Posts Tagged ‘IgE’

Mast cells, immunoglobulins and our dog Yoda

Saturday, September 22nd, 2012

We just lost a beloved family member, our ten-year-old Tibetan terrier Yoda, to a malignancy that I'd never heard of, an enormous mast cell tumor. It made its initial appearance only eight days previously while I was in Memphis at a 90th birthday celebration. My wife called me and said Yoda had swelling in his neck and a cough.

She took him in to the multi-veterinarian clinic where he's been going for ten-plus years and they were puzzled. They were unsure of which of four possible diagnoses was causing his problems. He got an antihistamine and a broad spectrum antibiotic and improved considerably. When he lost his appetite  on a Sunday afternoon, we spoke to the on-call veterinarian who felt he should be seen early on the next morning.

By then his neck was swelling again and we were promptly referred to the CSU Veterinary School's hospital. They got him into their urgent care system, aspirated some cells from his neck and told us he had a mast cell tumor. The literature they supplied said these are extremely rare in humans, but common in dogs.

a tropical frigate bird with his pouch inflated

A short while later his neck was swollen to the point where he needed to be intubated in order to breathe. The only creatures I had ever seen with a similar appearance were  great frigate birds in the Galapagos. In their case, the pouch is inflated by the male birds to attract a possible mate; in Yoda's case the malignant mast cells had "degranulated" releasing histamine and other mediators of immunity.

Our surrogate son, now in his second medical career, had never seen a mast cell tumor and both of us had to return to memories of our freshman years in medical school (mine considerably before his) and to Google the term to remember exactly what a mast cell is and what physiologic role it plays.

I went back to the Web and read about mast cells and their companions in allergic inflammation; it was a highly technical article written for allergists and immunologists, so I struggled a bit. Let's start with the immunoglobulins, our antibodies. There are five classes of these chemicals which are manufactured by the body in response to foreign substances (antigens) such as pollen, bacteria, or cancer cells. Three of them, termed IgA, IgG and IgM were familiar to me.

IgA antibodies protect our body surfaces (e.g., nose, digestive tract, eyes & ears) that are often bombarded with outside antigens. IgG antibodies are the smallest, the only immunoglobulin that can pass through the placental barrier to a fetus, and make up nearly 80% of all of these immunity chemicals. They help protect us against bacterial and viral infections. IgM antibodies are much larger, play an important role in our initial line of defense versus infections and are produced, to a large extent, in the spleen.

IgD was the mystery antibody for many years; recently it has been felt to be a surveillance system, binding to one kind of blood cells and setting off an intricate series of protective processes.

So that left IgE whose connections with allergic reactions was clear. Along with blood cells known as basophils and eosinophils and "tissue-based" mast cells, IgE is a crucial factor in inflammation associated with allergy.

I mentioned that mast cells are tissue-based; they're not something you'd see in a normal CBC (complete blood count), but "hang out" in association  with blood vessels and on epithelial surfaces (your skin is classed as such, but epithelial tissues also line the cavities and surfaces of structures throughout the body, and also form many glands). Mast cells are "cousins" to basophils, similar in appearance and function, and containing histamine and heparin, but are thought to be generated in the bone marrow from different precursor (ancestor) cells.

They have a highly significant part in the inflammatory process and team up with IgE which coats their outside surface. They have key roles in asthma, a variety of itches, and allergic rhinitis (one form of this disorder would be "There's pollen in the air so my nose gets clogged up and I sneeze."). They're also crucial in immediate hypersensitivity, severe kinds of allergic reactions that can be life-threatening. One example of this would be a person who has a severe, potentially fatal reaction to a bee sting. The medical term for this is anaphylaxis.

A human mast cell cancer; the dark-staining areas are filled with malignant tumor cells.

Mast cells can cause diseases in people; one type leads to pigmented skin areas that when stroked develop hives. Rarely do human mast cells lead to malignancies. I talked to a physician friend who had seen one case in her career and found an online series that had a total of three cases.

