Question

Describe the basis of an autoimmune disease.

Graves’ disease, myasthenia gravis, rheumatoid arthritis and systemic lupus erythematosus are four quite common autoimmune diseases.

Describe the major mechanism of tissue damage seen in each of these diseases and the results.

Answer 1

All individuals are tolerant of their own potentially antigenic substances, and failure of self tolerance is the fundamental cause of autoimmunity.

Autoimmune diseases develop when self-reactive lymphocytes escape from tolerance and are activated. Is thought that this atypical response of immune system,  result from a combination of genetic variants, acquired environmental triggers such as infections,hormonal influences and stochastic events. In fact, some susceptibility genes has been identified but this is not a general rule

So, in autoimmune diseases , immune responses to specific self-antigens contribute to the ongoing tissue damage that occurs in that disease. This process may be either tissue-specific (e.g., thyroid, β-cells of the pancreas), where unique tissue-specific antigens are targeted, or may be more systemic, in which multiple tissues are affected, and a variety of apparently expressed auto antigens are targeted.

The immune system typically produces both T cells and B cells that are capable of being reactive with self-antigens, but these self-reactive cells are usually either killed prior to becoming active within the immune system, placed into a state of anergy (silently removed from their role within the immune system due to over-activation), or removed from their role within the immune system by regulatory cells.

When any one of these mechanisms fail, it is possible to have a reservoir of self-reactive cells that become functional within the immune system.

So, many theories try to explain autoimmune responses. One of them is named as molecular mimicry . This theory propose that some infections, have antigens that are similar to our own self-molecules triggering cross antibody reactions now against self antigens. Activation of autoimmune B cells and T cells can be influenced by innate immune receptors, which primarily recognize pathogen-derived molecular structures but may cross-react with host molecules.

Examples of autoimmune diseases

GRAVES DISEASE

This disease causes hyperthyroidism as a consequence of the attack of  immune system to the thyroid and causes it to make more thyroid hormone . Thyroid-stimulating immunoglobulins recognize and bind to the thyrotropin receptor (TSH receptor) which stimulates the secretion of thyroxine (T4) and triiodothyronine (T3)

Thyroxine receptors in the pituitary gland are activated , suppressing additional release of TSH in a negative feedback loop. The result is very high levels of circulating thyroid hormones and a low TSH level.

MYASTHENIA GRAVIS

This autoimmune disease causes weakness in the skeletal muscles, which are responsible for breathing and moving parts of the body, including the arms and legs.

Is caused by an error in the transmission of nerve impulses to muscles. It occurs when normal communication between the nerve and muscle is interrupted at the neuromuscular junction—the place where nerve cells connect with the muscles they control.Usually, the nerve impulse transmission is mediated by the release of neurotransmitter molecules in the synaptic space

This altered transmission of the nerve impulse is the result of the action of antibodies that block, alter, or destroy the receptors for acetylcholine ( neurotransmitter) at the neuromuscular junction, which prevents the muscle from contracting.

In most individuals with myasthenia gravis, this is caused by antibodies to the acetylcholine receptor itself. However, antibodies to other proteins, can also lead to impaired transmission at the neuromuscular junction.

RHEUMATOID ARTHRITIS

Causes pain and swelling in the wrist , knees, and small joints of the hand and feet.

Primarily starts as a state of persistent cellular activation leading to autoimmunity and immune complexes in joints and other organs where it manifests .The initial site of disease is the synovial membrane, where swelling and congestion lead to infiltration by immune cells. Three phases of progression are:

- initiation phase (due to non-specific inflammation)

- amplification phase (due to T cell activation)

-chronic inflammatory phase, with tissue injury

SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)

Common symptoms include painful and swollen joints, fever, chest pain, hair loss, mouth ulcers, swollen lymph nodes, feeling tired, and a red rash which is most commonly on the face.

In SLE, the immune system produces antibodies against against proteins in the cell nucleus.

One of the main characteristics of this condition is the development of defects in apoptotic clearance, and the damaging effects caused by apoptotic debris. Early apoptotic cells express cell-surface proteins acting as inductors to immune cells to engulf them.

But apoptotic cells also express signals, to attract macrophages and dendritic cells. When apoptotic material is not removed correctly by phagocytes, they are captured instead by antigen-presenting cells, which leads to development of antinuclear antibodies.