This document provides an overview of the complement system submitted by five MSc students to their professor. It describes that complement was first discovered in 1890 and plays a major role in innate immunity through lysis of cells, opsonization, and inflammation. It summarizes the three pathways of complement activation (classical, lectin, and alternative), components and regulation of the complement system, and consequences of complement activation including cell lysis, inflammation, opsonization, viral neutralization, and solubilization of immune complexes.
The complement system was discovered in 1894 and consists of over 30 proteins that contribute to the innate immune system. It has 3 major pathways of activation: the classical pathway activated by antibody-antigen binding, the alternative pathway activated by microbial surfaces independently of antibody, and the lectin pathway activated by mannose-binding lectin binding to pathogens. The complement system carries out important immune functions like opsonization to enhance phagocytosis, inflammation, lysis of foreign cells, and clearance of immune complexes.
This document summarizes the complement pathway. It discusses the history and components of the complement system. There are three complement activation pathways: the classical pathway which is antibody-dependent, the lectin pathway which is activated by mannan-binding lectin, and the alternative pathway which is antibody-independent. All three pathways lead to the formation of the membrane attack complex which forms pores in cell membranes to lyse bacteria and viruses. The complement system is important for both innate and adaptive immunity but must be tightly regulated to prevent damage to host cells. Deficiencies can increase susceptibility to certain infections. Complement also plays a role in the inflammatory response to COVID-19.
The complement system consists of over 30 serum and cell surface proteins that play a key role in both innate and adaptive immunity. It can be activated through three pathways - the classical pathway triggered by antigen-antibody complexes, the lectin pathway activated by mannose-binding lectin, and the alternative pathway activated spontaneously by microbial surfaces. All three pathways converge on the formation of C3 and C5 convertases that activate downstream components, ultimately forming the membrane attack complex to lyse microbial cells. The complement system functions to opsonize pathogens, induce chemotaxis, activate the inflammatory response, and aid in immune clearance.
The complement system is a group of proteins in the blood that helps antibodies and phagocytic cells destroy pathogens. It is activated via three pathways - classical, lectin, and alternative. Activation leads to a cascade of reactions that results in the formation of the membrane attack complex, which punches holes in the pathogen's cell membrane, killing it. Complement also aids in inflammation, phagocytosis, and immune adherence. The system is tightly regulated to prevent damage to host cells. Deficiencies can cause diseases like hereditary angioedema.
The classical pathway of complement activation begins with the formation of antigen-antibody complexes that induce conformational changes in IgM or IgG antibodies, exposing a binding site for the C1 complex. C1 complex consists of C1q and C1r and C1s molecules. Binding of C1q to the antibody causes C1r to activate C1s as a protease. C1s then cleaves C4 and C2, forming the C3 convertase C4b2a that cleaves C3 into C3a and C3b. C3b binds to C4b2a to form the C5 convertase that cleaves C5, initiating formation of the membrane attack complex.
This document discusses B lymphocytes and their generation, differentiation, and maturation. It contains the following key points:
- B lymphocytes comprise 30% of circulating lymphocytes and about 1 billion are produced daily in the bone marrow.
- B cell development starts from hematopoietic stem cells and involves gene rearrangements leading through various stages from pro-B cells to immature B cells.
- Maturation can occur independently in the bone marrow or depend on antigen exposure in the periphery, leading to plasma cells and memory B cells. Class switching allows expression of different antibody classes.
- Activation can occur through T cell dependent or independent pathways, influencing the strength and type of antibody response.
The complement system consists of three pathways - the classical, lectin, and alternative pathways. The lectin pathway is activated when mannose-binding lectin (MBL) binds to mannose sugars on microbial surfaces. This binding activates MASP-1 and MASP-2, analogous to C1r and C1s in the classical pathway. MASP-1 and MASP-2 then cleave C4 and C2 to form the C3 convertase, which activates the remainder of the complement cascade. The lectin pathway thus provides an antibody-independent mechanism for complement activation in response to microbial pathogens.
The complement system was discovered in 1894 and consists of over 30 proteins that contribute to the innate immune system. It has 3 major pathways of activation: the classical pathway activated by antibody-antigen binding, the alternative pathway activated by microbial surfaces independently of antibody, and the lectin pathway activated by mannose-binding lectin binding to pathogens. The complement system carries out important immune functions like opsonization to enhance phagocytosis, inflammation, lysis of foreign cells, and clearance of immune complexes.
This document summarizes the complement pathway. It discusses the history and components of the complement system. There are three complement activation pathways: the classical pathway which is antibody-dependent, the lectin pathway which is activated by mannan-binding lectin, and the alternative pathway which is antibody-independent. All three pathways lead to the formation of the membrane attack complex which forms pores in cell membranes to lyse bacteria and viruses. The complement system is important for both innate and adaptive immunity but must be tightly regulated to prevent damage to host cells. Deficiencies can increase susceptibility to certain infections. Complement also plays a role in the inflammatory response to COVID-19.
The complement system consists of over 30 serum and cell surface proteins that play a key role in both innate and adaptive immunity. It can be activated through three pathways - the classical pathway triggered by antigen-antibody complexes, the lectin pathway activated by mannose-binding lectin, and the alternative pathway activated spontaneously by microbial surfaces. All three pathways converge on the formation of C3 and C5 convertases that activate downstream components, ultimately forming the membrane attack complex to lyse microbial cells. The complement system functions to opsonize pathogens, induce chemotaxis, activate the inflammatory response, and aid in immune clearance.
The complement system is a group of proteins in the blood that helps antibodies and phagocytic cells destroy pathogens. It is activated via three pathways - classical, lectin, and alternative. Activation leads to a cascade of reactions that results in the formation of the membrane attack complex, which punches holes in the pathogen's cell membrane, killing it. Complement also aids in inflammation, phagocytosis, and immune adherence. The system is tightly regulated to prevent damage to host cells. Deficiencies can cause diseases like hereditary angioedema.
