The complement system is comprised of over 30 circulating and membrane-bound proteins that act in a cascade to help mediate innate and acquired immunity. It functions through three main pathways - classical, lectin, and alternative - that involve a chain of enzymes cleaving complement proteins and forming complexes that activate other proteins in the cascade. The final steps are identical for all three pathways and allow the complement system to help clear pathogens through mechanisms like opsonization, inflammation, and lysis. Tight regulation is needed since complement is nonspecific and can damage host cells - regulatory proteins inhibit activity and many components have short half-lives.
presented by HAFIZ M WASEEM
university of education LAHORE Pakistan
i am from mailsi vehari and studied in lahore
bsc in science college multan
msc from lahore
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.
Complement system and innate immunity - classical & alternative pathways neeru02
The complement system is part of the innate immune system that enhances the ability of antibodies and phagocytes to clear pathogens. It consists of around 20 proteins that are activated via three pathways: the classical pathway activated by antigen-antibody complexes, the lectin pathway activated by lectins binding to pathogens, and the alternative pathway which is continuously active at low levels. Complement activation leads to the formation of the membrane attack complex that forms pores in pathogen cell membranes to kill them directly or mark them for phagocytosis.
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.
B cell generation-activation_and_differentiationDUSHYANT KUMAR
B cells develop through several stages:
1) Generation in the bone marrow or fetal liver
2) Activation in the lymph nodes through interaction with antigens and T cells
3) Differentiation into plasma cells, which secrete antibodies, or memory B cells
The key events in B cell activation and differentiation are Ig gene rearrangement, affinity maturation through somatic hypermutation, class switch recombination, and formation of plasma cells and memory cells mediated by AID and specific cytokines in germinal centers. B cells can be activated through T cell dependent or independent pathways.
The term ‘complement’ refers to set of serum proteins that cooperate in both innate and adaptive immune system to eliminate blood tissue pathogens.
It was 1st identified as heat labile component of serum.
Major effectors of hormonal branch of immune system.
Paul Ehrlich in Berlin independently carried out similar experiments & coined the term COMPLEMENT, defining it as ‘’ the activity of blood serum that completes the action of antibody.’’
In later years it was revealed that the action of complement is basically the result of interaction of large & complex group of proteins.Most of the components of complement system are synthesized in liver by hepatocytes, epithelial cells of gastrointestinal & genitourinary tracts.
it consist up of 15% of globular proteins fraction in plasma & combined conc. Is about 3 mg/ml.
These are the glycoproteins distributed among blood plasma & cell membrane.After activation several components interact in regulated cascade to carry out no. of basic functions…..
Lysis if cells .( bacteria , virus)
Opsonization, that promote phagocytosis of particulate antigens.
Activation of inflammatory response.
Immune clearance.
Chemotaxis.
Lysis refers to the breaking down of the cells' membrane , by viral, enzymic, or osmotic mechanisms that compromise its integrity.
A fluid containing the contents of lysed cells is called a "lysate".
Cell lysis is used to break open cells to avoid shear forces that would denature or degrade sensitive proteins and DNA.
presented by HAFIZ M WASEEM
university of education LAHORE Pakistan
i am from mailsi vehari and studied in lahore
bsc in science college multan
msc from lahore
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.
Complement system and innate immunity - classical & alternative pathways neeru02
The complement system is part of the innate immune system that enhances the ability of antibodies and phagocytes to clear pathogens. It consists of around 20 proteins that are activated via three pathways: the classical pathway activated by antigen-antibody complexes, the lectin pathway activated by lectins binding to pathogens, and the alternative pathway which is continuously active at low levels. Complement activation leads to the formation of the membrane attack complex that forms pores in pathogen cell membranes to kill them directly or mark them for phagocytosis.
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.
B cell generation-activation_and_differentiationDUSHYANT KUMAR
B cells develop through several stages:
1) Generation in the bone marrow or fetal liver
2) Activation in the lymph nodes through interaction with antigens and T cells
3) Differentiation into plasma cells, which secrete antibodies, or memory B cells
The key events in B cell activation and differentiation are Ig gene rearrangement, affinity maturation through somatic hypermutation, class switch recombination, and formation of plasma cells and memory cells mediated by AID and specific cytokines in germinal centers. B cells can be activated through T cell dependent or independent pathways.
The term ‘complement’ refers to set of serum proteins that cooperate in both innate and adaptive immune system to eliminate blood tissue pathogens.
It was 1st identified as heat labile component of serum.
Major effectors of hormonal branch of immune system.
Paul Ehrlich in Berlin independently carried out similar experiments & coined the term COMPLEMENT, defining it as ‘’ the activity of blood serum that completes the action of antibody.’’
In later years it was revealed that the action of complement is basically the result of interaction of large & complex group of proteins.Most of the components of complement system are synthesized in liver by hepatocytes, epithelial cells of gastrointestinal & genitourinary tracts.
it consist up of 15% of globular proteins fraction in plasma & combined conc. Is about 3 mg/ml.
These are the glycoproteins distributed among blood plasma & cell membrane.After activation several components interact in regulated cascade to carry out no. of basic functions…..
Lysis if cells .( bacteria , virus)
Opsonization, that promote phagocytosis of particulate antigens.
Activation of inflammatory response.
Immune clearance.
Chemotaxis.
Lysis refers to the breaking down of the cells' membrane , by viral, enzymic, or osmotic mechanisms that compromise its integrity.
A fluid containing the contents of lysed cells is called a "lysate".
Cell lysis is used to break open cells to avoid shear forces that would denature or degrade sensitive proteins and DNA.
This study investigated the role of integrin-linked kinase (ILK) in bladder cancer invasion and progression. The researchers found that invasive bladder cancer cells have high ILK expression, which plays a role in epithelial-to-mesenchymal transition by regulating E-cadherin expression. Knocking down ILK in invasive bladder cancer cells suppressed cell invasion by regulating E-cadherin and MMP-9. Analysis of human bladder cancer samples also showed that high ILK expression correlates with increased invasiveness. Therefore, this study suggests that ILK is important for EMT in bladder cancer and could be a new therapeutic target to suppress tumor progression.
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 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.
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.
1. The complement system consists of over 20 proteins that interact to promote inflammation and cell injury. It has three activation pathways: classical, lectin-binding, and alternative.
2. Complement activation results in the formation of C3 and C5 convertases that generate inflammatory anaphylatoxins like C3a and C5a, and opsonins like C3b that promote phagocytosis.
3. The membrane attack complex forms from C5b, C6, C7, C8 and multiple C9 molecules, causing pores in cell membranes and lysing bacteria, viruses, and other pathogens. This is a major effector mechanism of innate immunity.
The document summarizes the complement system, which comprises a group of serum proteins that play an important role in innate and adaptive immunity. There are three pathways of complement activation - classical, lectin, and alternative. All three pathways lead to cleavage of C3 and C5, generating factors that opsonize pathogens, recruit inflammatory cells, and directly kill pathogens. Complement activation is tightly regulated to prevent damage to host cells. Deficiencies in complement proteins can increase susceptibility to certain infections.
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.
Identify the organs of primary and secondary immune system- lymphoid organs, Know the functions of lymphoid organs, Understand the importance of lymphoid organs and Lymphatic circulatory system
1. The document discusses the two pathways that the immune system uses to process endogenous and exogenous antigens for presentation to T cells.
2. The cytosolic pathway processes endogenous antigens within the cytoplasm, where they are degraded by proteasomes and transported by TAP proteins to associate with class I MHC molecules in the ER.
