VMED 5172 - Autoimmunity

Autoimmunity

When the immune response is stimulated by a self-antigen, this is known as?

Self cells and microbiota

What broad categories of cells may be affected by an autoimmune reaction?

Helper T cells (CD4+ T cells)

What cell type is present in all autoimmune disease?

Autoantibodies and cytotoxic T cells

What cell types can mediate autoimmune diseases?

Based on where in the body lymphocytes develop tolerance; central and peripheral tolerance

There are two types of self-tolerance based on what? What are these two types?

Central tolerance

Self-tolerance developed in the primary lymphoid organs is known as?

In peripheral or secondary lymphoid organs

Lymphocytes either peripheral tolerance develop tolerance where in the body?

Due to random generation of antigen binding receptors; self-reactive cells are suppressed via checkpoints

Up to 50% of T- and B-cell receptors bind self-antigen. Why is this, and how does the body compensate?

Insulin

Within the thymus, tissue specific antigens such as ___ are expressed for training of lymphocytes

Autoimmune Regulator; turns on many genes which produce tissue-specific proteins, leading to deletion of self-reactive cells

What is AIRE and what is its function?

Increased autoimmune disease, increased reactivity to self-antigen

Without AIRE, the main detriment to the immune system would be...

Organ-specific and systemic

Autoimmune disease can be of what two classifications?

Abnormal, normal

The most common type of autoimmunity is a ___ response to a ___ antigen

B and T cells

Both of these cell types can be involved in tissue damage due to autoimmunity

Red blood cells are phagocytized once they reach the end of their life span

Describe an autoimmune function which is not harmful to the body

Eyes, brain, testis, uterus

Which sites of the body are considered immunologically 'privileged'?

Some antigens are hidden in privileged sites where lymphocytes cannot reach; these antigens may be released via tissue damage or infection and an autoimmune response will occur

Why might some autoreactive lymphocytes may be quiescent? When do these cells react?

Those which accumulate in privileged sites

Which antigens most tend to be the targets of autoimmune attack?

Thymus

Where is central tolerance exercised for T cells?

B cells

The fetal liver and bone marrow are the main site of central tolerance for which cell type?

Deletion or differentiation into Treg cells

What is the fate of T cells which are discovered as autoreactive in the thymus?

Receptor editing

Other than deletion, how can autoreactive B cells be changed to reduce self-reactivity?

Apoptosis

Mature B cells can no longer undergo receptor editing, and those that are autoreactive have what fate?

The immune system develops an immune response to epitopes which are different from the disease-causing epitope

Describe the process of epitope spreading

Molecular mimicry

When self and foreign antigen shape an epitope and can cross-react, this is known as?

If they receive the help of T cells

In the process of molecular mimicry, B cells only produce autoantibody under what circumstances?

The body's defensive mechanisms, such as pro-inflammatory cytokines, suppressed regulation of T cells, and autoreactive cells are more easily activated

Physiologically, why can infection or inflammation cause autoreactive issues to worsen?

Major histocompatibility complex (MHC) halotypes

The strongest genetic associations with autoimmune disorders are?

Medications, vaccinations, allergens, and diet

What factors other than genetics can contribute to autoimmunity?

Low, reduced

With ___ genetic diversity, the increased incidence of autoimmunity issues

Hypersensitivity

Autoimmune diseases can be induced and amplified by ___ reactions

Thyroiditis with hypothyroidism

The most common autoimmune endocrine disease in dogs is?

T cells

Thyroiditis is an attack of thyroid cells mediated by what cells?

T cells attack and damage the cells which produce thyroxin and other thyroid hormone

Why is hypothyroidism associated with thyroiditis?

Immune-mediated hemolytic anemia; autoantibodies trigger destruction of red blood cells

What does IMHA stand for and what process occurs within it?

Neuromuscular junctions

Myasthenia gravis is an autoimmune disease which affects what part of the body?

Autoantibodies block ACh receptors, which causes receptor degradation

What physiological process occurs within myasthenia graves that causes a weakened muzzle?

Systemic lupus erythematosus

An example of a systemic autoimmune disease in animals is SLE, or?

Antinuclear antibody test; tests for SLE

What is an ANA test and what does it test for?

Detects antibodies against nuclear components such as DNA and histones via fluorescent microscopy

How does an ANA test work?

The eye; seen commonly in horses

Recurrent uveitis is an autoimmune disease of what organ? In which animals is this commonly seen?