11.1 Innate immune responses to viral infections
5 min read•august 1, 2024
Viruses are masters of deception, but our bodies have a secret weapon: the innate immune system. This first line of defense uses to spot viral invaders and sound the alarm. It's like having security cameras that can detect even the sneakiest intruders.
Once alerted, our bodies unleash a powerful antiviral response. and act as chemical messengers, rallying immune cells to battle stations. , , and other innate defenders swoop in to contain the viral threat and set the stage for adaptive immunity.
Pattern Recognition Receptors in Viral Detection
Types and Functions of PRRs
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- Pattern recognition receptors (PRRs) detect conserved molecular patterns associated with viruses
- Specialized proteins expressed by innate immune cells
- Recognize pathogen-associated molecular patterns (PAMPs)
- PAMPs include viral nucleic acids, proteins, and glycoproteins
- Toll-like receptors (TLRs) recognize various viral PAMPs
- TLR3 detects double-stranded RNA
- TLR7/8 detects single-stranded RNA
- TLR9 detects unmethylated CpG DNA
- RIG-I-like receptors (RLRs) detect viral RNA in the cytoplasm
- Include RIG-I and MDA5
- NOD-like receptors (NLRs) and cytosolic DNA sensors detect intracellular viral components
- cGAS serves as a crucial cytosolic DNA sensor
PRR Signaling and Immune Activation
- PRRs initiate signaling cascades upon viral PAMP recognition
- Activate transcription factors (NF-κB and IRFs)
- Induce expression of antiviral genes
- Trigger production of inflammatory mediators
- Signaling leads to diverse cellular responses
- Upregulation of antiviral proteins
- Secretion of pro-inflammatory cytokines (TNF-α, IL-1β)
- Production of type I interferons
- PRR activation enhances antigen presentation
- Increases expression of MHC molecules
- Promotes maturation of
- PRR signaling bridges innate and adaptive immunity
- Stimulates T cell activation
- Enhances B cell responses
Interferons and Cytokines in Antiviral Response
Interferon Types and Functions
- Interferons (IFNs) play critical roles in innate antiviral responses
- Three main types: Type I (IFN-α and IFN-β), Type II (IFN-γ), and Type III (IFN-λ)
- Type I IFNs rapidly produced during viral infections
- Induce antiviral state in neighboring cells
- Upregulate expression of interferon-stimulated genes (ISGs)
- ISGs encode proteins with diverse antiviral functions
- Inhibit viral replication (OAS/RNase L system)
- Block protein synthesis (PKR)
- Prevent viral entry (IFITM proteins)
- ISGs encode proteins with diverse antiviral functions
- Type II IFN (IFN-γ) primarily produced by natural killer cells and T cells
- Enhances antigen presentation
- Activates macrophages
- Promotes development of adaptive immune responses
- Type III IFNs (IFN-λ) provide antiviral protection at mucosal surfaces
- Act primarily on epithelial cells
Pro-inflammatory Cytokines and Chemokines
- Pro-inflammatory cytokines contribute to antiviral responses
- TNF-α, IL-1β, and IL-6 key players
- Induce fever (IL-1β)
- Promote
- Recruit immune cells to infection sites
- direct migration of immune cells
- CXCL10 attracts activated T cells
- CCL5 recruits monocytes and T cells
- CXCL8 (IL-8) attracts neutrophils
- Cytokine and chemokine networks orchestrate overall immune response
- Coordinate innate and adaptive immunity
- Regulate inflammation
- Shape the development of virus-specific T and B cell responses
Innate Immune Cells in Viral Control
Natural Killer Cells and Cytotoxicity
- Natural killer (NK) cells play crucial role in early viral control
- Recognize and kill virus-infected cells through cytotoxic mechanisms
- Release perforin and granzymes
- Induce in target cells
- Recognize and kill virus-infected cells through cytotoxic mechanisms
- NK cells use complex receptor systems to identify infected cells
- Activating receptors (NKG2D, NCRs) recognize stress-induced ligands
- Inhibitory receptors (KIRs) detect reduced MHC class I expression
- NK cells produce cytokines to shape immune responses
- IFN-γ enhances antiviral state
- TNF-α promotes inflammation
Macrophages and Antigen-Presenting Cells
- Macrophages contribute to antiviral defense through multiple mechanisms
- Phagocytose and destroy virus-infected cells
- Produce pro-inflammatory cytokines (TNF-α, IL-1β, IL-6)
- Secrete chemokines to recruit other immune cells
- Dendritic cells (DCs) bridge innate and adaptive immunity
- Capture and process viral antigens
- Present antigens to T cells in lymphoid organs
- Produce type I interferons
- Neutrophils release neutrophil extracellular traps (NETs)
- NETs trap and neutralize viruses
- Produce reactive oxygen species
- Secrete antiviral proteins (α-defensins)