The classical pathway of complement activation begins with the formation of antigen-antibody complexes that induce conformational changes in IgM or IgG antibodies, exposing a binding site for the C1 complex. C1 complex consists of C1q and C1r and C1s molecules. Binding of C1q to the antibody causes C1r to activate C1s as a protease. C1s then cleaves C4 and C2, forming the C3 convertase C4b2a that cleaves C3 into C3a and C3b. C3b binds to C4b2a to form the C5 convertase that cleaves C5, initiating formation of the membrane attack complex.
This document discusses B lymphocytes and their generation, differentiation, and maturation. It contains the following key points:
- B lymphocytes comprise 30% of circulating lymphocytes and about 1 billion are produced daily in the bone marrow.
- B cell development starts from hematopoietic stem cells and involves gene rearrangements leading through various stages from pro-B cells to immature B cells.
- Maturation can occur independently in the bone marrow or depend on antigen exposure in the periphery, leading to plasma cells and memory B cells. Class switching allows expression of different antibody classes.
- Activation can occur through T cell dependent or independent pathways, influencing the strength and type of antibody response.
The complement system consists of three pathways - the classical, lectin, and alternative pathways. The lectin pathway is activated when mannose-binding lectin (MBL) binds to mannose sugars on microbial surfaces. This binding activates MASP-1 and MASP-2, analogous to C1r and C1s in the classical pathway. MASP-1 and MASP-2 then cleave C4 and C2 to form the C3 convertase, which activates the remainder of the complement cascade. The lectin pathway thus provides an antibody-independent mechanism for complement activation in response to microbial pathogens.
T CELL ACTIVATION AND IT'S TERMINATIONpremvarma064
T cell activation requires two signals: 1) recognition of antigens displayed on antigen-presenting cells by T cell receptors and 2) co-stimulatory signals through molecules like CD28. This leads T cells to proliferate, differentiate into effector and memory cells, and perform effector functions. Proper activation requires interaction between T cells and antigen-presenting cells in lymphoid tissues, where costimulatory molecules are highly expressed. Dysregulation of T cell activation can lead to autoimmunity or susceptibility to infection.
The document summarizes key aspects of the complement system. It describes the three complement activation pathways - classical, lectin, and alternative. It explains the proteins involved in each pathway and their roles. The classical pathway is activated by antibody binding, while the alternative pathway is antibody-independent and acts as part of innate immunity. Complement activation results in the formation of the membrane attack complex that can lyse target cells.
Defective tolerance or regulation of self-reactive lymphocytes is the underlying cause of all autoimmune diseases. There are four known mechanisms that can lead to this regulatory failure: negative selection of autoreactive cells in the thymus, insufficient numbers or function of regulatory T cells, defective apoptosis of mature autoreactive lymphocytes, and inadequate inhibitory signaling through receptors on lymphocytes. Genetic factors like polymorphisms in MHC and non-MHC genes interact with environmental triggers like infections and tissue damage to induce the immunological abnormalities that result in autoimmunity. Molecular mimicry and bystander activation during infections can cause cross-reactivity between foreign and self-antigens.
Describes the complement system components and their activation pathways, the regulation of the complement
system, the effector functions of various complement components,
and the consequences of deficiencies in them.
B-cells develop and mature in the bone marrow from stem cells through distinct stages marked by specific cell surface markers and patterns of immunoglobulin gene expression. Mature B-cells leave the bone marrow and travel to peripheral lymphoid tissues where they are activated upon encountering antigen to produce plasma cells that secrete antibodies and memory B-cells. B-cell activation involves proliferation, somatic hypermutation, selection, and potential class switching in germinal centers to produce high affinity antibodies and long-lasting immunological memory. This allows for a rapid secondary immune response upon re-exposure to the same antigen.
1. Humoral immunity is mediated by antibodies that are secreted and perform effector functions at distant sites from their production. Antibodies neutralize microbes and microbial toxins.
2. The complement system assists antibodies in lysing bacteria. It involves a cascade of proteins that are activated sequentially and amplify the immune response. Activation can occur via the classical, lectin, or alternative pathways.
3. The classical pathway is initiated by the binding of the C1 complex to antibodies bound to pathogens. This activates a protease cascade leading to formation of the membrane attack complex that lyses microbes. The lectin pathway uses mannose-binding lectin and ficolins instead of antibodies. The alternative pathway is antibody
B cell development begins with stem cells in the bone marrow that undergo VDJ recombination and rearrangement of immunoglobulin genes. B cells that produce a functional antibody are selected to mature, while those that bind self-antigens undergo deletion or anergy. Mature naive B cells circulate until they encounter antigen, then proliferate and differentiate into either plasma cells that secrete antibody or memory B cells that mount a stronger secondary response. This process ensures B cells produce a diverse repertoire of antibodies while avoiding autoimmunity.
The humoral immune response involves B cells differentiating into plasma cells upon activation by antigens presented by antigen presenting cells like macrophages and dendritic cells. Plasma cells produce antibodies that function to neutralize pathogens and toxins, enhance phagocytosis through opsonization and complement activation, and induce inflammation. Antibodies are Y-shaped proteins composed of two light chains and two heavy chains that confer antigen specificity through variable regions and determine the antibody class through constant regions. The five major antibody classes in humans are IgM, IgD, IgG, IgE, and IgA, which have different structures and roles in immune protection.
The document summarizes the complement system. It is part of the immune system and consists of proteins that interact in a regulated cascade to eliminate pathogens and damaged cells. There are over 20 complement proteins that are activated via the classical, alternative, or lectin pathways and work in both innate and adaptive immunity. The complement system opsonizes pathogens, causes cell lysis, promotes inflammation, and clearance of immune complexes. Deficiencies or dysregulation of complements can cause diseases.
