Immune System Regulation Immunotherapy Flashcards
Why is it so important that the immune system
regulates its responses?
Avoiding Autoimmunity: The immune system needs to distinguish between the body’s own cells and foreign invaders. Failure to do so can result in autoimmunity, where the immune system mistakenly attacks the body’s own tissues and cells. Proper regulation helps prevent autoimmune diseases.
Preventing Excessive Inflammation: An overactive immune response can lead to excessive inflammation, which can be harmful to the body’s own tissues. Chronic inflammation is associated with various diseases, including autoimmune disorders, allergies, and certain chronic conditions.
Minimizing Tissue Damage: The immune system’s responses, such as the release of inflammatory molecules, can cause collateral damage to surrounding tissues. Proper regulation helps to minimize this damage, promoting overall tissue health.
Adaptation to Changing Threats: The immune system needs to adapt its responses to different types of pathogens and changing environmental conditions. A well-regulated immune system can efficiently respond to new threats while avoiding unnecessary responses to harmless substances.
Preventing Allergic Reactions: Allergies occur when the immune system reacts to substances that are usually harmless, such as pollen or certain foods. Proper regulation helps prevent exaggerated immune responses that lead to allergic reactions.
Maintaining Immune Memory: The immune system retains a memory of previously encountered pathogens, allowing for a faster and more effective response upon subsequent exposure. Regulation is important for ensuring that this memory is targeted specifically against harmful invaders.
Avoiding Immunodeficiency: On the other hand, an underactive immune system can lead to immunodeficiency, where the body is more susceptible to infections. Proper regulation ensures that the immune system responds appropriately to protect against infections without causing harm to the body itself.
explain how immune regulation involves a complex interplay between various regulatory pathways and components
Complex Interplay of Regulatory Pathways:
The immune system employs numerous regulatory pathways to modulate its responses. This includes mechanisms to activate, enhance, dampen, or terminate immune reactions as needed.
Contribution to a Balanced Immune Response:
The intricate regulation ensures that the immune response is proportionate to the threat. Balancing the activation and inhibition of immune components is crucial for preventing both underactivity and overactivity of the immune system.
Restoration of the Immune System to a Resting State:
Once the threat is eliminated, the immune system needs mechanisms to return to a resting state. This involves down-regulating immune responses, resolving inflammation, and eliminating effector cells.
Factors Influencing Immune Response Outcome:
Various factors influence the outcome of an immune response, including:
Antigen: As discussed earlier, the characteristics of the antigen can impact the immune response.
Antibodies: These molecules play a key role in recognizing and neutralizing pathogens, influencing the course of the immune response.
Cytokines: Signaling molecules that regulate immune cell communication and function, influencing the intensity and nature of the immune response.
Antigen-Presenting Cells (APCs): Cells that present antigens to other immune cells, playing a crucial role in initiating immune responses.
T Cells: These cells are central to the adaptive immune response, and their activation is influenced by various factors.
Immune Complexes: Complexes formed by the binding of antibodies to antigens, influencing the clearance of pathogens.
Major Histocompatibility Complex (MHC) Proteins: These proteins present antigens to T cells and play a key role in immune recognition.
The interactions among these factors form a highly regulated network, and the outcome of an immune response is the result of their coordinated efforts.
outline the primary goals of the immune system in responding to threats and maintaining overall health
Recognize the Invader:
The immune system must accurately identify and distinguish between self and non-self, recognizing pathogens and other foreign substances.
Generate a Sufficient Response:
Once the invader is identified, the immune system needs to mount an effective response that is proportionate to the threat. This involves activating various components of the immune system, such as antibodies, T cells, and other immune cells.
Prompt Effective Down-Regulation:
After the danger has been resolved, it’s crucial for the immune system to down-regulate its response. This prevents prolonged inflammation and potential damage to healthy tissues. Effective down-regulation is essential for returning the immune system to a state of balance.
Eliminate Effector Cells:
Effector cells, which are activated immune cells responsible for carrying out the immune response, need to be eliminated or deactivated once their job is done. This helps prevent a persistent immune response that could harm the body’s own tissues.
