Tag Archives: Antigens

Bloody Ramble: from Typos to Chaplin

I am not a hematologist. Nor an immunologist or a virologist. Just an aspiring amateur writer who has recognized that typos fall into two dominant categories. Regular readers have no doubt spotted more than a few.

The first kind of typo comes from stream of consciousness – such as just getting the initial thoughts and sentences tapped in.  Misspellings, poor grammar, dreary or ambiguous word choice, double words, lazy punctuation.  The long list continues: verb/noun mismatch; change of tense within a paragraph; chronological inconsistencies; using “their” or “your” for “they’re” and “you’re” …

These are all forgivable, and relatively painless. Many make it to draft status, when well over 90% can be cleaned up by a few proofreading passes.

It’s the second kind of typo that is really painful.  These result from late edits.  The eleventh-hour flash of brilliance that results in a “catastrophic improvement.”  At the final moment, with the cake fully iced, the product is ready for a la mode, and full reader enjoyment! 

But no! Those last flourishes require just as much proof reading as the original drafts.  Yet, it is so easy to skip. I’ve done it many times. Slow learner.

To my readers: Thank you.  Many of you have gently suggested improvements and corrections to my typos and “facts.”  The rest of you have kindly ignored them; or, perhaps in your brilliance, merely read what I intended, not what I wrote.  Exhibit A: My last essay enfolded references to (a) a famous bathroom fixture company, (b) its founder, (c) the label for a common convenience, and (d) my regular tapestry of  history, factoids, and observations.  During some post-published proof-reading I found a few major hiccups. It’s better now, but only after some help and a couple of paragraph re-writes.
 

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Not only are there two kinds of typo; there are two kinds of Type-O.  Positive and negative.  We’re talking blood here.

I am O-positive.  That’s the most common blood type, nearly 40% of humans have it, despite O’s transmission on a recessive gene.  About 85-90% of people in need of transfusion can accept my blood. If I didn’t carry the Rh-positive antigen, 100% could take my blood.

Through the magic of genetics and natural anti-bodies, I am quite valuable to blood banks.  There is a virus connection here.  How appropriate for this time of novel coronavirus, SARS CoV-2 and international tumult.

Most adult humans have, at some point in their lives, contracted the Cytomegalo Virus (or CMV). As much as 80%.  Of those affected, nearly 100% who contract it suffer from only mild symptoms, if any. Except infants. CMV can cause severe long-term damage to new arrivals – especially “preemies” – as their immune systems are just waking up. 

Of the many scores of herpes viruses discovered, only eight are known to regularly affect humans.  Once infected, our bodies almost always eventually mount a swift and decisive victory, driving the virus from the battlefield – our homeland: tissues, organs, blood.  Better, our well-evolved immune systems retain intermediate and long-term immunity via anti-bodies (of the five main types Immunoglobulin-M and -G antibodies are of the most interest here).

Like many types of virus, the herpes family is insidious.  Even though thoroughly thwarted by a superior foe, they execute a strategic retreat, never quite leaving the body.  They “hang out” in nerve cells. Lying dormant for long intervals, they occasionally “wake up” to see if their host – us! – is healthy enough to fight them off for another round of battle.  If the response is “yes”, they retreat again to the sanctuary of our nerves, a place a proper immune system has been trained to not attack.

This happens over and over again, until we die, as sufferers of HSV 1 and 2 can attest (Herpes Simplex 1 or 2); that is, repeated blistering around the mouth, or even in the mouth.  Those episodes of re-occurrence are only mildly annoying when compared to what can happen with the Chicken Pox virus (Vicella Zoster Virus, or VZV); later in life it can manifest as what’s commonly called “Shingles” – with an agonizing and often debilitating rash accompanied by stabbing pains.

Since CMV is in the Herpes family there is always a likelihood it is in someone’s blood; that is, if they have ever had it in their life. Hence, their blood must never be used for transfusions to infants.

My blood always tests negative for CMV anti-bodies, both IgM and IgG. This means it is not lying dormant somewhere and I am a safe donor for infants.

I donate blood as often as practicable.  I am of some use to society. We Type-Os are also delicious to mosquitoes. My wife says that having me around is better than using insect repellant.

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Until the previous turn of the century, blood types were unknown.  The micro-biological processes of transfusions and outcomes were a mystery, so it was practiced sparingly and as a last resort. Sometimes with spectacular success.  But more often with horrible, painful, fatal results.

At that time Austrian scientist Karl Landsteiner was wondering about this. He hit upon the idea of simply mixing blood from various people together to see what happened. No chemistry. No microscopes. In hindsight, this seems most unsophisticated – even elementary; but no one had done it. 