Other Innate Immune Cells
- Innate lymphoid cells (ILCs) contribute to antiviral immunity
- Produce cytokines at mucosal surfaces
- ILC1s produce IFN-γ
- ILC2s enhance tissue repair after viral damage
- Eosinophils release antiviral proteins
- Eosinophil-derived neurotoxin (EDN) degrades viral RNA
- Mast cells act as sentinel cells in tissues
- Release inflammatory mediators upon viral detection
- Recruit other immune cells to infection sites
Innate vs Adaptive Immunity in Viral Infections
Initiation and Shaping of Adaptive Responses
- Innate immune response provides first line of defense against viruses
- Crucial for initiating and shaping subsequent adaptive immunity
- Antigen-presenting cells process and present viral antigens
- Dendritic cells migrate to lymph nodes
- Activate virus-specific T cells through antigen presentation
- Type I interferons enhance adaptive immune activation
- Promote antigen presentation
- Support T cell activation and differentiation
- Enhance B cell responses and antibody production
Cytokine-Mediated Immune Coordination
- Cytokines and chemokines create inflammatory environment
- Support recruitment of adaptive immune cells
- IL-12 promotes Th1 differentiation
- IL-6 and TGF-β support Th17 development
- Natural killer cells promote adaptive immunity
- Produce IFN-γ to enhance T cell responses
- Support antibody production by B cells
- Innate immune cells provide co-stimulatory signals
- CD80/CD86 on APCs interact with CD28 on T cells
- Enhance T cell activation and proliferation
Long-term Protection and Memory
- Adaptive immune response provides specific, long-lasting protection
- Cytotoxic T cells eliminate virus-infected cells
- Helper T cells support B cell and CD8+ T cell functions
- Neutralizing antibodies prevent viral entry into cells
- Memory T and B cells contribute to rapid secondary responses
- Provide quick protection upon re-exposure to same or similar viruses
- Memory CD8+ T cells rapidly expand and eliminate infected cells
- Memory B cells quickly differentiate into antibody-producing plasma cells
- Innate immune memory (trained immunity) enhances future responses
- Epigenetic changes in innate immune cells
- Leads to heightened responsiveness to subsequent infections
Key Terms to Review (18)
Apoptosis: Apoptosis is a programmed cell death process that occurs in multicellular organisms, allowing for the elimination of damaged, unwanted, or potentially harmful cells without causing inflammation. This mechanism plays a crucial role in maintaining cellular homeostasis and is significantly influenced by various factors in viral infections, innate immune responses, and mechanisms of viral-induced cellular damage.
Chemokines: Chemokines are a family of small cytokines, or signaling proteins, that play a crucial role in immune responses by directing the movement of immune cells to sites of infection or inflammation. They are key players in the innate immune system, guiding leukocytes to areas where they are needed to combat viral infections and coordinate the overall immune response.
Complement activation: Complement activation is a crucial part of the immune system that enhances the ability of antibodies and phagocytic cells to clear pathogens from an organism. It involves a series of proteins that are activated in a cascade, leading to opsonization, inflammation, and cell lysis. This process is vital in the context of viral infections, where it helps eliminate viruses and infected cells while also playing a role in the immunopathology that can arise during such infections.
Cytokines: Cytokines are small proteins released by cells that play a crucial role in cell signaling during immune responses. They act as messengers between cells, facilitating communication and coordination among immune cells to respond effectively to viral infections. Cytokines help to regulate the intensity and duration of immune responses, and they are pivotal in both promoting inflammation and resolving it.
Dendritic Cells: Dendritic cells are a type of antigen-presenting cell that play a crucial role in the innate immune response by capturing, processing, and presenting antigens to T cells. They serve as a bridge between the innate and adaptive immune systems, initiating the body's immune response to viral infections by activating T cells and triggering subsequent adaptive responses.
Immune evasion strategies: Immune evasion strategies are tactics used by viruses to avoid detection and destruction by the host's immune system. These strategies can manipulate various components of the immune response, leading to a successful infection and persistence in the host. By employing these mechanisms, viruses can undermine the innate immune responses, which serve as the first line of defense against viral infections.
