#immunoglobulin

The Antibody Odyssey

Have you ever wondered about the tiny superheroes zipping around your body, keeping you safe from invaders? No capes, no tights, but these incredible warriors are essential for our health: antibodies! These Y-shaped proteins play a crucial role in identifying and neutralizing these invaders, safeguarding our health. Produced by specialized white blood cells called B lymphocytes (B cells), antibodies are highly specific molecules, each designed to recognize a unique signature on a foreign substance, known as an antigen. This specificity, akin to a lock-and-key mechanism, ensures that antibodies only target the invading pathogens and not our own healthy tissues.

The earliest glimpse of antibodies came in 1890 when Emil von Behring and Shibasaburo Kitasato made a groundbreaking discovery. They observed that serum from animals immunized against diphtheria could protect other animals from the disease. This landmark finding laid the foundation for the concept of "antibodies" and paved the way for further exploration. In the early 20th century, Paul Ehrlich, renowned as the "father of immunology," proposed the "side-chain theory." This theory postulated the existence of specific receptors on cells that could bind to specific antigens (foreign molecules). This concept laid the groundwork for understanding the remarkable specificity of antibody-antigen interactions.

The 1960s witnessed a significant breakthrough with the work of Rodney Porter and Gerald Edelman. They elucidated the primary and secondary structure of antibodies, revealing their Y-shaped structure and intricate details of their amino acid sequences. This paved the way for a deeper understanding of their function and diversity. The process of antibody creation begins when a B cell encounters an antigen. This triggers the B cell to activate and divide rapidly, forming a clone of identical cells. These clones, called plasma cells, become antibody factories, churning out millions of antibodies specific to the encountered antigen. These antibodies then circulate throughout the bloodstream and lymphatic system, patrolling for their matching antigens.

Recognizing and Eliminating Threats: The Multifaceted Arsenal of Antibodies

Once an antibody encounters its specific antigen, it binds to it with remarkable precision. This binding initiates a multi-pronged attack on the pathogen:Neutralization: By binding to critical structures on the antigen, such as the viral envelope or bacterial toxins, antibodies can render them ineffective, preventing them from infecting cells or causing harm. Opsonization: Antibodies act as flags, coating the antigen with a special tag that attracts other immune cells, such as phagocytes (white blood cells that engulf and destroy foreign particles). This process, called opsonization, marks the antigen for destruction. Activation of the complement system: Antibodies can trigger a cascade of protein reactions called the complement system, which further aids in the destruction of the pathogen.

But, did you know that there's not just one type of antibody? These versatile molecules come in various forms, each with its unique structure and function. The type of antibody produced also plays a crucial role in the immune response. There are five main classes of antibodies (IgG, IgA, IgM, IgD, and IgE), each with distinct properties and functions:

Immunoglobulin G (IgG): The Mighty Defender - This is the most abundant antibody type, constituting around 70-80% of all antibodies in the bloodstream. IgG has four subclasses (IgG1-4) with subtle differences in function and lifespan. IgG is like a versatile soldier, capable of: Neutralizing toxins and viruses: By binding to pathogens, IgG prevents them from infecting cells. Triggering phagocytosis: It flags pathogens for specialized immune cells called phagocytes, which engulf and destroy them. Passing immunity to newborns: IgG antibodies can cross the placenta, offering newborns temporary protection against infections until their own immune system develops.

Immunoglobulin M (IgM): The First Responder - IgM is the first antibody produced by B cells in response to an infection. While less effective at neutralizing pathogens individually, it compensates through its: Pentameric structure: Five Y-shaped units join together, increasing the "avidity" or overall binding strength to pathogens. Complement activation: IgM can activate the complement system, a cascade of proteins that attracts immune cells and promotes pathogen destruction.

