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Tiny Bombs in your Blood - The Complement System

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Immune System

Explore the basics about the immune system with The Amoeba Sisters! This video talks about the three lines of defense and also compares cell-mediated response with the humoral response.

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Factual References:

Clark, M. A., Douglas, M., & Choi, J. (2018). Biology 2e. Houston, TX: Biology Stax.

Reece, J. B., & Campbell, N. A. (2011). Campbell biology. Boston: Benjamin Cummings / Pearson.

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Further Reading Suggestions:

Discover many other types of white blood cells here!

More about antibody classes?

More detail about the cell-mediated and humoral response?
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The Amoeba Sisters videos demystify science with humor and relevance. The videos center on Pinky's certification and experience in teaching biology at the high school level. Amoeba Sisters videos only cover concepts that Pinky is certified to teach, and they focus on her specialty: secondary life science. Learn more about our videos here:

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Tiny Bombs in your Blood - The Complement System

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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.


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Complement system immunology in hindi | opsonization immunology | inflammatory response lecture

complement system immunology in hindi | opsonization immunology | inflammatory response lecture
THE COMPLEMENT SYSTEM |Tiny Bombs in your Blood | complement System Made Easy- Immunology

Hello,my name is AAGAM SINGH SISODIYA and in this video we are going to learn about complement system which is a part of Humoral Immunity ,which helps the Antibody and phagocytosis cells to enhance there ability to clear the microbes and the damaged cells for the body of an organism , also act in inflammation ,cell membrane attacks of the pathogens
so all the information related to complement is available in the video with some examples I hope you will be helpful after watching the video ,I you are helpful from this video then please hit the Subscribe ???? button to subscribe #BiologywithAAGAMSINGH channel to get more videos on some important topics like that

Queries solved in this video

What are the four major functions of the complement system?

Is complement system innate or adaptive?

Why is the complement system important?

What are the three functions of complement?

What activates complement system?

How does complement cause inflammation?

Does the complement system kill viruses?

How does complement work?

How does the complement system kill bacteria?

Which complement protein is responsible for inflammation?

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How Bacteria Rule Over Your Body – The Microbiome

What happens when microbes talk to your brain?


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How Bacteria Rule Over Your Body – The Microbiome

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The Complement System – Soundtrack (2019)

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The Complement System

The complement system is part of the immune system. Its main function is to guide phagocytic cells and clear microbes and damaged cells from an organism. In this video, we introduce the role of C3 protein and how the protein can kill bacteria with/without the help from the other parts of the immune system. The video ends with an illustration of how those powerful tiny bombs (proteins) contribute to the progression of Alzheimer’s disease.

This video was made by McMaster students Jiawen Deng, Jiawei Sun, Simran Saini, Gurratan Gill in collaboration with the McMaster Demystifying Medicine Program.

Copyright McMaster University 2020

References:
Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P. Analyzing Protein Structure and Function. In: Molecular Biology of the Cell. 4th edition. New York, US: Garland Science, 2002.

Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P. Protein Function. In: Molecular Biology of the Cell. 4th edition. New York, US: Garland Science, 2002.

Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P. The Shape and Structure of Proteins. In: Molecular Biology of the Cell. 4th edition. New York, US: Garland Science, 2002.

Bayly-Jones C, Bubeck D, Dunstone MA. The mystery behind membrane insertion: a review of the complement membrane attack complex. Philos Trans R Soc Lond B Biol Sci 2017; 372. DOI:10.1098/rstb.2016.0221.

Bohlson SS, O’Conner SD, Hulsebus HJ, Ho M-M, Fraser DA. Complement, c1q, and c1q-related molecules regulate macrophage polarization. Front Immunol 2014; 5: 402.

Carson MJ, Doose JM, Melchior B, Schmid CD, Ploix CC. CNS immune privilege: hiding in plain sight. Immunol Rev 2006; 213: 48–65.

Daneman R, Prat A. The blood-brain barrier. Cold Spring Harb Perspect Biol 2015; 7: a020412.

Hartz AMS, Bauer B, Soldner ELB, et al. Amyloid-β contributes to blood-brain barrier leakage in transgenic human amyloid precursor protein mice and in humans with cerebral amyloid angiopathy. Stroke 2012; 43: 514–23.

Lodish H, Berk A, Zipursky SL, Matsudaira P, Baltimore D, Darnell J. Section 15.2: Overview of Membrane Transport Proteins. In: Molecular Cell Biology. 4th edition. New York, US: W. H. Freeman, 2000.

Merle NS, Noe R, Halbwachs-Mecarelli L, Fremeaux-Bacchi V, Roumenina LT. Complement System Part II: Role in Immunity. Front Immunol 2015; 6: 257.

Morgan BP. Complement in the pathogenesis of Alzheimer’s disease. Semin Immunopathol 2018; 40: 113–24.

Noris M, Remuzzi G. Overview of complement activation and regulation. Semin Nephrol 2013; 33: 479–92.

Ow S-Y, Dunstan DE. A brief overview of amyloids and Alzheimer’s disease. Protein Sci 2014; 23: 1315–31.

