Complement Flashcards

1
Q

What are till like receptors (TLR)

A

Plasma membrane and intracellular vesicles hat recognise intracellular microorganisms like tuberculae
Upon activation they induce gene expression changes
-antimicrobial peptides
-cytokines

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2
Q

What types of TLR are there

A

C type lectin receptors: carbohydrate receptors on cell membrane
Node-like receptors: in cytosome to recognise cytosolic proteins

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3
Q

Describe characteristics of TLR

A

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

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4
Q

What is the humoral part of the innate immune system

A

Complement

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5
Q

What is the humoral part of the adaptive immune system

A

Antibodies

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6
Q

Why does humoral mean

A

Mobile in liquid - soluble

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7
Q

Characteristics of complement

A
  • Straddles dendritic cells
  • Recognition of pathogens based on PAMPs NOT antigens
  • Most component are proteases sects by liver, leukocytes and epithelium
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8
Q

What is the function of complement

A

Lysis of cells
Opsonisation —> phagocytosis
Triggering inflammation and cytokines release
Clearance of immune complexes

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9
Q

Explain the nomenclature of complement

A

Named by letter and number like C1
Fragments are named with small letters like C1a and C1b, C1b > C1a In length
Except C2a>C2b

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10
Q

What are the pathways of complement activation

A

Classical pathway
Lectin pathway
Alternative pathway

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11
Q

How is the classical pathway basically activated

A

Activated by formation of antigen-antibody complexes

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12
Q

How is the alternative pathway basically activated

A

Antibody-independent activation: spontaneous hydrolysis of C3

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13
Q

How is the lectin pathway basically activated

A

By binding MBL to mannose residues on microorganisms

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14
Q

Describe the steps of classical path activation from C1 to C3 convertase

A
  • 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
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15
Q

Explain the steps of classical complement activation from C3 convertase to C5 convertase

A
  • Hydrolysis of C3 to C3a and b by C3 convertase
  • some C3b + C3 convertase = C5 convertase
  • some C3b can activate Alternative pathway
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16
Q

Explain the steps of classical compliment pathway from C5 convertase to formation of the membrane attack complex

A

Hydrolysis of C5 to C5a and C5b by C5 convertase

- C5b + C6 initiates complex formation of a membrane-attack complex

17
Q

Does complement work on bacterial infections

A

Only worked on membranes so it won’t work on gram POSITIVE bacteria due to thick peptidoglycan layer, lytic protein is needed

18
Q

Explain the steps of alternative pathway activation

A
  • 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
19
Q

Explain the steps of the Lectin complement pathway

A
  • 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
20
Q

Explain the steps of formation of the membrane attack complex

A
  • 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
21
Q

Describe the mechanisms for the control of complement

A
  • 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
22
Q

What can the membrane attack complexes attack

A

Gram negative bacteria
Some fungi
Envelopes viruses
Erythrocytes and uncleared cells

23
Q

Characteristics of the membrane attack complex

A

Can lyse bacteria, fungi, viruses and host cells

Some microorganisms can produce complement or MAC inhibitory proteins

24
Q

How does receptor covering work

A

Molecules cover surface of pathogen so they can’t bind to host cells