Immunoglobulin A (IgA): The Sentinel at the Gates - This antibody is primarily found in mucosal secretions like tears, saliva, and breast milk. IgA acts as the first line of defense against infections at these entry points by: Preventing pathogen attachment: It binds to pathogens, hindering their ability to adhere to and colonize mucosal surfaces. Neutralization and exclusion: IgA neutralizes pathogens and facilitates their removal through mucus flow.

Immunoglobulin D (IgD): The Enigmatic Player - IgD remains the least understood antibody type, making up only a tiny fraction (around 0.02%) of the total. While its exact function is still being unraveled, it's believed to be involved in: B cell activation: IgD might play a role in stimulating B cells to mature and produce other antibodies. Regulation of immune response: It's thought to be involved in fine-tuning the immune response by preventing B cells from overreacting.

Immunoglobulin E (IgE): The Double-Edged Sword - IgE is responsible for triggering allergic reactions. It binds to allergens (substances perceived as threats) on mast cells, which then release histamine and other chemicals. This leads to the characteristic symptoms of allergies like runny nose, itchy eyes, and wheezing. However, IgE also plays a role in expelling parasites, It can trigger the release of substances that help expel parasitic worms from the body.

The Building Blocks: Chains and Domains

An antibody is comprised of four polypeptide chains: two identical heavy chains and two identical light chains. Each chain folds into distinct regions called domains, which are responsible for specific functions.

Variable (V) domains: Located at the N-terminus (amino-terminal end) of both heavy and light chains, these domains boast highly diverse sequences. This variability allows the antibody to recognize a vast array of unique structures on antigens, the foreign molecules it targets.

Constant (C) domains: The C-terminus (carboxy-terminal end) of the heavy chains contains these domains. They determine the antibody's class (isotype), which influences its ability to interact with other components of the immune system and trigger specific effector functions.

The Architecture: Y-Shaped Majesty : The four chains assemble in a specific manner, forming the characteristic Y-shaped structure. The arms of the "Y" are formed by the Fab (fragment antigen-binding) fragments, each consisting of one light chain and one heavy chain linked together. These Fab fragments house the antigen-binding site, the crucial pocket where the antibody specifically recognizes and binds to its target antigen. The base of the "Y" is the Fc (fragment crystallizable) fragment, solely composed of the C domains of the heavy chains. This region interacts with immune cells and molecules, dictating the antibody's fate and activating various immune responses.

A Hinge for Flexibility and Diversity : Connecting the Fab and Fc fragments is a flexible hinge region. This hinge allows the Fab arms to have some degree of movement, enabling them to bind to antigens with different shapes and sizes. This flexibility also contributes to the remarkable diversity of antibody specificities, allowing the immune system to recognize and combat a wide range of pathogens.

When we encounter an antigen for the first time, our B-cells take a snapshot of its "fingerprint" and create a specific antibody to fight it. These "memory B-cells" then stick around, so if the same antigen tries to attack again, our bodies can respond quickly with a trained army of antibodies, preventing us from getting sick again. This is the genius behind vaccinations! Vaccines introduce weakened or inactive antigens, training our B-cells to create memory for specific villains, so we're prepared if they ever try to invade for real.

The knowledge gained from antibody research has revolutionized healthcare. Here are some notable examples:

Vaccines: By exposing the immune system to weakened or inactive forms of pathogens, vaccines stimulate the production of specific antibodies, providing long-term protection against diseases.

Diagnostic Tools: Antibody-based tests, like ELISA (Enzyme-Linked Immunosorbent Assay), are widely used to detect and diagnose various diseases, including viral infections and autoimmune disorders.

Therapeutic Antibodies: Monoclonal antibodies, produced in the lab to target specific antigens, have emerged as a powerful tool for treating various diseases, including cancer, autoimmune diseases, and infectious diseases.