What he found was rather amazing. Some samples got along well together, and most others did not; they made globules: which was the observable effect of one blood trying to obviate the other; or each other.  Landsteiner had discovered blood types!  For this he was awarded the Nobel Prize in Medicine, decades later, in 1930.

At first he identified 3 types: he labeled them A, B and C.

Red Blood Cells

In the scaled down world of micro-biology and microbes, red blood cells are like titans. Thin and disk-like, they average about 7 microns in diameter, with a thickness of 2 microns, which “squishes” down to about 1 micron at the center, not unlike Life Saver candies. [From now on, I will give sizes in microns, with no units, for simplicity]. This topography gives the red cell a very large surface area compared to its mass and size, which is useful for its main duty: ferrying oxygen and carbon dioxide molecules around the body and passing them across its surface membrane.

A CMV virion’s size is about 0.2. The SARS nCoV-2 is probably smaller than that: about 0.1.  Bacteria, like staph and strep are bigger, but still smaller than a reddie: size, on average, about 1.

Cytomegalovirus CMV, a DNA-type virus from Herpesviridae family. 3D illustration. CMV mostly causes diseases in newborns and immunocompromised patients

A and B blood types were found to carry antigens on their surface. Antigens are anything that triggers an “attack” from antibodies. These red blood cell antigens are, surprisingly, sugars of the D-galactose family, size about 0.0005 (or 1/2000th the average thickness of a red blood cell). 

A blood type which has no sugar antigens, C, was re-named O, which basically means zero, or none. A little later it was discovered that some types carry both A and B antigens, so they were naturally named “AB” – pretty rare.  These 4 types (A, B, AB and O) comprise 99.9+% of all blood types.

Now it’s not at all complicated to tell who can take whose blood for a transfusion. Since my O has no sugar antigens, anyone can take my blood.  But my body will “see” the A, B, and AB cells as invaders. We Type-Os are picky. Although anyone can take my blood, I can only take Type-O.

But wait, not quite so simple. There were still problems.

Rh markers were found a few decades later, around 1940 (also, sort of, by Landstein [1]) – just in time for most of WW2, resulting in fewer multiple-transfusion complications … and a better understanding of baby-to-mother Rh mismatch for the baby-boom that followed WW2.

The Rh markers are proteins (there are actually about 49 of them; the most common is type-D), about size 0.003.  About 90% of people have Rh-positive blood.

Floating nearby in the plasma are anti-bodies.  For mammals these are about size 0.1 – quite small.  In Rh-negative people, these little workers are always “on the ready” to identify Rh proteins as “bad guys.”  And also to identify foreign A and B antigens.

People, especially prospective mothers, with no Rh proteins (i.e. Rh-negative) must be careful with donations and pregnancies.  The first time the body encounters the Rh antigen the process or pregnancy is usually OK.  But the body is stirred up, and it remembers. The next time it’s “attack.” If a Rh-negative patient gets more than one Rh-positive transfusion — or a Rh-negative mom gets a second Rh-positive baby in utero — it can be bad news.

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Returning to the red blood cell.  It is quite large; a workhorse of the vascular system. Yet, one might wonder: why have we evolved so that its surface is laden with thousands of tag-a-longs and stowaways that seem more trouble than their load is worth?

Well, maybe those labels are a bit harsh.  Research suggests that the Rh proteins can provide a sort of osmotic-efficient pathway for the relatively large CO2 molecules (compared to oxygen) to slither through the cell membrane.  And it appeared millions of years ago – before anything like a hominoid walked on two legs. [2]

We can consider these ancient genetic tweaks as a sort of typo: a minor transcription mistake in typing out genetic text from DNA to RNA and back again to the DNA of a new cell, thus creating a new or different function for such genes.

Sugar antigens, similar to A and B, appear in the blood of all mammals. Again, these evolved in our pre-hominoid ancestors long ago. [3] Just why this is so, is a bit of a mystery.  Perhaps it was for a weird but clever type of “trick play herd immunity.”  A virus sees cell coatings as something that can provide an attach point on, or even pathway into, a cell.  If a population has a random collection of these sugars and proteins, then a single type of virus pandemic cannot wipe out the entire species.

Here I like to imagine a sports team cleverly crafted to beat any team at, say, a football match. That team is the Evil Virus. The first games for team EV are easy victories. The next several matches they stampede confidently onto apparently identical pitches, only to be confronted with rules for cricket. Or golf. And then tennis. Then speed skating.  Result?  Team EV fails. –  The species survives; the virus must go off and mutate further or die out.