Inflammation: Inflammation is the body's natural response to injury, infection, or harmful stimuli, characterized by redness, heat, swelling, and pain. This process involves the activation of immune cells and the release of signaling molecules that work to eliminate the cause of injury and initiate healing. In the context of viral infections, inflammation plays a crucial role in mobilizing the innate immune system to combat pathogens while also being a double-edged sword, as excessive inflammation can lead to tissue damage.
Interference with signaling pathways: Interference with signaling pathways refers to the mechanisms by which viruses disrupt the communication networks within host cells that are crucial for immune responses. This disruption can prevent the activation of immune defenses, allowing viruses to evade detection and establish infection more effectively. By manipulating these signaling pathways, viruses can inhibit the production of antiviral proteins, alter cell death pathways, and evade the host’s innate immune response.
Interferons: Interferons are a group of signaling proteins produced and released by host cells in response to the presence of pathogens, particularly viruses. They play a crucial role in the immune response by interfering with viral replication, activating immune cells, and enhancing the adaptive immune response. This multifaceted role makes interferons vital in the body’s defense against viral infections and also highlights their significance in understanding viral immune evasion tactics.
Macrophages: Macrophages are a type of white blood cell that play a crucial role in the immune system, particularly in recognizing and eliminating pathogens such as viruses. They act as professional phagocytes, engulfing and digesting cellular debris, dead cells, and foreign substances, thereby contributing to both innate and adaptive immune responses. Their ability to present antigens to T cells also links them to the adaptive immune system, making them vital in the body's defense against viral infections.
Natural Killer Cells: Natural killer (NK) cells are a type of lymphocyte that play a crucial role in the innate immune response by identifying and destroying virus-infected cells and tumor cells. They are essential for early defense against viral infections, functioning without the need for prior sensitization to antigens, which distinguishes them from other immune cells.
Pattern Recognition Receptors: Pattern recognition receptors (PRRs) are a class of proteins expressed by cells of the innate immune system that play a crucial role in recognizing and responding to pathogens, including viruses. These receptors identify molecular patterns associated with microbial infections, such as viral RNA or specific proteins, leading to the activation of immune responses that help protect the host from viral infections.
Phagocytosis: Phagocytosis is a cellular process in which certain cells, known as phagocytes, engulf and digest pathogens, cellular debris, and foreign particles. This mechanism plays a crucial role in the innate immune response, helping to eliminate viral infections and maintain tissue homeostasis. Phagocytosis not only aids in clearing pathogens but also activates other components of the immune system, promoting a more coordinated immune response.
Tissue damage: Tissue damage refers to the injury or destruction of cells and tissues within an organism, often resulting from infection, inflammation, or other pathological processes. This condition is crucial in understanding how viral infections can lead to clinical symptoms, as it involves the interaction between viruses and host tissues, impacting overall health and immune responses.
Tlr signaling pathway: The TLR (Toll-like receptor) signaling pathway is a crucial part of the innate immune response, recognizing pathogen-associated molecular patterns (PAMPs) and initiating an immune response. This pathway activates various transcription factors that lead to the production of pro-inflammatory cytokines and type I interferons, which are vital for combating viral infections. By bridging the recognition of viral components with the activation of immune cells, TLR signaling plays a fundamental role in shaping the overall immune response to viruses.
Type I Interferon Response: The type I interferon response is a crucial component of the innate immune system that is activated in response to viral infections, primarily through the production of interferon-alpha (IFN-\alpha) and interferon-beta (IFN-\beta). This response plays a significant role in establishing an antiviral state within infected and neighboring cells, enhancing the immune system's ability to combat viruses. By promoting the expression of various antiviral genes and modulating immune cell activities, the type I interferon response helps limit viral replication and spread.
Viral clearance: Viral clearance refers to the process by which the immune system effectively eliminates a virus from the body, resulting in the cessation of viral replication and restoration of health. This process is crucial in recovering from viral infections and is influenced by various factors including immune responses, viral characteristics, and host factors. Successful viral clearance can lead to long-term immunity and reduced risk of reinfection.
Viral rna sensing: Viral RNA sensing is the process by which cells detect the presence of viral RNA, triggering an immune response to combat viral infections. This detection is crucial for initiating innate immune responses, as it helps the host identify and respond to viral threats quickly, often involving pattern recognition receptors (PRRs) that recognize specific features of viral RNA.