3. The endocytic pathway processes exogenous antigens that are taken up by endocytosis, degraded within acidic endosomes and lysosomes, and associate with class II MHC molecules aided by the invariant chain and HLA-DM/DO proteins.
This document discusses cellular immune response and the roles of its key components. It describes how antigen presenting cells present antigens to T lymphocytes via MHC molecules, providing the necessary stimulatory and co-stimulatory signals for T cell activation. Activated T cells then differentiate into effector and memory T cells. Effector CD8+ T cells induce apoptosis of infected cells, while effector CD4+ T cells secrete cytokines to activate macrophages. The interactions between these immune cells are regulated by cytokines. The document also discusses antigen presentation pathways, T cell maturation in the thymus, and the roles of superantigens and cytokines in the immune response.
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.
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
Cytokines are low molecular weight polypeptides or glycoproteins that are secreted by cells and have various functions including mediating and regulating immune responses and inflammatory reactions. Cytokines are produced by lymphocytes, monocytes, macrophages, mast cells, glial cells and other cells. They act through autocrine, paracrine or endocrine mechanisms and initiate their actions by binding to specific membrane receptors. Cytokines have pleiotropic, redundant, synergistic and antagonistic effects and form a cytokine network. The major classes of cytokines include interleukins, tumor necrosis factors, interferons, colony stimulating factors, transforming growth factors and chemokines. Cytokines play important roles in various diseases and their therapeutic uses include treatment
T cells are activated through the recognition of antigen peptides presented on MHC complexes on antigen presenting cells (APCs). This leads to T cell proliferation and differentiation into effector T cells. Cytotoxic T cells recognize endogenous antigens on MHC I to kill infected cells, while helper T cells recognize exogenous peptides on MHC II and secrete cytokines to stimulate macrophage activation or B cell antibody production. Full T cell activation requires both antigen recognition by the TCR and co-stimulatory signaling between molecules such as B7 and CD28.
The B cell receptor is a transmembrane protein on B cells that is composed of a membrane-bound immunoglobulin molecule and a signal transduction moiety. The B cell receptor consists of an Ig molecule anchored to the cell's surface and has two key functions: signal transduction upon antigen interaction and internalization of antigens for processing and presentation to T cells. The B cell co-receptor is a complex of CD19, CD21, and CD81 expressed on mature B cells.
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.
Cell adhesion molecules help cells stick to each other and their surroundings through proteins. There are several types of cell adhesion molecules including immunoglobulin super family CAMs, integrins, selectins, and cadherins. Cadherins like E-cadherin form adherens junctions between cells and link to actin through catenins. Changes in cell adhesion can lead to diseases such as cancer where reduced adhesion allows cancer cells to invade other tissues. Cell adhesion molecules are important for tissue development and function.
The complement system consists of approximately 20 proteins that are mainly synthesized by the liver and play an important role in innate immunity. It has three main effects: lysis of cells, generation of inflammatory mediators, and enhancement of phagocytosis. There are three pathways of complement activation: the classical, lectin, and alternative pathways. The classical pathway is part of acquired immunity and requires antigen-antibody complexes, while the lectin and alternative pathways are part of innate immunity and activate in response to microbial surfaces. Complement activation leads to opsonization and lysis of pathogens as well as inflammatory responses. The system is tightly regulated to prevent damage to host cells. Deficiencies in complement proteins predispose individuals to certain infections
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.
Innate immune system is very important in case of fish. Complement system is the part of innate immune system. In this presentation there is a overview of the complement system.
This study investigated the role of integrin-linked kinase (ILK) in bladder cancer invasion and progression. The researchers found that invasive bladder cancer cells have high ILK expression, which plays a role in epithelial-to-mesenchymal transition by regulating E-cadherin expression. Knocking down ILK in invasive bladder cancer cells suppressed cell invasion by regulating E-cadherin and MMP-9. Analysis of human bladder cancer samples also showed that high ILK expression correlates with increased invasiveness. Therefore, this study suggests that ILK is important for EMT in bladder cancer and could be a new therapeutic target to suppress tumor progression.
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 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.
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.
1. The complement system consists of over 20 proteins that interact to promote inflammation and cell injury. It has three activation pathways: classical, lectin-binding, and alternative.
2. Complement activation results in the formation of C3 and C5 convertases that generate inflammatory anaphylatoxins like C3a and C5a, and opsonins like C3b that promote phagocytosis.
3. The membrane attack complex forms from C5b, C6, C7, C8 and multiple C9 molecules, causing pores in cell membranes and lysing bacteria, viruses, and other pathogens. This is a major effector mechanism of innate immunity.
The document summarizes the complement system, which comprises a group of serum proteins that play an important role in innate and adaptive immunity. There are three pathways of complement activation - classical, lectin, and alternative. All three pathways lead to cleavage of C3 and C5, generating factors that opsonize pathogens, recruit inflammatory cells, and directly kill pathogens. Complement activation is tightly regulated to prevent damage to host cells. Deficiencies in complement proteins can increase susceptibility to certain infections.
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.
Identify the organs of primary and secondary immune system- lymphoid organs, Know the functions of lymphoid organs, Understand the importance of lymphoid organs and Lymphatic circulatory system
1. The document discusses the two pathways that the immune system uses to process endogenous and exogenous antigens for presentation to T cells.
2. The cytosolic pathway processes endogenous antigens within the cytoplasm, where they are degraded by proteasomes and transported by TAP proteins to associate with class I MHC molecules in the ER.
3. The endocytic pathway processes exogenous antigens that are taken up by endocytosis, degraded within acidic endosomes and lysosomes, and associate with class II MHC molecules aided by the invariant chain and HLA-DM/DO proteins.
This document discusses cellular immune response and the roles of its key components. It describes how antigen presenting cells present antigens to T lymphocytes via MHC molecules, providing the necessary stimulatory and co-stimulatory signals for T cell activation. Activated T cells then differentiate into effector and memory T cells. Effector CD8+ T cells induce apoptosis of infected cells, while effector CD4+ T cells secrete cytokines to activate macrophages. The interactions between these immune cells are regulated by cytokines. The document also discusses antigen presentation pathways, T cell maturation in the thymus, and the roles of superantigens and cytokines in the immune response.
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.
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
Cytokines are low molecular weight polypeptides or glycoproteins that are secreted by cells and have various functions including mediating and regulating immune responses and inflammatory reactions. Cytokines are produced by lymphocytes, monocytes, macrophages, mast cells, glial cells and other cells. They act through autocrine, paracrine or endocrine mechanisms and initiate their actions by binding to specific membrane receptors. Cytokines have pleiotropic, redundant, synergistic and antagonistic effects and form a cytokine network. The major classes of cytokines include interleukins, tumor necrosis factors, interferons, colony stimulating factors, transforming growth factors and chemokines. Cytokines play important roles in various diseases and their therapeutic uses include treatment
T cells are activated through the recognition of antigen peptides presented on MHC complexes on antigen presenting cells (APCs). This leads to T cell proliferation and differentiation into effector T cells. Cytotoxic T cells recognize endogenous antigens on MHC I to kill infected cells, while helper T cells recognize exogenous peptides on MHC II and secrete cytokines to stimulate macrophage activation or B cell antibody production. Full T cell activation requires both antigen recognition by the TCR and co-stimulatory signaling between molecules such as B7 and CD28.
The B cell receptor is a transmembrane protein on B cells that is composed of a membrane-bound immunoglobulin molecule and a signal transduction moiety. The B cell receptor consists of an Ig molecule anchored to the cell's surface and has two key functions: signal transduction upon antigen interaction and internalization of antigens for processing and presentation to T cells. The B cell co-receptor is a complex of CD19, CD21, and CD81 expressed on mature B cells.
