Things I never knew

Antibodies = Immunoglobulins

They’re the same thing! I remember in one of our first Immunology lectures, the lecturer just threw that one casually into a slide, and my and my friend turned to look at each other with an expression of dawning amazement. Episodes of House suddenly made so much more sense! Lots of things just clicked into place.

I love those moments.

Antibodies are the secreted form of B-lymphocyte receptors and are a part of adaptive immunity, but how are these proteins formed?

Above is a diagram illustrating Paul Ehlrich’s Side Chain Theory of Antibody Formation. Ehlrich proposed that immunoglobulin molecules, a fundamental component of adaptive immunity, served as membrane bound proteins that bound to particular threats, similarly to the former “key in lock” view of enzymes in catalyzing biological reactions. Ehrlich also suggested that the action of binding a pathogenic molecule to the receptor would generate a signal to stimulate the production of more receptors of the same specificity. These “side chains” that were added on would then break off from the cell surface and become what we call antibodies.

 We now know, however, that soluble immunoglobulin receptors are specially manufactured to be secreted as antibody, rather than just “breaking off” of the lymphocyte, even though they have the same specificity as their membrane-bound counterparts.

“Strawberry tongue” is a characteristic symptom of Kawasaki Disease, an autoimmune disorder that, if not correctly diagnosed and treated, can result in heart damage in children and possible death.

For KD, a model T (cell)

Kawasaki Disease is a severe childhood illness that can, without treatment, result in damage to coronary arteries and, possibly, premature death. There is currently no diagnostic test for KD and standard treatment – a single infusion of intravenous immunoglobulin (IVIG) – is not without its problems and concerns.

KD, though, is self-limiting. That is, the body produces a type of cell called regulatory T cells or Treg that act to mitigate the inflammatory effects of KD and related damage to coronary arteries.

In a paper published in the journal Autoimmunity, first author Alessandra Franco,MD, PhD, an associate professor in the Department of Pediatrics at UC San Diego School of Medicine, Division of Allergy Immunology and Rheumatology and Rady Children’s Hospital-San Diego, and colleagues elucidate the role of Treg in KD and the mechanism for IVIG treatment.

The researchers have identified the underlying mechanism that explains why IVIG stimulates production of a particular type of Treg that recognizes the heavy constant region of antibodies and reduces inflammation and pediatric vasculitis of coronary arteries.

More broadly, Franco and colleagues say “natural Treg,” which is derived from the thymus during fetal development, has beneficial effects beyond KD. It also helps prevent plaque formation in atherosclerosis, a major form of heart disease.

The findings have significant clinical implications. IVIG is an expensive treatment. It is not available in many parts of the world where KD patients are common. “With current recombinant peptide technology, it should be possible to develop a stable, peptide-based therapeutic for testing as an optimized treatment,” Franco said. “Beyond KD, such a therapeutic may have applications in other vasculopathies, including atherosclerosis.”

You can read Franco’s paper, with co-authors Ranim Touma, Yali Song, Chisato Shimizu, Adriana H. Tremoulet, John T. Kanegaye and Jane C. Burns, all at UC San Diego, here.

outstealingashtrays  asked:

I was born with no IgA, and I've been told my whole life that this affects the immunity of my mucous membranes. I have a two-fold question about this. The first part is that I was wondering if you could explain the mechanism for this particular immunity in layman's terms, because all of my immunologists have kind of just shrugged when I asked them what IgA actually does. The second part is: is it safe for me to get a tattoo? (I'm too lazy to log out; feel free to answer publicly!)

Oh thaaaat’s why I’ve been keeping my immunology book all these years!

You are right, my friend. IgA does protect your mucus membranes. It’s one of your first lines of defense from germs. Let’s break down how that works.

IgAs are immunoglobulins, which is a long word for good guys that bind up a bad molecules and other invaders like viruses and small bacteria to make the bad guys harmless. 

Think of IgA as ground troops in a war who are protecting a military base. They form a perimeter around the base, which holds all the really big guns and tech and such. They’re in bunkers watching (and profiling) for bad guys to sneak up and try to gain control of the larger base.  IgAs lock down or destroy invaders so they can’t get in through skin cells to infect you.

IgAs are produced inside plasma cells, which is a type of white blood cell. Plasma cells spit them out into the blood, where they are paired up and are then bound to receptors on the inside-your-body-side of epithelial (skin) cells. 

Now remember that skin cells line every surface of your body that has any contact with the “outside world”. This includes the inside of your gut, the lining of your trachea and lungs, and of course the inside of your nose, mouth, vagina, and anus. These linings are the walls that protect the goods.

This is where IgAs do their duty. IgA doesn’t just hang out on skin cells. It is actually spit out from epithelial cells into your various bodily fluids (including sweat, sputum, nasal mucus, saliva, and even breast milk). Once it’s spit out it binds up any bad guys it encounters in that fluid, BEFORE they even get a chance to enter your body. Then the bad guys are carried out through the fluid which is partially why you sneeze and get a runny nose when you first get sick. 

The vast majority of immunoglobulins your body makes are IgAs, but you won’t see them as the majority if you measure blood levels because it’s being spit out in other body fluids all the time. Even with it being the first defense against invaders, it really only offers a little bit of protection. That’s why if you’re going to have an immune deficiency, this is probably the one you want. You may get more colds and sniffles than the average person, but you still have the “big guns” on the inside intact.

