lecture 19- immunology study guide.pdf

Effector mechanisms of humoral immunity Ø Secreted antibodies eliminate antigens and associated microbes Ø Involves collaboration with components of the innate immune system Ø Antibodies perform effector functions at locations distant from site of production Ø Primary targets include: Extracellular...

Effector mechanisms of humoral immunity Ø Secreted antibodies eliminate antigens and associated microbes Ø Involves collaboration with components of the innate immune system Ø Antibodies perform effector functions at locations distant from site of production Ø Primary targets include: Extracellular bacteria and fungi Viruses (pre-infection and post-release) Ø Primary basis of vaccine protection Ø May contribute to tissue damage in certain immune diseases and transplant rejection Effector mechanisms of humoral immunity involve the actions and functions of antibodies produced by B cells. These antibodies play a crucial role in eliminating antigens and microbes associated with those antigens. Here's a detailed explanation of the key points mentioned in your text: 1.Role of Antibodies: Antibodies are proteins produced by B cells in response to specific antigens. They are secreted into the bloodstream and extracellular fluid, allowing them to reach the site of infection or antigen presence. Antibodies recognize and bind to antigens, marking them for destruction or neutralization by other components of the immune system. 2.Collaboration with the Innate Immune System: While antibodies are part of the adaptive immune response, they collaborate with components of the innate immune system. This collaboration enhances the immune response and facilitates the clearance of pathogens. 3.Distance from Site of Production: Antibodies are often produced at a distance from the site of infection. They travel through the bloodstream and extracellular fluid to reach the location where they are needed, such as the site of infection or antigen presence. 4.Targets of Antibodies: Antibodies primarily target extracellular bacteria and fungi. They can also target viruses, either before they infect host cells or after they have 1 been produced in infected cells and released into the extracellular space. 5. Vaccine Protection: Antibodies play a central role in vaccine-induced immunity. Vaccines stimulate the production of antibodies specific to particular antigens, providing protection against subsequent infection by the pathogen. 6.Potential for Tissue Damage: While antibodies are essential for immune defense, they can also contribute to tissue damage under certain circumstances. Antibodies can trigger immune responses that inadvertently damage normal tissues, leading to autoimmune diseases or contributing to transplant rejection. 7.Balance in the Immune Response: Like other components of the immune system, the action of antibodies must be carefully regulated to maintain a balanced immune response. Excessive antibody production or activity can lead to immune-mediated tissue damage and contribute to the development of immune-related disorders. In summary, effector mechanisms of humoral immunity involve the actions of antibodies produced by B cells to eliminate pathogens and neutralize antigens. While antibodies play a critical role in immune defense, their activity must be carefully regulated to prevent tissue damage and maintain immune homeostasis. 1 Antibody functions (or “Effector mechanisms of humoral immunity”) 1. Neutralization of microbes and toxins 2. Opsonization and phagocytosis of microbes Primary mechanism by which antibodies confer “immunity” 3. Cell-mediated cytotoxicity via NK cells 4. Complement-dependent cytotoxicity Certainly, let's break down the different mechanisms of response in which antibodies are involved, as mentioned in your text: 1.Neutralization of Microbes and Toxins: Neutralization is a primary mechanism by which antibodies confer immunity. Antibodies can bind to the surface of viruses, bacteria, or toxins, blocking their ability to infect cells or exert toxic effects. By neutralizing pathogens and toxins, antibodies prevent them from causing harm to the body and facilitate their clearance by other components of the immune system. 