Immunology 2 Flashcards
What are the three components of the innate immune system?
The activation of the complement system, phagocytosis by macrophages, and neutrophils and destruction by natural killer cells.
What are the functions of the complement system?
- To produce MACs – Membrane Attacking Complexes which pierce the membrane of pathogen.
- Produce anaphylatoxins – important to increase vascular permeability and act as chemo-attractors for neutrophils and macrophages to the site of infection.
- Prime pathogens for phagocytosis through opsonisation
- Attract neutrophils to the site of injury
What are the three pathways in which the complement cascade can be activated?
- Classical pathway
- Lectin-Mannose binding pathway
- Alternative pathway
How is the classical pathway initiated?
The production of an antigen-antibody complex. It therefore is not the first pathway to occur as it requires activation of the adaptive immune system.
What type of protease enzymes are complement proteins?
Serine proteases (serpins). They are highly specific – one complement protein cleaves another in a specific site.
What is the product of the classical pathway?
Opsins, anaphylatoxins and MACs.
What is the classical pathway?
C1 binds to the antigen-antibody complex and cleaves C2 into C2a and C2b. This complex also cleaves C4 into C4a and C4b. C2a and C4b form a complex to cleave C3 into C3a and C3b. C2a/C3b/C4b all work together to cleave C5 into C5a and C5b. C5b works with C6, C7, C8 and C9 to form MACs.
What anaphylatoxins are produced in the classical pathway?
C5a, C3a, C4a and C2b.
What is the lectin-mannose binding pathway?
The MBL (mannose binding lectin) – opsins – bind to mannose. This is a group of sugars only found on the surface of pathogens – not mammalian cells. MBL binds to mannose on the pathogen surface, this binds to MASP 1 (MBL associated serine protease) and MASP 2 activate C2 and C4. The rest of the pathway is identical to the classical pathway.
What does MASP stand for?
MBL Associated Serine Protease
Give examples of pathogens that have mannose on their surface?
Bacteria such as Streptococci and Salmonella
Fungi such as Candida albicans
Viruses such as Influenzas and HIV
Parasites such as Leishmania
What is the alternative pathway?
There is always a small amount of auto-activation. C3 can be auto activated to form C3a and C3b. This is very slow. Upon contact with bacteria, auto-activated C3b binds with Factor B and properdin which rapidly activates more C3 and C5. The rest of the pathway is the same as the classical pathway.
Which complement pathway is most likely to be activated upon a first infection with Candida albicans?
Lectin mannose-binding pathway
Alternative pathway
What is the role of anaphylatoxins?
- Increase permeability of the blood vessels and increase smooth muscle contraction
- Chemoattraction of phagocytes (C3a and C5a)
- Act as opsins – C3b
- Trigger degranulation of endothelial cells, mast cells and phagocytes
How does C3b act as an opsin?
C3b is cleaved to iC3b. The macrophage contains receptors for iC3b, facilitating phagocytosis of the bacteria by the macrophage.