Question

4230 medical immunology class

Please TYPE your answers, it’s hard for me to read hand written answers.

Thank you!

Concept Check . What are the outcomes/functions of the complement system? . What do all pathways have in common? . What would you expect to happen in an individual deficient in C3? . Macrophages have receptors for C3b. What is the biologic significance of this fact?

Answer 1

Outcomes/ Functions of Complement System

1. The complement system works in all the tissues of our body, providing an immediate response to injury and foreign bodies.

The system has four major functions:

1. Opsonization -Marking invading pathogens and damaged tissues as targets for disposal
2. Phagocytosis - Triggering their elimination
3. Anaphylatoxins -Production of inflammatory signaling agents
4. MAC (Membrane Attack Complex) - Destroying of cells by insertion of the membrane attack complex (MAC) into cell surfaces.

2. There are 3 pathways in complement system.

Classical, Alternative and Lectin pathways where all these 3 pathways converge to this common terminal pathway, culminating with cell lysis and death.

3. An Individual with C3 deficiency will have the following symptoms

• Recurring infection
• Auto-immune disorders
• Glomerulonephritis
• Joint problems (manifestation)
• Lung function (MBL variant alleles)
• Angioedema
• Dermatomyositis
• Vasculitis
• Anaphylactoid purpura

4. The complement receptors on macrophage are responsible for their binding and ingestion of opsonized targets.

The two established receptors are CR1, which recognizes C3b, and CR3, which recognizes iC3b, the natural product of C3b from cleavage by the complement control protein factor I and its cofactors. CR1 belongs to a group of proteins that contain a structural element characterized by its size of 60-65 amino acids, and four conservatively positioned cysteines, which engage in a self-contained 1-3, 2-4 disulphide arrangement. This structural unit is called SCR (short consensus repeat) and is found in the complement proteins C1r, C1s, C2, factor B, factor H, C4BP, DAF, MCP and CR2, each of which interacts with some cleavage products of C3 and/or C4. CR1 has 30 SCR units accounting for its entire extracellular structure.

It has a transmembrane segment and a small cytoplasmic domain. CR3 is a heterodimer containing an alpha and beta subunit held together by non-covalent forces. The beta subunit is also found in the two leukocyte antigens, LFA-1 and p150,95, which have alpha subunits distinct from that of CR3. The beta subunit contains 56 cysteine residues, 42 of which lie in a span of 256 residues immediately adjacent to the transmembrane segment. It shares extensive sequence homology with subunits of membrane protein complexes that bind fibronectin and vitronectin, implicating that they all belong to an extended set of surface adhesion molecules not restricted to the immune system. p150,95 is expressed on macrophages and it has iC3b binding activity. It also shares some functional properties with CR3 as an adhesion surface molecule.