Innate Immunology Flashcards
What are the main roles of the innate immune system?
- to trigger a proinflammatory response
- signal to the adaptive arm of the immune system
resolve infection and promote angiogenesis
What are examples of inflammatory inducers?
- Bacterial lipopolysaccharides
- ATP in the cytosol
- Urate crystals
What cells are sensor cells?
- macrophages
- neutrophils
- DCs, mast cells
- all are APCs
What are opsonic receptors?
They tag pathogen to allow ingestion by phagocytosis
Examples of opsonic receptors.
- Fc receptors
- Complement receptors
- Fibronectin mannose binding lectin (MBL)
*these are all found on the surfaces of phagocytes
What are the function of the complement system?
- opsonise microbes for phagocytosis
- signalling to promote inflammation and chemotaxis
- direct killing by MAC
What is a Zymogen?
an inactive substance which is converted into an enzyme when activated by another enzyme
Describe the classical complement activation.
- C1q binds to Fc region of antibody bound to a surface molecule of a microbe.
- this activates serine proteases C1r and C1s
- initiates a proteolytic cascade involving other complement proteins, CD4 and CD2
What are the cleavage products of C3? + function?
C3a - binds to pathogen surface and acts a as an opsonin
- initiates amplification of the alternative pathway
- binds C5 for cleavage by C2a
C3b - peptide mediator for inflammation
What are the cleavage products of C1? + function?
C1s - cleaves C4 and c2
C1q - binds directly to pathogen surfaces or indirectly to Fc portion of antibodies bound to microbial surface proteins
C1r - cleaves C1s to active protease
What are the cleavage products of C2? + function?
C2a - active enzyme of classical pathway C3/C5 convertase (cleaves C3 and C5)
C2b - precursor of vasoactive C2 kinin
What are the cleavage products of C4? + function?
C4a - peptide mediator of inflammation
C4b - covalently binds to pathogen and opsonises it
what is the C3 convertase? and which pathway is this formed in? which molecules allows its formation?
C4bC2a
Lectin
MASP-2
Explain the cleavage of C3.
- C3 consists of an alpha and beta chain which is bound together with a disulphide bond
- TED bond in C3a contains a highly reactive thioester bond
- cleavage of C3 releases C3a from the complex causing a conformational change in C3b which exposes thioester bond
Explain the cleavage of C3.
- C3 consists of an alpha and beta chain which is bound together with a disulphide bond
- TED bond in C3a contains a highly reactive thioester bond
- cleavage of C3 releases C3a from the complex causing a conformational change in C3b which exposes thioester bond
MBL or MASP- 2 deficiencies.
individuals experiences significantly more respiratory diseases by common extracellular bacteria during early childhood
What is the dominant complement pathway during homeostasis?
The Alternative pathway
What is the C3 convertase of the alternate pathway?
C3bBb
- it produces C3b so it generates more of itself
How is the alternative pathway activated?
2 WAYS
1. Lectin and Alternative pathway
2. Spontaneous hydrolysis of C3
What stabilises C3(H2O)Bb
Properdin, secreted by neutrophils at sites of inflammation to positively regulate AP activity by stabilising C3