Gather Round

The immune system's B cells recognise their foe (antigens) with receptors (also known as immunoglobulin or antibody) on their cell surface. Here, super resolution microscopy combined with 4D image analysis reveals how these receptors on the cell surface localise into clusters as ridges and finger-like projections called microvilli to aid recognition of their targets

Read the published research paper here

Video adapted from work by Deniz Saltukoglu and colleagues

Department of Molecular Immunology, Biology III, Faculty of Biology, University of Freiburg, Freiburg, Germany

Video originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)

Published in The EMBO Journal, January 2023

bonds with highly specific molecules

has a crystallizable fraction

contains a variable protein chain

is synthesized by plasmatic B-cells

opsonizes pathogens setting them to be recognized and digested by macrophages

One of the distinct characteristics of Adaptive Immunity is Immunological Memory. Immunological memory aids the immune system to mount a faster and more efficient response to reinfection. However, this exclusivity has been challenged in the last two decades with evidence coming forth of immunological memory exhibited in innate immunity. The memory characteristic of innate immunity is termed as 'Trained Immunity' and it results in an elevated response to secondary infection.

It is important to note that despite being the same concept, the functioning of the memory characteristic of both types of immunity varies greatly. Unlike adaptive immunity which utilizes genetic recombination, trained immunity is mediated by epigenetic reprogramming of the transcriptional pathways within cells.

Trained immunity is said to last from 3 months to 1 year and in cases of live vaccines up to 5 years as opposed to adaptive immunological memory that lasts for an individual's lifetime.

Another interesting feature of trained immunity is its non-specificity. After an infection, the innate immune system is 'primed' for a stronger response to reinfection not only to the primary pathogen but also to several other unrelated ones.

An example of the non-specific nature of trained immunity is the protection provided by the BCG vaccine. Apart from priming the immune system against Mycobacterium tuberculosis, it also provides protection against Candida albicans and Schistosoma mansoni. The response to these unrelated pathogens has been confirmed to be produced by the innate immune system.

The BCG vaccine can also be applicable in cases of cancer treatments since studies have shown successful tumour remission as a result of trained immunity. The BCG vaccine is currently being employed as an FDA approved immunotherapeutic strategy to treat bladder cancer in the USA and is also used in some cases of lymphomas and melanomas.

Trained Immunity is a new discovery that drastically changes our view of innate immunity and the immune system as a whole. These new findings might lend us hand in understanding the several unexplained and unanswered questions that we still have about the system that has evolved with the sole aim to protect us. Trained immunity could also explain the evolutionary success of 97% of earth's lifeforms that depend upon innate immunity for protection against pathogens since adaptive immunity is an exclusive feature of vertebrates. Some studies suggest a link between trained immunity and autoimmune diseases. More knowledge about trained immunity could also usher in a new era of vaccines that target the innate immune system. Trained Immunity is a new and exciting avenue for future research in Immunology.

a. Persistent anemia and bone problems

b. Flattened villi and cell crypt abnormalities

c. A positive immunoglobulin IgA-transglutaminase assay

d. No improvement in GI symptoms following a low FODMAP diet

I wasn’t sure about this on the exam for GI, but I got it right. I think I was thinking about how there are two types of Inflammatory Bowel Disease, Crohn’s and Ulcerative Colitis. And the fact that in UC, you will see crypt cell abnormalities and crypt branching. But the differentiating factor for this question itself is the fact that the tissue transglutaminase test is specific to Celiac Disease. You aren’t looking at immunoglobulin IgA-transglutaminase assays in Inflammatory Bowel Disease (in neither Crohn’s nor UC, thus it is clear that c is the answer).

IgM

I just have to say

I was possibly exposed to Rabies and came to Tumblr for help and advice and was THOROUGHLY AND DISTURBINGLY DISAPPOINTED WITH THE RABIES TAG.

Omg

I was convinced I was going to die and searching anything Rabies related was UNHELPFUL AF. Not judging but y'all did not help lol.