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.
Cell adhesion molecules help cells stick to each other and their surroundings through proteins. There are several types of cell adhesion molecules including immunoglobulin super family CAMs, integrins, selectins, and cadherins. Cadherins like E-cadherin form adherens junctions between cells and link to actin through catenins. Changes in cell adhesion can lead to diseases such as cancer where reduced adhesion allows cancer cells to invade other tissues. Cell adhesion molecules are important for tissue development and function.
The complement system consists of approximately 20 proteins that are mainly synthesized by the liver and play an important role in innate immunity. It has three main effects: lysis of cells, generation of inflammatory mediators, and enhancement of phagocytosis. There are three pathways of complement activation: the classical, lectin, and alternative pathways. The classical pathway is part of acquired immunity and requires antigen-antibody complexes, while the lectin and alternative pathways are part of innate immunity and activate in response to microbial surfaces. Complement activation leads to opsonization and lysis of pathogens as well as inflammatory responses. The system is tightly regulated to prevent damage to host cells. Deficiencies in complement proteins predispose individuals to certain infections
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.
Innate immune system is very important in case of fish. Complement system is the part of innate immune system. In this presentation there is a overview of the complement system.
this slide can help you to know full details about the major type of antigen based on its activity on B or T cell. This slide consists of images to clarify your doubts
This document provides an overview of antigens and receptors. It discusses the different types of antigens, including immunogens, haptens, and tolerogens. It also describes the basic recognition unit of antigens, which are epitopes. There are two main types of receptors: preformed receptors of the innate immune system, such as pattern recognition receptors and Fc receptors; and somatically generated receptors of the adaptive immune system, such as B cell receptors and T cell receptors. The engagement of antigens with their corresponding receptors triggers immune responses.
This document summarizes key information about antibodies (immunoglobulins). It discusses:
- The structure of antibodies, including their Y-shape consisting of two heavy and two light polypeptide chains, variable and constant regions, and antigen binding sites formed by hypervariable regions.
- The five classes of antibodies in humans (IgG, IgM, IgA, IgD, IgE) which differ in size, charge, domains, and biological functions such as complement activation and placental transport.
- Monoclonal and polyclonal antibodies, how they differ in being derived from single or multiple B cell clones, and the discovery of monoclonal antibodies by Kohler and Milstein in 1975.
The document summarizes key aspects of innate immunity and the complement system. It describes how the complement system recognizes microbes via three pathways: the classical, lectin, and alternative pathways. It also outlines the three main functions of complement in host defense: opsonization, chemotaxis, and formation of the membrane attack complex. The summary concludes by mentioning how deficiencies in complement proteins can increase susceptibility to certain infections.
The document discusses cytokines, which are low-molecular-weight regulatory proteins or glycoproteins secreted by immune cells and other cells. Cytokines play major roles in immune, inflammatory, and hematopoietic systems by binding to specific cell receptors and altering gene expression. They have pleiotropic, redundant, synergistic, antagonistic, and cascading properties. Cytokines are classified into families based on structure and receptors. They signal through receptor families like immunoglobulin, class I and II cytokine receptors, TNF receptor, and chemokine receptors to regulate the immune response.
This document contains lecture notes for Biology 151 Introduction to Immunology. It discusses antigens and immunogens, factors that influence immunogenicity such as foreignness, molecular size, and adjuvants. It also provides instructions for a journal article assignment and outlines topics to be covered including antibody structure and classes.
This document provides an overview of cytokines, which are proteins that mediate cell-to-cell communication during immune responses. Cytokines are secreted by white blood cells and other cells in response to stimuli. They regulate immune cell development and functions such as inflammation. Cytokines bind to specific cell surface receptors and initiate signaling pathways that regulate gene expression. The document discusses the four main families of cytokines, their properties, functions, receptors, and antagonists. It also describes how T-helper 1 and T-helper 2 cells secrete different cytokine profiles that determine the type of immune response mounted.
Cytokines by Dr Rahul , Physiology SMS MEDICAL JAIPUR MOBILE NO-8764324067Dr.Rahul ,Jaipur
-CYTOKINES
-THEIR PROPERITIES
-TYPES OF CYTOKINES
-CYTOKINES RECEPTOR FAMILY
-CYTOKINES AND PYREXIA
-CYTOKINES AND OBESITY RELATED DISEASE
-CYTOKINES AS DRUGS
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.
The complement system is an important part of the innate immune system that activates through three pathways - classical, lectin, and alternative. Activation leads to the formation of C3 and C5 convertases that generate inflammatory molecules like C3a and C5a, and opsonins like C3b that promote phagocytosis. It ultimately forms the membrane attack complex that lyses target cells. Complement is tightly regulated to prevent damage to host cells and excessive inflammation. Deficiencies in complement components can increase risk of certain infections.
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.
1. Dendritic cell eats bugs and displays antigens to naïve T cells using MHC class II. T cells mature.
2. Neutrophil eats and kills bugs with toxic chemicals. NK cell kills infected cells.
3. Helper T cell tells macrophage to eat bugs and tells B cell to make antibodies. Cytotoxic T cell finds and kills infected cells that display antigens using MHC class I.
4. B cell makes antibodies that coat bugs to neutralize and opsonize them, making them targets for macrophages.
For More Medicine Free PPT - http://playnever.blogspot.com/
For Health benefits and medicine videos Subscribe youtube channel - https://www.youtube.com/playlist?list=PLKg-H-sMh9G01zEg4YpndngXODW2bq92w
Antigen-antibody interactions can be quantified using various serological tests. Common types include precipitation tests like immunodiffusion that form visible precipitate lines, agglutination tests where antigens clump together, neutralization tests using viruses and complement fixation assays. Enzyme-linked immunosorbent assays (ELISAs) are now widely used as they are sensitive, specific and can be quantitative or qualitative. Fluorescent antibody techniques use fluorescent dyes to label antibodies or cells for detection under a microscope.
An antigen is any substance that reacts with lymphocytes, while immunogens generate immune responses. Haptens are small molecules that require coupling to carriers to induce responses. Antibody-antigen binding depends on weak interactions between sites on antibodies and epitopes on antigens. Antibodies are produced with a wide variety of binding sites to recognize different antigenic determinants. Factors like foreignness, size, structure, and route of administration influence a substance's immunogenicity.
This document presents information about anti-bacterial activity screening techniques. It discusses bacteriostatic agents, which prevent bacterial growth without killing bacteria, and assessments of bacteriostatic activity including serial dilution methods in fluid and solid media as well as cup plate and gradient plate methods. It also discusses bactericidal agents, which kill bacteria, and assessments of bactericidal activity including end-point or extinction time methods such as the Phenol coefficient test and varying the concentration or contact time of disinfectants. The document was presented to Dr. Chaluvaraju KC by Mr. Pradeep on the topic of anti-bacterial activity and screening techniques.
The document describes a high-throughput screen that identified small molecule compounds that can enhance the pharmacological effects of oligonucleotides. Several "hit" compounds were discovered that potentiated the actions of splice-switching oligonucleotides, antisense oligonucleotides, and siRNAs in cell culture. The hit compounds preferentially caused the release of fluorescent oligonucleotides from late endosomes. Studies in transgenic mice indicated the hit compounds could enhance the in vivo effects of a splice-switching oligonucleotide without significant toxicity. The findings suggest selected small molecules may help advance oligonucleotide-based therapeutics by modulating intracellular trafficking and endosomal release.
