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ANTIVIRAL IMMUNITY © The host have multiple layers to detect and control pathogens including viruses. C Antiviral immune responses help to; 1. Prevent viral replication, 2. Clear infected cells, and 3. Establish immunological memory © Antiviral immunity can be categorized as 1. Innate immune responses. 2. adaptive immune responses. Components of the Innate Antiviral Immunity © Innate immune system is the first line of defense against viral infections. O It acts rapidly, within hours of infection, and it is non-specific in nature C Innate antiviral immunity comprises; . Physical and chemical barriers. . Pattern Recognition Receptors (PRRs) . Type I Interferons (IFN-a/B) 1 2 3 4. Natural Killer (NK) Cells 5. Complement System 6 . Inflammatory Cytokines ANTIVIRAL IMMUNITY A. Physical and Chemical Barriers. © These barriers comprise the foremost defense against viral infections. A. The skin; * The outermost layer of the skin (stratum corneum) is tough and resistant to viral penetration. “ It acts as a physical barrier, blocking viruses from directly accessing underlying tissues. * The constant shedding of skin cells removes microbes, including viruses. “* The skin-associated immune cells (e.g., Langerhans cells which specialized dendritic cells) detect and respond to viral entry attempts A. Physical and Chemical Barriers. B. Mucosal Surfaces; * Mucous membranes line the respiratory, gastrointestinal, and urogenital tracts, which are common portals of viral entry. * Mucus is produced and secreted by goblet cells and glands. * The mucus trap and prevent viruses from reaching epithelial cells. * Has commensal microbiota which compete with pathogens and modulate local immune responses ANTIVIRAL IMMUNITY Double-stranded RNA (dsRNA) | TLR3, RIG-I, MDA5 Single-stranded RNA (ssRNA) TLR7, TLRS, RIG-I DNA (viral genomes) TLR9, cGAS-STING pathway Viral glycoproteins TLR2, TLR4 B. Pattern Recognition Receptors (PRRs) “* Outcome of PRR activation by viruses. 1. Type I interferon production (IFN-a, IFN-8): Induces antiviral state in infected and neighboring cells. 2. Productions of proinflammatory cytokines: IL-6, TNF-a, IL-1B recruit and activate immune cells. 3. Apoptosis and autophagy which helps eliminate infected cells. 4. Activation of Adaptive Immunity by enhancing antigen presentation and T as well as B cell responses. ANTIVIRAL IMMUNITY C. Type I Interferons (IFN-a/p). © Type I interferons are key antiviral cytokines produced early during viral infection. © Virus Infected cells detect viral PAMPs using PRR such as RIG-I, MDAS, and TLRs. © Detection of PAMPs triggers signaling pathways (e.g IRF3/IRF7 activation) that lead to © Activation of transcription factors such as NFkB. © Production & secretion of IFN-o and IFN-B. C IFN-a and IFN-8 bind to type I Interferon Receptor (IFNAR) on cell surface and induces an “antiviral state”. C. Type I Interferons (IFN-a/p). C IFN-a« and IFN-8 bind to type I Interferon Receptor (IFNAR) and induces an “antiviral state”. C Major antiviral effects include; 1. Upregulation of Interferon-Stimulated Genes (ISGs) that inhibit different stages of viral replication: ANTIVIRAL IMMUNITY D. Natural Killer (NK) Cells. © NK cells are cells of the innate immune system. © They kill infected cells without without prior sensitization (unlike CD8* T cells). © They play a crucial role early in viral infections before the adaptive immune response develops. © NK cells detect cells with reduced MHC class I expression, which is a common viral immune- evasion strategy. D. Natural Killer (NK) Cells. © NK cells integrate signals from: 1. Activating receptors (detect stress or viral ligands) 2. Inhibitory receptors (detect MHC I). CO NK cells is activated by reduction of inhibitory signal (reduction of MHC-I on infected cells. ANTIVIRAL IMMUNITY D. Natural Killer (NK) Cells. U Effector mechanism of involves: 1. Cytotoxic killing of virus infected by releasing: % Perforin which forms pores on cell membrane of infected cells. % Granzymes enter through pores formed and induce apoptosis. 2. Production of cytokines such as Interferon-y (IFN-y), which: “* Enhances macrophage activity * Boosts antigen presentation * Strengthens the antiviral state in surrounding cells E. Complement System. © It is a group of plasma proteins (C1-C9 and regulatory factors) that form part of the innate immune response. C Complement proteins are activated during viral infections. © Role of the complement system during viral infection: 1. Opsonization: © Virus are coated by activated complement protein i.e. C3b. © The C3b promotes phagocytosis and clearance of virus particles by phagocytes such as macrophages and neutrophils. ANTIVIRAL IMMUNITY E. Complement System. 3. Enhances Adaptive Immunity: © Complement improves’ adaptive antiviral responses by: 1. Enhancing B cell activation (via complement receptor 2, CR2). 2. Increasing antigen uptake and presentation by dendritic cells. 3. Promoting formation of immune complexes that are more efficiently cleared. O This is results in stronger antibody responses and more effective long-term immunity. ANTIVIRAL IMMUNITY (Classical pathway ) C Lectin pathway » (Alternative pathway ) Main trigger: = Antigen-antibody reaction = Mannose vs lectin (MBL) Microbes or injured tissue Ciq le Continuous cir Cis _ yMASP-2 spontaneous hydrolysis of C3 a) -— c1in#—4 a ‘Antigen ep : Pathogen Factor B, c4, C2 baie | oA Factor D, , Properdin @)“ convertase ey ny Opsonization a . eee Phagocytosis ‘©? L C3aR, (3) C5 convertase (ce) Ea Ree Inflammation e. C5aR. Clusterin Fe ra ¢ Vitronectin 8 co59— on Membrane Attack Complex (MAC) Cell C5b-9 membrane Cell lysis F. Inflammatory Cytokines . O Inflammatory cytokines are early immune mediators released by macrophages, dendritic cells, and infected tissues after viral detection. O They help coordinate the body’s response to infection O Key roles of inflammatory cytokines during antiviral immunity: 1. Recruit immune cells to infection site e.g TNF-a, IL-1, IL-6: 2. Induce fever by raising body temperature to slow down viral replication e.g. IL-1 and IL-6 act on the hypothalamus 3. Enhance antiviral defenses promoting § activation § of macrophages and NK cells 
