Well, we just spent a whole week looking at a complex system of checks on the adaptive immune system. What could possibly go wrong? Yet here I am standing in the middle of a bunch of my own cells and molecules, surrounded by threads, and about to begin a lecture series on the different kinds of problems you can get when your adaptive immune system launches an attack on you. Biology is all about trade-off and maximizing your reproductive success. We could have an immune system, that made almost no mistakes and yet eliminated every pathogen that got into us, but it would cost us so much energy. We would have a hard time getting enough food, never mind having the strength for courting or child rearing. So, we have to decide how to optimize the expenditure of our resources. This lecture begins with a quote from Estelle Ramey. "Men were designed for short, nasty, brutal lives. Women are designed for long, miserable ones." She's referring to the relative mortality rates of men and women. Men die earlier on average, but women tend to be more disabled and troubled by longterm medical problems in old age. So, those extra years aren't much of a gift. The relevance to this lecture is that women tend to be more susceptible to autoimmune diseases. It's possible they spend a greater amount of their resources fighting disease and consequently are somewhat more likely to misdirect their efforts or looked at another way. Ancestral Stone Age humans placed rather different demands on men and women, and we've inherited the consequences of differential selection forces. So, let's begin by looking at some of those specific consequences. So, we're going to begin here by looking at some specific systemic autoimmune diseases. Autoimmune diseases are generally put into two categories, systemic, which attacks the body all over the place, and organ-specific which by definition goes after a specific organ or tissue. Now, like in many biological categorizations, it's not perfect. But we will look at these two diseases because they're generally considered good examples of systemic diseases that is situations where the attacks are widely disseminated throughout the body, and again, not confined to a particular organ or tissue. This picture shows the classic butterfly rash symptom that presents commonly but not always with Systemic Lupus Erythematosus or SLE or Lupus. Now, Lupus is often very difficult to diagnose, and if you get this rash, that is the first thing you want to think about. But it typically takes two or more years between the time somebody starts going to the doctor because they don't feel well and the doctor figures out that Lupus is at the heart of it all. Nonetheless, if somebody shows up in someone's office with this particular rash, Lupus is something that they ought to check for first thing out the gate. Now, what happens with this is that people, and they're typically women by a factor of eight or ten to one, who get this will begin to make antibodies against a variety of their own body antigens, self-antigens. They just lose tolerance for a number of different antigens in their body, and over time they will even become immune to more and more different antigens, something called antigen spreading. So, that a full-grown case of this disease, somebody can be attacking their own histones, their own blood surface proteins, clotting proteins, and sometimes even their own DNA. This can, of course, cause problems all throughout the body. One of the big problems that it causes is the production of excessive clumps of antigen-antibody complexes. These things can activate complement, which again activates all kinds of inflammatory signals, affects the blood vessels. The complement-activated inflammatory responses can lead to widespread tissue damage particularly attacking red blood cells causing anemias, can lead to bleeding disorders, and anytime you have a lot of gunk in your blood, you can clog up your kidneys and get kidney damage. So, hence the word systemic. We have a similar situation with rheumatoid arthritis, that is, in this case, arthritis refers to joint inflammation. The rheumatoid refers to the fact that you're going to be making antibodies through the Fc stems of your own G-class antibodies. So, that again makes a similar situation that we had in the previous case of having lots and lots of clumps of antibody complexes, in this case, they're called rheumatoid factors. That refers to the IgM joining to the IgGs, and then again making massive clumps of these antibody complexes. When the clumps of IgM and IgG complexes get deposited in the joints, that leads to inflammation, and deformation, and pain, and again, the characteristics symptoms of rheumatoid arthritis. Sadly, there are other symptoms because these clumps may overwhelm the ability of neutrophils and macrophages to clear the debris, not just in the joints, but throughout the body. So, you can have a general activation of complement inflammation widespread damage again to any system that it happens to attach to. Again your kidneys are going to be at risk because these complexes can make the function of the glomerulus compromise because it's basically getting plugged up. Now, these are two examples the SLE and rheumatoid arthritis. Again, these are examples. Another one you may have heard of is Scleroderma. In this case, you begin to attack your own skin, and your skin essentially becomes by radic and hard. That's where the name comes from. Multiple sclerosis is sometimes also considered a systemic disease, but I'm going to discuss it with the neuromuscular diseases. In this case, the antibodies are attacking the coatings, myelin sheath, of the nerves, and since the nerves are all over the body, that leads to inflammation all over the body. But I'm going to discuss it later because of the specific target of the attack.
