Kurzgesagt – In a Nutshell
Sources – Complement System
One of the key players of our immune system is the complement system. An army of millions and trillions of tiny bombs, which work together in a complex and elegant dance to stop intruders in your body. Never heard of this system? Well, then it is definitely time to honor these fascinating little proteins, which keep you from getting sick.
Scientific advice and editing by:
- James Gurney
Doctor of microbiology, Atlanta
- Amyad Raduan
Medical Doctor specializing in the fields of Family and Emergency Medicine
Sources
– But one of the most important defenses of our body is largely unknown: The complement system.
Short version:
#Complement System, retrieved 2019
Long version:
#The complement system and innate immunity, 2001
https://www.ncbi.nlm.nih.gov/books/NBK27100/
– It evolved over 700 million years ago and is an army of over 30 different proteins, that work together in a complex and elegant dance to stop intruders.
#Analysis of C3 Suggests Three Periods of Positive Selection Events and Different Evolutionary Patterns between Fish and Mammals, 2012
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0037489
#Alterations in the Immune Response, Apoptosis and Synaptic Plasticity in Posttraumatic Stress Disorder: Molecular Indicators and Relation to Clinical Symptoms, 2012
#Complement diversity: a mechanism for generating immune diversity?, 1998
https://www.sciencedirect.com/science/article/pii/S0167569998013413
#Alterations in the complement cascade in post-traumatic stress disorder, 2010
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2834673/
– All in all, about 15 quintillion complement proteins are saturating every fluid in your body right now.
A healthy adult has about 5.3 micro molar of C3 in their blood. For this calculation, well round it to 5.
One micro molar equals 6.022 x 10^17 molecules in a liter.
An average adult contains roughly 5 liters of blood.
So 6 x 10^17 x 5 x 5 = 1.5x 10 ^19, or 15 quintillion.
Reference:
#A Revised Mechanism for the Activation of Complement C3 to C3b. A molecular explanation of a disease-associated polymorphism, 2014
http://www.jbc.org/content/290/4/2334.full
– Many other parts of the immune system are just tools to activate the complement system.
#The complement system and innate immunity, 2001
https://www.ncbi.nlm.nih.gov/books/NBK27100/
– The complement system does three things: It cripples enemies, it activates the immune system and it rips holes in things until they die.
#The complement system and innate immunity, 2001
https://www.ncbi.nlm.nih.gov/books/NBK27100/
– In your active shape however, you might, for example, change the shape of other proteins, activating them so they can activate others.
#Complement System Part I – Molecular Mechanisms of Activation and Regulation, 2015
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4451739/
– Our complement attack begins with C3.
#Complement System Part I – Molecular Mechanisms of Activation and Regulation, 2015
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4451739/
Comment:
To be precise, the activation of the complement system starts in three different ways: they are called the classical, lectin, and alternative pathway. But the attack itself is initiated with C3 in all three cases.
– All you really need to know is that C3 breaks into two smaller proteins (C3a and C3b) that are now activated.
#Complement System Part I – Molecular Mechanisms of Activation and Regulation, 2015
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4451739/
#Overview of Complement Activation and Regulation, 2013
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3820029/
This source gives a very good overview of the different attack methods of the complement system, which all run via the formation of C3a and b:
– One of these parts, the C3b protein, is like a seeker missile specialized in bacteria, fungi and viruses.
#Physiology, Opsonization, 2018
https://www.ncbi.nlm.nih.gov/books/NBK534215/
#Defining Targets for Complement Components C4b and C3b on the Pathogenic Neisseriae, 2007
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2223645/
#Chapter 4: The complement system, 2013
https://www.ncbi.nlm.nih.gov/books/NBK459482/
#Complement and viral pathogenesis, 2011
https://www.sciencedirect.com/science/article/pii/S0042682210008135?via%3Dihub
– It has a fraction of a second to find a victim or it will be neutralized by water molecules.
#Generation of Multiple Fluid-Phase C3b:Plasma Protein Complexes during Complement Activation: Possible Implications in C3 Glomerulopathies, 2014
https://www.jimmunol.org/content/192/3/1220.long
#The complement system and innate immunity, 2001
https://www.ncbi.nlm.nih.gov/books/NBK27100/
– The C3b anchors itself very tightly to its surface and does not let go. Finally it transforms itself into a recruiting platform, the so called C3 convertase.
#The complement system and innate immunity, 2001
https://www.ncbi.nlm.nih.gov/books/NBK27100/
– C3a is like a distress beacon.
Older but complete version:
#The Role of the Anaphylatoxins in Health and Disease
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2725201/
Newer version (paywall):
#The role of the anaphylatoxins in health and disease, 2009
https://www.sciencedirect.com/science/article/pii/S0161589009001965?via%3Dihub
Older but complete version:
Complement: a key system for immune surveillance and homeostasis, 2010
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2924908/
– The more alarm proteins immune cells encounter, the more aggressive they get.
#Physiology, Opsonization, 2018
https://www.ncbi.nlm.nih.gov/books/NBK534215/
– Phagocytes. Which means: „Cells that swallow you whole, trap you in a tiny prison and then kill you with acid“.
#Phagocyte, retrieved 2019
https://www.britannica.com/science/phagocyte
Comment:
Strictly speaking it means “mature cell that eats”, but this description explains better what they actually do.
– A Membrane Attack Complex.
#Structural basis of complement membrane attack complex formation, 2016
https://www.nature.com/articles/ncomms10587
– The enemy it might be the most useful against are viruses. Outside of cells they are completely defenseless.
#Complement Evasion Strategies of Viruses: An Overview, 2017
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5472698/
– For example when the Vaccinia virus infects a cell, it forces it to produce a protein that shuts complement activation down.
#Virus complement evasion strategies, 2003
#The Vaccinia Virus Complement Control Protein Modulates Adaptive Immune Responses during Infection, 2010
https://jvi.asm.org/content/85/6/2547
– Some bacteria for example, can grab certain molecules from the blood that keep the complement system calm and make themselves invisible.
#Hijacking Complement Regulatory Proteins for Bacterial Immune Evasion, 2016