Slideshow is from the University of Michigan Medical
School's M1 Immunology sequence
View additional course materials on Open.Michigan:
openmi.ch/med-M1Immunology
The complement system is a group of serum proteins that participate in the innate and adaptive immune response. It is activated via three pathways: the classical, alternative, and lectin pathways. The complement system helps destroy invading microorganisms through the membrane attack complex, which forms pores in target cells leading to cell lysis. It also contributes to inflammation, opsonization of pathogens for phagocytosis, viral neutralization, and clearance of immune complexes.
Bcell activation , differentiation and memory AkshitaMengi12
This document discusses B cell activation, differentiation, and memory. It defines B cells as lymphocytes involved in humoral immunity that develop in the bone marrow and express B cell receptors on their surface. Upon activation in secondary lymphoid organs by antigen binding, B cells can differentiate into plasma cells that secrete antibodies or memory B cells. Differentiation requires T cell-dependent or T cell-independent activation pathways and involves biochemical signaling events. The document also describes the various cell types that B cells can differentiate into and the role of memory B cells in recall responses.
When a pathogen enters the body, it’s confronted by elements of the innate immune system, which constitute the first line of defense.
Once breached, the adaptive response takes over, but it typically takes few days to be effective.
Immunity is the processes that occur to defend the body against foreign organisms or molecules.
Immunity includes:
Inflammation.
Complement activation.
Phagocytosis.
Antibody synthesis.
Effector T lymphocytes.
The complement system is a part of the immune system that helps or complements the ability of antibodies and phagocytic cells to clear pathogens from an organism. It is part of the innate immune system, which is not adaptable and does not change over the course of an individual's lifetime.
consists of three pathways: 1. alternative
2. classical
3. lectin pathway
The document discusses the complement system, which consists of over 30 proteins produced by the liver that function in the immune system but are not antibodies. It works as a cascade system where one activation triggers another in a chain reaction. Complement activation can lead to cell lysis and generation of inflammatory substances. It plays a role in defense against bacteria and in inflammatory and autoimmune diseases. There are three complement activation pathways: classical, alternative, and lectin. The classical pathway is antibody-dependent while the alternative and lectin pathways are antibody-independent. Complement activation results in opsonization, inflammation, clearance of immune complexes, and lysis of pathogen cells.
This document provides an overview of the immune response and immune system. It describes the mechanisms of innate immunity including anatomical, physiological, cellular, and inflammatory barriers that provide non-specific protection. Adaptive immunity is induced when innate immunity fails, and has antigen specificity and immunological memory. B and T lymphocytes mediate humoral and cell-mediated immunity respectively. The process of phagocytosis and antibody production are explained. Primary and secondary immune responses differ in lag period, magnitude, and antibody class. Innate and adaptive immunity cooperate to eliminate pathogens.
B lymphocytes differentiate into plasma cells that secrete antibodies. The development of mature B cells from pre-B cells occurs independently of antigens. However, the activation of B cells into plasma cells that produce antibodies is dependent on antigens. Mature B cells have surface receptors that allow specific antigens to bind to them, which then causes the B cells to differentiate into plasma cells that secrete antibodies with the same specificity. T helper cells are involved in the process of antibody class switching by B cells. In addition to antibody production, B cells also function as antigen presenting cells.
Dr. Prem Mohan Jha presented on complement physiology. The complement system is part of the innate immune system and helps antibodies clear pathogens. It involves a biochemical cascade that is activated via three pathways: classical, lectin, and alternative. Complement activation leads to the formation of the membrane attack complex (MAC) which lyses cells. The complement system is tightly regulated to prevent damage to host cells. Deficiencies in complement components or regulators result in increased susceptibility to infections.
The T cell receptor signaling pathway involves T cells binding antigens presented by MHC proteins on antigen presenting cells. When the T cell receptor binds to its antigen, it activates the kinase Lck which phosphorylates proteins in the CD3 complex. This leads to phosphorylation of the adapter protein ZAP70 which then phosphorylates LAT and SLP76, recruiting downstream molecules. This results in calcium release, NFAT and NF-κB activation, and expression of cytokines and other proteins through similar pathways as in B cell signaling, including the Ras pathway. T cell signaling also regulates adhesion molecules and chemokines to influence T cell localization.
The document discusses the complement system, which consists of over 20 proteins that play a key role in the immune system. There are three complement activation pathways: the classical pathway, which is initiated by the binding of antibodies to antigens; the lectin pathway, which is initiated when mannose-binding lectin binds to pathogens; and the alternative pathway, which is spontaneously activated by pathogens. All three pathways result in the formation of the membrane attack complex that causes lysis of pathogens. The complement system enhances phagocytosis, causes inflammation, and lyses cells through its activation cascade and production of factors such as C3a and C5a.
The complement system is a collection of circulating and cell membrane proteins that play important roles in host defense against microbes and in antibody mediated tissue injury. It has three major pathways of activation - the classical, alternative, and lectin pathways. Activation leads to the generation of effector molecules that help eliminate microbes through lysis, opsonization, and inflammation. Deficiencies in complement components increase susceptibility to certain bacterial and viral infections as well as immune complex diseases.
T CELL ACTIVATION AND IT'S TERMINATIONpremvarma064
T cell activation requires two signals: 1) recognition of antigens displayed on antigen-presenting cells by T cell receptors and 2) co-stimulatory signals through molecules like CD28. This leads T cells to proliferate, differentiate into effector and memory cells, and perform effector functions. Proper activation requires interaction between T cells and antigen-presenting cells in lymphoid tissues, where costimulatory molecules are highly expressed. Dysregulation of T cell activation can lead to autoimmunity or susceptibility to infection.
