Alternative Pathway of Complement System
HTML-код
- Опубликовано: 7 сен 2024
- 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.
You actually helped me during my undergrad days back 2012- 2014 for my physiology and now im in grad school and still watching your vids! Thank you so much for your concise explanation and beautiful art.
thanks for appreciation.. glad it helps ✌️
Just amazing.
Thumbs up 🤝❤️
thank you sir
I'm preparing for my undergraduate exam
you made it so easy to understand
thanks Azalea for appreciation..Glad it helps...All the best
Great video!
This was amazing, thank you!
thanks Lucie for appreciation..Glad it helps
Very nice sir!! Thanku so much for your videos
Great and simple explanation. Thank you, sir.
thanks for appreciation
Allah save you ,🤲
thank you so much ,it was really helfull 🙏🙏
thanks Jasmine for appreciation...Glad it helps ✌️ Allah bless u
Impressive 👏👏👏
You should plug your Patreon more! I just now realized you had one
thanks buddy
Wow nice topic
Sir. Could you please(!) upload your version of the lectin pathway ASAP? I have an exam this week and I loved the way you described the classical pathway aswell as the alternative pathway. Please, thank you!
He is from captured kashmir.
How can he upload video??
Its 24th day of curfew in Kashmir.
:( Pray for him nd his family well-being
will be published tomorrow
Brilliant explaination.....thank you so much.....🙂
thanks for appreciation.. Glad to know that it helps ✌️
Hello sir, I have been watching all ur videos....starting from pheromones to complement system. Ur way is so crisp n easy to understand, even tough topics can be easily understood.
Well I can see, u've not uploaded videos since past few days.
It's a humble request, 😞😔can u please upload more n more videos. I hope everything is ok with you.☺️😊
@Mehwish Nawaz hi mehwish....I understand all the concerns....but don't worry everything will be alright. We all love our Kashmiri brothers n sisters ❣️❣️ trust me.
@Mehwish Nawaz ☺️😊😉 hey cheer up... everything will be alright. Nice to talk to you 🤗
@@smriti220 Yeah but it's 24th day of curfew now ; (
I m worried about people living there.
Just pray for him and his family well-being.
@@mbbsmadeeasy3205 yes I understand....even I m not very happy with the recent happenings
Uploading from Delhi now .....The lectures resume.
I love your channel bhaiyya😍
Wow amazing ❤️👌😍
thank you for all your hard work! appreciate this
Good job
Totally concrete knowledge 👌👌👌 the way u explain things are really marvellous ❤️❤️❤️
thanks for appreciation..Glad to know that it helps ✌️
Nice sir
Thank you king!!
thanks for appreciation
It's good... i have understood it after seeing this
thanks for appreciation..Glad to know that it helps ✌️
nice explanation thanks
thanks for appreciation
Keep going..
thanks Nazma for appreciation
It's really helpful for me..😊😘👍sir why it's called fluid phase C3 convertase???
Thank you ,, It was so helpful
3 days before final exam P1 😓
P G H M T P I F T ... AMIN 🤲🏻
Edit: Alhamdulillah , I passed the Exam, and now I'm officially in third Stage ☺️
18/ Jun /2023
All the best ❤️
😍😊😊😊😊😊😊😊Thanku Thanku Thanku Thanku
Wlcm Wlcm Wlcm
❤❤❤❤❤
Have you heard of c3gn and if so how can it be calmed down or treated
Hello sir what is role of factor H and I in this pathway...
Arabian pass from here
great.. Glad to know that
@@hussainbiology you are brilliant 😘🔥🔥ممتاز والله العظيم
@@abdoelkoody4691 thanks Abdo... Allah bless u
Are You Shabir From UK??
he is from captured kashmir
@@mbbsmadeeasy3205 Occupied Bro!
@@DrYY97 yes indian occupied kashmir
pronounce word properly,btw lecture was very helpful.
thank you
What