Parra-Medina R, Quintero-Ronderos P, Rodríguez ÉG. Chapter 4: The complement system. In: Anaya JM, Shoenfeld Y, Rojas-Villarraga A, Levy RA, Cervera R, eds. Autoimmunity: From Bench to Bedside. Bogota, Colombia: El Rosario University Press, 2013.

Priego N, Valiente M. The Potential of Astrocytes as Immune Modulators in Brain Tumors. Front Immunol 2019; 10: 1314.

Sarma JV, Ward PA. The complement system. Cell Tissue Res 2011; 343: 227–35.

Singhrao SK, Neal JW, Rushmere NK, Morgan BP, Gasque P. Spontaneous classical pathway activation and deficiency of membrane regulators render human neurons susceptible to complement lysis. Am J Pathol 2000; 157: 905–18.

Yang I, Han SJ, Kaur G, Crane C, Parsa AT. The role of microglia in central nervous system immunity and glioma immunology. J Clin Neurosci 2010; 17: 6–10.

The Complement System

The complement system is an important part of the immune system. It is a set of proteins that acts (sometimes in concert with antibodies and white blood cells) to kill germs, destroy unnecessary cells that need to be removed, and to clean up the debris afterward. Through these normal processes, the complement system promotes inflammation.1 The complement system consists of more than 40 proteins, which are normally present in an inactive state. However, they can be activated by a process called cleavage, which means that a portion is split off, usually through the action of an enzyme. When one of these complement proteins becomes activated, it can act as an enzyme to activate another kind of complement protein. This chain reaction, in which one kind of complement protein sequentially activates another, is called a cascade. Activation of the complement system can start from any of 3 pathways, all of which trigger the cascade reaction that leads to cell destruction and removal.1

The 3 complement pathways include the classical pathway, the lectin pathway, and the alternative pathway. The classical complement pathway is activated when an antibody binds to an antigen, which is usually a foreign protein, such as a protein on a bacterium or virus. In contrast, the lectin pathway activates complement when a protein called mannose-binding lectin binds to a foreign carbohydrate, such as those found on the outside of many bacteria, viruses, protozoa, or fungi. The alternative complement pathway can be initiated by spontaneously activated complement attaching to pathogens or cells.1

All 3 pathways (classical, lectin, and alternative) eventually lead to the cleavage of complement factor C3 into C3a and C3b. The cleavage of C3 must occur for the complement system to have its intended effects on cells. C3a promotes inflammation, while C3b opsonizes (labels) cells so that they will be cleared from the system by white blood cells. C3b also activates C5 by splitting it into C5a and C5b. C5a promotes inflammation by attracting inflammatory cells. C5b makes up part of the membrane attack complex (MAC), which kills cells by forming a hole in their cell membrane, resulting in their lysis (rupture).1

In a healthy person, the complement system is under tight control, to keep an immune response from damaging the body itself.

1. Murphy K, Weaver C. Innate immunity: the first lines of defense. In: Janeway's Immunobiology. 9th ed. London, UK: Garland Science; 2016.

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Tiny Bombs in your Blood - The Complement System


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Activation Of Complement System Immunology [HD Animation ]

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The Ebola Virus Explained — How Your Body Fights For Survival

What does the Ebola virus actually do in your body? Why is it so dangerous and why does it kill so many people? We take a look at the apocalyptic war that rages in the body after an infection by the Ebola virus and the soldiers fighting.


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The Ebola Virus Explained — How Your Body Fights For Survival

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The Complement System [HD Animation ]

Complement Cascade

This video looks at some components of the complement cascade.

Activation of the Complement System Animation

The complement system, also known as the complement cascade, forms a part of the innate immune system. Complement components are generally made in the liver and circulate in their inactive form until they are needed.

The overall aim of the complement system is to support other parts of the immune response by opsonising pathogens and triggering inflammation.

This article shall cover the activation of the complement system, its roles in the immune response and relevant clinical conditions.
Activation of the Complement System

There are three ways to activate the complement system, involving different molecules initially but converging to produce the same effector molecules. Each involves activation of enzymes that cleave their substrates to form a cascade, so that the complement response is amplified.

The Classical Pathway
The Mannose-Binding Lectin Pathway
The Alternative Pathway

All three pathways produce C3 convertase, an enzyme which triggers further effects downstream. The effects of C3 convertase are discussed below.
The Classical Pathway

The classical pathway is activated when a complement protein called C1q binds either directly to a pathogen, or onto an antigen-antibody complex. This will then trigger cleavage of the subsequent complement proteins in the cascade, resulting in production of C3 convertase and it’s downstream effects.

