This file contains detail study of the complement system of immunology. This document includes the introduction to complement system, different pathways including classical pathway, alternative pathway and lectin pathway and also the functions of complement system.
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
COMPLEMENT - A group of serum proteins which can be activated (= "fixed") by antigen-antibody complexes or other substances, which may result in lysis of a microbial target, or a variety of other biological effects important in both innate and adaptive immunity. (The majority of these proteins are produced by the liver.)The complex of serum proteins known as COMPLEMENT plays key roles in the lytic and inflammatory properties of antibodies. The CLASSICAL pathway is initiated
by antigen-antibody complexes (via complement components C1, C4, and C2), while the activation of the ALTERNATE pathway (via components B, D and P), and the MBLECTIN ("mannan-binding lectin") pathway may be initiated by other substances independently of adaptive immune responses; all three pathways share those complement components involved in the inflammatory and lytic consequences, namely C3, C5, C6,
C7, C8 and C9. The INFLAMMATION which is a consequence of complement fixation is illustrated by the manifestations of SERUM SICKNESS, and complement is also seen
to be central to the normal process of clearing immune complexes, which is important in preventing IMMUNE COMPLEX DISEASE.
The complement system, also known as complement cascade, is a part of the immune system that enhances (complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promote inflammation, and attack the pathogen's cell membrane. This pathway involves complement components C1, C2, and C4. The pathway is triggered by antibody-antigen complexes binding to C1, which itself has three subcomponents C1q, C1r, and C1s. Typically, the complement system acts as a part of the innate immune system, but it can work with the adaptive immune system if necessary. The classical complement pathway typically requires antigen-antibody complexes for activation (specific immune response), whereas the alternative pathway can be activated by spontaneous complement component 3 (C3) hydrolysis, foreign material, pathogens, or damaged cells. Anaphylatoxins generated through complement activation interact with their receptors expressed on various cells, thereby modulating their inflammatory properties. Mast cells are widely distributed in the connective tissue around blood vessels and are among the first responders during inflammation.
Through this presentation you will be able to learn about the detailed knowledge of complement system and its functions along with the complement activation pathways [classical, alternative, lectin pathway ]
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.
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.
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
COMPLEMENT - A group of serum proteins which can be activated (= "fixed") by antigen-antibody complexes or other substances, which may result in lysis of a microbial target, or a variety of other biological effects important in both innate and adaptive immunity. (The majority of these proteins are produced by the liver.)The complex of serum proteins known as COMPLEMENT plays key roles in the lytic and inflammatory properties of antibodies. The CLASSICAL pathway is initiated
by antigen-antibody complexes (via complement components C1, C4, and C2), while the activation of the ALTERNATE pathway (via components B, D and P), and the MBLECTIN ("mannan-binding lectin") pathway may be initiated by other substances independently of adaptive immune responses; all three pathways share those complement components involved in the inflammatory and lytic consequences, namely C3, C5, C6,
C7, C8 and C9. The INFLAMMATION which is a consequence of complement fixation is illustrated by the manifestations of SERUM SICKNESS, and complement is also seen
to be central to the normal process of clearing immune complexes, which is important in preventing IMMUNE COMPLEX DISEASE.
The complement system, also known as complement cascade, is a part of the immune system that enhances (complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promote inflammation, and attack the pathogen's cell membrane. This pathway involves complement components C1, C2, and C4. The pathway is triggered by antibody-antigen complexes binding to C1, which itself has three subcomponents C1q, C1r, and C1s. Typically, the complement system acts as a part of the innate immune system, but it can work with the adaptive immune system if necessary. The classical complement pathway typically requires antigen-antibody complexes for activation (specific immune response), whereas the alternative pathway can be activated by spontaneous complement component 3 (C3) hydrolysis, foreign material, pathogens, or damaged cells. Anaphylatoxins generated through complement activation interact with their receptors expressed on various cells, thereby modulating their inflammatory properties. Mast cells are widely distributed in the connective tissue around blood vessels and are among the first responders during inflammation.
Through this presentation you will be able to learn about the detailed knowledge of complement system and its functions along with the complement activation pathways [classical, alternative, lectin pathway ]
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.
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.
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 complement system, also known as complement cascade, is a part of the immune system that enhances (complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promote inflammation, and attack the pathogen's cell membrane.
This presentation is organized with the help of other presentations, text book of immunology and some internet resources for better understanding of students.
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2. Complement System | Muhammad Yousaf
Complement System
Complement system , a part of immune system, is biological cascade of reactions due to the
more than 20 proteins mainly formed by the liver cells and always found in blood circulation by reacting
with each other in an order or manner, on the surface of the pathogens. These proteins are also present
inside the body and get activated when stimulated by some triggers by an antigen when it is bound to
antigen. This complement system helps the immune system to eliminate the outsider and invader
bacteria, viruses and pathogens by helping macrophages and mast cells. The proteins in complement
system are called “Complements, Zymogens and Proenzymes”. Complement system helps the immune
system by means of opsonization, apoptosis, inflammation, phagocytosis and chemotoxicity.
These complements were first identified by Jules Bordet in 1895 as heat sensitive components
in blood that causes the opsonization and killing of bacteria. These proteins are actually the precursors
of some enzymes in inactive form. Complements are simply denoted by capital letter C with numbers
are they were discovered like C1, C2, C3 and so on. Others are represented by alphabets like B, D. Some
are simply represented by names like homologous restriction factor. Some of the proteins have further
subunits like C1 has three subunits which are C1q, C1r and C1s. C2 and C5 have two components i.e. a
and b. Larger subunits are denoted by b while smaller are denoted by a except in case of C2a which is
larger than its C1b.