Keep Memory for Future Challenges:
The immune system retains a memory of past infections to respond more rapidly and effectively upon re-exposure. This memory involves the production of specific antibodies and the generation of memory T cells. This adaptive immune memory is crucial for long-term protection.
explain the complexity of immune regulation
The immune system’s ability to distinguish between ‘self’ and ‘non-self’ is crucial to avoid harmful autoimmune reactions. Striking a balance between an effective response and avoiding excessive reactions is indeed a delicate task. Here are some additional points that further emphasize the complexity of immune regulation:
Tolerance to Self-Antigens: The immune system must develop tolerance to the body’s own cells and molecules. Failure to establish this tolerance can result in autoimmune diseases where the immune system mistakenly attacks healthy tissues.
Precision in Recognition: The immune system needs to precisely recognize and target specific pathogens. This specificity is crucial for an effective immune response without causing damage to healthy cells.
Fine-Tuning of Responses: The immune system should be capable of fine-tuning its responses based on the type and severity of the threat. This involves activating different components of the immune system in a coordinated manner.
Resolution of Inflammation: Once the threat is eliminated, the immune system needs to resolve the inflammatory response. Chronic inflammation can lead to tissue damage and contribute to various diseases, so the immune system must have mechanisms to downregulate its activity.
Memory and Adaptation: The immune system’s memory allows it to respond more rapidly and effectively upon re-exposure to a previously encountered pathogen. This memory needs to be well-regulated to avoid inappropriate responses.
Communication Between Immune Cells: Various components of the immune system need to communicate with each other to coordinate responses. This communication is tightly regulated to ensure a harmonized and effective immune reaction.
Recognition of Emerging Threats: The immune system must be capable of recognizing and responding to new and emerging pathogens. This requires a degree of flexibility and adaptability in its regulatory mechanisms.
Avoiding Hyperactivity: Excessive immune responses can lead to hypersensitivity reactions, allergies, and other immune-mediated disorders. Effective regulation prevents the immune system from overreacting to harmless substances.
In what ways can the antigen itself influence the fate of an immune response?
Antigen Size and Complexity:
The size and complexity of an antigen can affect how it is processed and presented to immune cells. Larger or more complex antigens may be processed differently and may lead to a more robust immune response.
Antigenicity:
Antigenicity refers to the ability of an antigen to induce an immune response. Some antigens are highly immunogenic, meaning they strongly stimulate the immune system, while others may be less immunogenic. The degree of antigenicity can influence the strength and nature of the immune response.
Foreignness of the Antigen:
The immune system is more likely to mount a strong response against antigens that are perceived as foreign. Antigens that closely resemble the body’s own molecules may be tolerated to a greater extent, potentially leading to immune tolerance.
Persistence of the Antigen:
The duration for which an antigen persists in the body can impact the immune response. Chronic exposure to an antigen may lead to sustained immune activation, potentially contributing to chronic inflammatory conditions.
Antigen Presentation:
Antigen-presenting cells (APCs) play a crucial role in presenting antigens to other immune cells. The efficiency of antigen presentation can influence the strength of the immune response. Professional APCs, such as dendritic cells, are particularly effective in this regard.
T Cell Activation:
T cells are a key component of the adaptive immune response, and their activation is influenced by antigens. The interaction between antigens and T cell receptors determines whether T cells become activated and initiate immune responses.
Epitope Accessibility:
Epitopes are specific regions on antigens that are recognized by immune cells. The accessibility and exposure of these epitopes can impact the immune response. Some epitopes may be hidden within the structure of the antigen, affecting how effectively they can trigger an immune reaction.
Antigen Modulation:
Some pathogens have evolved mechanisms to modulate or evade the immune response by altering their antigens. This can hinder effective recognition by the immune system and contribute to immune evasion.
Cross-Reactivity:
Cross-reactivity occurs when the immune system responds to a different but structurally similar antigen. This phenomenon can influence the specificity and diversity of the immune response.