Which leads me to your second question: is it safe for a person with IgA deficiency to get a tattoo? Well considering that your tattoo ink and any potential bacteria contaminating it are going to go inside your skin, the IgA shouldn’t really be a problem because you’re bypassing that system altogether. It’s like parachuting bad guys into the military base instead of having them sneak in on the ground. Those bacteria are going to be attacked by white blood cells and macrophages. As long as your other immune defenses are intact, like the myeloperoxidase inside your neutrophils that will gobble up any stray Staph or Strep that gets in through your little skin breaks from your tattoo, your risk of infection should not be any higher than the average IgA-having person.

Panel Outlines New Diagnostic Criteria for Central Nervous System Disorder

New diagnostic criteria were introduced for neuromyelitis optica, now called neuromyelitis optica spectrum disorder, which is an inflammatory disease of the central nervous system that is sometimes mistaken for multiple sclerosis.

An international consensus panel, chaired by Mayo Clinic neurologists Dean Wingerchuk, M.D., and Brian Weinshenker, M.D., reviewed the medical literature and recent scientific discoveries relating to NMOSD to develop new diagnostic criteria. The Guthy-Jackson Charitable Foundation sponsored this panel.

NMOSD can affect the optic nerves, brain stem, spinal cord and brain. It can cause a spectrum of symptoms, including visual loss, paralysis and episodes of persistent hiccups, nausea and vomiting. Detection of aquaporin-4 immunoglobulin G antibodies (AQP4-IgG), using a blood test that was developed by Mayo Clinic investigators, is highly specific for NMOSD and facilitates the diagnosis. Some patients have the key features of NMOSD, but do not have detectable antibodies. The new criteria address both possibilities.

The IPND’s paper outlining the new diagnostic criteria is published online in the journal Neurology. Access the paper for free.

“It’s very important for clinicians to know about these updated criteria,” explains Dr. Wingerchuk. “An accurate diagnosis is necessary for selecting the right therapy. We treat NMOSD differently than we treat MS, and some MS therapies actually aggravate NMOSD.

Some differences between the old criteria and the new include:

  • Diagnosis was not possible by identifying a single clinical symptom. Now it is.
  • The 2006 criteria also required a diagnosis of optic neuritis and myelitis; whereas, the new 2015 criteria require neither if an AQP4-IgG blood test proves positive.

“These criteria unite a group of syndromes that have been separated in the past somewhat arbitrarily, but are now believed to be different manifestations of NMOSD largely because of their association with a specific antibody, AQP4-IgG,” says Dr. Weinshenker. “It’s still not clear if patients with similar clinical presentations who do not carry the AQP4-IgG antibody have NMOSD. However, it appears that their clinical disease is sufficiently similar to that of patients with the antibody to warrant a diagnosis of NMOSD without AQP4-IgG antibodies.”

NMOSD is estimated to affect 1 to 2 percent of patients who visit MS clinics in the U.S. Even though it can strike in infancy and as late as a person’s eighties, the median age of onset is 40 years old – 10 years later than the median onset age for MS. It’s also more likely to affect women. While it’s an uncommon condition across all cultures, it’s relatively more common in Asia.

"We hope the 2015 criteria will increase awareness, understanding and earlier, more accurate diagnosis and treatment of NMOSD, leading to better outcomes for people with the disease,” says Dr. Wingerchuk.

Immunoglobulin Summary

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Slapped Cheek Syndrome

Also called Erythrovirus and ‘fifth disease’, as it was historically number five in the list of diseases commonly contracted by kids. Ooo, history facts…

It is caused by Parvovirus B19, and is usually unremarkable and self limiting - by the time the rash appears, it is nearly over.

However, it can cause an aplastic crisis - bone marrow stops making RBCs. This is serious if RBC turnover is reduced:

  • Sickle-cell
  • Thalassaemia
  • Spherocytosis
  • HIV

Rarely this leads to transfusion and admission of immunoglobulins. 

In Pregnancy:

  • 10% chance of fetal death
  • 3% chance of hydrops fetalis (prenatal form of heart failure) - treat with intrauterine blood transfusion
  • Can also cause IUGR, inflammation of fetal organs, fetal organomegaly
  • 1% risk of congenital abnormality

Med school is nothing if not an endless parade of trying to make a Normal Face while looking at a body part do something it definitely shouldn’t.

Yesterday I saw someone with HepC-associated vasculitis. The immunoglobulin that attacks HepC somehow triggers your own immune system, which launches another immunoglobulin to attack that immunoglobulin, and then all three of them–virus, attack, and inappropriate counterattack–get stuck together and lodge in your little bitty blood vessels. Which you need, a lot. She had a bad case. Her legs looked like… you know, I can’t even come up with a clever comparison. Her legs were mottled purple and red, with purpura scattered everywhere, and ulcerated lesions oozing and bleeding, a bandage wrapped around one foot because otherwise the pain was too excruciating to wear even a pair of fuzzy slippers.

And she’d been skipping appointments that were necessary to getting her HepC treatment started, which is the only thing that is going to help her vasculitis.

If you’re on meds, take them. If you know you need to go to a doctor, do it. I’m casting the stone from a very glassy house here, but seriously. Blood pressure meds? Take them. Smoking? Don’t do it. Vaccines? Get them. Get the damn flu shot. Prescribed antibiotics? Take the whole course. There are parts of modern medicine that are bullshit but the scary truth is that most people are no better prepared to confront whether their doctor’s advice is sound than I am to decide whether a mechanic is screwing me over. So, don’t decide on your own that you don’t need to follow the advice your doctor gives you–get a second opinion. Some people with really awful bedside manner do know what they’re talking about. And some of the most engaging doctors I’ve seen are dangerous fucking lunatics. Second opinions are a long way from perfect, but they’re the best tool you’ve got.