COMPLEMENT SYSTEM BY SADDAM

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The complemet system PRESENTED BY:- SADDAM KHAN M.SC.(BIOTECH)II ND SEM NIET ,NIMS UNIVERSITY JAIPUR

COMPLEMENT SYSTEM:

The term "complement" was coined by Paul Ehrlich to describe the activity in serum. The complement system helps or “complements” the ability of antibodies and phagocytic cells to clear pathogens from an organism . It is found in serum and all tissue fluids except urine and Crebrospinal fluid(CSF). COMPLEMENT SYSTEM

COMPONENT OF COMPLEMENT SYSTEM:

A defensive system consisting of over 30 proteins produced by the liver, macrophages and intestinal epithelial cells . Fibroblasts and intestinal epithelial cells make C1, while the liver makes C3, C6, and C9. They are present in the circulation as inactive molecules . Several complement proteins are zymogens ( proenzymes ). COMPONENT OF COMPLEMENT SYSTEM

A Cascade system:

The complement works as a cascade system. Cascade is when one reaction triggers another reaction which trigger others and so on. These types of systems can grow exponentially very fast. During activation, some complement components are split into two parts. The larger part of the molecule called "b" while the smaller fragment called "a" may diffuse away. A Cascade system

PATHWAYS OF COMPLEMENT ACTIVATION:

The complement activation can be divided into three pathways:- Classical : most specific (antibody dependent activation, binds C1 ) Lectin binding: some specificity (mannose binding protein, binds C4 ) Alternative : most primitive (non-specific, auto-activation of C3) PATHWAYS OF COMPLEMENT ACTIVATION

CLASSICAL PATHWAY:

It was the first complement pathway to be work out so it is called classical pathway. The classical pathway is triggered by activation of the C1- complex . The C1-complex is composed of C1qr2s2. This occurs when C1q binds to IgM or IgG Complexed with antigens . Binding of C1q to Ag- Ab complexes results in autocatalysis of C1r. CLASSICAL PATHWAY

CLASSICAL PATHWAY:

The altered C1r cleaves C1s and this cleaved C1s is capable of cleaving both C4 and C2 into C4b,C4a,C2b and C2a. C4b2a complex is known as C3 convertase . C3 convertase , in the presence of Mg ++ , cleaves C3 into C3a and C3b . C3b binds to the membrane to form C4b2a3b complex whereas C3a remains in the microenvironment. C4b2a3b complex functions as C5 convertase , which cleaves C5 into C5a and C5b. CLASSICAL PATHWAY

CLASSICAL PATHWAY:

C5b initiates the formation of membrane attack complex. C1qrs can also bind to a number of agents including some retroviruses, mycoplasma , poly- inosinic acid and aggregated IgG , and initiate the classical pathway CLASSICAL PATHWAY

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Cytolysis Caused by Membrane Attack Complex

Lectin Binding Complement Pathway:

C4 activation can be achieved without antibody and C1 participation via the lectin pathway . Three proteins initiate this pathway namely a mannan -binding lectin /protein (MBL), and two mannan -binding lectin -associated serine proteases (MASP and MASP2 ). MBL binds to certain mannose residues on many bacteria and subsequently interacts with MASP and MASP2 . The MBL-MASP-MASP2 complex is similar to Ab - C1qrs complex (of classical pathway) and leads to activation of C4, C2 and C3. Lectin Binding Complement Pathway

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Lectin Binding Complement Pathway Bacteria C4 C2 C3 C5 MBP C4b C4a

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Lectin Binding Complement Pathway Bacteria C4 C2 C3 C5 MBP C4b C4a C2b C2a

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Lectin Binding Complement Pathway Bacteria C4 C2 C3 C5 MBP C4b C4a C2b C2a C3b C3a C5b C5a Animation complete

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Lectin Binding Complement Pathway Bacteria C6 C7 C8 C9 MBP C4b C2a C3b C5b C6 C7 C8 C9 C9 C9 C9 C9 C9 Animation complete

ALTERNATIVE PATHWAY:

Alternate pathway is so called because it bypasses the requirement of antigen-antibody complex, C1, C2 and C4 components. It begins with the spontaneous activation of C3 in serum and requires Factors B and D and Mg++, all present in normal serum . A C3b-like molecule (C3i) is generated by slow hydrolysis of native C3. C3i binds factor B, which is cleaved by Factor D to produce C3iBb. ALTERNATIVE PATHWAY

ALTERNATIVE PATHWAY:

C3iBb cleaves native C3 into C3a and C3b. C3b binds factor B, which is again cleaved by Factor D to produce C3bBb (now C3 convertase ). ALTERNATIVE PATHWAY

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Bacteria B C5 C3b C3 C3a Alternative Complement Pathway

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Bacteria B C5 C3b C3 C3a Bb Alternative Complement Pathway

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Bacteria C5b C3b Bb C6 C7 C8 C9 C6 C7 C8 C9 C9 C9 C9 C9 C9 C9 Alternative Complement Pathway Animation complete

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REGULATION OF COMPLEMENT SYSTEM

FUNCTION OF COMPLEMENT SYSTEM:

Lysis of cells Induce Inflammation Induce Phagocytosis :- FUNCTION OF COMPLEMENT SYSTEM

DEFICIENCY OF COMPLEMENT:

Early components: auto-immune disease Middle and late components: Pyogenic bacterial and Neisseria infections Most common congenital deficiency: C2 C1INA deficiency: Hereditary Angioedema DAF(decay accelerating factor) deficiency: Paroxysmal Nocturnal Hemoglobinuria DEFICIENCY OF COMPLEMENT

ACKNOWLEDGMENT:

Dr. Sandeep Kumar (HOD) Department of Biotechnology NIET, Nims University Jaipur Dr. Sandeep Tripathi (Assistant Professor) Department of Biotechnology NIET, Nims University, Jaipur All Faculty members All seniors, Batch mates & Juniors ACKNOWLEDGMENT

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