This document summarizes a study investigating the epigenetic changes that occur during the transdifferentiation of pancreatic acinar cells (HPACs) to hepatocyte-like cells. The study found that DNA methylation in HPACs peaks at 24 hours after treatment with dexamethasone, and the cells display phenotypic changes associated with hepatocytes after 7 days. The study also examined the promoter sequence of the SGK1 gene, which is involved in the transdifferentiation process. The results suggest therapeutic potential for producing hepatocytes from pancreatic cells to treat liver disease in a more cost-effective manner than current alternatives.
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 review article summarizes our current understanding of the complement system. It describes complement as an intricate immune surveillance system that distinguishes between healthy host cells, cellular debris, apoptotic cells, and foreign intruders. Complement acts through pattern recognition, activation, amplification, and regulation to eliminate microbes and cellular debris while also signaling immune responses. The review highlights the classical, lectin, and alternative pathways of complement activation and the roles of C3 convertases. It describes how complement contributes to homeostasis but can also attack healthy cells if not properly regulated.
A team of scientists developed an optimized peptide toxin derived from ShK, a peptide from sea anemone venom, for potential treatment of autoimmune diseases. They used a systematic approach called MAPS (Multi Attribute Positional Scan) analoging to chemically synthesize 132 variants of ShK with single amino acid substitutions throughout the peptide. These variants were tested for their ability to inhibit the Kv1.3 potassium ion channel while sparing the closely related Kv1.1 channel. Two lead variants showed improved selectivity for Kv1.3 over Kv1.1. One variant was further modified with a PEG polymer to improve its pharmacokinetic properties. In primate studies, the PEGylated peptide
The document discusses the complement system and immunoglobulins. It provides an overview of:
- The components and pathways of the complement system and its role in host defense.
- The structure and classes of immunoglobulins, including IgG, IgA, IgM, IgE, and IgD.
- Deficiencies in the complement system and immunoglobulins that can cause increased susceptibility to infection.
2 complemento receptores - segunda apresentaçãoufamimunologia
The document summarizes complement regulators and inhibitory proteins that control the complement system. It begins by explaining that the complement system helps remove microorganisms and modified self cells, but must be tightly regulated to prevent damage to healthy tissues. It then discusses the complement cascade and its initiation, amplification and progression. Finally, it focuses on the regulators that modify and control the complement system to ensure activation only occurs at the proper time and locations.
The complement system is made up of around 30 proteins that augment the immune response. It was first identified in the 1890s as heat-labile components of serum that helped antibodies kill bacteria. There are three pathways of complement activation: the classical pathway which is antibody-dependent, the lectin pathway which resembles the classical pathway, and the alternative pathway which is antibody-independent. All three pathways involve a cascade of complement components that ultimately form the membrane attack complex (MAC) which can lyse target cells. The complement system plays important roles in opsonization, chemotaxis, inflammation, and clearance of pathogens.
Complement system and its synthesis + activationVaisHali822687
Proteins normally found in serum in inactive form, but when activated they augment the immune responses.
Complements constitute about 5% of normal serum proteins.
Their level does not increase following either infection or vaccination.
There are four main stages in the activation of any of the complement pathways.
Initiation of the pathway
Formation of C3 convertase
Formation of C5 convertase
Formation of membrane attack complex (MAC)
This presentation summarizes the complement system. It discusses that complement proteins are part of the innate immune system and act as a bridge between innate and adaptive immunity. It describes the three pathways of complement activation - the classical, lectin, and alternative pathways. It also explains the components and functions of the complement system, including recognizing and marking pathogens, stimulating immune responses, and directly killing microbes via membrane attack complexes.
The document provides an overview of the complement system including:
1) It describes the three pathways of complement activation - the classical, lectin, and alternative pathways. It explains the proteins involved in each pathway and their functions.
2) Regulatory mechanisms of complement activation are discussed including factors and receptors that inhibit inappropriate complement activation on host cells.
3) The biological functions of complement activation are summarized including opsonization, initiation of inflammation, and direct lysis of pathogens.
4) Complement-related disorders are briefly mentioned including those associated with deficiencies in early classical pathway components.
Mice lacking the integrin β3 gene (Itgb3-/-) were subjected to unpredictable chronic mild stress (UCMS) to examine their behavioral and neurochemical responses to stress compared to wild-type mice (Itgb3+/+). Itgb3-/- mice displayed increased anxiety-like behaviors and decreased activity in an open field test after UCMS compared to Itgb3+/+ mice. UCMS led to reductions in dopamine turnover in the midbrains of Itgb3+/+ mice but not Itgb3-/- mice, suggesting disrupted stress regulation of dopamine homeostasis. Chronic stress also altered synaptic expression of proteins in the midbrains of Itgb3-/- mice compared to Itgb3+/+
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 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.
Notch signaling is essential to maintain skeletal muscle stem cells in quiescence. However, the
precise roles of different Notch receptors are incompletely defined. Here, we demonstrate a
role for Notch3 (N3) in the self-renewal of muscle stem cells. We found that N3 is active in quiescent C2C12 reserve cells (RCs), and N3 over-expression and knockdown studies in C2C12 and
primary satellite cells reveal a role in self-renewal.
This experiment aimed to identify genes that were overexpressed in BU.MPT cells resistant to apoptosis compared to normal BU.MPT cells. RNA from the two cell populations underwent subtractive hybridization to identify differences. Eight colonies were sequenced, with one gene of interest identified as cysteine and histidine rich protein 1 (Chrp). Chrp is known to bind specifically to galectin-3, keeping it localized in the cytoplasm where it can activate anti-apoptotic pathways and properties. This binding of Chrp to galectin-3 provides a potential explanation for the resistance to apoptosis in the selected BU.MPT cells.
The complement system refers to a series of >20 proteins that are normally inactive but become sequentially activated in an enzyme cascade in response to microorganisms. Complement activation can lead to cytolysis, opsonization, and stimulation of inflammation. The classical, lectin, and alternative pathways activate the complement cascade through different mechanisms but all lead to formation of the membrane attack complex. Complement proteins are regulated to prevent attack of host cells but deficiencies can lead to diseases like hereditary angioedema where swelling occurs.
The document summarizes programmed cell death or apoptosis. It describes apoptosis as a naturally occurring, genetically programmed process where a cell undergoes an organized breakdown. During apoptosis, cells shrink, break into membrane-bound fragments called apoptotic bodies, and are removed by phagocytes without causing inflammation. The document outlines the major pathways of apoptosis, including the intrinsic mitochondrial pathway and extrinsic death receptor pathway, and discusses the roles of caspase proteases and Bcl-2 family proteins in apoptosis signaling and regulation.
The document provides an overview of the complement system in fish. It discusses:
1) The complement system consists of soluble and membrane-bound proteins that play a critical role in the host defense through interactions with both the innate and adaptive immune systems.
2) The complement system has three pathways - classical, lectin, and alternative - that recognize pathogens and promote their clearance through lysis, opsonization, and inflammation.
3) Complement components are produced as inactive zymogens and activated through proteolytic cleavage in cascading reactions on pathogen surfaces to form the membrane attack complex, which lyses cells.
Kupffer Cells Mediate Leptin-Induced Liver Fibrosis.