Very long explanation of why I thought I was going to die:

Waking up to a bat (2 nights in a row) is not automatic cause to assume you will die but it is, I found out after talking to the Dept. Of Agriculture and their Epidemiologist, an immediate cause to go straight to the ER and get shot up with the vaccine and immunoglobulin so you DON'T POTENTIALLY DIE. It is not something the doctors can argue against and it is not something you should postpone. Especially since I was "under the influence" (Nyquil) at the time and even less likely to notice if I had gotten scratched or bitten. My being unaware was the key point in the urgency of going to the ER.

The ER doc was highly annoyed I knew just what to say ("I woke up with a bat in my face") and he grumpily admitted he was bound to follow CDC protocol. His annoyance was so obvious he repeatedly told me how unlikely it was I was bit and explained how "intense" the shots would be. I assume he felt the medicine could be put to better use on someone who was 100% sure and/or was injured. When I asked him what would happen to me if I WAS bitten and didn't get the shot like he wanted, he sighed and admitted "Well, you die."

"Well, shoot me up, doc!"

That night I got 7 shots. One in my arm, which hurt so bad--I guess because my nurse was new and may habe gone too deep because the subsequent shots I have gotten in the same arm haven't been anywhere near as painful-- and 6 in my buttcheeks. 3 in each.

Waking up from my Nyquil coma to a bat in my face was not fun. I had never related to those movie scenes of people screaming and running around afraid if bats. But jessuz. They are fast. And this one was swooping around my living room and deliberately getting super close to me. I had to hide under my blanket and in my fevered state this made me sweat. Trying to herd it to my now opened windows did not help. I tried to call police, fireman andnanimal control; the 1st two were useless and the 3rd was not open at 1am.

Eventually I reached out to my townie facebook group and got advice. White towels attract them. Or make it dark and quiet and hide--I did this as I was not going to run around with a towel in my undies like that video--which worked. 2 very concerned people urged me to go to a doctor.

"You say you have flu-like symptoms and a constant fever and you sleep in that room a lot. You really need to go to the ER. Rabies is so dangerous."

And after 2 nights of dealing with bats and my fever spiking right around the time they show up, I existed in a dark hole of stress. So much so that the second morning I woke up to my hand twitching erratically and my thumb muscle spasming and I started bawling. I had already gotten the shots the day before so I knew if I encountered anything rabid I should be okish (I still had 3 more to go before I was fully protected) but now, with my glitchy hand, I was panicking about "WHAT IF I ALREADY HAD IT?!"

Urgent Care had ruled out Strep twice for my odd sickness and had assured me I have a random virus and to just stay in bed for a few days. Which I had been doing faithfully, before getting bored and moving to my livingroom nest. I like to sleep in there a lot and often do when the weather is nice. I just made sure to drink water and tea and get sunlight and all the things. Including Nyquil. But my fevers were getting worse. I was feeling like crap. And now what we all assumed to be A Normal Virus was morphing into my worst nightmare.

Probably egged on by 101 temperatures, I called around until someone was willing to explaon to me whether I was dying or not. Getting told "You'll be fine. It is SO RARE," did not calm me down. I needed someone to explain how the long incubation period (months to a year) and symptoms (flu like, emotional, twitchy) did not match me.

I slept in that room on accident and on purpose since moving in almost 9 months ago. I'm a heavy sleeper and don't wake up easily. Iffff I had been bitten during one of my all-nighters doing math homework or essay writing, it makes sense I would suddenly get a random "virus" that isn't going away. I had it all worked out in my head. I was getting headaches in the sun and stores. I forced myself outside and out and about when I felt ok because fuck it if I was going to let this be a symptom I had. I was getting anxious in the shower but, knowing fear of water was a symptom, I forced myself to stay in it. (Turns out my paranoia was right. The water was starting to be hard and my skin was breaking out. It is very annoying. The timing was just horrendous)

All the doctors and nurses kindly told me I was safe since I had started the shots but no one had an answer for me when I asked if they helped if I hadddd it already. They weren't sure. The amount of information they have or are willing to share is astonishingly low.

