Question

3. Differentiate the three types of complement responses 4. Macrophages are known as professional phagocytes because of their role in the immune system. What molecules allow the macrophage to detect bacteria and engulf them? A brief discussion of each (location on the cell, ligand targets, etc) will be acceptable. 5. Toll-like receptors (TLRs) are a family of receptors known to be important in detecting bacteria and viruses. Once TLRs bind to their ligand, they alter the cells gene expression profile. Please discuss how the signal from a single TLR can be amplified to alter the expression profile of the cell and what the resulting products are from this pathway. Original illustrations are acceptable here 6. Your clinical facility is seeing a patient presenting with reoccurring bacterial infections. The infections were always susceptible to antibiotics and were typically caused by Streptococcus pneumoniae, Staphylococcus aureus, and Pseudomonas aeruginosa. An analysis on white blood cells from the patient showed that stimulation with lipopolysaccharide (LPS) failed to induce TNF-alpha expression. The patient's father and sister did express TNF-alpha in response to LPS (See Figure 1). Further analysis of the IRAK4 protein revealed a smaller sized in the patient's IRAK4 protein than normal IRAK4 protein (Figure 2).

Answer 1

Q3. The complement system consists of a number of proteins that acts in a cascade to induce the opsonisation and lysis of target microbe. There are three types of complement system that differs in the process of activation

a) the classical complement pathway: This complement pathway is activated upon the binding of C1q to the antibody complexed on the surface of microbe.

b) the mannam binding lectin pathway: this pathway is initiated by the binding of a serum protein, mannose binding lectin to the mannose residues present on the surface of a bacterial cell and some viruses.

c) the alternative complement pathway: this pathway is activated by the spontaneous hydrolysis of C3 to generate a C3 convertase.

All the three complement pathways converge at the C3 convertase step which hydrolyses C3 into C3a and C3b. C3b covalently binds to C3 convertase and further hydrolyses C5 that recruits the terminal downstream proteins (C6,7,8 and 9) to form the membrane attack complex on the cell wall of bacteria leading to its rupture.

Alternative Pathway Classical Pathway Lectin Pathway Microbe -Mannose AlgG antibody Binding of complement proteins to microbial cell surface or antibody MASP1 MASP Mannose binding Qe Sectin card C3 convertase <C402 Formation of C3 convertase C3 convertase C3 convertase Cleavage of C3 < la C5 Formation of C5 convertase C5 convertase CS C5 convertase convertase Abbas.Cellular and molecular immunology 7 edition

Alternative Pathway Classical Pathway Lectin Pathway Microbe -Mannose AlgG antibody Binding of complement proteins to microbial cell surface or antibody MASP1 MASP Mannose binding Qe Sectin card C3 convertase <C402 Formation of C3 convertase C3 convertase C3 convertase Cleavage of C3 < la C5 Formation of C5 convertase C5 convertase CS C5 convertase convertase Abbas.Cellular and molecular immunology 7 edition