intracellular pathogens and the regulation of humoral immunity, TH17 cells represent an important and distinct subset of T helper cells that play a critical role in the immune response against extracellular pathogens and the pathogenesis of various diseases.

In conclusion, Th cells play a major role in the immune system by regulating the activation and differentiation of other immune cells. The type of Th cell that is produced depends on the combination of cytokines that are present at any given time. This can determine whether you develop a Th1 or Th2 response, which can lead to either a pro-inflammatory or an anti-inflammatory state. Differentiation of Th cells into specific effector subsets allows for fine tuning of the immune response and helps to ensure that it remains effective against potential threats. While there is still much to learn about how T helper cells contribute to disease, understanding the basics of their differentiation and function is an important step in finding better treatments for these conditions. Thanks for reading!‚Äč

Written by Jahnavi Konduru

Jahnavi Konduru completed her undergraduate degree in Biotechnology before completing her masters in Immunotherapeutics at Trinity College Dublin. She now works as an Assay Development Scientist at Epona Biotech.

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9th Mar 2022 Jahnavi Konduru Naga, Msc

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