After 2 hours of phone tag I was finallly able to get an appointment with an Infectious Disease Doctor. She told me that if I did have it there was no real evidence about the vaccine helping, especially since I had only had the first dose at that point. She told me it would be fast though and they couldn't tell until "you're foaming at the mouth." She asked to look in my mouth and when I told her about my drooliness she said to let her know if it got worse. She asked about my hand. I told her. She asked about numbness and I freaked cuz my arm did go numb at one point.

I askwd her about tests. I had read that there were a few--spinal fluid, spit, blood--that were not really reliable. She said since I had the vaccine and immunoglobulin in my system already they would show up and it would be pointless.

My only option was to wait. And chill. And try not to dwell on the fact that there is no answer or cure or way to find out if I should plan my trip to Oregon and die or if I should allow my boyfriend to visit me.

He was firmly in the You Don't Have Rabies camp and came over anyway to feed me soup and hang out. But I refused to kiss him. It made him very sad and probably extremely exasperated.

My boss was so done with me when he asked if I could come in the next day. "Sasha. You cannot have Rabies. Just come to work. You'll be fine." And I realized how crazy I sounded but I still warned all my coworkers.

Anyway, my lowgrade fever continued, my twitchiness stopped, my drooling stopped, my water was hard so I avoided the shower but cleaned my good bits, and once I doubled up my water intake my headaches disappeared. I went into a mini death spiral for a day but decided to force myself into believing I was fine.

When I started getting confused and fainty, I bought Iron supplements. When I started getting angry and anxious, I called my friends and got distracted. When it was time to get another shot, I made sure to update everyone of the weirdness Just In Case.

One nurse took the time to sit me down and listwn. That's really all I needed since no one had answers. I just needed my mind soothed and concerns not dismissed. She couldn't explain the muscle spasm but could definitely see why I was freaking out. She was the one who tested me for peace of mind. She looked into Lyme disease. She found my anemia. She explained that the amount of time that had elapsed made her sure I was going to be ok. She had watched people die in Africa from this and shw said it happens So Fast it is tragic. I would not be able to organize a trip to Oregon to die. I would become incoherent and slip away within days.

That was what I needed. A timeframe. A legit explanation of what it looks like and how it happens. And why I don't fit. This whole time I had been wondering how to tell my friends. Whether I could write all their numbers down in case I couldnt function enough to call them or remember my phone password. I was planning on cleaning my apartment so good so the landlord couldn't bash me when I was bouncing off the walls and hissing at him. I was deciding who I really needed to contact and who I could live without wasting breath on. I was planning a goodbye party. I told all 3 of my lovers ("´hey, I have this thing there is no real test for while you're alive but there is once you die so you can't get tested, and you may have it so got get shot up but no one is sure if that will help much," but I did tell them and it was hilarious to them. My favorite response being "RIP" and "F") And this all had put me in such a dark place that, coupled with a few shitty days at work with my bully of a manager, I also asked for a psych person to visit me after the Rabies shot.

After her talk I was like, oh. Thank godddd. And kinda annoyed at having to wait an extra hour in the ER for a talk that could wait til morning. But I chatted with rhem and asked for referral to a shrink since this had just highlighted how much I need help with my anxiety. Especially since the temporary issue of Rabies was being resolved but my cruel manager was still going to exist now that I was going to survive this beef with nature. It was nice to think of that way "my rabies beef is getting cooked" and the pscyh lady got me help. So that was nice. I just mainly needed to get healthy again so I could

I mean. Almostbarelybutnotreally facing a cruel death was a great way to look at life and reflect on some things. There are messes I am not at fault for, messes I avoid that I shouldn't, people and things I value and the objects that matter to me more than others for ridiculous reasons. I was so grateful to the staff for putting up with me. And for you for reading.

All of this just to say

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