Immunological Tolerance:
The immune system strives to maintain tolerance to self-antigens and harmless substances. Failure of tolerance mechanisms can lead to autoimmune responses. The presence of certain antigens may contribute to the development of tolerance or, conversely, trigger autoimmune reactions.
How does the immune system manage to generate a balanced immune response?
Recognition and Discrimination:
The immune system must recognize and discriminate between self and non-self. This is crucial for avoiding autoimmune reactions where the immune system mistakenly targets the body’s own cells. Tolerance mechanisms ensure that the immune system does not attack healthy tissues.
Antigen Presentation:
Antigen-presenting cells (APCs), such as dendritic cells, macrophages, and B cells, play a central role in presenting antigens to other immune cells. The efficient presentation of antigens helps activate the appropriate immune responses and contributes to the specificity of the reaction.
Activation and Inhibition Signals:
Immune cells receive both activation and inhibition signals. These signals come from various molecules, including cytokines, costimulatory molecules, and inhibitory receptors. The balance between these signals determines the outcome of the immune response.
Tight Regulation of Cytokines:
Cytokines are signaling molecules that mediate communication between immune cells. The immune system tightly regulates the production and action of cytokines to control the intensity and duration of immune responses. This helps prevent excessive inflammation and tissue damage.
Role of Regulatory T Cells (Tregs):
Regulatory T cells (Tregs) are a specialized subset of T cells that play a key role in suppressing immune responses. They help maintain immune tolerance and prevent excessive immune reactions. Tregs actively suppress the activation of other immune cells.
Clearance of Immune Complexes:
Immune complexes, formed by the binding of antibodies to antigens, are efficiently cleared from the body. This prevents the accumulation of immune complexes, which could contribute to autoimmune reactions or chronic inflammation.
Apoptosis (Programmed Cell Death):
Immune cells that have completed their tasks or are no longer needed undergo apoptosis, a form of programmed cell death. This helps in the resolution of the immune response and prevents the persistence of effector cells that could cause harm.
Balance Between Effector and Regulatory Responses:
The immune system maintains a balance between effector responses (which eliminate pathogens) and regulatory responses (which dampen immune reactions). This balance is crucial for preventing both underactivity and overactivity of the immune system.
Immunological Memory:
The immune system generates memory cells during an immune response. These memory cells “remember” previous encounters with specific pathogens, leading to a faster and more robust response upon re-exposure. This memory contributes to a more balanced and efficient immune reaction.
Adaptability to Different Threats:
The immune system is adaptable and can tailor its responses to different types of pathogens. This adaptability allows it to mount specific and appropriate responses without triggering unnecessary reactions.
give an overview of key regulatory mechanisms within the immune system, particularly focusing on the crucial role played by T cells, especially regulatory T cells (Tregs)
Regulatory Mechanisms Involving Transcription Factors, Receptors, and Inhibitory Molecules:
The immune system employs a range of regulatory mechanisms at the molecular level. Transcription factors, immunomodulatory receptors, and inhibitory molecules play essential roles in modulating immune responses. These mechanisms contribute to the precise control and balance needed for an effective but controlled immune response.
Central Role of T Cells in Immune Regulation:
T cells, a type of lymphocyte, are central to immune regulation. They coordinate and modulate immune responses, ensuring an appropriate reaction to pathogens while preventing excessive or misguided reactions.
Negative Regulation by T Cells:
Some T cells, known as regulatory T cells (Tregs), play a negative regulatory role. Their function is to suppress or dampen immune responses, preventing them from becoming exaggerated, chronic, or potentially leading to autoimmune reactions.
Natural T-Reg Cells:
Natural T-regulatory cells (nTregs) are a subset of Tregs that develop mainly in the thymus as CD4+CD25+ cells. They are crucial for maintaining immune tolerance and preventing autoimmunity.
Adaptive (Inducible) T-Reg Cells:
Another subset of Tregs, called adaptive or inducible T-regulatory cells (iTregs), can develop in the periphery from classic CD4+CD25- T cells. Their development is induced in response to specific triggers, such as infections or other immune challenges. This adaptability allows the immune system to fine-tune its regulatory responses based on the context.
