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NNadir

(33,516 posts)
Sat Aug 7, 2021, 11:58 AM Aug 2021

Fun With Poverty: The Immunology of How Cockroaches Make People Sick.

The paper to which I'll refer in this post is this one: Prangtaworn, P., Chaisri, U., Seesuay, W. et al. Tregitope-linked Refined Allergen Vaccines for Immunotherapy in Cockroach Allergy. Sci Rep 8, 15480 (2018). The article is open sourced, anyone can read it.

There's therefore no need for me to excerpt a lot of it, but I'll make a few editorial comments before posting some brief excerpts and a graphic or two.

It is my privilege to be asked serious questions to explain subjects about which I know nothing at all. This inspires me to find things out. This brief post is about one of those adventures.

Over the years, I've garnered some impressions of immunology by osmosis, mostly connected with proteomics issues in my work, and of course, Covid has inspired additional desultory interest in the subject, but effectively, I know nothing at all. So this weekend I'm watching recorded lectures on the topic and reading lots and lots of papers on the subject. It really is fascinating, thrilling actually, particularly since the immune system, as recorded on chromosome six, can illuminate the disease history of various ethnic groups, going back tens of thousands, hundreds of thousands of years. There are very real genetic differences between ethnic groups with respect to their immune systems.

This is shown in a graphic, with some explanation required, from this paper: McKinney, D.M., Southwood, S., Hinz, D. et al. A strategy to determine HLA class II restriction broadly covering the DR, DP, and DQ allelic variants most commonly expressed in the general population. Immunogenetics 65, 357–370 (2013):




The caption:

Allelic coverage. The HLA class II alleles represented in the panel of 46 single transfected cell lines provide coverage of the majority of HLA class II types expressed in a cohort of 190 donors recruited for two different studies in the San Diego area. The fraction of all donors for which the panel provides coverage of zero to eight possible class II types expressed is shown in the bar graph (a). The cumulative fraction of donors covered is shown in the line plot (a). This coverage is consistent across different donor cohorts from geographically disparate regions (b)


I recently listened to a lecture by one of the authors of the paper from this graphic who explained that San Diego's subjects were ethnically diverse, Denver's mostly Caucasian, Baltimore's mostly African American, and Cape Town, of course, African although whether the Cape Town subjects were mostly native African and/or Euro-Africans. The near homology with the Baltimore subjects suggests the former. (Note this data was accumulated in the context of other studies, and was not generated in studies connected with determining allele frequency.)

"Tregitope" is a compound word; like German, although not quite as broadly, English allows for compound words. "Tregitope" is a compound word of "Treg" for regulatory T-Cells, T-cells that shut off immune responses after the antigen insult has been addressed. The "-itope" is a truncation of "epitope," an "epitope" being the business sequence of a protein, a short sequence of those amino acids that actually bind to a target, whether the target is actually an antigen like, say, the S-Protein of SARS-Cov-2 of Covid frame, or a physiological target for instance for the release of digestive enzymes, or binding to a receptor that increases heart rate during exercise. The bulk of many proteins is actually involved in exposing, hiding, or changing the geometry of epitopes.

Anyway, Cockroach immune responses - in this case allergies - can make you feel horrible, and/or even kill you.

From the introductory text of the open sourced paper:

Cockroach (CR) is a pestiferous source of human pathogen and allergen1,2. Exposure to CR-derived proteins is associated with high risk of developing allergies, including allergic dermatitis, allergic rhinitis, and atopic asthma3. It has been reported that 26–61% of allergic patients have positive skin test to cockroach extract4,5,6,7. Morbidity caused by CR allergens is usually more severe and prolonged than morbidity caused by other indoor allergens, such as house dust mites (HDM) and pets8. After allergen exposure, the sensitized subject develops predominant Th2 immune response9,10,11. Specifically, naïve CD4+ T cells transform to Th2 cells, which produce the following Th2 cytokines: interleukin (IL)-4, IL-5, IL-9, and IL-13. The immune response may be aggravated by IL-25, IL-31, and IL-33 produced by activated T cells, alveolar macrophages, epithelial cells, and dendritic cells (DCs)10,11,12,13,14. Secreted IL-4 and IL-13 influence class-switching of B cells to secrete an excessive amount of specific IgE that fixes to Fc epsilon receptors (Fc?RI) on the surface of tissue mast cells and blood basophils. The sensitized subject also has allergen-specific memory B and Th2 cells, and a high level of serum IgE. Upon re-exposure, the allergen cross-links IgE located on the surface of sensitized mast cells and basophils, causing the cells to release mediators that result in allergic symptoms that can be as severe as atopic asthma or life-threatening immediate anaphylaxis...


I added the bold so you can see the good...I mean bad...part.

A picture of mouse lung cells from cockroach allergic mice and normal mice and those injected with the vehicle but not the allergen (sham mice):

Figure 3



The caption:

Histological appearances and grades of lung sections of mice after staining with Periodic Acid-Schiff (PAS). (A–D) Grades 0–3, respectively, of goblet cells (stained pink/red; black arrow heads) in the lung epithelia. (E) Comparative average goblet cell grades of normal, sham and allergenized mice. The allergenized mice had significantly higher average goblet cell grade than the normal and sham mice (p??0.05).


As for the word "poverty" in the title of this post, coupled with the (hopefully recognized as sarcastic) word "fun," I don't know whether you've ever lived around cockroaches, but I have, but only in those "fun" portions of my life where I was, um, "down and out."

This rather ignored issue, allergies to cockroaches, may be just one reason that life-expectancy is lower for the impoverished than for the relatively wealthy or, for that matter, the super wealthy.

If this paper is to be believed, cockroach exposure can kill people.

I have convinced myself, to the extent that I consider social issues and recognizing some over-simplification, that many of the world's most intractable problems are related to poverty. There is a difference between a person who parks his shiny new Tesla electric car in the driveway of his McMansion, its roof strewn with solar cells, so all his or her neighbors know how "green" she or he is, and a person who is trying to keep the babies alive by pouring contaminated water over them in an extreme heat outbreak. If the latter person has to burn coal to run a pump to get the water, or have someone else burn coal to do so, they are not likely to have the time or energy to worry about climate change.

I often hear from people whose per capita climate impacts are greater than those of 50 citizens of the Central African Republic that "population" is the problem. In cultures where the future of elderly adults in entirely contingent on care by their offspring, and where infant and child mortality is high, one may be inclined to have more children to address the probability of having someone to care for them. This is why, I suspect, that birthrates are below the replacement rate in precisely those countries where people can feel secure with healthcare, are secure in their homes, and have access to health care, generally.

Simplistic, to be sure, but I may be on to something.

Bill Gates's children didn't have a cockroach allergy problem. Neither did mine.

But I'd guess billions of people do.

Have a pleasant weekend.





5 replies = new reply since forum marked as read
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Fun With Poverty: The Immunology of How Cockroaches Make People Sick. (Original Post) NNadir Aug 2021 OP
I would be curious to learn Nictuku Aug 2021 #1
I don't know, but I can point out that the authors of this paper are from Thailand. NNadir Aug 2021 #3
I got allergy tested I_UndergroundPanther Aug 2021 #2
I wonder how much this varies with the species of cockroach. eppur_se_muova Aug 2021 #4
That's an interesting question. NNadir Aug 2021 #5

Nictuku

(3,607 posts)
1. I would be curious to learn
Sat Aug 7, 2021, 12:51 PM
Aug 2021

I would be curious to learn if any studies are done in tropical places where cockroaches exist, everywhere, whether poverty is present or not.

I lived in Hawaii, and the fuckers are EVERYWHERE. No matter how clean you are able to keep the place. In brand newly built apartment buildings, they are there before the people move in.