The document summarizes key aspects of the complement system. It describes the three complement activation pathways - classical, lectin, and alternative. It explains the proteins involved in each pathway and their roles. The classical pathway is activated by antibody binding, while the alternative pathway is antibody-independent and acts as part of innate immunity. Complement activation results in the formation of the membrane attack complex that can lyse target cells.
Defective tolerance or regulation of self-reactive lymphocytes is the underlying cause of all autoimmune diseases. There are four known mechanisms that can lead to this regulatory failure: negative selection of autoreactive cells in the thymus, insufficient numbers or function of regulatory T cells, defective apoptosis of mature autoreactive lymphocytes, and inadequate inhibitory signaling through receptors on lymphocytes. Genetic factors like polymorphisms in MHC and non-MHC genes interact with environmental triggers like infections and tissue damage to induce the immunological abnormalities that result in autoimmunity. Molecular mimicry and bystander activation during infections can cause cross-reactivity between foreign and self-antigens.
Describes the complement system components and their activation pathways, the regulation of the complement
system, the effector functions of various complement components,
and the consequences of deficiencies in them.
B-cells develop and mature in the bone marrow from stem cells through distinct stages marked by specific cell surface markers and patterns of immunoglobulin gene expression. Mature B-cells leave the bone marrow and travel to peripheral lymphoid tissues where they are activated upon encountering antigen to produce plasma cells that secrete antibodies and memory B-cells. B-cell activation involves proliferation, somatic hypermutation, selection, and potential class switching in germinal centers to produce high affinity antibodies and long-lasting immunological memory. This allows for a rapid secondary immune response upon re-exposure to the same antigen.
1. Humoral immunity is mediated by antibodies that are secreted and perform effector functions at distant sites from their production. Antibodies neutralize microbes and microbial toxins.
2. The complement system assists antibodies in lysing bacteria. It involves a cascade of proteins that are activated sequentially and amplify the immune response. Activation can occur via the classical, lectin, or alternative pathways.
3. The classical pathway is initiated by the binding of the C1 complex to antibodies bound to pathogens. This activates a protease cascade leading to formation of the membrane attack complex that lyses microbes. The lectin pathway uses mannose-binding lectin and ficolins instead of antibodies. The alternative pathway is antibody
B cell development begins with stem cells in the bone marrow that undergo VDJ recombination and rearrangement of immunoglobulin genes. B cells that produce a functional antibody are selected to mature, while those that bind self-antigens undergo deletion or anergy. Mature naive B cells circulate until they encounter antigen, then proliferate and differentiate into either plasma cells that secrete antibody or memory B cells that mount a stronger secondary response. This process ensures B cells produce a diverse repertoire of antibodies while avoiding autoimmunity.
The humoral immune response involves B cells differentiating into plasma cells upon activation by antigens presented by antigen presenting cells like macrophages and dendritic cells. Plasma cells produce antibodies that function to neutralize pathogens and toxins, enhance phagocytosis through opsonization and complement activation, and induce inflammation. Antibodies are Y-shaped proteins composed of two light chains and two heavy chains that confer antigen specificity through variable regions and determine the antibody class through constant regions. The five major antibody classes in humans are IgM, IgD, IgG, IgE, and IgA, which have different structures and roles in immune protection.
The document summarizes the complement system. It is part of the immune system and consists of proteins that interact in a regulated cascade to eliminate pathogens and damaged cells. There are over 20 complement proteins that are activated via the classical, alternative, or lectin pathways and work in both innate and adaptive immunity. The complement system opsonizes pathogens, causes cell lysis, promotes inflammation, and clearance of immune complexes. Deficiencies or dysregulation of complements can cause diseases.
Slideshow is from the University of Michigan Medical
School's M1 Immunology sequence
View additional course materials on Open.Michigan:
openmi.ch/med-M1Immunology
The complement system is a group of serum proteins that participate in the innate and adaptive immune response. It is activated via three pathways: the classical, alternative, and lectin pathways. The complement system helps destroy invading microorganisms through the membrane attack complex, which forms pores in target cells leading to cell lysis. It also contributes to inflammation, opsonization of pathogens for phagocytosis, viral neutralization, and clearance of immune complexes.
Bcell activation , differentiation and memory AkshitaMengi12
This document discusses B cell activation, differentiation, and memory. It defines B cells as lymphocytes involved in humoral immunity that develop in the bone marrow and express B cell receptors on their surface. Upon activation in secondary lymphoid organs by antigen binding, B cells can differentiate into plasma cells that secrete antibodies or memory B cells. Differentiation requires T cell-dependent or T cell-independent activation pathways and involves biochemical signaling events. The document also describes the various cell types that B cells can differentiate into and the role of memory B cells in recall responses.
When a pathogen enters the body, it’s confronted by elements of the innate immune system, which constitute the first line of defense.
Once breached, the adaptive response takes over, but it typically takes few days to be effective.
Immunity is the processes that occur to defend the body against foreign organisms or molecules.
Immunity includes:
Inflammation.
Complement activation.
Phagocytosis.
Antibody synthesis.
Effector T lymphocytes.
The complement system is a part of the immune system that helps or complements the ability of antibodies and phagocytic cells to clear pathogens from an organism. It is part of the innate immune system, which is not adaptable and does not change over the course of an individual's lifetime.
consists of three pathways: 1. alternative
2. classical
3. lectin pathway
The document discusses the complement system, which consists of over 30 proteins produced by the liver that function in the immune system but are not antibodies. It works as a cascade system where one activation triggers another in a chain reaction. Complement activation can lead to cell lysis and generation of inflammatory substances. It plays a role in defense against bacteria and in inflammatory and autoimmune diseases. There are three complement activation pathways: classical, alternative, and lectin. The classical pathway is antibody-dependent while the alternative and lectin pathways are antibody-independent. Complement activation results in opsonization, inflammation, clearance of immune complexes, and lysis of pathogen cells.