2.Opsonization and Phagocytosis of Microbes: Opsonization refers to the process by which antibodies coat the surface of pathogens, marking them for recognition and ingestion by phagocytic cells such as macrophages and neutrophils. Antibodies enhance the efficiency of phagocytosis by promoting the attachment of phagocytes to the surface of pathogens. Once bound, phagocytes engulf and destroy the opsonized pathogens, aiding in their clearance from the body. 3.Cell-Mediated Cytotoxicity via NK Cells: Natural Killer (NK) cells are a type of lymphocyte that plays a crucial role in the innate immune response. Antibodies can facilitate the destruction of target cells, such as virus-infected or cancerous cells, by binding to their surface antigens and marking them for recognition by NK cells. NK cells then induce apoptosis (programmed cell death) in the target cells, effectively eliminating them from the body. 2 4. Complement-Dependent Cytotoxicity: The complement system is a group of proteins that work together to enhance the immune response. Antibodies can activate the complement system through a process called complement fixation. Once activated, complement proteins form pores in the membranes of target cells, leading to cell lysis (bursting) or the formation of membrane attack complexes that disrupt cellular function. This mechanism, known as complement-dependent cytotoxicity, contributes to the elimination of pathogens and infected cells from the body. In summary, antibodies play diverse roles in the immune response through various effector mechanisms of humoral immunity. These include neutralizing pathogens and toxins, facilitating phagocytosis of microbes, promoting cell-mediated cytotoxicity via NK cells, and inducing complement-dependent cytotoxicity. Each of these mechanisms contributes to the overall effectiveness of the immune response in defending the body against infection and disease. 2 Neutralization of microbes and toxins by antibodies Antibody binding: increases size of antigen or microbe blocks ability of microbe to infect host cell blocks ability of microbial toxin to harm host cell Requires only antigen-binding region (Fab) => Any isotype could “work” Mainly IgA in gut Mainly IgG in blood Neutralization of microbes and toxins by antibodies is a critical mechanism of the immune response, primarily mediated by the binding of antibodies to specific antigens on the surface of pathogens or toxins. Here's a detailed explanation of the process, as described in your text: 1.Antibody Binding: Antibodies have a Y-shaped structure composed of two identical heavy chains and two identical light chains. The top of the Y-shaped antibody molecule contains antigen-binding regions, also known as the antigen-binding fragment (Fab). These Fab regions are responsible for recognizing and binding to specific antigens on the surface of microbes or toxins. 1. Requires Only Antigen-Binding Region (FAB): The ability of antibodies to neutralize microbes and toxins primarily depends on the antigen-binding region (Fab) of the antibody molecule. Any isotype of antibody (e.g., IgA, IgG) can potentially perform this function as long as it possesses the Fab region. 2. Mainly IgA in the Gut and IgG in the Blood: Different isotypes of antibodies are predominant in various body compartments. For example, IgA antibodies are mainly found in mucosal surfaces, such as the gut, where they play a crucial role in neutralizing microbes. In contrast, IgG antibodies are the predominant isotype in the blood and are involved in 3 systemic immune responses. 2. Mechanisms of Neutralization: 1. Blocking Penetration of Epithelial Cell Barrier: In some cases, antibodies coat the surface of microbes, creating larger complexes that are less likely to penetrate epithelial cell barriers. By increasing the size of the antigenmicrobe complex, antibodies make it more challenging for the microbe to enter tissues and initiate infection. 2. Preventing Microbe-Cell Interaction: Antibodies can also prevent microbes from infecting host cells by blocking their interaction with cellular receptors. Many pathogens exploit specific cellular receptors to gain entry into host cells. When antibodies bind to these pathogens, they interfere with their ability to recognize and bind to cellular receptors, thus preventing infection. 3. Neutralizing Toxins: Antibodies can neutralize toxins produced by microbes by binding directly to the toxin molecules. Toxins often exert their harmful effects by interacting with specific receptors on host cells. By binding to toxins, antibodies prevent them from interacting with their cellular receptors, thereby neutralizing their toxic effects. 3.Functional Significance: Neutralization of microbes and toxins by antibodies is crucial for preventing infection and limiting the spread of pathogens within the body. By neutralizing pathogens and toxins, antibodies contribute to the overall effectiveness of the immune response in protecting against infectious diseases. In summary, neutralization of microbes and toxins by antibodies involves the binding of antibodies to specific antigens, which interferes with the ability of pathogens to penetrate tissues, infect host cells, or exert toxic effects. This mechanism plays a vital role in immune defense and is essential for preventing infection and maintaining host health. 