Th1 e Th2

Immunity Mediated by T Lymphocytes

Activation of T Lymphocytes

• The lesson begins with an overview of T lymphocyte immunity, emphasizing the activation process and their presence in blood circulation and lymph nodes.

• A key requirement for T cell activation is the presence of antigen-presenting cells, particularly dendritic cells, which process antigens and present them to naïve T cells.

• Three signals are necessary for T cell activation:

• Signal 1: Interaction between MHC on dendritic cells and TCR on T cells.

• Signal 2: Binding of B7 molecules on dendritic cells to CD28 on T cells.

• Signal 3: Cytokines produced by dendritic cells.

Differentiation of Activated T Cells

• Following activation, naïve T cells differentiate into effector T cells based on the type of cytokines received during activation.

• Different types of microorganisms influence the cytokine profile; thus, activated T cells can differentiate into Th1, Th2, or Th17 subtypes depending on these signals.

Understanding Th Cell Types

• The "Th" designation stands for "T helper," indicating their supportive role in immune responses:

• Th1: Helper type 1

• Th2: Helper type 2

• Th17: Helper type 17

Cytokine Profiles and Their Functions

• Dendritic cell-derived IL-12 promotes differentiation into Th1, leading to production of interferon-gamma (IFN-γ).

• For differentiation into Th2, IL-4 is required; this subtype produces IL-4, IL-5, IL-10, and IL-13 as characteristic cytokines.

Role of Th17 Cells

• To generate Th17 cells, both IL-6 and IL-21 are needed; these produce specific cytokines such as IL-17 and IL-22 that play roles in inflammation.

Summary of Cytokine Characteristics

• All discussed cytokines are proteins that facilitate communication between immune system components. They have distinct names but share a common function in mediating immune responses.

Immune Response Types Based on Microorganisms

• The Th1 response is primarily generated against intracellular microorganisms (e.g., certain bacteria like Listeria monocytogenes).

Mechanism Behind Intracellular Responses

• When intracellular pathogens invade host cells (like viruses), they trigger a robust Th1 response characterized by specific signaling pathways involving dendritic cell interactions with naive CD4+ T lymphocytes.

Understanding TH1 and TH2 Cell Responses

Mechanism of TH1 Cell Activation

• The L12 receptor on the cell recruits a transcription factor called Stat4, which is crucial for gene expression leading to messenger RNA production.

• This process results in the production of interferon-gamma (IFN-γ), a key cytokine associated with TH1 responses, essential for combating intracellular pathogens.

Role of Interferon-Gamma

• Once a TH1 cell is activated, it produces IFN-γ that enhances macrophage activity, transforming them into more effective phagocytes.

• IFN-γ acts as a signal to macrophages, improving their ability to digest intracellular microorganisms and increasing their overall efficiency.

Effects on Macrophages

• Activated macrophages exhibit increased expression of MHC molecules and produce reactive oxygen species (ROS) and nitric oxide (NO), enhancing their destructive capabilities against pathogens.

• The presence of IFN-γ leads to elevated levels of pro-inflammatory cytokines like IL-1 and TNF-alpha, further promoting inflammation and recruitment of immune cells.

Interaction with B Cells

• IFN-γ also influences B cells by prompting class switching from IgM to IgG antibodies, which are more effective in immune responses.

Class Switching Mechanism

• When B cells receive signals from activated T helper cells (TH1), they switch from producing IgM to IgG antibodies, enhancing their ability to opsonize pathogens for better phagocytosis.

The Role of TH2 Cells in Immune Response

Activation Signals for TH2 Cells

Helminths and Immune Response

Understanding Helminths and Allergic Responses

• Helminths are intestinal worms that can cause allergic reactions in sensitive individuals, particularly through a Th2 immune response.

• The differentiation of naive T cells into Th2 cells requires the presence of IL-4, which also initiates transcription processes leading to cytokine production.

• Key cytokines associated with the Th2 response include IL-4, IL-5, IL-10, and IL-13; these play crucial roles in mediating immune responses against helminths.

Mechanisms of Cytokine Action

• IL-4 promotes B cell class switching from IgM to IgE or IgG, enhancing the body's ability to respond to parasitic infections.

• In the presence of IL-4, B cells switch their antibody production primarily towards IgE, which is critical for combating helminth infections.

Effects on Intestinal Function

• The Th2 response leads to increased mucus production and enhanced peristalsis in the intestines as a mechanism to expel parasites.

• Eosinophils are activated by IL-5; they play a direct role in targeting helminths due to their unique properties.

Eosinophil Activation and Function

• Eosinophils increase in number during helminth infections due to Th2 cytokine signaling; this results in an elevated eosinophil count observable in blood tests.

• While the immune system attempts to eliminate helminths through mucus production and peristalsis, it often fails without pharmacological intervention (e.g., antihelminthic drugs).

Antibody Dependent Cellular Cytotoxicity (ADCC)

• Eosinophils enhance their cytotoxic capabilities when activated by antibodies bound to parasites; this process is known as ADCC.

• The presence of specific cytokines like IL-5 stimulates eosinophil differentiation from progenitor cells within bone marrow.

Role of Antibodies in Immune Response

• Eosinophils release toxic granules upon activation via Fc receptors binding with antibodies attached to pathogens; this is part of their mechanism against larger organisms like helminths.

Summary of Immune Interactions

• Both eosinophils and mast cells possess receptors for the constant region of IgE antibodies, facilitating targeted responses against parasites.

• When eosinophils bind with antibodies through Fc receptors, they degranulate releasing cytotoxic substances aimed at destroying invading organisms.

• This process highlights how antibody-mediated mechanisms contribute significantly to fighting off parasitic infections despite challenges posed by large size differences between host cells and parasites.

• The term "Antibody-dependent cellular cytotoxicity" (ADCC), describes how eosinophils become toxic upon activation by bound antibodies.

Understanding Allergic Reactions and TH2 Response

Mechanism of Allergic Reactions

• The allergic response involves the release of histamines, which are blocked by antihistamines to alleviate allergy symptoms. This is linked to the TH2 immune response, particularly in individuals with allergies.

• Mast cells play a crucial role in allergic reactions; they release granules containing histamines and prostaglandins upon activation. These substances contribute significantly to the manifestation of allergic symptoms.

• Allergic reactions are triggered by Immunoglobulin E (IgE), which binds to receptors on mast cells, leading to the release of inflammatory mediators like histamines and cytokines.

Immune Response Dynamics

• In cases of intestinal helminth infections or allergies, a TH2 response is generated. B cells switch class to produce IgE, which interacts with mast cells, resulting in an allergic reaction.