This document provides an overview of the immune response and immune system. It describes the mechanisms of innate immunity including anatomical, physiological, cellular, and inflammatory barriers that provide non-specific protection. Adaptive immunity is induced when innate immunity fails, and has antigen specificity and immunological memory. B and T lymphocytes mediate humoral and cell-mediated immunity respectively. The process of phagocytosis and antibody production are explained. Primary and secondary immune responses differ in lag period, magnitude, and antibody class. Innate and adaptive immunity cooperate to eliminate pathogens.
B lymphocytes differentiate into plasma cells that secrete antibodies. The development of mature B cells from pre-B cells occurs independently of antigens. However, the activation of B cells into plasma cells that produce antibodies is dependent on antigens. Mature B cells have surface receptors that allow specific antigens to bind to them, which then causes the B cells to differentiate into plasma cells that secrete antibodies with the same specificity. T helper cells are involved in the process of antibody class switching by B cells. In addition to antibody production, B cells also function as antigen presenting cells.
Dr. Prem Mohan Jha presented on complement physiology. The complement system is part of the innate immune system and helps antibodies clear pathogens. It involves a biochemical cascade that is activated via three pathways: classical, lectin, and alternative. Complement activation leads to the formation of the membrane attack complex (MAC) which lyses cells. The complement system is tightly regulated to prevent damage to host cells. Deficiencies in complement components or regulators result in increased susceptibility to infections.
The T cell receptor signaling pathway involves T cells binding antigens presented by MHC proteins on antigen presenting cells. When the T cell receptor binds to its antigen, it activates the kinase Lck which phosphorylates proteins in the CD3 complex. This leads to phosphorylation of the adapter protein ZAP70 which then phosphorylates LAT and SLP76, recruiting downstream molecules. This results in calcium release, NFAT and NF-κB activation, and expression of cytokines and other proteins through similar pathways as in B cell signaling, including the Ras pathway. T cell signaling also regulates adhesion molecules and chemokines to influence T cell localization.
The document discusses the complement system, which consists of over 20 proteins that play a key role in the immune system. There are three complement activation pathways: the classical pathway, which is initiated by the binding of antibodies to antigens; the lectin pathway, which is initiated when mannose-binding lectin binds to pathogens; and the alternative pathway, which is spontaneously activated by pathogens. All three pathways result in the formation of the membrane attack complex that causes lysis of pathogens. The complement system enhances phagocytosis, causes inflammation, and lyses cells through its activation cascade and production of factors such as C3a and C5a.
The complement system is a collection of circulating and cell membrane proteins that play important roles in host defense against microbes and in antibody mediated tissue injury. It has three major pathways of activation - the classical, alternative, and lectin pathways. Activation leads to the generation of effector molecules that help eliminate microbes through lysis, opsonization, and inflammation. Deficiencies in complement components increase susceptibility to certain bacterial and viral infections as well as immune complex diseases.
The complement system consists of over 30 proteins that work together in three pathways - the classical, lectin, and alternative pathways - to help eliminate pathogens from the body. It enhances phagocytosis through opsonization, causes inflammation, and forms the membrane attack complex (MAC) to lyse bacteria. Complement is tightly regulated to prevent damage to host cells and serves as a bridge between innate and adaptive immunity. Deficiencies in complement proteins increase susceptibility to certain infections.
This presentation is organized with the help of other presentations, text book of immunology and some internet resources for better understanding of students.
The complement system consists of over 20 proteins that are part of the innate and adaptive immune system. There are three pathways of complement activation - the classical, lectin, and alternative pathways. All three pathways result in the formation of the membrane attack complex that causes cell lysis. The complement system functions to opsonize pathogens, induce inflammation, clear immune complexes, and lyse cells. It is tightly regulated to prevent damage to host cells. Deficiencies in specific complement proteins can increase susceptibility to certain pathogens.
The document describes the complement system, which is part of the innate immune system. It enhances antibody and phagocyte ability to opsonize pathogens and recruit immune cells. There are over 30 complement proteins involved in three pathways - classical, lectin, and alternative. The classical pathway is activated by antibody-antigen complexes and involves C1-C9. The lectin pathway involves mannose-binding lectin and MASPs. The alternative pathway does not require pathogen recognition. All three pathways converge in generating C3 convertase and forming the membrane attack complex to lyse cells. The functions and roles of complement proteins in the pathways are also outlined.
This presentation describes the Fish Complement system and different types of pathways involved and the mechanism behind the regulation of complement proteins. It gives a basic and a detailed explanation regarding the topic.
The document discusses the complement system, including:
1) Complement represents a group of serum proteins that augment immune responses when activated. They constitute about 5% of normal serum proteins and are synthesized mainly in the liver.
2) There are three complement pathways - classical, alternative, and lectin. The classical pathway is antibody-dependent while the alternative and lectin pathways are antibody-independent.
3) Complement activation occurs via cleavage of inactive zymogens into active fragments. This activation cascade leads to formation of the membrane attack complex (MAC) which causes target cell lysis.
This document provides information on complement, including:
- It defines complement and describes the classical, alternative, and lectin pathways.
- Complement proteins are synthesized in the liver as inactive zymogens and are activated by proteolysis, cleaving them into larger and smaller fragments.
- The pathways differ in their initiation but then follow identical later stages, forming C3 convertase, C5 convertase, and the membrane attack complex (MAC).
- Complement has roles in targeting cell lysis, inflammation, opsonization, immune complex removal, and viral neutralization. Microorganisms have evolved mechanisms to evade complement. Regulatory proteins tightly control complement activation. Deficiencies can increase disease susceptibility
The complement system comprises around 30 proteins that work together to help antibodies clear pathogens from the body. There are three complement pathways - classical, lectin, and alternative. They differ in their initiation mechanisms but later stages are similar. Activation produces fragments that opsonize pathogens, induce inflammation, lyse cells, and remove immune complexes. Complement activation enhances phagocytosis and the innate immune response.