GASTROENTEROLOGY 2009;137:713–723
JIANHUA WANG,* ISABELLE LECLERCQ,‡ JOANNE M. BRYMORA,* NING XU,* MEHDI RAMEZANI–MOGHADAM,* ROSLYN M. LONDON,* DAVID BRIGSTOCK,§ and JACOB GEORGE*
*Storr Liver Unit, Westmead Millennium Institute, University of Sydney and Westmead Hospital, Westmead, Australia; ‡Laboratory of Gastroenterology, Faculty of
Medicine, Université Catholique de Louvain, Brussels, Belgium; and §Center for Cell and Vascular Biology, Children’s Research Institute, Columbus, Ohio
瘦素(Leptin)是一由脂肪細胞(Adipocyte)所分泌之荷爾蒙,是調控體重及新陳代謝之重要因子。過去研究發現病態肥胖(Obese)、脂肪肝(Nonalcoholic steatohepatitis)及酒精性肝炎(Alcoholic liver disease)等病患之血液循環中,Leptin量有明顯增加。而近期研究報告指出leptin具有促進肝臟纖維化(Liver fibrosis)之能力,當中分子機理並未明確。
在肝纖維化過程中,肝臟星狀細胞(HSC)會被活化增生及促進胞外基質(ECM)產生,而鄰近之Kupffer細胞(KC)則已知可透過促發炎因子(Proinflammatory factor)和促纖維化因子(Profibrogenic factors)例如TGF-β1和ROS影響HSC表現。雖然HSC是肝纖維化過程中重要角色,前人研究卻發現leptin似對HSC無任何調控作用。故本篇作者針對Leptin是否透過間接作用於HSC鄰近之KC,刺激其產生促纖維化因子,以活化HSC。
為探討leptin直接或間接影響HSC之分子機理,本篇作者透過RT-PCR、Immunoblot等分子生物學方法,分別測定leptin刺激後HSC及KC中Collagen I、TIMP1等促纖維化因子基因及蛋白表現,發現leptin雖可促使HSC增生,但對其纖維化能力之影響甚微。而leptin可刺激KC中TGF-β1及CTGF/CCN2等肝纖維化中重要之cytokines表現。另發現Leptin-treated KC-conditioned培養液可刺激HSC增生及增加其中Collagen I、TIMP1等表現,得出了leptin是透過刺激KC來活化HSC之推論。作者亦於後續實驗中,透過磷酸化測定、EMSA等方法探討leptin訊號傳遞作用,發現leptin可活化KC中STAT3、ERK1/2、AKT等路徑,及下游因子AP-1、NF-κB,而此兩種蛋白具有增強TGF-β1及CTGF/CCN2基因表現之能力。
This document provides definitions and information related to infection and infection control in dentistry. It begins with definitions of key terms like infection, disease, virulence, and modes of transmission. It then discusses the normal flora of humans and stages of infection. Virulence factors and toxins are explained. The objectives and types of infection control are outlined, including universal precautions, routes of spread, and measures for pretreatment, chairside, and post-treatment infection control.
Mycology is the study of fungi. Fungi are eukaryotic organisms that include molds, yeasts, and mushrooms. They obtain nutrients by absorbing organic compounds from dead or living organisms. Many fungi are harmless saprophytes, but some can cause diseases (mycoses) in humans and other animals. Common superficial fungal infections in humans include ringworm, athlete's foot, and yeast infections. Deeper fungal infections can also occur, especially in immunocompromised individuals. Proper identification of fungal species relies on examining their morphology and growth characteristics under the microscope and in culture.
This document discusses antibiotic sensitivity testing (AST), including the Kirby-Bauer disk diffusion method and minimum inhibitory concentration (MIC) method. It provides details on selecting media, control strains, preparing antibiotic discs and inoculum, and interpreting zone sizes. AST is useful but has limitations as it only measures in vitro drug activity, not in vivo effects. Proper technique and quality controls are important for accurate results. New automated methods can generate reports faster than traditional AST.
1. Bacteria are unicellular prokaryotes that vary in size from 0.5-10 micrometers. They have distinct cell shapes including cocci, bacilli, spirilla, and vibrios.
2. The bacterial cell contains a cell membrane, cell wall, cytoplasm, and varying structures like flagella, pili, capsules, and endospores. The cell wall structure differs between gram positive and gram negative bacteria.
3. Gram staining allows bacteria to be classified as either gram positive or gram negative based on differences in their cell wall structures. Specialized structures like flagella, pili and capsules serve functions like motility, adhesion and virulence.
This document provides information on culture media and methods used to culture bacteria. It discusses the requirements bacteria have for growth and how laboratory culture media aims to provide a captive environment for bacteria to grow. Various types of culture media are described, including solid, liquid and semi-solid media made with ingredients like agar. Special media like enriched, selective, differential and indicator media are also outlined. Common biochemical tests performed on cultured bacteria like TSI, oxidase, indole and citrate are briefly explained. The document provides an overview of basic microbiology laboratory techniques for culturing and identifying bacteria.
This document discusses Staphylococcus bacteria, including S. aureus and coagulase-negative species. S. aureus is a major human pathogen that can cause skin and soft tissue infections or serious infections like pneumonia, sepsis, and toxic shock syndrome by producing various exotoxins and virulence factors. Coagulase-negative Staphylococcus like S. epidermidis commonly reside on human skin and mucous membranes but can opportunistically cause infections associated with medical devices and in immunocompromised patients. The document covers taxonomy, microbiological characteristics, pathogenic mechanisms, diseases caused, diagnosis, treatment and prevention of Staphylococcus infections.
This document discusses hypersensitivity reactions, specifically focusing on Type 1 hypersensitivity reactions. It defines hypersensitivity as injurious consequences in a sensitized host following contact with a specific antigen. Type 1 reactions are immediate or anaphylactic hypersensitivities that involve IgE antibodies and mast cells or basophils. Upon re-exposure to an antigen, pre-bound IgE is crosslinked, causing degranulation and release of inflammatory mediators like histamine. This leads to symptoms of anaphylaxis such as hives, swelling, breathing difficulties, and low blood pressure. Food allergies, hay fever, and asthma are examples of Type 1 hypersensitivity reactions.
The complement system is comprised of over 30 circulating and membrane-bound proteins that act in a cascade to help mediate innate and acquired immunity. It functions through three main pathways - classical, lectin, and alternative - that involve a chain of enzymes cleaving complement proteins and forming complexes that activate other proteins in the cascade. The final steps are identical for all three pathways and allow the complement system to help clear pathogens or immune complexes through lysis, opsonization, and inflammatory responses. Tight regulation is needed since complement is nonspecific and can damage host cells - regulatory mechanisms include short half-lives of proteins and inhibitors that block activity.
Histololgy of Female Reproductive System.pptxAyeshaZaid1
Dive into an in-depth exploration of the histological structure of female reproductive system with this comprehensive lecture. Presented by Dr. Ayesha Irfan, Assistant Professor of Anatomy, this presentation covers the Gross anatomy and functional histology of the female reproductive organs. Ideal for students, educators, and anyone interested in medical science, this lecture provides clear explanations, detailed diagrams, and valuable insights into female reproductive system. Enhance your knowledge and understanding of this essential aspect of human biology.
TEST BANK For Basic and Clinical Pharmacology, 14th Edition by Bertram G. Kat...rightmanforbloodline
TEST BANK For Basic and Clinical Pharmacology, 14th Edition by Bertram G. Katzung, Verified Chapters 1 - 66, Complete Newest Version.
TEST BANK For Basic and Clinical Pharmacology, 14th Edition by Bertram G. Katzung, Verified Chapters 1 - 66, Complete Newest Version.
TEST BANK For Basic and Clinical Pharmacology, 14th Edition by Bertram G. Katzung, Verified Chapters 1 - 66, Complete Newest Version.
TEST BANK For Basic and Clinical Pharmacology, 14th Edition by Bertram G. Katzung, Verified Chapters 1 - 66, Complete Newest Version.
