Intro & Rationale

When I was a kid eating certain foods would get me painfully sick. If I had a bite of cheese for example, within minutes a rash would appear over my face and body, and a slow drip of mucous would begin to trickle down the back of my throat until i spend the night retching and heaving on my own bodily fluids. This food allergy is my dairy allergy; the more mild of the two.

I also have a hypersensitivity to wheat, which i inherited from my father. Left untreated this manifests as diarrhea, a rash on the torso that can last a month, cysts on the back and chest, other food allergies (which either go away or become far more mild after quitting wheat), varicose veins and arthritis. When I was a child i only had to deal with the first symptom. Once I entered my late teens-early 20’s the rash and cysts started to appear. Per my dad the other food allergies began appearing in his late 20’s, and the arthritis and varicose veins manifested in his early 40’s, until he quit consuming wheat (while both are not completely gone, both conditions improved dramatically after the change in diet).

The purpose of this series is to figure out exactly why some of us have to go through this bullshit, to gain an understanding of what exactly goes wrong in the body to make some people unable to be exposed to certain things, and to explore some avenues of research that may lead to a cure in the future. So without further adieu, here’s an …

Overview of immune system

The immune system comes in two main layers. The first is relatively simple as it consists of physical barriers to the body’s delicious internal organs: namely the skin, the intestinal lining, and membranes in the lungs, eyes and ears. The second line of defense is far more complicated. The body’s internal defense system consists of cells located in the thymus, bone marrow, lymph nodes and cells that migrate through the bloodstream and other interstitial spaces (spaces between tissues) so that they can respond quickly to various forms of attack. The nature of these cells can be further sub-divided by their respective roles in the two main phases of immune response, innate & adaptive.

The Innate immune system

The Innate immune system exists to respond to new micro-organisms and substances (called antigens). When a person who develops an allergy to wheat consumes it for the first time, none of the usual symptoms appear, because only the innate response is at work. The innate immune response consists of phagocytic cells such which devour unwanted materials, Antigen Presenting cells which kidnap samples of foreign material and deliver it to the adaptive immune system for “training” purposes, Mast cells, which play a big role in cell signaling particularly with histamine and allergy responses, and other innate lymphoid cells and blood proteins such as cytokines and mediators of inflammation.

The adaptive immune system

The adaptive immune system serves to eliminate recurrent or long-lasting infections. It consists of B cells, T cells and memory cells that have optimized to attack a specific antigen.
(B and T lymphocytes) also called B and T cells, the term “lymphocyte” comes from cutting open lymph nodes and seeing them contain primarily these cells.
“B” cells get their name from the “Bursa of Fabricus,” which is an organ located in a bird’s ass, where those cells were first discovered.  Bird’s ass lymphocytes are the ones responsible for producing antibodies (also called immunoglobulin), which glob to specific foreign molecules and either mark them for destruction or impair them directly. Unlike birds, the human body makes B cells in  the bone marrow. I’ve heard T cells referred to as “terminator” cells, which makes sense given that T “helper” cells and T “killer” cells work in teams to kill host cells that have been infected with a microbe, but it is more likely that “T” cells are so named because, while they are initially produced in the bone marrow, they mature in the Thymus[1].
The thymus will be relevant when we talk about allergies.

(Fun question: why is the first exposure to an allergic antigen characterized by a lack of symptoms and all symptoms thereafter are the result of the adaptive immune response, whereas symptoms of most infectious diseases are only seen on the initial infection with no symptoms appearing afterward after the body developed specific immunity to it? I have a tentative explanation which I will submit at the end of this post.)

So to recap with our intention in mind: the innate cells have pre-built receptors to determine various unspecified (in that I don’t know about them yet) types of antigens. Many (both innate and adaptive) summon more immune cells by sending out cytokines as a signaling molecule. Many of these cells (especially dendritic cells), kidnap some of the foreign antigen and drag it to the lymph nodes to present it to the bird-ass lymphocytes that design antibodies to bind, mark, and enable the attack of exactly the offending agent. After the infection is repelled, a few of the bird ass lymphocytes that were trained to deal with this antigen distribute throughout the body and live on as “memory cells,” allowing for a rapid specific immune response should the infection ever return.

As we delve deeper into the immune system, here are some questions I will be using to frame the the investigation:
Given that predispositions for allergies are strongly heritable, can that be traced to a malformed receptor on one or more cell types in the innate immune system?
If the former is true, could the genetic modification of those cells be sufficient to stop an allergy, or do the memory cells also need to be dealt with?
In an allergy, what specifically is going wrong with the body’s ability to distinguish self from non-self, or a harmful foreign substance from a harmless one?

My tentative answer to the fun question: when someone accidentally consumes something he/she is allergic to, he is likely consuming billions of times more of the substance than occurs when someone is initially infected with a disease, hence the lack of a reaction when a person is infected after having acquired immunity. Couple this with the fact that the adaptive immune response takes some time to learn a new antigen, what probably happens when someone gets a cold is that most of the symptoms appear days after the initial infection, when the adaptive immune system finally responds, and the invading micro-organism has had enough time to proliferate throughout the body until (kinda similar to the allergen) the amount of infected tissue can be measured in grams and not atoms.

References:
Cellular and molecular Immunology 9th ed., ABul K. Abbas, Andrew H.H. Lichtman, Shiv Pillai, Chapter 1