There are three pathways of complement activation: the classical pathway, which is triggered directly by pathogen or indirectly by antibody binding to the pathogen surface; the MB-lectin pathway; and the alternative pathway, which also provides an amplification loop for the other two pathways
The complement system consists of over 30 proteins that circulate in the blood and tissues. It helps destroy harmful microbes via opsonization, phagocytosis, cytolysis, and inflammation. There are 3 major pathways - classical, lectin, and alternative - that are initiated by different mechanisms but all generate C3 and C5 convertases and the membrane attack complex (MAC). Complement proteins include initiators, enzymes, opsonins, anaphylatoxins, membrane attack components, receptors, and regulators. Together they help bridge the innate and adaptive immune responses.
Complement System comprises of Complement proteins that function to augment the antibodies in killing bacteria by the formation of Membrane Attack Complex.
This ppt describes the different pathways of activation complement proteins and MAC formation.
The document discusses several topics related to the complement system and immunoassays:
1) It describes the complement system as part of the immune system that enhances the ability of antibodies and phagocytes to clear pathogens. It is activated via three pathways: classical, lectin, and alternative.
2) It explains the processes of complement activation, including the formation of C3 and C5 convertases that cleave complement proteins and amplification of the response.
3) It discusses two types of immunoassays - radioimmunoassay (RIA) and immunofluorescence. RIA uses radioactive labels on antigens or antibodies to measure concentrations via competition binding assays. Immunofluorescence utilizes fluorescent-labeled antibodies to detect target antigens
The complement system is a biochemical cascade that facilitates clearance of pathogens. It consists of over 30 plasma and cell surface proteins that are activated through three pathways - classical, lectin, and alternative. Complement activation results in opsonization, anaphylatoxin production, and direct killing of pathogens. The system is tightly regulated to prevent damage to host cells through inhibitors and cell surface regulators.
The complement system consists of over 30 proteins that work together to eliminate pathogens from the blood and tissues. There are three pathways of complement activation - the classical, lectin, and alternative pathways. They all converge on generating C3 and C5 convertases that cleave C3 and C5, producing fragments that opsonize pathogens, induce inflammation, and form the membrane attack complex to kill pathogens. The classical pathway is initiated by antibody binding, while the lectin pathway uses mannose-binding lectin and ficolins that recognize carbohydrates on microbes. Both result in the same C3 and C5 convertases. The alternative pathway is antibody-independent and activates via C3 hydrolysis.
The complement system is part of the innate immune system and consists of over 30 proteins. It was originally identified in the 1890s by Jules Bordet and Paul Ehrlich as a heat-labile component of serum that enhanced the ability of antibodies to kill bacteria. There are three complement activation pathways: the classical pathway which is initiated by antibody-antigen complexes, the lectin pathway which is activated by mannose-binding lectin, and the alternative pathway which is spontaneously activated by microbial surfaces. Complement activation results in opsonization, inflammation, and formation of the membrane attack complex to kill microbes. Deficiencies in specific complement components can increase susceptibility to certain infections.
The document discusses the complement system of teleost fish. It has three pathways - the classical pathway, lectin pathway, and alternative pathway. All three pathways involve a cascade of complement components that ultimately lead to the formation of the membrane attack complex (MAC) on pathogen surfaces. The MAC forms pores that lyse pathogens. The complement system also opsonizes pathogens and generates inflammatory peptides like C3a and C5a. Strict regulation is needed to prevent damage to host cells, mediated by factors such as C1 inhibitor, factor H, decay accelerating factor, and CD59.
Similar to The complement system in immunology (20)
The tumour microenvironment consists of cells, molecules and blood vessels that surround and support tumour cells. It includes cancer-associated fibroblasts, myeloid suppressor cells, tumour infiltrating lymphocytes, and the extracellular matrix. Hypoxic conditions in the tumour microenvironment activate HIF signalling pathways and cause changes that promote cancer progression in both tumour and stromal cells. Immune cells in the microenvironment like regulatory T cells and myeloid suppressor cells suppress antitumour immune responses and help tumours escape immune surveillance. Targeting the microenvironment may be a promising approach for future cancer immunotherapies.
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Disclaimer: No one is perfect, so please mind that there might be mistakes and typos.
dtubbenhauer@gmail.com
Corrected slides: dtubbenhauer.com/talks.html
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The complement system in immunology
1. • SUBMITTED TO:
• Dr. BINDU BATTAN
• ASSISTANT PROFESSOR
• (DEPARTMMENT OF
BIOTECHNOLOGY)
• IMMUNOLOGY
• SUBMITTED BY:
• SHASHI (1)
• TEENA(5)
• MEHEK(9)
• CHITRANGNA(15)
• KIRTI(16)
• (MSc. FINAL YEAR STUDENTS)
2. COMPLEMENT SYSTEM
• Major effector of the humoral branch of immune
system .
•Research on complement began in 1890 when Jules
Border at Institute Pasteur in Paris showed that sheep
antiserum to the bacterium Vibrio cholerae caused lysis of
the bacteria and that heating the antiserum destroyed it's
activity.
•Paul Ehrlich coined term 'complement' defining it
as"activity of blood serum that completes the action of
antibody".
Activation of complement cascade may be initiated by
bye several proteins that circulate in normal
serum.These molecules, termed accused face protein
acute phase protein, dresses pattern recognition
capacity and undergo changes in concentration during
inflammation.
3. Functions of the complement
• Lysis of cells ,bacteria and viruses
• Opsonization, which promotes phagocytosis of
particulate antigen
• binding to specific complement receptors on cells of
the immune system, triggering specific cell functions,
inflammation, and secretion of immunoregulatory
molecules
• Immune clearance, which removes immune
complexes from the circulation and deposits them in
the spleen and liver
4.