3 Antibody functions (or “Effector mechanisms of humoral immunity”) 1. Neutralization of microbes and toxins 2. Opsonization and phagocytosis of microbes 3. Cell-mediated cytotoxicity via NK cells 4. Complement-dependent cytotoxicity Cells have receptors for Fc region Fc region Complement binds Fc region Which of these will occur for a particular infection depends on antibody isotype - True - => isotype switching “follows” type of pathogen Certainly, let's delve into the detailed explanation of the antibody functions mentioned, specifically focusing on isotype switching, opsonization and phagocytosis, and complement-dependent cytotoxicity: 1.Isotype Switching and Pathogen Specificity: 2.Isotype switching, also known as class switching, refers to the process by which B cells change the class of antibody they produce while retaining specificity for the same antigen. Different classes of antibodies, or isotypes, have distinct effector functions and are effective against different types of pathogens. For example: 1. IgM: Predominantly involved in the early stages of an immune response. It is effective against bacteria and viruses and is the first antibody produced during an infection. 2. IgG: Predominant in the blood and tissues, IgG antibodies provide longterm immunity against pathogens. They can cross the placenta to confer passive immunity to the fetus and are effective against bacteria, viruses, and toxins. 3. IgA: Predominantly found in mucosal secretions such as saliva, tears, and breast milk. IgA antibodies provide localized immunity at mucosal surfaces and protect against pathogens entering the body through these routes. 4 3. The choice of antibody isotype produced by B cells depends on the type of pathogen encountered. For example, IgA is more prevalent in mucosal areas, where pathogens commonly enter, while IgG is predominant in systemic circulation, providing broad protection against various pathogens. 4.Opsonization and Phagocytosis: 5.Opsonization is the process by which antibodies coat the surface of pathogens, marking them for recognition and ingestion by phagocytic cells such as macrophages and neutrophils. Antibodies bind to antigens on the surface of microbes through their Fab regions, while their Fc regions interact with Fc receptors on the surface of phagocytes. 1. Role of Fc Receptors: Phagocytic cells express Fc receptors that specifically bind to the Fc region of antibodies. This interaction triggers the engulfment of the opsonized pathogen by the phagocyte, leading to its degradation and clearance from the body. Fc receptors ensure that only antibody-bound pathogens are targeted for phagocytosis, enhancing the efficiency of the immune response. 6.Complement-Dependent Cytotoxicity: 7.The complement system is a group of proteins that work together to enhance the immune response. Complement proteins can bind to the Fc region of antibodies bound to pathogens, leading to the activation of the complement cascade. This cascade results in the formation of membrane attack complexes (MACs) on the surface of the pathogen, leading to cell lysis and destruction. 1. Role of Antibody Tagging: Antibodies act as tags that mark pathogens for complement activation. The binding of complement proteins to the Fc region of antibodies enhances the ability of complement proteins to recognize and target pathogens for destruction. Complement-dependent cytotoxicity amplifies the immune response and contributes to the clearance of pathogens from the body. In summary, antibody functions such as isotype switching, opsonization and phagocytosis, and complement-dependent cytotoxicity play crucial roles in the immune response against pathogens. These mechanisms ensure the efficient recognition, neutralization, and clearance of pathogens from the body, contributing to the overall effectiveness of humoral immunity in protecting against infections. 4 How do various leukocytes recognize antibody Fc regions? Through Fc receptors Þ Receptor promotes response that depends on: Antibody isotype Leukocyte type Best understood are Fcg receptors Vary in affinity Vary in IgG subclass specificity Most induce activation of leukocyte response ITAM = immunoreceptor tyrosine-based activation motifs ITIM =immunoreceptor tyrosine-based inhibitory motifs The recognition of antibody Fc regions by various leukocytes is mediated by Fc receptors (FcRs). These receptors promote immune responses that depend on the antibody isotype and the type of leukocyte involved. Here's a detailed explanation of the process, as described in your text: 1.Fc Receptors (FcRs): 2.Fc receptors are cell surface receptors expressed by various immune cells, including macrophages, neutrophils, dendritic cells, and NK cells. These receptors specifically bind to the Fc region of antibodies, allowing immune cells to recognize and respond to antibody-bound antigens. 