Question

2.9 True or False: Mucins secreted at a mucosal surface exhibit direct microbicidal activities.

Answer 1

2.9.

• Mucins are glycoproteins with high molecular weight.
• Released in the gastrointestinal tract, mucin helps in the mucosal functions and its protection.
• Mucin act as physiochemical barrier against intestinal pathogens.
• It may interact with antimicrobial peptides to exhibit certain microbicidal functions.
• Mucin directly does not exhibit microbicidal properties, but act as barrier against microbial invasion.

Answer: False.

2.11.

• The Paneth cells present in the bottom of the intestinal epithelium and neutrophils made by them, secrete defensins, which act as antimicrobial protection.
• The defensins are in inactive for (alpha defensins), which are proteolytically cleaved to form active antimicrobial peptides, on activation.

Answer: True.

2.12.

C3 convertase is part of complement pathways.

The three-major pathway of complement activation and cascade reaction include:

I) Classical pathway- It is part of both innate and adaptive immunity. Classical pathway activated by IgG1, IgG2, IgG3 and IgM, forming antigen-antibody complex or immune complex.

Steps include:

1) C1 component (C1qr2s2 complex) is first activated and C1q portion binds to fragment, crystallizable” (or ) portion on antibody (C1q may also directly bind to some pathogens).

2) C1r coverts to active serine protease enzyme, , which splits C1s to active enzyme .

3) acts on C4 component hydrolyzed to a smaller C4a (act as anaphylatoxin) and larger C4b fragments.

4) C4b fragment bind on target surface near C1.

5) C2 component bind to binding site of C4b. Bound C2 component is then cleaved by

Producing complex

6) act as C3 convertase, hydrolyzing C3 molecules into to C3a and C3b (amplification step).

7) C3b binds to forming , a C5 convertase.

8) C5 is cleaved to C5a and C5b. C5b binds to C6 initiating formation of membrane attack complex (MAC).

II) Alternative pathway- It is a part of innate immunity and does not require antigen-antibody complex for activation. It is activated foreign cell surface constituents of pathogen (like components of Gram negative and positive bacterial cell wall). Steps includes:

1) Slow cleavage of thioester bond of C3 molecules, leading to a spontaneous hydrolysis of C3 into C3a and C3b.

2) C3b binds to surface of foreign substances, which further activates a serum protein, called factor B.

3) Factor B binds with C3b, and then acts as a substrate for active component called factor D.

4) Factor D cleaves the C3b bound factor B, into, and Ba (that diffuses).

5) act on unhydrolyzed C3 molecules to generate more C3b components.

6) C3b components thus generated, add on to producing complex.

7) complex act as C5 convertase and generates C5b, which binds to antigenic surface, initiating MAC activity.

III) Lectin pathway- this pathway involves lectin proteins, that have the property to bind with carbohydrate molecules. Lectin involved in complement activation, requires binding to mannose residues and are called mannose-binding lectin (MBL). The pathway is therefore also called mannose-binding lectin pathway. Steps involved are:

1) This pathway is initiated by binding of MBL to pathogen surface.

2) MB-associated serine proteases (MASP), MASPI and MASPII, then bind to MBL.

3) The complex thus formed acts on C4 and C2 (MASP activity being similar to C1s and C1r activities). The remaining pathway is similar to classical pathway, leading to formation of C5 convertase and thus membrane attack complex.