5. Components of complement
• Soluble proteins and glycoproteins synthesized mainly by liver
hepatocytes
• Constituted 5% of the serum global in fraction in functionally
inactive form as proenzyme or zymogens.
• Complement components are designated by numerals (C1-C8),by
letter symbols (eg factor D) or by trivial names(eg homologous
restriction factor). Peptide fragment formed by activation of
component are denoted by small letters.
• the larger fragments bind to the target near the site of activation
and the smaller fragment diffuse from the side and can initiate
localised inflammatory response is binding to the specific receptors.
• The complement fragments interact with one another to form
functional complexes, those complexes that have enzyme attack
activity are designated by bar over the number of symbol(eg C42a,
C3Bb)
6. Complement activation
• The early steps culminating in the formation of C5b
can occur by classical pathway, the alternative
pathway or the lectin pathway.
• the final steps that lead to the formation of the
membrane attack complex or MAC are identical in
all three pathways.
7. Classical Pathway
• The classical pathway of complement activation is
considered part of adaptive immune response since it
begins with the formation of antigen-antibody complexes.
• These complexes may be soluble, or they may be formed
when an antibody binds to antigenic determinants, or
epitopes, situated on viral, fungal, parasitic, or bacterial
cell membranes.
• Only complexes formed by IgM or certain subclasses of
IgG antibodies are capable of activating the classical
complement pathway.
• The initial stage of activation involves the complement
components C1, C2, C3 and C4, which are present in
plasma as zymogens.
8. • The formation of an antigen-anribody complex induces
conformational changes in the nonantigen-binding (Fc)
portion of the antibody molecule. This conformational
change exposes a binding site for the C1 component of
complement.
• In serum, C1 exists as a macromolecular complex complex
consisting of one molecule of C1q and two molecules each of
serine proteases, C1r and C1s, held together in a Ca+²
stabilized complex.
• The C1q molecule itself is composed of 18 polypeptide chains
that associate to form six collagen like triple helical arms, the
tips of which bind the CH² domain of antigen bound antibody
molecule.
• Binding of C1q to the CH²domains of Fc regions of the antigen
complexed antibody molecule induces a conformational
change in one of the C1r molecules that converts it to an
avtive serine protease enzyme.This C1r molecule then cleaves
and activate its partner C1r molecule.
9.
10. • The two C1r proteases then cleave and activate the two
C1s molecules.C1s has two substrates, C4 and C2.C4 is
activated when C1s hydrolyzes a small fragment (C4a) from
the amino terminus of one of its chains.
• The C4b fragment attaches covalently to the target
membrane surface in the vicinity of C1, & then binds
C2.On binding C4b, C2 becomes susceptible to cleavage by
the neighboring C1s enzyme, and the smaller C2b
fragment diffuses away, leaving behind an enzymatically
active C4b2a complex. C4b2a complex is called C3
convertase.
• The membrane bound C3 convertase enzyme, C4b2a,now
hydrolyzes C3, generating two unequal fragments; the
small anaphylatoxin C3a and the pivotal fragment C3b.
11.
12. • C3b acts in three important and different way to protect
the host.
① Similar to that of C4b, C3b binds covalently to microbial surfaces,
providing a molecular "tag" & thereby allowing phagocytic cells with
C3b receptors to engulf the tagged microbes.This process is called
Opsonization.
② C3b molecules can attach to the Fc portion of antibodies
participating in soluble antigen-antibody complexes. These C3b -
tagged immune complexes are bound by C3b receptors on
phagocytes or red blood cells, & are either phagocytosed, or
conveyed to the liver where they are destroyed.
③ Some molecules of C3b bind the membrane - localized C4b2a
enzyme to form the trimolecular, membrane bound, C5 convertase
complex C4b2a3b.The C3b component of this complex binds C5 , &
the complex then cleaves C5 into two fragments: C5b and C5a.
• This trio of tasks accomplished by C3b molecule places it
right at the centre of complement attack pathways.
13.
14.
15. LECTIN PATHWAY
• Also called as MBL pathway.
• The pathway is independent of antibodies for
its activation like classical pathway
• For initiation of complement activation
process this pathway uses lectin proteins that
recognise specific carbohydrate components
primarily found on microbial surface as it’s
receptor molecules.
16. MBL-mannose binding lectin, the first lectin
demonstrated to be capable of Initiating complement
activation.
MBL are found in several microorganisms such as
Salmonella, Listeria and Niesser of bacteria.
Cryptococcus neoformans and Candida albicans strains.
MBL also recognise structure in addition to mannose,
including N- acetylglucosamine, D-glucose and L-fucose.
17.
18.
19. LECTINPATHWAY
• After MBL binds to the surface of a cell or a pathogen, MBL
associated Serine protease, MASP- 1 and MASP-2, binds to
MBL.
• The active complex formed by this association causes
cleavage and activation of C4 and C2 .
• The MASP-1 and MASP-2 proteins have structural similarity to
C1r and C1s and mimic their activities .
• This means of activating the C2-C4 components to form a C3
andC5 convertase without need for specific antibody binding
represents an important innate defence mechanism
comparable to the alternative pathway , but utilising the
elements of the classical pathway except for C1 protein.
21. TheAlternativePathway
• The alternative pathway generates bound C5b, the same product
that the classical pathway generates, but it does so without the
need for antigen-antibody complexes for initiation.
• Because no antibody is required, the alternative pathway is a
component of the innate immunesystem.
• This major pathway of complement activation involves four serum
proteins: C3,factor B,factor D,andproperdin.
• The alternative pathway is initiated in most cases by cell-surface
constituents that are foreign to the host . For example, both gram-
negative and gram-positive bacteria have cell-wall constituents that
canactivate the alternativepathway.