Its involvement in antigen-antibody complexes means it has a role in the adaptive immune response as well as the innate.
The Mannose-Binding Lectin (MBL) Pathway

Mannose-Binding Lectin (MBL) is a protein produced in the liver. Its role is to detect carbohydrates containing mannose on the surface of pathogens, activating a protease called MASP. MASP is responsible for cleaving complement components, which activates a similar cascade to the classical pathway, eventually producing C3 convertase.
The Alternative Pathway

The alternative pathway is usually activated by bacterial endotoxin, a lipopolysaccharide present on the outer membrane of gram negative bacteria. This results in spontaneous hydrolysis of C3 into small amounts of factor C3b, which combines with other factors to produce C3 convertas


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Alternative Pathway of Complement System

The complement system 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. It is part of the innate immune system, which is not adaptable and does not change during an individual's lifetime. The complement system can, however, be recruited and brought into action by antibodies generated by the adaptive immune system.
The complement system consists of a number of small proteins that are synthesized by the liver, and circulate in the blood as inactive precursors. When stimulated by one of several triggers, proteases in the system cleave specific proteins to release cytokines and initiate an amplifying cascade of further cleavages.
Most of the proteins and glycoproteins that constitute the complement system are synthesized by hepatocytes. But significant amounts are also produced by tissue macrophages, blood monocytes, and epithelial cells of the genitourinary system and gastrointestinal tract. The three pathways of activation all generate homologous variants of the protease C3-convertase. 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. The mannose-binding lectin pathway can be activated by C3 hydrolysis or antigens without the presence of antibodies (non-specific immune response). In all three pathways, C3-convertase cleaves and activates component C3, creating C3a and C3b, and causes a cascade of further cleavage and activation events. C3b binds to the surface of pathogens, leading to greater internalization by phagocytic cells by opsonization.

The classical pathway is triggered by activation of the C1-complex. The C1-complex is composed of 1 molecule of C1q, 2 molecules of C1r and 2 molecules of C1s, or C1qr2s2. This occurs when C1q binds to IgM or IgG complexed with antigens. A single pentameric IgM can initiate the pathway, while several, ideally six, IgGs are needed. This also occurs when C1q binds directly to the surface of the pathogen. Such binding leads to conformational changes in the C1q molecule, which leads to the activation of two C1r molecules. C1r is a serine protease. They then cleave C1s (another serine protease). The C1r2s2 component now splits C4 and then C2, producing C4a, C4b, C2a, and C2b (historically, the larger fragment of C2 was called C2a but is now referred to as C2b). C4b and C2b bind to form the classical pathway C3-convertase (C4b2b complex), which promotes cleavage of C3 into C3a and C3b. C3b later joins with C4b2b to make C5 convertase (C4b2b3b complex).
This change in shape allows the binding of plasma protein Factor B, which allows Factor D to cleave Factor B into Ba and Bb.

Bb remains bound to C3(H2O) to form C3(H2O)Bb. This complex is also known as a fluid-phase C3-convertase. This convertase, the alternative pathway C3-convertase, although only produced in small amounts, can cleave multiple C3 proteins into C3a and C3b. The complex is believed to be unstable until it binds properdin, a serum protein. The addition of properdin forms the complex C3bBbP, a stable compound which can bind an additional C3b to form alternative pathway C5-convertase.

The C5-convertase of the alternative pathway consists of (C3b)2BbP (sometimes referred to as C3b2Bb). After the creation of C5 convertase (either as (C3b)2BbP or C4b2a3b from the classical pathway), the complement system follows the same path regardless of the means of activation (alternative, classical, or lectin). C5-convertase cleaves C5 into C5a and C5b. C5b binds sequentially to C6, C7, C8 and then to multiple molecules of C9 to form membrane attack complex.

Complement System - How your Immune System Works (Cells at Work Parody)

Alternative Pathway of Complement Activation - PERSONIFIED!

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#CellsAtWork #CheapVersion #AlternativePathway #immunology #immunesystem #complementsystem #fordummies

Complement System ( part 1)

Complement System ( part 1)

The Complement System - Let us guide you on the Complement Path

The complement system is an important part of the immune system. However, overactivation can cause disease. Find out about the Complement system and how we can assist in your drug development project.

Let us guide you on the complement path

Complement Proteins Responsible for Protecting the Body

There is a system in the body that protects it at all times. Complement proteins, one component of that system, are programmed to attack virtually every cell in the body. Although they exist to protect the body, they regard all the cells that comprise that body as hostile. This is really astonishing.

Complement proteins are manufactured in the liver, from where they enter the bloodstream and under normal conditions, travel through the bloodstream at random, producing no effects. When stimulated, however, they suddenly decide to eradicate all the cells they encounter.

However, harmless cells belonging to the body have been created in such a way as to defend themselves against complement proteins. As soon as complement proteins make contact with cells, the cells neutralize those proteins.

On the other hand, any foreign organisms that have entered into the body, will be subjected to an unexpected assault from these security guards.

When one complement protein attaches itself to a foreign organism, it changes its own shape. Then other proteins belonging to the complement system adhere to the bacterium, one by one. The final element in the complement system opens a hole in the now-defenseless bacterium's cell membrane. Following this attack, the bacterium absorbs water and explodes.

All this demonstrates that a single bacterium entering the body, and the molecules that wage war on it, are all the work of a single Creator, our Lord God. Bacteria are well aware of the dangers they will encounter. Body cells, take precautionary measures before even recognizing a bacterium that may enter the body. It is utterly irrational to claim that unconscious cells could take these measures themselves. It is God, Lord and Ruler of the entire universe, Who creates this system.

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