Understand Autoimmunity

Scroll below to understand the basics of autoimmune diseases and the immune system's lines of defense.

Basic Definitions + Terminology

What is a pathogen?

A pathogen is any disease-causing agent that needs the host's nutrients, protection settings, and transport mechanisms to survive.

- This may include a bacterium, fungus, virus, or other particle.

- AKA the intruder or foreigner to a organism's body

What is the immune system?

The immune system is a collective of interactions between certain cells, proteins, and other important molecules that works to protect the host's tissues and body against pathogens.

- The immune system consists of 3 lines of defense: barrier, other innate, and adaptive/acquired

Breakdown of the Immune System

Barrier

Includes the mucous membranes and skin, which serve as the first barrier against pathogen entry.

Other Innate

Once pathogen entry occurs, the general attack by phagocytic cells, dendritic cels, eosinophils, and more.

Adaptive/Acquired

A more specific attack of pathogens, includes the humoral (B cells, blood, lymph) and cell-mediated response (cytotoxic T cells)

Barrier Defenses

Membranes that line the digestive, respiratory, urinary, and reproductive tracts produce a substance called mucus, which can trap pathogens and other particles.

Saliva and tears are also sources which prevent pathogen entry into the organism; by secreting lysozymes, enzyme proteins, the secretions create an environment unstable for the pathogen, as lysozymes can break down bacterial cells.

Moreover, the acidic environment created by oil and sweat as well as the stomach is suboptimal for a pathogen's survival and serves as a 1st line of defense.

Innate Response

The innate response is a collective of a variety of cells, proteins, and other signaling molecules that work in tandem to promote a general, unspecified attack against a foreign invader.

Lymphatic system: a system of vessels which allocate a fluid known as lymph throughout the body

Toll-like receptors: pathogens attach to extracellular portion, signals produced intracellularly to destroy pathogen

Phagocytic cells: neutrophils and macrophages

- Neutrophils: circulate through the blood, are called to action by signals from infected tissues

- Macrophages: AKA "big eaters," can migrate throughout blood or ride permanently in a given location

Dendritic cells: inhabit tissues in contact with the environment (skin)

Eosinophils: inhabit tissues underlying the epithelium (outer layer of body cavities/surface/organs) and release destructive enzymes against multicellular invaders (e.g. parasitic worms)

Natural Killer (NK) cells: work by means of detecting surface proteins and releasing toxins

Antimicrobial peptides and proteins: include the release of peptides that directly engage with pathogens through tagging or destroying. The complement system is a unique feature of this defense line to vertebrates.

Inflammatory response: occurs when macrophages become activated and release cytokines (signaling molecules) to the site of infection/injury, causing blood to flow and promoting neutrophils to the location for digestion.

- Mast cells release a hormone known as histamine, allowing blood vessels to become more permeable such that blood supply increases, and skin temperature does as well.

Adaptive Response: Humoral and Cell Mediated

This 3rd line of defense, more specific to a given pathogen, is reliant on cells that originate from the bone marrow, called lymphocytes. Cells that start in the bone marrow and migrate to the thymus are known as T cells, whereas those that stay in the bone marrow for the duration of their lives are known as B cells.

Antigen: any substance which induces a B or T cell response (note: an antigen varies from a pathogen in that an antigen is limited to firing up the adaptive immune response)

Both humoral and cell-mediated responses are aided by helper T cells, yet where the humoral response mainly involves B cells and antibodies, the cell-mediated response mainly involves killer/cytotoxic T cells.

- When an antigen is present and the correct shape, it can bind to receptors on the helper T cell, causing proliferation of helper T cells and activation of B cells or cytotoxic T cells.

In order to bind to antigens, B and T cells require an antigen receptor specific to the given lymphocyte. A B cell antigen receptor is Y-shaped, whereas a T cell antigen receptor is I-shaped.

- The epitope is the part of the pathogen where the receptor binds to.

- Within each antigen receptor are binding sites, variable regions, constant regions, and other interactions.

After a B cell is activated, it proliferates and differentiates into memory B cells and antibody-secreting plasma (effector) cells.

- Memory B cells give rise to a secondary humoral response, which leads to the production of more plasma cells. This secondary response is much faster and effective in the case of a 2nd entry.

- Plasma cells secrete antibodies, which are tagging molecules that defend against extracellular pathogens by binding to antigens. This binding can either cause the neutralization of pathogens or make pathogens better targets for phagocytic cells and complement proteins (innate).

After T cells are activated, they can defend against infected cells through lysis (i.e. intracellular pathogens). Two types of T effector cells: helper and cytotoxic.

- Helper T cells: bind to antigen-presenting cells (macrophages, dendritic cells, or B cells), which display antigens on their surface.

- MHC molecules (class I and II both present in antigen-presenting cells) bind helper T cells to the epitope with the help of accessory proteins like CD4 (class II) and CD8 (class I).

- Cytotoxic T cell: binds to an infected cell and releases perforin molecules, creating pores in the infected cells, and granzymes, enzymes that break down proteins

- Memory T cells, which are a product of the activation of the cytotoxic T cell, can give rise to a secondary cell-mediated response, which leads to the production of more active cytotoxic T cells

Source: Urry, Lisa A.,, et al. Campbell Biology. Eleventh edition. New York, NY, Pearson Education, Inc, 2017

Not Understanding?

Watch this video by the Amoeba Sisters to understand the basics and gain some cool visuals. Click the button below to start learning about current applications!

Resources

Autoimmune Diseases

What is an autoimmune disease?

An autoimmune disease is one where the immune system targets specific molecules of the body (i.e. instead of activating in the presence of a foreign invader, the immune system attacks self)

What are T-regulatory cells?

T regulatory cells are specialized T cells that help regulate immune system activity and prevent response to self-antigens. A current focus of research is figuring out how these cells play a role in autoimmune disorders.

Clinical Trials: The Basics

Clinical trials come in many forms and involve the participation of patients to better understand the extend of change a drug/treatment is causing across a group of people. Many protocols and diversity measures are taken to ensure accuracy and equality, and an Institutional Review Board is implemented to monitor the status of a trial. For alopecia, many clinical trials are of the "treatment trial" category. Click here to read more.

Phases of a Trial

Phase 1

beginning

20 - 80 person group (small)
Purpose: is it safe, are there side effects?

Phase 2

moving forward

100 - 300 person group (larger)
Purpose: is it effective, is it safe?

Phase 3

final stages

1,000 - 3,000 person group (large)
Purpose: validate effectiveness, monitor side effects, compare to other treatments, and gather health information about the drug

Phase 4

final stages

approved by FDA, available for consumption by the public
safety tracked by researchers to understand potential benefits and future use

U.S. Department of Health and Human Services. (2022, October 3). The basics. National Institutes of Health. https://www.nih.gov/health-information/nih-clinical-research-trials-you/basics