Trigger-Induced Development of iTregs:
iTregs are not naturally present but are induced in response to particular triggers. For example, after an infection or exposure to certain antigens, iTregs may develop to help modulate the immune response and prevent excessive reactions.
These regulatory T cells, both nTregs and iTregs, exert their effects through various mechanisms, including the secretion of immunosuppressive cytokines and direct cell-to-cell interactions. They are critical for maintaining immune homeostasis and preventing immune responses from causing harm to the host.
explain how both classic CD4+ T cells and Tregs have CD4 molecules on their cell surface
Importance of CD4 Expression:
Recognition of MHC Class II:
CD4 is a co-receptor that interacts with major histocompatibility complex class II (MHC-II) molecules on the surface of antigen-presenting cells (APCs). This interaction is crucial for the initiation of immune responses. Classic CD4+ T cells recognize antigens presented by MHC-II molecules, leading to their activation and differentiation into effector T cells.
Helper T Cell Function:
Classic CD4+ T cells are often referred to as helper T cells because they help coordinate immune responses. Once activated, they release cytokines that influence the activities of other immune cells, such as B cells, cytotoxic T cells, and macrophages.
T-Reg Cell Function:
Regulatory T cells (Tregs), despite expressing the CD4 marker, have a distinct function compared to classic CD4+ T cells. Tregs play a crucial role in suppressing immune responses. They help maintain immune tolerance, prevent autoimmune reactions, and modulate the intensity and duration of immune reactions.
Immunological Self-Tolerance:
The CD4 molecule on Tregs is essential for their function in promoting immunological self-tolerance. Tregs recognize self-antigens and prevent the immune system from mounting an excessive or harmful response against the body’s own tissues.
Preventing Autoimmunity:
The ability of Tregs to recognize self-antigens and suppress immune responses is vital for preventing autoimmune diseases. Dysfunction or deficiency in Tregs can lead to uncontrolled immune reactions against self-tissues, resulting in autoimmune disorders.
Expression of Foxp3:
While CD4 expression is a shared feature, Tregs are further characterized by the expression of the transcription factor Foxp3. Foxp3 is considered a master regulator for the development and function of Tregs.
explain natural CD25+ regulatory T cells (nTregs), highlighting their key characteristics and functions within the immune system
Frequency and Composition:
Natural CD25+ regulatory T cells constitute a subset of CD4+ T cells and typically make up 5-10% of circulating CD4+ T cells. They are an essential component of the immune system’s regulatory network.
Expression of CD25 Receptor:
CD25 is the alpha chain of the interleukin-2 (IL-2) receptor. The expression of CD25 allows nTregs to respond to IL-2, a cytokine that plays a crucial role in T cell proliferation and survival.
Expression of CTLA-4 Receptor:
Cytotoxic T lymphocyte-associated protein-4 (CTLA-4) is a receptor expressed by nTregs. CTLA-4 acts as a checkpoint inhibitor, inhibiting T cell responses and contributing to the suppression of immune reactions. It competes with CD28 for binding to B7 molecules on antigen-presenting cells (APCs), downregulating T cell activation.
Expression of Foxp3 Transcription Factor:
Foxp3 is a transcription factor that is critical for the development and function of regulatory T cells. Its expression by nTregs is a hallmark of their regulatory identity. Foxp3 promotes the differentiation of CD4+ T cells into regulatory T cells, ensuring their suppressive function.
Suppression of Different Cell Types:
CD25+ regulatory T cells exert their suppressive effects on various immune cell types. They can suppress the activation and function of CD4+ T cells, CD8+ T cells, B cells, and antigen-presenting cells (APCs). This broad suppression is crucial for maintaining immune homeostasis and preventing excessive immune reactions.
Self-Check of the Immune System:
CD25+ Tregs provide a vital self-check mechanism for the immune system. By suppressing potentially harmful immune responses, they prevent autoimmune reactions and contribute to the establishment of immune homeostasis.