All these rule changes – different cell coatings among individuals among the same species – makes our bodies suspicious of one another.  When there’s a transfusion mismatch the coatings are identified as antigens and marked for destruction by those tiny antibodies. 

Interestingly, something similar might be happening with the virus du jour, SARS CoV-2 which causes Covid-19. Early analyses of cases (and deaths) in hard hit areas of Europe suggest that those with Type-A blood are disproportionately susceptible. [6] How or why this happens is not understood but could give virologists and immunologists an understanding of the virus and our bodies’ machinations.  Perhaps the A-type sugar is a sort of 5th column for the virus; or the presence of B-type antibodies somehow distracts, diminishes, or delays the body’s defense.

I expect there will be a plethora of studies of many sorts regarding this coronavirus, its impact, and our reactions in the months and years to come. Brace yourselves.

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Classic Charlie Chaplin Photo

The improvement and acceptance of blood type science went beyond medicine and into forensics. It helped reduce Charlie Chaplin’s embarrassment, but only a little.

Chaplin, the famous actor-comedian-film maker, was married four times and a well-know philanderer, as well as a misogynist. [4] A paternity suit against him in the ‘40s resulted in blood testing, and eventually changed family law. 

In the 1940s a young actress (with whom he was “friendly” – this during his 3rd marriage) claimed he was the father of her child. She sued him for child support. Blood tests on Chaplin, the child and mother showed that he could not possibly be the father. 

Chaplin, with recessive Type-O, could not have been the father of a Type-B child whose mother was Type-A.  Case dismissed?  No. She pressed her allegation, nonetheless.

Astounding to us in the 21st century, accustomed as we are to such quotidian data as DNA matching, blood tests were not permitted as evidence at the time. Chaplin lost the court case and was compelled to pay child support.  Worse: His trysting filled the pages of the days’ print media. His reputation was trashed.[5]

The law was changed a few years later.  But not in time for Chaplin.  He was so disgraced that – combined with other bad press and McCarthy-era distrust – he was even denied re-entry to the United States, in 1952. (He was not a US citizen, although he’d lived there for over 40 years).

He resided in self-imposed exile in Switzerland for the rest of his life. He returned to America only once before he died, for a few days in 1972, then aged 83, to receive a Lifetime Achievement Award at the Oscars.  On stage, with Jack Lemon, he received a 12-minute standing ovation – the longest in Academy Awards history.

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Even though Type-O is recessive, it has survived. Not surprisingly, its prevalence is about the same for whites and blacks; we are one race, after all.

Recessive?  Well, we Type-Os are sometimes weak, as attested to by Chaplin’s behavior.

That’s a wrap, from typos to Type-Os. Thanks for any corrections or suggestions.

Until next time, peace to you.

Joe Girard © 2020

Thanks for reading. As always, you can add yourself to the notification list for when there is newly published material by clicking here. Or emailing joe@girardmeister.com

Final footnote on Chaplin.  He was soon married a fourth time.  He reportedly approached the young 18-year old Oona O’Neill with the line: you look like my next ex-wife. As he was 38 years her elder (in fact nearly the same age as her father, famous playwright Eugene O’Neill) he was disgraced again. Next ex-wife?  Wrong! They stayed married for over 30 years, until his death, producing 8 children.  The eldest, Geraldine, starred remarkably with Omar Shariff and Julie Christie in Dr Zhivago: at the tender age of 20 when filmed.

[1] Who discovered the Rh factor?  http://www.rvdoon.com/rh-negative-blood-blood-feud-which-scientist-discovered-the-rh-factor/

[2] Possible purpose of Rh proteins: https://phys.org/news/2005-05-rh-protein-biological-role.html

[3] Blood Types over 20 million years ago: https://www.smithsonianmag.com/science-nature/the-mystery-of-human-blood-types-86993838/

Could be as recent as 3.5 million years ago: https://www.livescience.com/33528-why-blood-types-exist-compatible.html

[4] Charlie Chaplin: https://www.dailymail.co.uk/news/article-2597412/2-000-lovers-comedy-genius-didnt-like-women-New-book-reveals-Charlie-Chaplins-obsession-young-girls-cruelly-treated-them.html

[5] Chaplin paternity, blood tests and court case: https://www.mentalfloss.com/article/63158/how-charlie-chaplin-changed-paternity-laws-america

[6] Type-A and COVID-19: https://www.news-medical.net/news/20200603/Blood-group-type-may-affect-susceptibility-to-COVID-19-respiratory-failure.aspx