In dogs, on the other hand, mast cell tumors are relatively common, but most are lumps that can be removed surgically. A smaller number of canines develop larger tumors and a few have even more malignant disease.

Unfortunately, our dog Yoda had one of the bad kind. His was the largest, most rapidly-growing mast cell cancer the Vet School's senior oncologist had ever seen.

We'll miss him. He was an important and much-loved part of our family.







Almost everything about blood except for mast cells.

Friday, September 21st, 2012

I started a post on mast cell tumors in humans and dogs, having learned about them the hard way...our dog died this week.

When the Colorado State University Veterinary Hospital first mentioned mast cells to me, three days ago, I had to struggle to remember what they were. I don't think the term has come to my attention since my freshman year in medical school, nearly fifty years ago.

These are typical red blood cells

I realized if I was going to write about them, first I needed to read about them and then I needed to write about blood and white blood cells in general and get to mast cells in humans and dogs in another post.

So let's start from scratch. I weigh 150 pounds, so my body contains roughly  ten and a half to twelve pounds of blood, about four and a half to five quarts worth. My blood performs a number of vital functions, especially those of transporting oxygen to my cells and getting rid of carbon dioxide. Those tasks are allotted to my red blood cells which make up 40 to 50% of my total blood volume (the percentage for men is a little higher than for women).

Most of us know something about red blood cells and since our blood has a red color it's easy to ignore its other blood components. But those are crucial as well: roughly 55% of our blood is a fluid called plasma. Over 90% of that is water, but there's some sugar, fat and even proteins (actually about 500 kinds of proteins). In addition, vitamins, minerals, hormones and enzymes as well as  thirteen blood clotting factors help make up plasma.

That doesn't leave much room for two other absolutely essential kinds of cells: platelets and white blood cells. Platelets are tiny, roughly a third the size of red blood cells, but they work together with the blood clotting factors to enable us to plug wounds. Sometimes they're too effective in causing clots; they apparently have their peak activity in the AM, so is presumably why strokes and heart attacks are somewhat more likely to occur then.

That brings us to white blood cells which only form about one percent of our blood volume, but are crucial to our survival. They are also found elsewhere in our bodies, especially in our spleen, liver and lymph nodes. When you have a CBC, a complete blood count, you should have 4,500 to 10,000 white cells in every milliliter of your blood. Over half of those are neutrophils, white blood cells that rush on ahead of their colleagues to gobble down bacteria, viruses and other infecting organisms. They're called neutrophils because when a typical microscopic examination of blood is done they don't pick up much of the stain used to show granules containing chemicals.

T-cell lymphocytes attacking a cancer cell

The next biggest chunk ( a quarter to a third) of your white cells are lymphocytes which come in three "flavors." NK or natural killer cells are a part of the innate immune system and play a major role in defending the host from both tumors and virally infected cells. T cells are involved in cell-mediated immunity whereas B cells are primarily responsible for humoral immunity (relating to antibodies). The function of T cells and B cells is to recognize specific “non-self” antigens. Once they have identified an invader, the cells generate responses that are tailored to maximally eliminate pathogen (invaders such as bacteria) or infected cells. B cells work by producing large quantities of  antibodies which then neutralize foreign objects like bacteria and viruses. In response to pathogens some T cells, called T helper cells produce chemicals called cytokines that signal other cells and, in doing so, help that direct the immune response while cytotoxic T cells produce enzymes which induce the death of infected cells.

Now we're down to small percentages, but some highly significant white cells: Eosinophils, whose granules strain red, and basophils with blue-staining granules. The eosinophils typically make up about 3% of your WBC count and mediate allergic reactions. Basophils amount to less than 1% of the WBCs in normal healthy people and their granules contain histamine, important in allergy, and heparin, an anti-clotting chemical, as well as other mediators of body reactions. When tissues are damaged, basophils can help bring about inflammation, essential to healing, and increase blood flow to the injured area.

So what about mast cells? They hang out elsewhere and I'll write about them tomorrow.