TEST BANK For An Introduction to Brain and Behavior, 7th Edition by Bryan Kol...rightmanforbloodline
TEST BANK For An Introduction to Brain and Behavior, 7th Edition by Bryan Kolb, Ian Q. Whishaw, Verified Chapters 1 - 16, Complete Newest Versio
TEST BANK For An Introduction to Brain and Behavior, 7th Edition by Bryan Kolb, Ian Q. Whishaw, Verified Chapters 1 - 16, Complete Newest Version
TEST BANK For An Introduction to Brain and Behavior, 7th Edition by Bryan Kolb, Ian Q. Whishaw, Verified Chapters 1 - 16, Complete Newest Version
Integrating Ayurveda into Parkinson’s Management: A Holistic ApproachAyurveda ForAll
Explore the benefits of combining Ayurveda with conventional Parkinson's treatments. Learn how a holistic approach can manage symptoms, enhance well-being, and balance body energies. Discover the steps to safely integrate Ayurvedic practices into your Parkinson’s care plan, including expert guidance on diet, herbal remedies, and lifestyle modifications.
8 Surprising Reasons To Meditate 40 Minutes A Day That Can Change Your Life.pptxHolistified Wellness
We’re talking about Vedic Meditation, a form of meditation that has been around for at least 5,000 years. Back then, the people who lived in the Indus Valley, now known as India and Pakistan, practised meditation as a fundamental part of daily life. This knowledge that has given us yoga and Ayurveda, was known as Veda, hence the name Vedic. And though there are some written records, the practice has been passed down verbally from generation to generation.
1. THE COMPLEMENT SYSTEM
• Important effector in both innate and
acquired immunity
• Over 30 circulating and membrane-bound
proteins (synthesized in liver and other
cells- immune and epithelial)
• Acts as a cascade (one event must occur before
another takes place)
Dr Reena Kulshrestha, M.Sc, PhD.
2. Cascade:
• Many of the components are enzymes
that become activated when cleaved into
two peptides
• The larger peptide (joins the cascade)
binds to the immune complex and
becomes a functional part of it
• The smaller peptide diffuses away and
can become an inflammatory mediator
(binds to a receptor)
Dr Reena Kulshrestha, M.Sc, PhD.
3. Complement is an acute phase protien.
It belongs to triggered enzyme cascade
system.
Every step has its own control
mechanism.
It is present in sera of all mammals.
Dr Reena Kulshrestha, M.Sc, PhD.
4. It is non-specific i.e. Complement of one species
can react with antibody of other species.
It constitute 5 % of normal serum protein & the
level rises during acute phase inflammation and is
not increased by immunization.
Fixation of complement is not influenced by nature
of antigen but class of immunoglobulin.
The complement binds on the fc part of
immunoglobulin CH2 (constant heavy domain) of
IgG & 4 of IgM.
Complement does not bind to free antigen &
antibody.
All classes of immunoglobulin do not fix
complement only IgM , IgG3 , IgG1 & IgG2 fix in
the respective order.
IgG4 , IgA , IgD & IgE do not fix complement.
Dr Reena Kulshrestha, M.Sc, PhD.
5. Four important functions:
• Lysis
• Opsonization
• Activation of inflammatory
response
• Clearance of immune
complexes
Dr Reena Kulshrestha, M.Sc, PhD.
11. Three pathways: Classical, Alternative, & Lectin
Final steps identical in all 3 pathways
1.Classical - Initiated by formation of an Ag- Ab
complex
2. Alternative - Antibody-independent
- Part of innate immunity
- Initiated by foreign cell
surfaces
3. Lectin - Initiated by host proteins binding
microbial surfaces
Dr Reena Kulshrestha, M.Sc, PhD.
20. Classical pathway
• Classical was discovered first (but
actually evolved later)
• Initiated by:
-formation of a soluble Ag-Ab complex
-binding of antibody to a target such as
a bacterial cell
• Only certain antibodies can initiate this
(IgM, some classes of IgG)
Dr Reena Kulshrestha, M.Sc, PhD.
35. Activator e.g.
endotoxin
C3b (bound)
factor BMg++
C3bB
C3bBb
Ba factor D
+
C3b in
circulation
Free C3b
inactivated
by factors
H and I.
(C3 convertase)Dr Reena Kulshrestha, M.Sc, PhD.
37. C567
Binds to cell
membrane and
prepares the cells for
lysis by C8 and C9
It also sensitises
bystander cells to
make them
susceptible to
lysis.
C8
C9
C3bBb3b5b6789
Cell damage or lysis.
Dr Reena Kulshrestha, M.Sc, PhD.
38. Differences Between classical and alternative pathway
1) Activators
Antigen antibody complex Bacterial endotoxins
Retroviruses IgA & IgD
C Reactive protein Cobra Venom
DNA Nephritic Factor
Trypsin like Enzyme Zymogene
2) Starting component
C1q C3
C3 activation by PZ(Properdin zymogene complex)
Mg++ Proteinase enzyme
C3a
C3
C3b
3) Attachment to Fc No attachment.
C1q has 6 combining sites.
Recognizes Fc of IgM & IgG.
4) Components
11 components C3 factors BDPH ,5,6,7,8,9
C1q, r,s,2,3,4,5,6,7,8,9
5) C3 convertase
________ _ ____
C1 4b 2b C3b Bb
Dr Reena Kulshrestha, M.Sc,
PhD.
39. Lectin pathway
• Lectin is a protein that binds to carbohydrate
• MBL (mannose-binding lectin) binds to
mannose on many bacterial cells
- MBL is produced by liver in acute-phase
inflammatory reactions
• Once MBL binds to target cell, 2 serine
proteases (MASP-1, MASP-2) bind
• Acts like C1
Dr Reena Kulshrestha, M.Sc, PhD.
41. Lectin pathway (mannose binding pathway)
Macrophages ingenst virus bacteria other foreign material
Release chemicals which stimulates
Liver cells
Acute phase proteins released like ( Mannose binding protein)
Binds to pathogens
Opsonisation Binds to lectin Binds to MASP
Phagocytosis Alternative pathway Mannose associated serine esteraseDr Reena Kulshrestha, M.Sc,
PhD.
42. Dr Reena Kulshrestha, M.Sc, PhD.
The Complement CascadeThe Complement Cascade
C5
C5a
Ba Properidin
D
C3 P C3a
B
The Alternative Pathway
C3b C3bB C3bBb C3bBbP C3bBb3
b
B
C3C3iC3iB
Ba
C3iBb
C3
C3a
The Tick-over Activation
C5b
C4
C4a
C2 C2b C3 C3a
The Classical Pathway
Antibody +
C1qrs
C4b C4b2a C4b2a3
b
43. Regulation of complement system
• Because it is nonspecific, several
regulatory mechanisms are involved
(otherwise there would be a lot of
“collateral damage”)
• Many components are very labile
• Many regulatory proteins block activity
through binding to target
Dr Reena Kulshrestha, M.Sc, PhD.
44. REGULATON OF COMPLEMENT
ACTIVATOR
[A] INHIBITOR
(1). C1 ESTERASE
* INHIBIT CLR,CLS BY BINDING TO ACTIVE SITE.
*MURAMINOGLYCOPROTEIN
*HEAT LABILE
*PREVENTS NORMAL CASCADE
*CHECKS AUTOCATALYTIC PROLONGATION
Dr Reena Kulshrestha, M.Sc, PhD.
