negative regulation of adaptive immune response

Definition

Target type: biologicalprocess

Any process that stops, prevents, or reduces the frequency, rate, or extent of an adaptive immune response. [GOC:add]

Negative regulation of adaptive immune response is a complex process that maintains immune homeostasis and prevents excessive or inappropriate immune reactions. This process involves various mechanisms that suppress or dampen the activity of T cells and B cells, the key players in adaptive immunity. Here are some key aspects of negative regulation:

1. **T cell suppression:**

* **Regulatory T cells (Tregs):** These specialized T cells actively suppress other T cells, preventing them from activating and attacking self-tissues or harmless antigens. Tregs express transcription factors like Foxp3 and produce immunosuppressive cytokines like IL-10 and TGF-beta.
* **T cell exhaustion:** Prolonged exposure to antigens can lead to T cell exhaustion, a state of functional impairment characterized by reduced cytokine production and proliferation. Exhausted T cells express inhibitory receptors like PD-1 and CTLA-4, which dampen their activation and effector functions.
* **Apoptosis of T cells:** Under certain circumstances, activated T cells undergo programmed cell death (apoptosis) to limit their lifespan and prevent excessive immune responses. This process can be triggered by factors like lack of co-stimulation, exposure to inhibitory cytokines, or engagement of death receptors.

2. **B cell suppression:**

* **Regulatory B cells (Bregs):** These B cell subsets produce anti-inflammatory cytokines like IL-10, which suppress the activation and differentiation of other B cells and T cells. Bregs can also directly interact with T cells to induce their suppression.
* **Apoptosis of B cells:** Similar to T cells, B cells can undergo apoptosis to limit their lifespan and prevent excessive antibody production. This can be triggered by factors like lack of T cell help, exposure to inhibitory cytokines, or engagement of death receptors.

3. **Immunosuppressive cytokines:**

* **IL-10:** This cytokine is produced by various immune cells, including Tregs and Bregs, and has potent immunosuppressive effects. IL-10 inhibits the activation and proliferation of T cells and B cells, and promotes the production of anti-inflammatory mediators.
* **TGF-beta:** This cytokine is produced by various cells, including Tregs and some epithelial cells. TGF-beta can suppress the activation and differentiation of T cells and B cells, and promote the generation of Tregs.
* **Other immunosuppressive cytokines:** Other cytokines, such as IL-35 and IL-27, also play roles in negative regulation of adaptive immune responses.

4. **Inhibitory receptors:**

* **CTLA-4:** This receptor is expressed on activated T cells and binds to the same ligands as CD28, a co-stimulatory receptor. CTLA-4 ligation delivers inhibitory signals that suppress T cell activation and proliferation.
* **PD-1:** This receptor is expressed on activated T cells, B cells, and other immune cells. PD-1 ligation by its ligands, PD-L1 and PD-L2, delivers inhibitory signals that dampen T cell function and promote T cell exhaustion.
* **Other inhibitory receptors:** Several other inhibitory receptors, including LAG-3, TIM-3, and BTLA, are also involved in negative regulation of adaptive immune responses.

5. **Anergy:**

* Anergy is a state of unresponsiveness to specific antigens. T cells can become anergic if they encounter antigens without proper co-stimulatory signals. This prevents T cells from becoming activated and causing unwanted immune reactions.

These mechanisms work together to maintain a delicate balance between immune activation and suppression, ensuring that the immune system effectively responds to pathogens while avoiding autoimmune diseases and hypersensitivity reactions.'
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