Activation of Complement System & Cell Lysis
Activation of complement system is done by three pathways.
• Classical Pathway – activated by antibody-antigen reaction.
• Alternative Pathway – activated on microbial surface
• Lectin Pathway – activated by plasma lectin that binds to mannose residues on microbes.
In these pathways, as they have different various steps, but all form the complexes like C3 Convertase
which cleaves the C3 into C3a and C3b, C5 Convertase which similarly cleaves the C5 into C5a and C5b.
When C5 convertase is formed, it activates the late components of complement system to form the
Membrane Attacking Complex (MAC) and kills the pathogens.
CLASSICAL PATHWAY
Classical pathway begins when antigen-antibody complex is formed. Only IgM or IgG are responsible for
triggering the attachment of proteases. After attachment with antigen, some of the conformational
changes are produced in Fc region of antibodies exposing the binding site for C1 proteins. For the
activation of complement system, it is necessary that antibody should binds with an antigen.
As C1 is a large protein, composed of five molecules, in which one molecule of C1q and two molecules of
each C1r and C1s subunits are present. Binding of C1 occurs by means of C1q at Fc region of protein
while C1r and C1s are involved in cleavage of C4 and C2.
3. Complement System | Muhammad Yousaf
Immune complex attached with C1 also cleaves the C4 when C4 contacts with this whole complex and
converted into C4a and C4b. C4b becomes activated and attached with target surface while C4a goes
away to performs its own function, involve in calling macrophages and also in chemotoxicity. C2 is
attracted by C4b cleaves the C2 into two subunits which are C2a and C2b. Similarly, the larger subunit
C2a binds with C4b while C2b goes away as it have smaller size and performs functions like C4a. Now,
the complex of C4bC2a is called as C3 Convertase and activates the C3 by cleaving it into C3a and C3b. A
single complex of C3 Convertase can cleave a lot of numbers of C3 molecules. C3b, now has two options,
either attached with target’s surface or attached with C3 Convertase. When C3 binds with C3
Convertase, the complex is now called as C5 Convertase.
Same like C3 Convertase, C5 Convertase also activates the C5 by cleaving it into C5a and C5b. C5a goes
away but C5b stabilize itself by successively binding with C6 and C7. This C5bC6C7 complex is injected
into the membrane of target cell and binds C8 with itself. This complex also binds with a number of C9
proteins to form a hole in membrane which is called membrane attack complex (MAC). MAC allows the
intracellular fluids to come outside of the cell and unwanted substances to get into the cell also with
some water leading to the lysis of the pathogenic cell. The formation of MAC is easier in Gram negatives
bacteria as compared to Gram positives because Gram positives have rigid thick layer of peptidoglycan.
As mentioned above, C3b also cover the target’s cell surface and work like opsonin and increases the
chances of phagocytosis which is also called opsonization.
ALTERNATIVE PATHWAY
The alternative pathway is initiated without any antigen-antibody complex formation. It is initiated by
the cell surface molecules or constituents of foreign cells or pathogens like lipopolysaccharides.
Entrance of any foreign pathogen like bacteria leads to inflammation and complements reach to that
site. C3 molecules, in this case, are activated by directly contacting with antigen. Hydrolysis of C3 occurs
which cleaves the C3 into its two subunits C3a and C3b. C3b attaches with target cell surface and binds
with another serum protein called factor B. The factor B is cleaved into Ba and Bb by means of
enzymatically active serum protein known as factor D because after attaching with C3b, factor B
exposes a site which acts as substrate to factor D. The cleaved Bb remains attached with C3b to form a
complex of C3bBb also known as C3 Convertase. So, as like in classical pathway, C3 Convertase leads to
the formation of C5 Convertase which ultimately forms the MAC and kills the pathogen’s cell.
MANNOSE BINDING LECTIN (MBL) PATHWAY
Some microorganisms like bacteria, such as Salmonella, Listeria and Neisseria strains, some fungi and
some viruses including HIV-1, can activate complement system without antibody and endotoxin. This
pathway works when circulating lectin (MBL) attaches with some mannose residue on glycoproteins and
carbohydrates on the surface of target cell. The concentration of MBL increases during inflammation
and also an acute phase protein.
4. Complement System | Muhammad Yousaf
As MBL gets attached with cell’s surface carbohydrates residues, it is bounded with two other
components which are MASP-1 and MASP-2 where MASP stands for MBL-associated serine proteases.
This leads to the formation of tetrameric complex same like C1s and C1r and also cleaves the C4 and C2
and form the C3 Convertase. This pathway also resembles with classical pathway as it further continues
to form C5 Convertase and MAC and finally killing of cells.
Functions of Complement System
Some of the major functions performs by the complement system are given below:
Cell Lysis:
Cell membrane of the pathogens is ruptured by the complex C5b6789 which ultimately leads to the
death of that organism.
Opsonization:
Surface of target cell is coated by C3b protein molecules, act like opsonin and enhances the chances of
opsonization or phagocytosis.
Chemotaxis:
Protein molecules which were gone away as they formed like C5a, C3a attracts the neutrophils, mast
cells and macrophages towards antigen and cause inflammation, i.e. chemotaxis.
Antibodies Production:
B cells also produce more antibodies as they have receptors for C3b which is an antibody producing
amplifier and form an effective defense mechanism to destroy pathogens.