How do steroids inhibit the immune response?

Q. We heard in class today that steroids are used for autoimmune diseases, and I’ve heard this before but never understood why. What is it about steroids that make them effective as immunosuppressants?

A. There are lots of mechanisms by which steroids dampen the immune response. Here are a few of them:

1. Suppression of T cells. Steroids interfere with production of cytokines (like interleukins), which are critical in the proliferation and interaction of T cells.

2. Suppression of B cells. Steroids interfere with the binding of interleukins to B cells, which means that the B cells have a hard time proliferating and making antibodies.

3. Suppression of neutrophils. Steroids inhibit just about everything that neutrophils do: adhesion, chemotaxis, phagocytosis, and the release of toxic substances.

4. Suppression of macrophages. Steroids down-regulate the expression of Fc receptors on macrophages – so macrophages are less able to phagocytose opsonized things.

5. Diminished production of prostaglandins and leukotrienes. Steroids inhibit cyclooxygenase and phospholipase A2, which decreases the production of pro-inflammatory arachadonic acid metabolites.

Steroids are used in a ton of different immune and inflammatory disorders, like asthma, vasculitis, arthritis, gout, multiple sclerosis, sarcoidosis, alopecia areata…the list goes on and on.

What is an anti-antibody?

Q. I just had a quick question as I was going through some immunology notes and wondering if you could clarify what they mean when a person develops an anti antibody? (more…)

Is comedocarcinoma malignant?

Q. How is comedocarcinoma malignant but also still in situ, that is, confined to the ducts and noninvasive? Is not invasiveness one of the criteria for malignancy? (more…)

What are the best pathology books?

Q. I’m will be starting my pathology residency in about a year. Any suggestions for getting prepared for residency? I have been reviewing www.enjoypath.com and others, but wanted to get your opinion.

A. Good for you! When many people think of pathology (do many people think of pathology?), they think of surgical pathology – stuff that comes out of the operating room, biopsies, etc. But there are many other parts to a pathology residency, such as hematopathology, microbiology, forensic pathology, and blood banking. I’ll run through some of the books used in these areas, then I’ll tell you what I would have done if I knew then what I know now.

Surgical pathology: Rosai’s Surgical Pathology is probably the most commonly-used book; another good source is the set of AFIP Fascicles (there’s a fascicle on pretty much every organ system). These sources are too in-depth for you now (with one exception that I’ll mention in a minute), and probably too expensive. They’re more for reference than for reading through on a Sunday night. You’ll use them until you’re nauseated when you’re a resident though.

Hematopathology: The best source for this is the AFIP Fascicle on the subject: Tumors of the Bone Marrow. This is the exception to what I said above about reading the fascicles before residency – this one would be great to go through ahead of time. There’s a lot to learn, and if you go through it once, it will make a lot more sense when you get to it in your residency. It’s small enough that you can certainly get through it in a few months.

Microbiology: We used Koneman in our residency program, and I think it is a good textbook. It’s more than you’d want to go through ahead of time though; I’d use something like Clinical Microbiology Made Ridiculously Simple. It has nice drawings and mnemonics, which is something you need in microbiology.

Forensic pathology: A couple good ones for this are put out by DiMaio: a textbook (long) and a handbook (short).

Blood banking: We used McCullough’s Transfusion Medicine text in residency. Nice and short and readable. Here’s a fun game that you might want to try too.

I think if I had it to do over again, I would do three things:
1. Read Robbins. All of it. Maybe twice. I know, I know, it is a “med-school” textbook, but we used it all the time in residency. So did the attendings at times, by the way. It’s no small feat, but should be possible in a year, and it would prepare you well. You might even take notes on the histologic appearance of different tumors and diseases; you would have those to refer to during residency. You can look at websites too (like Webpath and Ed’s Pathology Notes) – and you should – but Robbins will give you a systematic and thorough review.
2. Read the AFIP bone marrow fascicle. I actually did this before my med school rotation in hematopathology, and I was so glad I did. It will make you shine when you get to your rotation.
3. Not worry about the other stuff. The other rotations will be easy enough to go through without advance preparation.

Good luck!

What is array-based CGH?

Today’s post, authored by a very smart guest cytogeneticist, nicely describes array-based comparative genomic hybridization, a very cool DNA test that gives us a way to detect genetic abnormalities that are too small to be seen under the microscope. (more…)

What the heck is uniparental disomy?

We were talking about developmental pathology the other day in class – trisomies, sex chromosome numerical abnormalities, microdeletion syndromes etc. – and the term “uniparental disomy” came up.  (more…)