22. • In the classicalpathway,C3is rapidly cleaved to C3aand C3bby
the enzymatic activity of the C3convertase. In the alternative
pathway, serum C3,which contains an unstable thioester bond,
is subject to slow spontaneous hydrolysisto yield C3aand C3b.
• The C3b component can bind to foreign surface antigens (such
as those on bacterial cells or viral particles) or even to the host’s
own cells.
• The membranes of most mammalian cells have high levels of
sialic acid, which contributes to the rapid inactivation of bound
C3b molecules on host cells; consequently this binding rarely
leads to further reactions on the host cellmembrane.
• Because many foreign antigenic surfaces (e.g., bacterial cell
walls, yeast cell walls, and certain viral envelopes) have only low
levels of sialic acid, C3b bound to these surfaces remains active
for alonger time.
31. Regulato
-ry
Proteins
1. Factor H
• Regulate alternative pathway.
• Reduce amount of C5 convertase available .
• With both cofactor activity for the factor (-mediated C3b
cleavage, and decay accelerating activity.
2. Cl inhibitor
• Important regulator of classic pathway .
• A serine protease inhibitor (serpin).
• It acts by forming a complex with the C1 proteases, C1r2s2,
causing them to dissociate from C1q and preventing further
activation of C4 or C2 .
• C1INH inhibits both C3b and the serine protease MASP2.
• It is the only plasma protease capable of inhibiting the initiation
of both the classical and lectin complement pathways.
32. Regulat
-ory
Proteins
3. Factor I
• Cleaves cell-bound or fluid phase C3b and C4b into
inactivate fragments C3b and C4b .
4. Decay accelerating factor (DAF)
• Glycoprotein on surface of human cells .
• Accelerate the decay of the C4b2a on the surface of host
cells, including decay accelerating factor, or DAF (CD55),
CR1, and C4BP (C4 binding protein) .
• These decay accelerating factors cooperate to accelerate the
breakdown of the C4b2a complex into its separate
components.
• Th enzymatically active C2a diffuses away, and the residual
membrane-bound C4b is degraded by factor I.
• Acts on both classical and alternative pathway.
33. Regulat
ory
Proteins
6. C4b-binding protein (C4BP)
• Inhibits the action of C4b in classical pathway
• Splits C4 convertase and is a cofactor for
factor I
7. Complement Receptor 1 (CR-1)
• Co-factor for factor I, together with CD46
8. Protectin (CD59) and Vitronectin (S
protein)
• Inhibits formation of MAC by binding C5b678
• Present on "self" cells to prevent complement
from damaging them
34. Regulat
ory
Protein
10.Carboxypeptidases Can Inactivate the Anaphylatoxins C3a
and C5a
• Anaphylatoxin activity is regulated by cleavage of the
C-terminal arginine residues from both C3a and C5a by
serum carboxypeptidases, resulting in rapid inactivation
of
the anaphylatoxin activity .
• The specific enzymes that mediate the control of
anaphylatoxin concentrations are carboxypeptidases N,
B, and R.
• These enzymes remove arginine residues from the
carboxyl termini of C3a and C5a to form the so-called
des-Arg (“without Arginine”), inactive forms of the
molecules.
35.
36. Consequences
Of
Complement
System
1. Cell lysis by MAC
• MAC damages cell membrane by
making pores or channels in it and
allowing the free passage of various
ions and water in to the cell. This
ultimately leads to cell death.
Bacteria, enveloped viruses,
irreversibly damaged cells,
cancerous cells etc. are killed by
this mechanism commonly referred
to as complement mediated cell
lysis.
• Gram positive bacteria, which are
protected by their thick
peptidoglycan layer, bacteria with a
capsule or slime layer around their
cell wall, or non-enveloped viruses
are less susceptible to lysis.
37. 2. Inflammatory Response
• C3a, C4a and C5a are called anaphylatoxins. They bind to
receptors on mast cells and induce its degranulation leading to
release of histamine and other pharmacologically active
mediators of inflammation.
• They cause vasoconstriction and increase in vascular
permeability. Along with the C5b67, they also induce the
migration of neutrophils and monocytes to the site of
complement activation.
• This leads to an inflammatory response which is a local
protective response.
38. 3. Opsonization
• C3b and C4b act as major opsonin that coat the immune
complexes and particulate antigen.
• Phagocytic cells express receptors (CR1, CR3 and CR4) for
complement components (C3b, C4b etc.) and are able to bind
the complement coated antigen and enhance its phagocytosis.
• C5a augments this process by enhancing the CR1 expression
on phagocytes by 10 folds.
39. 4. Viral Neutralization
• Complement plays a very important role in viral neutralization
in many ways:
• Most viral particles bind to their serum antibody and form
particulate immune complex which stimulates the classical
pathway. Many viruses are also capable of activating the
alternative and lectin pathway in the absence of antibody. So,
the MAC is able to destroy the viruses.
• C3b helps in the formation of viral aggregates by acting as
opsonin and thus decrease the net number of infective viral
particles. This effect is enhanced in the presence of
serum antibody.
• Complement products also coat the viral particles. This coating
neutralizes the viral infectivity by blocking its attachment to
target cell and enhancing its phagocytosis by macrophages
through complement.
• Complement cytolyze most enveloped viruses causing
fragmentation and disintegration.
40. 5. Solubilization of Immune Complex
• C3b plays an important role in removing immune complex from
the blood. its binding to complexes facilitates their binding to
CR1 on RBCs.
• CR1 are present in higher number is granulocytes than the
RBCs, but because of much larger number of RBCs than
granulocytes in blood, RBCs account for the 90% of the total
CR1 in blood.
• Immune complexes bound to the RBCs are taken to liver and
spleen where they are phagocyted after separation from RBCs.