You have developed a mouse strain called XYZ that models the autiimmune disease

Question

You have developed a mouse strain called XYZ that models the autiimmune disease pemphigus, where autoantibodies are made that destroy the tight junctions in the dermis, resulting in blisters and exfoliation. This leads towards the life-threatening disease. As mice develop the disease over their first 24 weeks of age, the severity can be scored on a scale of zero (least severe) to five (most severe). Assume that you bred these mice to TRL7 qne TLR9 knockouts, creating both since and double knockouts.

Below is the question I need help with:

1. TLR9 is pexpressed in both B and T cells. Outline an experiment to determine if the role played by TLR9 in this disease is mediated by its expression in T versus B cells.

Explanation / Answer

The surface immunoglobulin that serves as the B-cell antigen receptor (BCR) has two roles in B-cell activation. First, like the antigen receptor on T cells, it transmits signals directly to the cell's interior when it binds antigen (see Section 6-1). Second, the B-cell antigen receptor delivers the antigen to intracellular sites where it is degraded and returned to the B-cell surface as peptides bound to MHC class II molecules (see Chapter 5). The peptide:MHC class II complex can be recognized by antigen-specific armed helper T cells, stimulating them to make proteins that, in turn, cause the B cell to proliferate and its progeny to differentiate into antibody-secreting cells. Some microbial antigens can activate B cells directly in the absence of T-cell help. The ability of B cells to respond directly to these antigens provides a rapid response to many important bacterial pathogens. However, somatic hypermutation and switching to certain immunoglobulin isotypes depend on the interaction of antigen-stimulated B cells with helper T cells and other cells in the peripheral lymphoid organs. Antibodies induced by microbial antigens alone are therefore less variable and less functionally versatile than those induced with T-cell help. The specific activation of the B cell by a T cell sensitized to the same antigen or pathogen depends on the ability of the antigen-specific B cell to concentrate the appropriate peptide on its surface MHC class II molecules. B cells that bind a particular antigen are up to 10,000 times more efficient at displaying peptide fragments of that antigen on their MHC class II molecules than are B cells that do not bind the antigen. Armed helper T cells will thus help only those B cells whose receptors bind an antigen containing the peptide they recognize. The requirement for linked recognition has important consequences for the regulation and manipulation of the humoral immune response. One is that linked recognition helps ensure self tolerance, as will be described in Chapter 13. An important application of linked recognition is in the design of vaccines, such as that used to immunize infants against Haemophilus influenzae type B. This bacterial pathogen can infect the lining of the brain, called the meninges, causing meningitis and, in severe cases, neurological damage or death. Protective immunity to this pathogen is mediated by antibodies against its capsular polysaccharide. Although adults make very effective thymus-independent responses to these polysaccharide antigens, such responses are weak in the immature immune system of the infant. To make an effective vaccine for use in infants, therefore, the polysaccharide is linked chemically to tetanus toxoid, a foreign protein against which infants are routinely and successfully vaccinated B cells that bind the polysaccharide component of the vaccine can be activated by helper T cells specific for peptides of the linked toxoid

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