45. REGULATON OF COMPLEMENT
ACTIVATOR
(2).S PROTIEN
*BINDS TO C567
*MODULATES CYTOLYTIC
ACTION OF MEMBRANE
ATTATCH COMPLEX
[B] INACTIVATOR
(1) Fac1
*SERUM BETA GLOBULIN
*C3B,C4B ARE CLEAVED & IN
ACTIVATED
Dr Reena Kulshrestha, M.Sc, PhD.
46. REGULATON OF COMPLEMENT
ACTIVATOR
*HOMEOSTATIC CONTROL OF C3 ACTIVATION.
*ENDOPEPTIDASE WHICH CLEAVES C3b & C4b.
(2) FACTOR H
*REGULATES ALTERNATIVE PATH WAY BY
PREVENTION FACTOR B TO BOUND TO C3
*BETA GLOBULIN FACTOR
*ACTS ALONG WITH FACTOR 1 MODULATIG C3
ACTIVATION.
Dr Reena Kulshrestha, M.Sc, PhD.
47. REGULATON OF COMPLEMENT
ACTIVATOR
(3) ANAPHYLATOXIN INACTIVATORS
*ENZYMATICALLY DEGRADES C3a,C4a,C5a
(4) C4 BINDING PROTEIN
*CONTROLS ACTIVITY OF ALL BOUND C4b
*BINDS TIGHTLY TO C4b & ENHANCES C4b
DEGRADATION.
Dr Reena Kulshrestha, M.Sc, PhD.
48. REGULATION OF COMPLEMENT
ACTIVATOR
(5) FACTOR P OR PROPERDIN
*BINDS TO A STABILIZER THE ALTERNATIVE PATH
WAY C3 CONVERTASE
*ACTIVATED PROPERDIN BINDS DIRECTLY TO BOUND
& UNBOUND C3b
*STABILIZE C3 & C5 CONVERTASE
Dr Reena Kulshrestha, M.Sc, PhD.
49. REGULATION OF COMPLEMENT
ACTIVATOR
*INDUCE FURTHER ACTIVATION OF COMPLIMENT
COMPONENT INDIRECTLY BY EXTENDING THE
HALF LIFE OF C3bBb
(6)COBRA VENOM FACTOR (COVF)
*PROTEIN FOUND IN COBRA VENOM ACTIVATES
COMPLEMENT & LYSES ERYTHROCYTES
Dr Reena Kulshrestha, M.Sc, PhD.
50. REGULATION OF COMPLEMENT
ACTIVATOR
*CAN COMBINE TO FACTOR B TO FORM COVF-Bb
COMPLEX i.e. EQUIVALENT TO C5 CONVERTASE
*VENOM IS RESISTANT TO ACTION OF
INACTIVATORS OF ALTERNATIVE PATH WAY
FACTOR H & I
Dr Reena Kulshrestha, M.Sc, PhD.
51. BIOLOGICAL EFFECTS OF
COMPLEMENT SYSTEM
(1) INFLAMMATORY RESPONSE : C3a & C5a
*ANAPHYLATOXINS
*RELEASES HISTAMINE & OTHER MEDIATOR BY
DEGRANULATION OF MAST CELLS
*CHEMOTATICE-C567
*INCREASE VASCULAR PERMEABILITY,CONTRACTION
OF SMOOTH MUSCLE,VASODILATION,COLLECTION
OF INFLAMATORY CELLS,INCREASE IN PHAGOCYTIC
ACTIVITY
Dr Reena Kulshrestha, M.Sc, PhD.
52. BIOLOGICAL EFFECTS OF
COMPLEMENT SYSTEM
(2)HYPER SENSITIVITY:TYPE II & TYPE III
(3) ENDOTOXIC SHOCK:
ALTERNATIVE PATH WAY,EXCESSIVE C3
ACTIVATION,PLATELET ADERENCE
(4) COAGULATION C3
*LYSES PROTHROMBIN
*THROMBIN RELEASES LARGE AMOUNT OF PLATELET
FACTOR
Dr Reena Kulshrestha, M.Sc, PhD.
53. BIOLOGICAL EFFECTS OF
COMPLEMENT SYSTEM
DISSEMINATED INTRAVASCULOR COAGULATION &
THROMBOCYTOPENIA
(5) IMMUNE ADHERENCE :
*C3 & C4
*ANTIGEN ANTIBODY COMPLEXES + C
ADHERE TO ERYTHROCYTES OR PLATELETS
ENHANCED PHAGOCYTOSIS
*PHAGOCYTIC CELLS HAVE RECEPTORS FOR C3b
Dr Reena Kulshrestha, M.Sc, PhD.
54. BIOLOGICAL EFFECTS OF
COMPLEMENT SYSTEM
(6) OPSONIZATION : CR1,CR2,CR9,CR4,CCq ON
MACROPHGES,NEUTROPHILL,MONOCYTES ETC.CR2
PRESENT OF B CELL
(7) AUTO IMMUNE DISEASES
E.G.-SLE & ANGIONEUROTIC OEDEMA
-DUE TO DEFICIENCY OF DOME COMPLEMENT FACTORS
Dr Reena Kulshrestha, M.Sc, PhD.
55. BIOLOGICAL EFFECTS OF
COMPLEMENT SYSTEM
(8) SUSCEPTIBILITY
GRAM NEGATIVE BACTERIA – LYSIS
GRAM POSITIVE BACTERIA- WITHOUT LYSIS
(9) C3 & C6 PARTICIPATE IN COAGULATION PROCESS
Dr Reena Kulshrestha, M.Sc, PhD.
60. Regulation of the ComplementRegulation of the Complement
CascadeCascade
Short half-time ofShort half-time of
C3bC3b
C3bBbC3bBb
C5bC5b
C1 inhibitorC1 inhibitor
Inhibits the C1s activityInhibits the C1s activity
Protein S in SerumProtein S in Serum
Binds to C5b67Binds to C5b67
→ Inhibits Formation of the Membrane AttackInhibits Formation of the Membrane Attack
ComplexComplex
Dr Reena Kulshrestha, M.Sc, PhD.
61. HRF or CD59HRF or CD59
Bind to C8Bind to C8
Inhibits C9 bindingInhibits C9 binding
Factor HFactor H
Binds to C3bBinds to C3b
→ Facilitates binding of Factor IFacilitates binding of Factor I
→ cleaves C3b to inactive iC3bcleaves C3b to inactive iC3b
→ cleaves C4b to inactive fragmentscleaves C4b to inactive fragments
Decay Accelerating FactorDecay Accelerating Factor
Increased dissociation ofIncreased dissociation of
C3 convertase (bothC3 convertase (bothDr Reena Kulshrestha, M.Sc, PhD.
62. Complement ActivationComplement Activation
GeneralGeneral
Hydrophobic surfacesHydrophobic surfaces
OxidesOxides
Strong binding of C3(b) to nucleophilicStrong binding of C3(b) to nucleophilic
groups (-NH2, -OH)groups (-NH2, -OH)
Higher absorption of C3 to crystalline TiOHigher absorption of C3 to crystalline TiO22
than to amorphousthan to amorphous
Kallikrein directly activates C5Kallikrein directly activates C5
Plasmin directly activates C5Plasmin directly activates C5
Dr Reena Kulshrestha, M.Sc, PhD.
63. Classical PathwayClassical Pathway
Antibodies IgM, IgG1, IgG2, IgG3Antibodies IgM, IgG1, IgG2, IgG3
Lectin via the mannan binding proteinLectin via the mannan binding protein
(MBP) “Lectin Pathway”(MBP) “Lectin Pathway”
Hageman Factor (F XIIa)Hageman Factor (F XIIa)
Rough surfacesRough surfaces
C-reactive protein (CRP)C-reactive protein (CRP)
(Zirkonium, transiently)(Zirkonium, transiently)
Dr Reena Kulshrestha, M.Sc, PhD.
