Question

1. List and describe at least 5 different ways in which genetic diversity in immunoglobulins arise.
   
2. Describe three ways in which complement acts to protect the host during infection.

Identify specific molecules/ convertases and their contributions to the immune response.

3. Complement activation can occur via the classical, alternative or lectin pathway.
4. Identify which pathway you would expect to be activated in a patient that had a seasonal flu shot in October 2019.
5. Streptococcus pneumoniae
6. Influenza virus
7. Escherichia coli

4. Present a scenario of infection in which you can describe the differences in cellular activation, cytokines, etc. in T-Dependent and T Independent antigens scenarios.

5. When a B cell is selected and activated by an antigen, it undergoes #1. proliferation and #2 2 class switching from the Ig class on its surface to a more specific Ig class under the direction of certain groups or individual cytokines.

Using the table below, indicate for each differentiation cytokine, which Ig class it will promote switching to or if it has a role in the expansion and proliferation of the B cells which is selected. (there may be multiple checks for several cytokines)

Differentiating cytokines	Ig Class produced by Plasma Cells
	IgG2a, IgG3	IgM	IgE, IgG1	IgA, IgG2b	Proliferation
IL-2
IFN-g
Il-4
Il-5
TGF b

6. You have prepared knockout mice with various gene mutations in complement components. Using the following table, Predict the effect of each mutation on the steps in complement activation and effector functions indidated in the table. Use the following short hand:  
   NE= no effect
   D = process/function decreased (not abolished)
   A = process/function abolished

	COMPLEMENT COMPONENT THAT WAS KNOCKED OUT
	C1q	C4	C3	C5	C9	Factor B
Formation of Classical Pathway C3 convertase
Formation of Alternative Pathway C3 convertase
Formation of Classical Pathway C5 convertase
Formation of Lectin Pathway C3 convertase
C3b mediated opsonization
Inflammation (PMN chemotaxis
Cell Lysis

Answer 1

1). Random mating, mutation, random fertilization. crossing over during meiosis and recombination are different ways by which genetic diversity arises.

2). There are 3 means by which the complement system guard against infection:

a). It produces huge numbers of triggered complement proteins that combine covalently to pathogens, that opsonize the antigen for engulfment by phagocytes consisting of receptors for a complement.

b). The miniature fragments of complement proteins act as chemoattractants to employ more phagocytes to the location of complement activation, and also to trigger these phagocytes.

c). The terminal complement components harm certain bacteria by generating pores in the bacterial membrane.

3). The three pathways (alternate, lectin, and classical) of the complement system of activation all produce homologous variants of the protease C3-convertase.

4). The classical complement pathway usually requires antigen-antibody complexes for activation, while the alternative pathway can be triggered by spontaneous complement component 3 (C3) hydrolysis, unknown material, pathogens, or injured cells. The lectin pathway can be triggered by hydrolysis of C3 or antigens devoid of the existence of antibodies. In all 3 pathways, C3-convertase cut and turn on component C3, producing C3a and C3b, and result in a surge of additional cleavage and activation actions. C3b attaches to the exterior of pathogens, significant to superior internalization by phagocytic cells by opsonization.

In the alternative pathway, C3b connects to Factor B. Factor D discharge Factor Ba from Factor B attaches to C3b. The compound of C3b(2)Bb is a protease that slice C5 into C5b and C5a. C5 convertase is also produced by the classical pathway when C3b binds C4b and C2b. C5a is an important chemotactic protein, serving to employ inflammatory cells. C3a is the originator of an essential cytokine (adipokine) named ASP and is usually rapidly cleaved by carboxypeptidase B. Both C3a and C5a have anaphylatoxin activity, directly triggering the degranulation of mast cells as well as increasing vascular permeability and smooth muscle contraction. C5b initiates the membrane attack pathway, which results in the membrane attack complex (MAC), consisting of C5b, C6, C7, C8, and polymeric C9. MAC is the cytolytic endproduct of the complement cascade; it forms a transmembrane channel, which causes osmotic lysis of the particular cell. Kupffer cells and macrophage cell types assist to clear complement-covered pathogens.