Complement Flashcards
What are till like receptors (TLR)
Plasma membrane and intracellular vesicles hat recognise intracellular microorganisms like tuberculae
Upon activation they induce gene expression changes
-antimicrobial peptides
-cytokines
What types of TLR are there
C type lectin receptors: carbohydrate receptors on cell membrane
Node-like receptors: in cytosome to recognise cytosolic proteins
Describe characteristics of TLR
13 cell membrane and intracellular receptors that each detect a distinct set of molecular carbohydrate; lipid or protein pattern not present in healthy vertebrate animals
What is the humoral part of the innate immune system
Complement
What is the humoral part of the adaptive immune system
Antibodies
Why does humoral mean
Mobile in liquid - soluble
Characteristics of complement
- Straddles dendritic cells
- Recognition of pathogens based on PAMPs NOT antigens
- Most component are proteases sects by liver, leukocytes and epithelium
What is the function of complement
Lysis of cells
Opsonisation —> phagocytosis
Triggering inflammation and cytokines release
Clearance of immune complexes
Explain the nomenclature of complement
Named by letter and number like C1
Fragments are named with small letters like C1a and C1b, C1b > C1a In length
Except C2a>C2b
What are the pathways of complement activation
Classical pathway
Lectin pathway
Alternative pathway
How is the classical pathway basically activated
Activated by formation of antigen-antibody complexes
How is the alternative pathway basically activated
Antibody-independent activation: spontaneous hydrolysis of C3
How is the lectin pathway basically activated
By binding MBL to mannose residues on microorganisms
Describe the steps of classical path activation from C1 to C3 convertase
- Formation of antibody complex (IgAny) exposes binding site for C1 on antibody
- C1s and r activate
- C1s cleaves C4 to C4a and C4b
- C4b + C1 cleaves C2 to C2a and C2b
- C2a + C4b = Active C3 convertase
Explain the steps of classical complement activation from C3 convertase to C5 convertase
- Hydrolysis of C3 to C3a and b by C3 convertase
- some C3b + C3 convertase = C5 convertase
- some C3b can activate Alternative pathway
Explain the steps of classical compliment pathway from C5 convertase to formation of the membrane attack complex
Hydrolysis of C5 to C5a and C5b by C5 convertase
- C5b + C6 initiates complex formation of a membrane-attack complex
Does complement work on bacterial infections
Only worked on membranes so it won’t work on gram POSITIVE bacteria due to thick peptidoglycan layer, lytic protein is needed
Explain the steps of alternative pathway activation
- Spontaneous hydrolysis of C3 to C3a and b
- Factor B + C3b and Mg2+ cleaves by factor D to make C3 convertase
- C3 convertase binds with properdin to stabilise
- C3b binds to C3 convertase to form C5 convertase
- Cleaves C5 to a and b to go on to initiate membrane attack complex like in classical
Explain the steps of the Lectin complement pathway
- MBLs recognise and bind carbohydrate targets on surface of some bacteria, fungi and viruses
- MBL-associated serine proteases MASPs bind to MBL —> similar complex to C1
- Cleavage of C4 and C2 as in the classical pathway and then joins classical pathway
Explain the steps of formation of the membrane attack complex
- C5 binds to surface of target cell rapid inactivation on its own
- Stabilisation of C5b Abu binding to C6
- (Steps above take place on hydrophilic surfaces)
- Binding of C5bC6 to C7 which attaches the complex to hydrophilic surfaces only
- Binding of C5bC6C7 to C8 to create a hole in the membrane
- 10-16 C9’s come to widen that hole and create a pore
Describe the mechanisms for the control of complement
- Production of highly liable components undergo inactivation is not stabilises e.g. C5a & C6
- Production of inhibitory proteins e.g. C1 inhibitor which dissociates C1q from C1r,s
- Steric factors e.g. C3b hydrolyses spontaneously if more than 40nm away from C3 Convertase
What can the membrane attack complexes attack
Gram negative bacteria
Some fungi
Envelopes viruses
Erythrocytes and uncleared cells
Characteristics of the membrane attack complex
Can lyse bacteria, fungi, viruses and host cells
Some microorganisms can produce complement or MAC inhibitory proteins
How does receptor covering work
Molecules cover surface of pathogen so they can’t bind to host cells