I shudder to remember a single basement type apartment I moved into back when I lived in Hawaii in the 90s. The walls (looked nice, made of lava stones), had literal holes in them. The first time I started up the oven in that flat I swear, I thought I was being attacked by them, they (the big ones, they fly - we called them 747s) ended up getting killed by a broom and me screaming at my boyfriend to DO SOMETHING. We ended up with a huge dead pile of them. Freaking disgusting!

I know this has nothing to do with the medical aspects of this story, but I do know I've never seen a cockroach in any of the places that I have lived except Hawaii. I know there are a ton of them in Florida too, and probably throughout the south where it is so humid in the summers.

NNadir

(33,516 posts)
3. I don't know, but I can point out that the authors of this paper are from Thailand.
Sat Aug 7, 2021, 01:05 PM
Aug 2021

From my somewhat limited understanding, there is an interplay of factors involved in immunological responses, some of which are genetic, and define the "Tregitopes" with which people are born.

It may be that people living in tropical areas may have more "tregitopes" that either moderate or conversely, sensitize people to cockroach allergens.

While natural selection may play a role in the survival of anti-vax Floridians by killing a lot of them off, it is possible that the descendants of the survivors - there will be some, some of whom will be at procreative age - may record the exposure to Covid in their genome in a statistical sense: Some may have epitopes favoring their survival already, perhaps from SARS exposures many generations ago, and those that do, will be those who leave the signature in their children, enriching the population, as those who lack the gene are less likely to survive, and thus less likely to have children.

To your point, it would be interesting to study Polynesian populations to understand their immune reaction to cockroaches. To my knowledge, it hasn't been done.

I_UndergroundPanther

(12,463 posts)
2. I got allergy tested
Sat Aug 7, 2021, 01:02 PM
Aug 2021

And reacted to the test
Allergic to cockroach poop.

Was exposed to cockroaches first time in 1980's again in 2009. No strong reactions to it.
This test was in 2020.

I had a reaction of a burning itchiness and strange enough barely controllable anger.

About a few seconds after the test I felt really agitated to the point I started yelling and picked up a little vase to smash it I was so mad.

The doctor was called over from the next room.

They gave me a heavy dose of anti histamines and I became calm again.

I asked the doctor if emotional reactions to allergens is common or normal.

He told me it happens more than you think.

This happened when I was going to an allergy doctor.

I wonder how much allergies contribute to fights,domestic violence or abuse of kids.

eppur_se_muova

(36,261 posts)
4. I wonder how much this varies with the species of cockroach.
Sat Aug 7, 2021, 06:49 PM
Aug 2021

Americans are most familiar with American and German cockroaches, although Asian (flying) cockroaches are now well-established in some parts of the country. And very far south we see "wood cockroaches", which mostly live outdoors and don't cause any real harm except panic in people who have never seen such big mother cockroaches before. (Of course, SA probably has a completely different set of species/subspecies.)

Close to the type we encountered in FL. They are most infamous for the incredibly loud crunching noise they make when you step on them.

NNadir

(33,516 posts)
5. That's an interesting question.
Sun Aug 8, 2021, 08:49 AM
Aug 2021

If I am understanding what I've been reading and hearing correctly, exposure to antigens leads to distinct signatures in the Human Leukocyte Antigen (HLA) genes. I'm still not clear yet on how and why these gene signatures lead to pathogenic states (allergic reactions, autoimmune diseases) or protection from pathogens.

I've never been a genome kind of guy, but I'm getting dragged in that direction, no longer kicking and screaming but rather with a healthy dollop of fascination.

Here's a cool review paper I came across this morning on the topic from one of the Nature/Springer journals: Shiina, T., Hosomichi, K., Inoko, H. et al. The HLA genomic loci map: expression, interaction, diversity and disease. J Hum Genet 54, 15–39 (2009).

I'm not sure it's open sourced; reach out if your interested and lack access.

I have an enormous load on my plate, personal and professional (along with uncontrollable desultory interests), and don't know when I'll get to read this review, but I'm sure it's worth understanding.

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