Role in Immune Homeostasis:
The regulatory function of CD25+ Tregs is essential for balancing the immune system’s responses. Their ability to dampen immune reactions helps prevent chronic inflammation, autoimmune diseases, and excessive tissue damage.
FoxP3 is a specific marker for T-reg cells.
Are there other immune cell types that express FoxP3?
Foxp3 is indeed considered a specific marker for regulatory T cells (Tregs), and its expression is crucial for the development and function of these cells. Foxp3 serves as a master regulator for the differentiation of Tregs, contributing to their suppressive properties.
While Foxp3 is most well-known for its association with Tregs, there have been reports of its expression in certain other immune cell types. However, it’s important to note that the expression of Foxp3 in these non-Treg cells is typically transient, and the cells do not acquire the full regulatory function characteristic of Tregs. Here are a few instances where Foxp3 expression has been observed in non-Treg cells:
Activated CD4+ T Cells:
In some situations, activated conventional CD4+ T cells (non-Treg cells) can transiently express Foxp3. This expression is often associated with the regulatory phenotype acquired during certain immune responses.
Peripheral Tolerance-Inducing Dendritic Cells:
Certain subsets of dendritic cells, particularly those with tolerogenic properties that contribute to peripheral tolerance, have been reported to express Foxp3. These dendritic cells play a role in inducing immune tolerance and suppressing immune responses.
Other CD4-Positive T Cells:
In rare cases, Foxp3 expression has been reported in CD4-negative T cells, suggesting some level of plasticity in the expression of this transcription factor.
It’s important to emphasize that while Foxp3 expression may occur in these cell types, it does not confer the full suppressive and regulatory function characteristic of bona fide regulatory T cells. The stable and heritable expression of Foxp3 is a defining feature of natural regulatory T cells (nTregs) and induced regulatory T cells (iTregs).
How do T-regulatory cells exert their suppressor effects?
Regulatory T cells (Tregs) exert their suppressor effects through various mechanisms, employing both cell-to-cell contact and the secretion of immunomodulatory molecules. These mechanisms are aimed at maintaining immune homeostasis, preventing excessive immune responses, and suppressing potentially harmful reactions. Here are key ways in which Tregs exert their suppressor effects:
Cell-to-Cell Contact and Inhibition:
CTLA-4 (Cytotoxic T Lymphocyte-Associated Protein 4): Tregs express high levels of CTLA-4, which competes with CD28 for binding to B7 molecules on antigen-presenting cells (APCs). By doing so, CTLA-4 inhibits the co-stimulatory signals necessary for full T cell activation, thus suppressing the activation of conventional T cells.
Production of Suppressive Cytokines:
IL-10 (Interleukin-10) and TGF-β (Transforming Growth Factor-beta): Tregs can secrete anti-inflammatory cytokines such as IL-10 and TGF-β. These cytokines have immunosuppressive effects, inhibiting the activation and function of various immune cells.
Consumption of IL-2:
Tregs express high levels of CD25, the alpha chain of the IL-2 receptor. By consuming IL-2, a crucial cytokine for T cell activation and proliferation, Tregs can limit the availability of IL-2 for other T cells, thereby suppressing their expansion and effector functions.
Direct Cytotoxicity:
Some Tregs have been reported to exhibit cytotoxic activity, directly killing target cells. However, this mechanism is not as prominent as the immunomodulatory effects mediated by cytokines and cell-to-cell contact.
Metabolic Disruption:
Tregs can interfere with the metabolism of effector T cells, inhibiting their energy production and compromising their function. This includes restricting the availability of nutrients necessary for the proliferation and activation of conventional T cells.
Modulation of Antigen-Presenting Cells (APCs):
Tregs can directly or indirectly influence the function of antigen-presenting cells (APCs), such as dendritic cells. This modulation can impair the ability of APCs to stimulate and activate effector T cells.
Induction of Apoptosis in Target Cells:
Tregs may induce apoptosis (programmed cell death) in target cells, further contributing to their suppressor effects.