1. Variety of Fc Receptors: There are several types of Fc receptors, each with distinct properties and functions. In the diagram provided, various Fc gamma receptors (FcγRs) are depicted. These receptors belong to the immunoglobulin (Ig) superfamily and possess Ig domains that enable them to bind to the Fc region of antibodies. 2. Diversity in Fc Receptors: Fc receptors vary in their affinity for antibody Fc regions, as well as their specificity for different IgG subclasses. This diversity allows for nuanced responses to different types of antibodies and antigens. 3.Role of Antibody Isotype: 5 1. Antibodies of different isotypes (e.g., IgG, IgM, IgA) elicit distinct immune responses and interact with specific Fc receptors on immune cells. 2. For example, Fc gamma receptors predominantly recognize IgG antibodies, while other Fc receptors may have specificity for IgM or IgA. 1.Leukocyte-Specific Responses: 1. Different leukocyte populations express specific Fc receptors, leading to cell type-specific responses to antibody-bound antigens. 2. For instance, macrophages and neutrophils express FcγRs, allowing them to phagocytose antibody-coated pathogens through opsonization. 2.Fc Receptor Signaling: 1. Upon binding to antibody Fc regions, Fc receptors initiate intracellular signaling pathways that modulate immune cell activation and function. 2. The immunoreceptor tyrosine-based activation motif (ITAM) is a common signaling motif found in the cytoplasmic domains of Fc receptors. Phosphorylation of ITAMs leads to the activation of downstream signaling cascades, resulting in cellular responses such as phagocytosis, cytokine production, or cytotoxicity. 3. Some Fc receptors may also contain immunoreceptor tyrosine-based inhibitory motifs (ITIMs) that dampen immune responses by inhibiting cell activation. 3.Functional Consequences: 1. Activation of Fc receptors typically leads to immune cell activation and effector functions, such as phagocytosis, antibody-dependent cellular cytotoxicity (ADCC), or cytokine release. 2. However, certain Fc receptors may also exert inhibitory effects, balancing immune responses to prevent excessive inflammation or tissue damage. In summary, Fc receptors play a crucial role in mediating immune responses to antibody-bound antigens. Through specific interactions with antibody Fc regions, Fc receptors modulate the activation and function of various leukocyte populations, contributing to the effective clearance of pathogens and maintenance of immune homeostasis. 5 6 Antibody-mediated opsonization & phagocytosis of microbes ROS / NO / hydrolytic enzymes IgG1 or IgG3 The process of opsonization and phagocytosis involves the recognition and ingestion of microbes by phagocytic cells, such as macrophages and neutrophils, facilitated by antibody binding. Here's a detailed explanation of this process, as described in your text: 1.Recognition of Microbes by Antibodies: 1. Antibodies, particularly IgG antibodies of the IgG1 or IgG3 subclasses, recognize and bind to specific antigens present on the surface of microbes. This binding event marks the microbe for recognition and ingestion by phagocytic cells. 2.Role of Phagocytic Cells: 1. Phagocytic cells, such as macrophages and neutrophils, play a crucial role in the innate immune response by engulfing and destroying pathogens through a process called phagocytosis. 2. These cells express a variety of receptors, including Fc receptors, pattern recognition receptors (PRRs), and others, allowing them to recognize and respond to microbial invaders. 3.Enhanced Phagocytosis through Opsonization: 1. While phagocytes have the innate ability to recognize and ingest 7 microbes, opsonization by antibodies significantly enhances this process. 2. When antibodies bind to microbes, they act as opsonins, increasing the efficiency and effectiveness of phagocytosis by promoting the attachment of phagocytes to the antibody-coated pathogens. 1.Fc Receptor-Mediated Phagocytosis: 1. Fc receptors (FcRs) expressed on the surface of phagocytes specifically bind to the Fc region of antibodies bound to microbes. 2. Binding of antibody-bound microbes to Fc receptors triggers intracellular signaling cascades, leading to the extension of the plasma membrane and engulfment of the microbe into a phagocytic vesicle called a phagosome. 2.Phagosome Maturation and Microbial Killing: 1. Once inside the phagocyte, the phagosome undergoes maturation, fusing with lysosomes to form a phagolysosome. 2. Within the phagolysosome, the microbe is exposed to a variety of antimicrobial substances, including reactive oxygen species (ROS), nitric oxide (NO), and hydrolytic enzymes. 