This presentation is organized with the help of other presentations, text book of immunology and some internet resources for better understanding of students.
This presentation describes the Fish Complement system and different types of pathways involved and the mechanism behind the regulation of complement proteins. It gives a basic and a detailed explanation regarding the topic.
This presentation is organized with the help of other presentations, text book of immunology and some internet resources for better understanding of students.
This presentation describes the Fish Complement system and different types of pathways involved and the mechanism behind the regulation of complement proteins. It gives a basic and a detailed explanation regarding the topic.
Assembly of Macromolecular Complexes
Carbohydrate
Proteins
Nucleic acid
*Presented By:
Abubakar Mustapha
Pharm. D Third Year, Integral University Lucknow, UP, India
"Complement" describes a system of about 20 proteins, many of which are enzyme precursors. The principal actors in this system are 11 proteins designated C1 through C9, B, and D,
All these are present normally among the plasma proteins in the blood as well as among the proteins that leak out of the capillaries into the tissue spaces.
The enzyme precursors are normally inactive, but they can be activated mainly by the so-called classic pathway.
Assembly of Macromolecular Complexes
Carbohydrate
Proteins
Nucleic acid
*Presented By:
Abubakar Mustapha
Pharm. D Third Year, Integral University Lucknow, UP, India
"Complement" describes a system of about 20 proteins, many of which are enzyme precursors. The principal actors in this system are 11 proteins designated C1 through C9, B, and D,
All these are present normally among the plasma proteins in the blood as well as among the proteins that leak out of the capillaries into the tissue spaces.
The enzyme precursors are normally inactive, but they can be activated mainly by the so-called classic pathway.
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.
There are three pathways of complement activation: the classical pathway, which is triggered directly by pathogen or indirectly by antibody binding to the pathogen surface; the MB-lectin pathway; and the alternative pathway, which also provides an amplification loop for the other two pathways
The 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.
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Complementary system
1. COMPLEMENT
SYSTEM IN FISH
PRESESNTED BY : ANJALI BALA NAIK
DEPARTMENT OF FISH PATHOLOGY AND HEALTH MANAGEMENT
FISHERIES COLLEGE AND RESEARCH INSTITUTE
TAMILNADU DR J. JAYALALITHAA FISHERIES UNIVERSITY
2. INTRODUCTION
The study of fish complement ,began in 1960,s- in cartilagenous fish and 1970,s in
teleosts.
The complement defensive system consists of 35 soluble proteins and membrane bound
proteins and cell receptors that plays a critical role in the host defence by interacting with
component of both innate and acquired immunity.
Characteristics of different complement system:
• More heat liable
• Lower reaction temperature
• Difficulty in preservation
• species/group specific
• High antimicrobial action
3. • FUNCTIONS OF THE COMPLEMENT SYSTEM ARE:
1. Immune clearance : removing immune complexes from the circulation
2. Lysis of bacteria , viruses and cells.
3. Opsonization; promoting phagocytosis of particulate antigen
4. Inflammation and secretion of immunoregulatory molecules.
4. COMPLEMENT COMPONENT
• Complement component are made up of proteins and glycoprotein produced in
the liver in an inactive form (zymogen). These zymogens circulate in the serum
as proenzymes which is functionally inactive.
• Activation is induced by the proteolytic cleavage.
• Constitute 5% of serum globulin fractions.
• The complement works as a cascade system.
(Cascade is when one reaction triggers another
reaction which triggers others and so on.
These types of systems can grow exponententially
very fast.
5. • Designated by numbers(C1-C9), by letters symbols, or by trivial names (factor-
D).
• The complement fragment interact with one another to form functional complexes
and these complexes having enzymatic activity are written by a bar over the
symbol or number (e.g- C4b2a3b).
• Complement proteins are often designated by an uppercase letter C and are
inactive until they are split into products(e.g.C1)
• When the products split they become active . The active products are usually
designated with a lower case a(smaller fragments) or b(larger
fragments) (e.g . C1a and C2b).
