Ch2 Innate Immunity: the Immediate Response to Infection Flashcards
complement system what is it and end goal
enzymatic (protease) cascade to label pathogens for destruction
what is the compliment system made of
soluble compliment proteins-liver
soluble compliment control proteins
cell surface receptors on immune cells
what is the outcome of compliment system
coat pathogen (opsonization)
compliment fixation
c3 is cleaved into c3a-Chemoattractant
anaphylatoxins sounds the alarm and c3b-opsonizes pathogen complement fixation tags for identification and destruction
what are the 3 pathways of compliment system and their order
- Alternative Pathway is first to activate during infection; innate immunity.
- Lectin Pathway is second to activate during an infection; innate immunity.
- Classical Pathway is last to activate during an infection; innate and adaptive immunity
how does C3 initiate the alternative pathway?
C3 hydrolyzes to iC3. Factor B is attracted to iC3 and binds to it. Factor D comes in and cleaves factor b into Bb and Ba. Ba is released and Bb stays on the iC3 making iC3Bb (soluble C3 convertase). ic3b cleaves C3 inta C3b and C3a. C3b binds to the pathogen
how does C3b multiply on the pathogen surface?
factor B binds to C3b and factor D comes and cleaves it. It turned into C3bBb(insoluble) and Ba. C3bBb keeps cleaving C3 into C3b and C3a.
what does Properdin do?
stabalizes the C3 convertase (C3bBb) on the pathogen surface. This is so it can keep making C3b to bond and fire up the immune system.
what does factor H do?
innactivates C3b. it binds to C3b and changes its conformation. Factor i comes in and cleaves iC3b into an inactive form. Now iC3b cant bind b.
DAF do to C3 convertase?
Decay accelerating factor binds to C3b and dislodges Bb when it tried to bind to C3b.
what does MCP do to c3 convertase?
membrane cofactor protein (MCP) binds to C3b and dislodges Bb. this allows factor I to cleave iC3b and disrupts C3 convertase.
What is the first effector cell to to encounter pathogens
macrophages
how to macrophages swallow pathogens?
Macrophages are professional APC tissues that express many cell surface receptors. CR1 (compliment receptor 1) binds C3b on the pathogen. The macrophage endocytosises the pathogen the macrophage membranes fuse together to create the phagosome. Lysosomes fuse with the phagosome to form a phagolyosome.
What other complement receptors bind to iC3b?
CR3 and CR4 (integrins) they have the same effect as CR1
What are terminal complement components
C5-C9
What are C5-C9 and what do they do?
they are terminal compliment components. They are used to form MAC (membrane attack complexes) which create holes in the membrane.
how is C5 activated
C5 is similar to C3 but no thioester bond and different function. It is activated by alternative pathway C5 convertase: C3b2Bb. This creates C5a and C5b.
How are Mac complexes formed
C5b binds C6 to make C5b6. C5b6 binds C7 which exposes a hydrophobic site for the pathogen to attach. C5b67 binds C8 which induces the polymerization of C9 molecules. 18 of the C9 molecules come together to form the MAC pore.
How is the pore stopped from forming on the human cell?
CD59 binds to C5b678 complex. This prevents the recruitment of C9 to form the pore.
Factors that prevent MAC pores from forming on the human cell?
Factor J, Protein S and clusterin- prevent the association of C5b, C6, C7
HRF (Homologous restriction factor) and C59 (protectin)- prevent polymerization of C9
C3a and C5a are….?
Anaphylatoxins= mast cells and basophils
Chemoattractant= monocytes and neutrophils
What are protease inhibitors?
Plasma proteins. The Alpha macroglobulin trick the protease with a bait region and engulf it. Macrophages then work to kill the protease.
How do alpha macroglibulins trap proteases?
The alpha macroglobulin with a C3 like thoeister bond has a bait region that the protease interacts with. once the protease is baited it is covalently bonded with the alpha macroglobulin and the conformational shape changes. This causes the macroglobulin to engulf the protease and the macrophages then kill it.
what are defensins and what are the 2 sub groups
defensins are a large family of anti microbial proteins. They are divided into 2 classes alpha defensin and beta defensin.
What do defensins do?
disrupt the 3D structure of toxins ; anti-chaperones
create pores in the pathogen’s plasma membranes
what is alpha defensin?
α defensins: myeloid and enteric [gut] defensins
❖ 4 are found in neutrophil granules
❖ HD5: human defensin 5 found in Paneth cells: small intestines ❖ HD6: human defensin 6 found in Paneth cells: small intestines.