3. These antimicrobial substances serve to kill and degrade the ingested microbe, ultimately eliminating it from the body. 3.Integration of Adaptive and Innate Immune Responses: 1. Opsonization and phagocytosis represent an interaction between components of the adaptive immune system (antibodies) and the innate immune system (phagocytes). 2. This collaboration enhances the efficiency of immune responses by leveraging the specificity of antibodies to target pathogens and the phagocytic capabilities of innate immune cells to eliminate them. In summary, opsonization and phagocytosis involve the recognition and ingestion of microbes by phagocytic cells, facilitated by antibody binding to microbial antigens. This process enhances the efficiency of immune responses by promoting the attachment and engulfment of pathogens by phagocytes, ultimately leading to their destruction and clearance from the body. 7 Antibody-dependent cell mediated cytotoxicity (ADCC) Virus-infected cell (or cancer cell) Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) is a mechanism of immune defense in which antibodies bind to target cells, marking them for destruction by immune cells, particularly natural killer (NK) cells. Here's a detailed explanation of ADCC, as described in your text: 1.Overview of ADCC: 1. Antibody-dependent cell-mediated cytotoxicity (ADCC) is a process by which immune cells, particularly natural killer (NK) cells, recognize and kill target cells that are coated with specific antibodies. 2. This mechanism is important for eliminating virus-infected cells, cancer cells, and other target cells that express surface antigens recognized by antibodies. 2.Antibody Coating of Target Cells: 1. ADCC begins with the binding of antibodies to surface antigens on target cells. These antibodies coat the surface of infected or cancerous cells, marking them for recognition and destruction by immune cells. 2. The antibodies used in ADCC are typically of the IgG class, although other antibody isotypes may also be involved. 8 3. Role of Natural Killer (NK) Cells: 1. NK cells are a type of lymphocyte that plays a crucial role in innate immunity. They are capable of recognizing and killing abnormal cells, including virus-infected cells and cancer cells. 2. NK cells express Fc receptors (FcRs) on their surface, which specifically bind to the Fc region of antibodies attached to target cells. 4.Triggering of NK Cell Activation: 1. When FcRs on NK cells bind to the Fc region of antibodies on the surface of target cells, it triggers NK cell activation and cytotoxicity. 2. This binding event stimulates the release of perforin and granzymes from the NK cell. 5.Mechanism of Target Cell Killing: 1. Perforin is a protein that forms pores in the target cell membrane, allowing entry of granzymes into the target cell. 2. Granzymes are proteases that induce apoptosis (programmed cell death) in the target cell by cleaving intracellular substrates. 3. The perforin-granzyme pathway ultimately leads to the destruction of the antibody-coated target cell, effectively eliminating it from the body. 6.Specificity and Efficiency of ADCC: 1. ADCC provides a highly specific mechanism for targeting and eliminating abnormal cells that express specific surface antigens recognized by antibodies. 2. This process allows for the efficient clearance of virus-infected cells and cancer cells from the body, contributing to immune surveillance and defense against infections and malignancies. In summary, ADCC is a mechanism of immune defense in which antibodies bind to target cells, marking them for recognition and destruction by natural killer (NK) cells. Through the release of perforin and granzymes, NK cells induce apoptosis in antibody-coated target cells, leading to their elimination from the body. ADCC provides an important mechanism for immune surveillance and defense against infections and cancer. 8 Which of the following cells also used perforins and granzymes to kill target cells? A. Neutrophils B. CTLs C. Eosinophils D. Macrophages CYTOTOXIC T lymphocytes 9 Features of Complement Consists of various serum and cell-surface proteins Complement proteins are only activated / interact under particular conditions Amplification Activated by microbes and antibodies attached to microbes* Activation involves sequential proteolysis of proteins to generate enzymes with proteolytic activity Products become active and covalently attach to microbial cell surfaces* Byproducts of complement activation stimulate inflammatory reactions to help eliminate pathogens Activation inhibited by regulatory proteins present on normal host cells and absent from microbes The complement system is a group of serum and cell-surface proteins that play a crucial role in the immune response against pathogens. Here's a detailed explanation of the features of complement and its activation process, as described in your text: 1.Composition of Complement: 1. Complement consists of various proteins found in serum (the liquid component of blood) and on the surface of certain cells. These proteins are synthesized by various cells in the body, including hepatocytes in the liver and immune cells. 