65. Biological effects of complement
activation
• Complement fragments must bind to
complement receptors
expressed by various cells
Dr Reena Kulshrestha, M.Sc, PhD.
68. AnaphylatoxinsAnaphylatoxins
Fragments C5a, C3a, C4aFragments C5a, C3a, C4a
Degranulation of PhagocytesDegranulation of Phagocytes
Reactive oxygen speciesReactive oxygen species
ProstaglandinsProstaglandins
MonocytesMonocytes
→→ IL-1, IL-6IL-1, IL-6
Mast cellsMast cells
→→ HistamineHistamine
ChemotaxisChemotaxis
Only C5aOnly C5a
Dr Reena Kulshrestha, M.Sc, PhD.
69. Consequences in vitro
• Lysis of “innocent” neighbour cells
– Red blood cells
• Activation of phagocytic cells
– Release of reactive oxygen species
– Release of mediators
Dr Reena Kulshrestha, M.Sc, PhD.
70. ConsequencesConsequences in vivoin vivo
Factors of complement activation at revised hipFactors of complement activation at revised hip
implantsimplants
One single studyOne single study ((Tang L.Tang L. et al.et al. J Biomed Mater ResJ Biomed Mater Res 4141: 333-340 (1998)): 333-340 (1998))
Au-Mercaptoglycerol induces strong inflammatoryAu-Mercaptoglycerol induces strong inflammatory
response in control animals.response in control animals.
No reaction in Complement-depleted animals.No reaction in Complement-depleted animals.
Dr Reena Kulshrestha, M.Sc, PhD.
71. Amplifies humoral response
Destroys invading bacteria and viruses
(lysis by MAC)
Inflammatory response
Opsonization of antigen (enhances
phagocytosis)
Virus neutralization
Clearance of immune complexes
Dr Reena Kulshrestha, M.Sc, PhD.
72. Some bacteria can resist lysis
• Gram-positive bacteria
• Some microbes produce inactivating
enzymes
• Nucleated cells are harder to lyse
• Not particularly effective against tumor
cells (they can endocytose MAC and
repair damage)
Dr Reena Kulshrestha, M.Sc, PhD.
74. Inflammation
• many of the released fragments help
develop an inflammatory response
• C3a, C4a, C5a- anaphylotoxins
bind to receptors on mast cells and
basophils; degranulation
(smooth muscle contraction; capillary
dilation; fluid influx)
• also play a role in blood cell chemotaxis
Dr Reena Kulshrestha, M.Sc, PhD.
76. Viral neutralization
• Some viruses activate alternative or lectin
pathway
• Antibody-mediated (classical) pathway is
more common
• Causes aggregation of viruses; can’t infect
host cells; more vulnerable to phagocyte
• Enveloped viruses can be lysed
Dr Reena Kulshrestha, M.Sc, PhD.
78. Consequences of complement deficiency
• Early components of classical pathway (C1,
C4, C2)- immune complex disease
• can’t generate C3b, which is needed
for solubilization
• Recurrent Staph and Strep infections
(can’t lyse bacteria but seem to control
infections)
• Early components of alternative pathway-
not as serious; tendency to infections
by NeisseriaDr Reena Kulshrestha, M.Sc, PhD.
79. •C3 deficiencies (can’t activate C5 and form
MAC)
•Recurrent severe bacterial infections
•MAC deficiencies- recurrent Neisseria
infections
•Regulatory protein deficiencies
1.edema
2.RBC lysis
Dr Reena Kulshrestha, M.Sc, PhD.
80. Dr Reena Kulshrestha, M.Sc, PhD.
Methods for Investigation
General/Common pathway
– Lysis of sheep red blood cells
– Solid phase methods (ELISA, RIA)
• Products: C3a, C5a, sC5b-9
• Consumption of C3
– Ellipsometry
Classical Pathway
– Measurement of C1qrs
– Measurement of C2b or C4b2a
Alternative Pathway
– Measurement of Ba or C3bBb
– Measurement of Properidin
81. CLASSICALCLASSICAL ALTERNATIVEALTERNATIVE LECTINLECTIN
ACTIVATINGACTIVATING
SUBS.SUBS.
IMMUNEIMMUNE
COMPLEXESCOMPLEXES
(IgG OR IgM)(IgG OR IgM)
LPS (bacterialLPS (bacterial
capsule)capsule)
IgAIgA
MannoseMannose
groups ongroups on
microbial cellmicrobial cell
RECOGNITIONRECOGNITION
UNITUNIT
C1q, C1r, C1sC1q, C1r, C1s C3, Factor B,C3, Factor B,
Factor DFactor D
MBP, MASP-1,MBP, MASP-1,
MASP-2MASP-2
C3C3
CONVERTASECONVERTASE
C4b2aC4b2a C3bBbC3bBb C4b2aC4b2a
C5C5
CONVERTASECONVERTASE
C4b2a3bC4b2a3b C3bBb3bC3bBb3b C4b2a3bC4b2a3b
MACMAC
C5b6789C5b6789
END RESULTEND RESULT
CELL LYSISCELL LYSIS
Dr Reena Kulshrestha, M.Sc, PhD.
82. Biosynthesis of C
1) C1 - Intestinal epithelium
2) C2 C4 - Macrophages
3) C5 C8 - Spleen
4) C3 C6 C9 - Liver
5) C7 - Not known
6) Factors - Macrophages
B,D,P & I
Dr Reena Kulshrestha, M.Sc, PhD.
83. Compliment deficiency and associated diseases
1) C1, C2, C3 &C4 disorders - Immune and rheumatic
2) C5, C6,C7,C8 disorders - Recurrent infection (Neisseria)
3) C1q disorders - Combined immunodeficiency states
4) C1r disorder - Many infections and lupus like symptoms
5) C1s disorder - Systemic Lupus Erythematossis
6) C4 disorder - Lupus like symptoms
7) C2 disorder - Increased susceptibility to infection
8) C3 disorder - Severe Pyogenic infections
9) C5 disorder - Recurrent infection of GIT
10) C6 C7 &C8 disorder - Disseminated gonococcal infections and recurrent
Mieningococcal Meningitis
11) C9 disorder - Not more susceptible to disease than other
individual in general populations.
12) C1 Inhibitors - Hereditary angioneurotic oedema
13) C3b inactivator factor 1
& factor D Properdin -Recurrent infection
Dr Reena Kulshrestha, M.Sc,
PhD.
84. Key Facts
1. The complement system, a multi component triggered enzyme cascade, attracts
phagocytic cells to the microbes which engulf them.
2. Complement can be activated by classical and alternative pathways.
3. The amount of complement present in the serum cannot be increased by
immunization.
4. Complement participates in type II and type III Hypersensitivity.
5. Several serum compliment components are lowered in many auto immune
diseases such as systemic lupus erythematosus & Rheumatoid arthritis. They may,
therefore, be involved in the pathogenesis of auto immune diseases.
6. Complement mediates immunological membrane damage.
7. C fragments released during cascade reaction help in amplifying the inflammatory
response.
8. C3 and C4 mediate immune adherence.
9. C3 and C6 participate in Coagulation process
Dr Reena Kulshrestha, M.Sc,
PhD.
85. Summary
The complement system comprises a group
of serum proteins which, when activated,
plays an important role in antigen
clearance.
The classical, alternative and lectin pathways
have been described.
Elaborate regulatory mechanisms are required
to prevent damage to normal cells.
Dr Reena Kulshrestha, M.Sc, PhD.