Chapter 11 -- Last blog post?!

1. Chapter 11 discsses autoimmune diseases, which come in three forms analogous to hypersensitivity types II, III, and IV (Ab's made against self cell surface or extracellular matrix, soluble immune complexes deposited in self tissues and reacted against, and effector T cell self-reactivity).  The first section of the chapter summarizes the effects of these autoimmune types and then illustrates them with an overview of several particular autoimmune diseases: autoimmune hemolytic anemia, Goodpasture's syndrome, Grave's disease, Hashimoto's disease, Type-I Diabetes, Systemic Lupus etythematosus, rheumatoid arthiritis, multiple sclerosis, and myasthenia gravis--the section also distinguishes between agonists, which are autoantibodies that facilitate receptor function, and antagonists which inhibit receptor function.  The second portion of the chapter discusses the origins of autoimmune diseases, citing mainly non self-tolerant T-cells due to failed negative selection in the thymus, or inability of T-regulatory cells to keep autoreactive T-Cells in check.  Genetic mutation, particularly in HLA genes, can promote autoimmune disease, as can environmental factors which degrade the body's tissues making them stimulate the immune system.

2.  Since the book has stopped introducing entirely new immune system components and mechanisms, the material has grown easier to understand.  Most challenging passages can be understood by referring back in the text.  I think the most challenging concepts for me to understand where the actual presentation of autoimmune disease in humans.  The symtpoms seem to be quite various and not always consistent from case to case for any particular disease (SLE, for instance), and though the underlying mechanisms are mostly clear, the presentation seems less so, I wonder if doctors have difficulty distinguishing between autoimmune disease and type II, III and IV hypersensitivity, as the mechanisms are identical.

3.  The book mentions how auto-reactive T cells are common even in healthy individuals, this leads me to question the efficacy of the negative selection system taking place in the thymus.  How are these auto-reactive cells making their way into the bodies circulation?  If the thymus could do it's job more effectively, there wouldn't be a need for T-reg cells, though as it is  I suppose I'm glad we've got them.  What are the exact mechanisms for negative selection in the thymus?  Is it possible for the body to prevent every potential T-cell with a cross section of every self-antigen it may encounter?  How does this presentation work?  Is the thymus the most diverse organ in the body, a meltin pot of self-peptides?  This idea intrigued me in chapter 5 as well.