2. The complement system includes multiple proteins, such as C1 to C9, factor B, factor D, and regulatory proteins like decay-accelerating factor (DAF) and membrane cofactor protein (MCP). 2.Activation Under Specific Conditions: 1. Complement proteins are only activated and interact under particular conditions, typically in response to the presence of microbes or antibodies bound to microbes. 2. Activation of complement is tightly regulated to prevent inappropriate activation and damage to host cells. It occurs only when necessary to eliminate pathogens. 3.Proteolytic Cascade Activation: 10 1. The activation of complement involves a proteolytic cascade, where sequential proteolysis of complement proteins leads to the generation of active enzymes with proteolytic activity. 2. This cascade amplifies the complement response, as each activated component triggers the activation of downstream components, resulting in a cascade effect. 1.Covalent Attachment to Microbial Surfaces: 1. The products of complement activation, including active enzymes, become covalently attached to the surfaces of microbial cells. 2. This covalent attachment targets the complement-mediated response specifically to the microbial surface, facilitating the destruction of pathogens while minimizing damage to host tissues. 2.Induction of Inflammatory Reactions: 1. Alongside the direct killing of pathogens, complement activation byproducts stimulate inflammatory reactions. 2. These reactions involve the activation of immune cells, such as macrophages and neutrophils, leading to the production of cytokines and chemokines that recruit additional immune cells to the site of infection. 3.Regulation of Activation: 1. Activation of complement is tightly regulated by various regulatory proteins present on normal host cells. 2. These regulatory proteins prevent excessive complement activation and protect host cells from complement-mediated damage. They include decay-accelerating factor (DAF), membrane cofactor protein (MCP), and others. In summary, the complement system plays a critical role in the immune response by recognizing and eliminating pathogens. Activation of complement involves a proteolytic cascade that leads to the covalent attachment of complement proteins to microbial surfaces and the induction of inflammatory reactions. However, complement activation is tightly regulated to prevent damage to host cells, with regulatory proteins ensuring that complement is only activated under appropriate conditions and is properly controlled to maintain immune homeostasis. 10 Complement activation depends on a proteolytic cascade IgG or IgM Signal amplification Complement activation relies on a proteolytic cascade involving sequential cleavage of complement proteins, leading to various effector functions. Here's a detailed explanation of complement activation and its consequences: 1.Recognition and Initiation of Complement Activation: 1. Complement activation can be initiated through three main pathways: the classical pathway, the lectin pathway, and the alternative pathway. 2. In the classical pathway, complement activation is triggered by the binding of C1 complex (composed of C1q, C1r, and C1s) to antigenantibody complexes, primarily IgM or IgG antibodies, bound to the surface of pathogens. In the lectin pathway, complement activation is initiated by the binding of mannose-binding lectin (MBL) or ficolins to microbial carbohydrates, such as mannose, on the surface of pathogens. In the alternative pathway, complement activation can be initiated spontaneously by the hydrolysis of C3. 2.Activation of C3: 1. Regardless of the pathway, complement activation converges on the cleavage and activation of C3, a central component of the complement cascade. 2. When C3 is cleaved by proteases, it generates two fragments: C3a and 11 C3b. C3a is an anaphylatoxin that promotes inflammation by stimulating the release of histamine and other inflammatory mediators. C3b, on the other hand, plays a critical role in opsonization and phagocytosis. 3. Opsonization and Phagocytosis: 1. C3b binds covalently to the surface of pathogens, serving as an opsonin that enhances phagocytosis by phagocytic cells, such as macrophages and neutrophils. 