Role of Complement in Host Defence

8/8/2019 Role of Complement in Host Defence

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ROLE OF COMPLEMENT INROLE OF COMPLEMENT INHOST DEFENCEHOST DEFENCEPRESENTED BY:PRESENTED BY:

MRINMOY RAJBONGSHIMRINMOY RAJBONGSHI

ROLL NOROLL NO--0202

GUIDED BY:GUIDED BY:

Dr. RAJIB SHARMADr. RAJIB SHARMA


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DEFINITION OF COMPLEMENTDEFINITION OF COMPLEMENT

Paul Ehrlich of Berlin coined the term complement.Paul Ehrlich of Berlin coined the term complement.

The activity of blood serum that completes theThe activity of blood serum that completes theaction of antibody.action of antibody.

The complement system is a biochemical cascadeThe complement system is a biochemical cascadewhich helps clear pathogens from an organism.(which helps clear pathogens from an organism.(from wikipedia.com).from wikipedia.com).

It is the complex of enzyme system and selfIt is the complex of enzyme system and self

aggregating protein responsible for destructionaggregating protein responsible for destructionand removal of antigen from the body.and removal of antigen from the body.


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PATHWAYS OF COMPLEMENTPATHWAYS OF COMPLEMENTACTIVATIONACTIVATION

Complement consists of about 30Complement consists of about 30proteins in blood plasma.proteins in blood plasma.

Present as zymogens.Present as zymogens.

The complement is activated throughThe complement is activated through3 pathways3 pathways------------

1)1) CLASSICAL PATHWAY.CLASSICAL PATHWAY.

2)2) ALTERNATE PATHWAYALTERNATE PATHWAY

3)3) MBL PATHWAY.MBL PATHWAY.


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MBL PATHWAYMBL PATHWAY

MBL pathway is homologous to classical pathway.MBL pathway is homologous to classical pathway. It involves mannose binding lectin( MBL) andIt involves mannose binding lectin( MBL) and

ficolins instead of C1q.ficolins instead of C1q.

Pathway begins when MBL binds to mannosePathway begins when MBL binds to mannose

residue on pathogen surface.residue on pathogen surface.

Activates MBL associated serine proteases, MASPActivates MBL associated serine proteases, MASP--1 and MASP1 and MASP--2.( similar to C1q and C1s)2.( similar to C1q and C1s)

They split C4 into C4a & C4b and C2 into C2a &They split C4 into C4a & C4b and C2 into C2a &C2b.C2b.

C2a and C4b then bind together to form the C3C2a and C4b then bind together to form the C3convertase.convertase.


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CONTINUED.CONTINUED.

The formation C3 convertase leads to activation asThe formation C3 convertase leads to activation asin classical pathway.in classical pathway.

Ficolins are homologous to MBL and function viaFicolins are homologous to MBL and function viaMASP in a similar way.MASP in a similar way.

Ficolins are very important in invertebratesFicolins are very important in invertebrateswithout an adaptive immune system.without an adaptive immune system.

Ficolins are diversified in them and compensate forFicolins are diversified in them and compensate forthe lack of pathogen specific recognitionthe lack of pathogen specific recognitionmolecules.molecules.


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IMPORTANCE OF COMPLEMENTIMPORTANCE OF COMPLEMENT

The complement system is very important as itThe complement system is very important as itprovidesprovides------

The actual protection from the response.The actual protection from the response.

The protection is provided by lysis, opsonization,The protection is provided by lysis, opsonization,inflammation & clearance of immune complex.inflammation & clearance of immune complex.

The interaction of antibodies and antigen providesThe interaction of antibodies and antigen providesthe specificity of the response.the specificity of the response.

In simplest way we can say, antibodies finger theIn simplest way we can say, antibodies finger thetarget complement destroys it.target complement destroys it.


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NEW RESEARCH AND FINDINGSNEW RESEARCH AND FINDINGS

The role of complement in host defenseThe role of complement in host defenseagainst pneumococcal bacteremia.against pneumococcal bacteremia.

The role of complement in host defenceThe role of complement in host defenceagainst Haemophilus influenzaagainst Haemophilus influenza by bothby bothclassical and alternate pathway.classical and alternate pathway.

The role of complement in host defeneThe role of complement in host defeneagainst streptococcus pneumoniae.against streptococcus pneumoniae.


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The role of complement in HIVThe role of complement in HIVpathogenesis.pathogenesis.

It has been worked out by Alexandra TrKola atIt has been worked out by Alexandra TrKola atUniversity hospital, Zurich.University hospital, Zurich.

Direct activation of complement through gp41 andDirect activation of complement through gp41 andgp120.gp120.

Activation of classical pathway by antibodies boundActivation of classical pathway by antibodies boundto the virus surface.to the virus surface.

Direct lysis of HIVDirect lysis of HIV--1 upon antibody mediated1 upon antibody mediatedactivation of the complement system has beenactivation of the complement system has beendemonstrated in vitro.demonstrated in vitro.

Complement can boost the activity of neutralizingComplement can boost the activity of neutralizingantibodies in vivo and in vitro.antibodies in vivo and in vitro.


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COMPLEMENT DEFICIENCIESCOMPLEMENT DEFICIENCIES

The complement system is becoming increasinglyThe complement system is becoming increasinglyimplicated in diseases of the central nervous system suchimplicated in diseases of the central nervous system suchasasAlzheimer's diseaseAlzheimer's disease, and other neurodegenerative, and other neurodegenerativeconditions.conditions.

Deficiencies of the terminal pathway predispose to bothDeficiencies of the terminal pathway predispose to both

autoimmune diseaseautoimmune disease andand infectionsinfections.. Mutations in the complement regulatorsMutations in the complement regulators factor Hfactor H andand

membrane cofactor proteinmembrane cofactor protein have been associated withhave been associated withatypical haemolytic uraemic syndrome.atypical haemolytic uraemic syndrome.

Moreover a commonMoreover a common single nucleotide polymorphismsingle nucleotide polymorphism inin

factor H (Y402H) has been associated with the commonfactor H (Y402H) has been associated with the commoneye disease 'eye disease 'age related macular degenerationage related macular degeneration'. Both of'. Both ofthese disorders are currently thought to be due to aberrantthese disorders are currently thought to be due to aberrantcomplement activation on host surfaces.complement activation on host surfaces.


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REFERENCESREFERENCES

Kindt TJ, Goldsby RA, Osborne BA, Kuby Immunology, 6Kindt TJ, Goldsby RA, Osborne BA, Kuby Immunology, 6thth

edition, W.H Freeman & Company, 168edition, W.H Freeman & Company, 168--188.188.

For photographsFor photographsKuby J, 5Kuby J, 5thth edition ( e edition),edition ( e edition),www,whfreeman,com/immunology.5ewww,whfreeman,com/immunology.5e

http//www.ermm_cbcu_cam_ac_uk_fig003pgc_gif.htmlhttp//www.ermm_cbcu_cam_ac_uk_fig003pgc_gif.html

htttp//www,wikipedia.comhtttp//www,wikipedia.com

TRKOLA_NeutNet_complement.pdfTRKOLA_NeutNet_complement.pdf

http//ncbi.nlm.nih.gov/sites/entrez/complementhttp//ncbi.nlm.nih.gov/sites/entrez/complement

http//ncbi.nlm.nih.gov/pubmed/complementhttp//ncbi.nlm.nih.gov/pubmed/complement

www.answer.comwww.answer.com

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Role of Complement in Host Defence