What is an "Autoimmune Disorder"?

Simply speaking, autoimmune disorders are when the host's inflammatory cells attack "normal/self" tissues causing damage to the host tissues.

Autoimmune disorders can occur as a result if B and T cells do not mature properly. Under usual circumstances, this occurs during a process called "tolerance" in which any T and B cells that respond to self-antigen would be either "re-trained" or "removed from duty".

Autoimmune disorders have genetic components, often related to HLA alleles, and can be triggered by environmental or infectious stimuli.

Women are more often affected than are males

B cells remain in the bone marrow for central tolerance: here, they are exposed to self-antigen. Remember- we don't want our soldier B cells to attack us, only the enemy

B cells that respond to self-antigen can either undergo receptor editing, in which they develop new receptors that do not react against self-antigen, or, they must die by apoptosis.

If a B cell is in the periphery (blood stream) and then reacts against a self-antigen, it enters an unresponsive state of anergy. It is thought the absence of co-stimulation by T cells renders B cells anergic.

T cells leave the bone marrow to undergo central tolerance in the thymus. Here is where they are exposed to self-antigen by antigen-presenting epithelial cells (APCs). If they are self- reactive, they can either choose to differentiate to become T regulatory cells, or, die via apoptosis.

Peripherally, T cells reactive to self-antigens may:

Unfortunately, some self-reactive B and T cells end up in the circulation, where they cause chronic, often progressive, damage.

Helper T cells release interferon gamma (activates macrophages) and IL-17 (recruits inflammatory PMNs & monocytes). Activated T cells express RANKL, which promotes bone resorption.

Macrophages release tumor necrosis factor and IL-1 → Trigger the release of degradative proteases.

Over time, the pannus on opposing bones forms a fibrous ankylosis, which may then become bony ankylosis.

These changes cause stiffness, swelling, and joint deformities.

Swan neck deformity: the proximal interphalangeal (PIP) joint is hyperextended and the distal interphalangeal (DIP) joint is flexed (thus, it looks like the neck of a swan).

Antibodies against citrullinated protein antigens (ACPAs), such as citrullinated fibrinogen, which is produced during inflammation.

Rheumatoid factor is also found in patients with rheumatoid arthritis; however, it's non-specific.

Scleroderma is a combination of autoimmunity, vascular damage, and fibrosis

Tumor growth factor Beta is a key mediator

Anti-centromere antibody (ACA)

Anti-Scl-70

Calcinosis,= calcified nodules form under the skin; they may progress to lesions.

Raynaud's phenomena = small vessels of the fingers and toes severely constrict in response to stress and/or cold. Initially, reduced blood flow turns the fingers white; as oxygen levels fall, the fingers appear bluish; and, finally, after blood flow is re-established, they become red.

Esophageal dysmotility = caused by collagen replacement of the muscularis layer of the esophagus; dysphagia and/or heart burn can result.

Sclerodactyly = hands take on a claw-like appearance because fibrosis of the dermis pulling the skin taught; dermal tightening can also occur in the face.

Telangiectasia =dilation of superficial micro-vessels; it commonly looks like a rash on the face or chest.

Manifests as widespread cutaneous fibrosis with quick progression to the viscera.

It is associated with Scl-70.

Examples of Organ Effects:

Characterized by damage to the lacrimal and salivary glands mediated by interferons (types 1 & 2)

Autoantibodies (anti-SSA/Ro, anti-SSB/La), which are anti-nuclear autoantibodies (also in systemic lupus erythematosus)

Destruction of salivary glands --> lead to ulcers and increased dental caries.

H&E of minor salivary glands: leukocyte infiltration that has damaged the tissues.

Destruction of the lacrimal gland (located laterally above the eye) --> dec tear production

Thus, the eyes become dry, irritated, and more susceptible damage; vision may be impaired.

Sjörgen's syndrome may have non-glandular effects, particularly in the joints, lungs, kidneys, and cardiovascular system.