2. The deposition of C3b on the surface of pathogens facilitates their recognition and engulfment by phagocytic cells, leading to their clearance from the body. 4.Amplification of Complement Activation: 1. The cleavage of C3 not only initiates opsonization and inflammation but also amplifies the complement cascade. 2. C3b can participate in the formation of the C5 convertase complex, which cleaves C5 into C5a and C5b. This step further amplifies the complement response and leads to the generation of the membrane attack complex (MAC). 5.Formation of the Membrane Attack Complex (MAC): 1. C5b, along with other complement proteins, forms the C5b-C9 complex, also known as the membrane attack complex (MAC). 2. The MAC inserts into the lipid bilayer of target cells, creating pores that disrupt the cell membrane integrity and ultimately lead to cell lysis and death. This process is crucial for eliminating pathogens, particularly bacteria. 6.Inflammatory Response: 1. Throughout complement activation, the release of complement fragments such as C3a and C5a promotes inflammation by recruiting and activating immune cells, stimulating the release of inflammatory mediators, and enhancing vascular permeability. 2. This inflammatory response helps to amplify the immune response, recruit additional immune cells to the site of infection, and facilitate the clearance of pathogens. In summary, complement activation involves a proteolytic cascade that leads to opsonization, inflammation, and the formation of the membrane attack complex (MAC), ultimately contributing to the elimination of pathogens. The process is tightly regulated to prevent excessive activation and damage to host tissues, with complement playing a crucial role in innate immunity and host defense against infections. 11 Functions of complement (1) Activating signals neutrophils and macrophages The function of complement in opsonization and phagocytosis is crucial for the immune system's ability to recognize and eliminate pathogens. Here's a detailed explanation of this process: 1.Opsonization: 1. Opsonization refers to the process by which pathogens are tagged for recognition and ingestion by phagocytic cells, such as macrophages and neutrophils. 2. Complement proteins, particularly C3b, play a central role in opsonization. When C3 is cleaved during complement activation, C3b is generated. C3b can covalently bind to the surface of pathogens, marking them for phagocytosis. 2.Covalent Attachment to Microbes: 1. C3b binds to specific molecular patterns on the surface of microbes, such as bacterial cell wall components or viral glycoproteins. This covalent attachment effectively labels the microbes as targets for phagocytosis. 2. The binding of C3b to microbial surfaces enhances the recognition and engulfment of pathogens by phagocytic cells. It serves as an opsonin, facilitating the interaction between pathogens and phagocytes. 3.Phagocytosis: 12 1. Phagocytic cells, including neutrophils and macrophages, express receptors for complement components, such as the receptor for C3b (CR1 or CD35). 2. Upon binding of C3b-coated pathogens to these receptors, phagocytic cells initiate the process of phagocytosis. They extend pseudopods to engulf the opsonized microbe, forming a phagosome. 3. Inside the phagosome, the microbe is enclosed within a vesicle, where it is subjected to antimicrobial mechanisms aimed at its destruction. 1.Microbial Killing: 1. Once engulfed, the phagosome containing the microbe fuses with lysosomes, forming a phagolysosome. Within the phagolysosome, the microbe is exposed to an array of antimicrobial agents. 2. Phagocytes produce reactive oxygen species (ROS), such as superoxide radicals and hydrogen peroxide, which exert oxidative damage on the microbe's cellular components. 3. Additionally, phagocytes release antimicrobial peptides and enzymes, including lysozyme and proteases, which degrade the microbial cell wall and intracellular components. 2.Signal Transduction and Activation: 1. Binding of C3b-coated pathogens to phagocytic receptors triggers signal transduction pathways within the phagocyte. 2. These signaling events lead to cytoskeletal rearrangements, membrane extensions, and engulfment of the microbe. Moreover, they stimulate the production of pro-inflammatory cytokines and chemokines, contributing to the recruitment and activation of additional immune cells to the site of infection. In summary, complement-mediated opsonization and phagocytosis play a vital role in the innate immune response against pathogens. By tagging microbes for recognition and ingestion by phagocytes, complement enhances the efficiency of the immune system's ability to eliminate infections. The process involves a series of coordinated events, from covalent attachment of complement proteins to microbial surfaces to the activation of phagocytic cells and subsequent microbial killing within phagolysosomes. 12