Inhibitory Receptors and Molecules:
Tregs express various inhibitory receptors and molecules that can negatively regulate immune responses. These include PD-1 (Programmed Cell Death Protein 1) and LAG-3 (Lymphocyte-Activation Gene 3), among others.
It’s important to note that Tregs employ a combination of these mechanisms in a context-dependent manner. The suppressive effects of Tregs are finely tuned to modulate immune responses without causing global immunosuppression. This delicate balance is crucial for preventing autoimmune reactions, maintaining tolerance to self-antigens, and regulating immune responses against pathogens.
explain the several factors Tregs depend on to effectively regulate immune responses
Regulatory T cells (Tregs) play a central role in maintaining peripheral tolerance, and their proper function is essential for preventing autoimmune reactions and maintaining immune homeostasis. Tregs depend on several factors to effectively regulate immune responses:
Antigen Dependency:
Tregs can be both antigen-dependent and antigen-independent. While some Tregs are specific for particular antigens, especially in the case of thymus-derived natural Tregs (nTregs), others are thought to exert their suppressive function in an antigen-independent manner. Antigen-dependent Tregs recognize specific antigens, including self-antigens, and contribute to the prevention of autoimmune responses.
Cytokine Dependency:
Tregs are influenced by various cytokines that can modulate their function. Importantly, interleukin-2 (IL-2) is crucial for Treg survival and maintenance. Tregs express high levels of the IL-2 receptor (CD25), and IL-2 signaling is vital for their development, homeostasis, and suppressive function. Additionally, Tregs can produce immunomodulatory cytokines such as IL-10 and TGF-β, which contribute to their suppressor effects.
CTLA-4 Dependency:
CTLA-4 (Cytotoxic T Lymphocyte-Associated Protein 4) is a key molecule expressed by Tregs, and its interaction with B7 molecules on antigen-presenting cells (APCs) plays a crucial role in Treg suppressor function. CTLA-4 competes with CD28 for binding to B7, resulting in the inhibition of co-stimulatory signals needed for the activation of conventional T cells. The expression of CTLA-4 is essential for Treg-mediated immune suppression.
Antigen-Presenting Cells (APCs):
Tregs do interact with antigen-presenting cells (APCs), but the nature of this interaction is distinct from that of conventional T cells. Tregs can modulate the function of APCs, leading to a tolerogenic phenotype. They may inhibit the maturation and activation of dendritic cells, impairing their ability to stimulate effector T cells. Tregs may also capture and process antigens, influencing the presentation of these antigens by APCs.
What is the function of CD28 receptor on T cells?
The CD28 receptor on T cells plays a crucial role in the activation of T lymphocytes, specifically in the context of the immune response. CD28 is a co-stimulatory molecule that interacts with its ligands on antigen-presenting cells (APCs), providing a second signal for T cell activation. The primary functions of CD28 include:
Co-Stimulation:
CD28 provides a co-stimulatory signal that is required in addition to the T cell receptor (TCR) signal for the full activation of T cells. The interaction of CD28 with its ligands, B7-1 (CD80) and B7-2 (CD86), on the surface of APCs enhances T cell activation and proliferation.
Enhancement of T Cell Activation:
When a T cell recognizes its specific antigen presented by an APC through the TCR, the engagement of CD28 with B7 molecules amplifies the T cell activation signal. This co-stimulatory signal is crucial for the initiation of an effective immune response.
Cytokine Production:
CD28 signaling enhances the production of various cytokines by activated T cells. Interleukin-2 (IL-2) is a key cytokine produced upon CD28 co-stimulation, and it plays a central role in T cell proliferation and differentiation.
Promotion of T Cell Survival:
CD28 signaling supports T cell survival by preventing activation-induced cell death. It contributes to the longevity and persistence of activated T cells, allowing them to carry out their effector functions over a more extended period.
Induction of T Cell Differentiation:
CD28 co-stimulation influences T cell differentiation, promoting the development of effector T cell subsets with specific functions. For example, CD28 signaling is involved in the generation of cytotoxic T cells and T helper cells with distinct cytokine profiles.