• the larger fragments binds to the target near the site of the activation and the
smaller fragments diffuse from the site and can initiate localized inflammatory
response by binding to specific receptors.
6. • The complement components isolated in teleost are C1q, C1r, C1s, MBL,
MASP, Bf, C2, C3, C4, C5, C6,C7, C8, C9 and factor D.
• The shark or the cartilagenous fish contains the classical and alternative
pathway.
• In cyclostomes, cytolytic activity of the complement is absent in serum and has
only alternative pathway of C3 activation.
• Like mammals fish also has both the pathways.
8. ACTIVATION OF COMPLEMENT SYSTEM
COMPLEMENT SYSTEM
CLASSICAL PATHWAY ALTERNATIVE
PATHWAY
LECTIN PATHWAY
RECRUITMENT OF
INFLAMMATORY CELLS
FACILITATING
PHAGOCYTOSIS
DIRECT KILLING OF
PATHOGENOPSONIZATION OF
PATHOGENS
COMPLEMENT ACTIVATION
9. CLASSICAL PATHWAY
• Activated by antibody complexes.
• C1q attaches to fc region of the complex and
activates C1r and cleaves C1s to activate
protease function.
• C1: first component of complement
Calcium dependent protein complexes
• Initial activation stage involves c1, c2, c3, c4
which are present in plasma but in functionally
inactive form.
• Larger subunit ‘b’ attached to cell and ‘a’
smaller subunit is released( except c2a is
attached and c2b is released).
• The last c5b along with c6, c7, c8 and c9
forms the membrane attack complex
10. ALTERNATIVE PATHWAY
• Single c3 convertase molecule can
generate over 200 molecules of c3b.
• C3 contains a unstable thioester bond
which spontaneously hydrolyses to C3a
and C3b.
• C3b gets deposited on cell surface(has
ability to bind to the antigen) by covalent
bonding thus serve as opsonin .
• FACTOR B: a protein homologous to C2
to form a complex ,stabilized by
magnesium ion.
• FACTOR D: A plasma serine protein.
• PROPERDIN: also called factor P, binds
to C3bBb to make it stable.
11. • C3bBbP make up the C3 activation
complex for alternative pathway.
• This complex binds to more C3 cleaving
it to C3a and C3b .
• Forming C3bBb3b which forms
C5convertase.
12. LECTIN PATHWAY
• Lectin proteins recognize and binds to specific
carbohydrate targets(lectin is a sugar binding
molecule).
• Pathway is initiated by binding of a protein
complex :Mannose- binding lectin(MBL) and
serine protease(mannose binding lectin
associated serum protease,MASP).
• MASP 1 and MASP 2 acts as c1 and cleaves
C4 and C2.
• Then the pathway continues as classical
pathway leading to formation of membrane
attack complex.
13. MEMBRANE ATTACK COMPLEX’
• The membrane attack complex starts creating pores
or channel through the cells membrane getting
deposited on it.
• The complex causes the cytolysis of cell by impairing
the membrane osmotic stability causing lysis of the
cell.
• The pathway can lyse gram negative bacteria, virus,
parasites, erythrocytes and nucleated cells.
• Gram positive bacteria are resistant to complement
mediated lysis because of thick peptidoglycan layer in
cellwall which prevents MAC insertion.
14. BIOLOGICAL EFFECTS OF COMPLEMENT
SYSTEM
• OPSONIZATION:C3b and C1q enhance phagocytosis.
• ANAPHYLATOXIN: C5a, C4a, C5a ;causes degranulation of mast cells
these are smaller complement fragments generated during complement
activation by cleavage called anaphylatoxins.
These anaphylatoxins induce smooth muscles contractions and increase vascular permeability
resulting in influxes of fluid carrying antibody and phagocytes to the site of antigen entry.
• CHEMOTAXIS: C5a and C5, 6, 7 complex attracts neutrophils.
• ENHANCEMENT OF ANTIBODY PRODUCTION: binding of C3b to its receptors on the surface
of activated Bcells enhance antibody production.