Maintenance of Tolerance:
CD28 signaling is also involved in the maintenance of peripheral tolerance. In certain contexts, CD28 co-stimulation can contribute to regulatory T cell (Treg) function, which is crucial for suppressing excessive immune responses and preventing autoimmunity.
The interaction between CD28 and its ligands represents a critical checkpoint in the immune response. It ensures that T cells receive appropriate co-stimulatory signals before committing to a full-fledged immune reaction. Dysregulation of CD28 signaling or its absence can lead to impaired T cell activation and contribute to immune deficiencies or inadequate immune responses.
explain how Tregs, once activated, can exert their suppressive effects on a broad range of immune responses, even those involving T cells with different antigen specificities
The suppressive function of regulatory T cells (Tregs) is indeed antigen-dependent at the initial activation stage, where the T-cell receptor (TCR) interacts with a specific antigen (Ag). However, once activated, Tregs can exert their suppressive effects on a broad range of immune responses, even those involving T cells with different antigen specificities.
To break it down:
Antigen-Dependent Activation:
Tregs, like other T cells, require activation through their TCR. This activation typically involves interaction with a specific antigen. For natural Tregs (nTregs), this antigen recognition often includes self-antigens encountered during their development in the thymus. For induced or adaptive Tregs (iTregs), the antigenic triggers can include foreign antigens encountered in the periphery.
Suppressive Function is Antigen-Dependent Initially:
The initial activation and acquisition of suppressive function are antigen-dependent. Tregs may recognize antigens presented by antigen-presenting cells (APCs), leading to their activation and subsequent regulatory function.
Non-Antigen-Specific Suppression:
Once activated, Tregs can exert suppressive effects on a variety of immune responses, irrespective of the specific antigen involved. This means that Tregs are not limited to suppressing T cells with the same antigen specificity. They have a broad suppressive capacity, allowing them to modulate the activities of various immune cell types, including T cells, B cells, and antigen-presenting cells.
Maintenance of Immune Homeostasis:
The non-antigen-specific suppressive function of Tregs is critical for their role in maintaining immune homeostasis. By suppressing a diverse range of immune responses, Tregs contribute to preventing excessive inflammation, autoimmunity, and immune-mediated tissue damage.
explain how the suppressive function of regulatory T cells (Tregs) involves the secretion of immunosuppressive cytokines, and how do these cytokines play a crucial role in modulating immune responses.
The suppressive function of regulatory T cells (Tregs) involves the secretion of immunosuppressive cytokines, and these cytokines play a crucial role in modulating immune responses. Here’s a breakdown of the key points you mentioned:
TGF-beta (Transforming Growth Factor-beta):
Inhibition of T Cell Activation: TGF-beta can block the activation of T cells by inhibiting the co-stimulatory pathway, including downregulation of CD28 expression. This inhibition helps prevent the full activation of T cells, contributing to immune suppression.
Induction of Treg Differentiation: TGF-beta has the ability to induce the differentiation of CD4+ T cells into regulatory T cells (Tregs). This is particularly important for the generation of induced Tregs (iTregs) in the periphery.
IL-10 (Interleukin-10):
Inhibition of Pro-Inflammatory Cytokines: IL-10 inhibits the production of pro-inflammatory cytokines, such as IL-2 and IL-6. By suppressing the release of these cytokines, IL-10 helps dampen inflammatory responses.
Modulation of Antigen Presentation: IL-10 inhibits the expression of major histocompatibility complex class II (MHC-II) on antigen-presenting cells (APCs). This, in turn, hinders antigen presentation and T cell activation.
Blockade of Macrophage Function: IL-10 can also block the function of macrophages, further contributing to the suppression of immune responses.
IL-35 (Interleukin-35):
Inhibition of T Cell Proliferation: IL-35 inhibits the proliferation of T cells, limiting their expansion and activation.
Induction of Treg Differentiation: Similar to TGF-beta, IL-35 can induce the differentiation of CD4+ T cells into regulatory T cells.
