Autoimmunity & Specific Autoimmune Diseases

Autoimmune disease

A disease caused by the adaptive immune system that becomes misdirected at healthy cells and tissues

B

T or F: Males are more often affected than females when it comes to autoimmune diseases

Self tolerance

Failures of the mechanisms that maintain __________________ lead to autoimmune disease

1. Negative selection in the bone marrow and thymus

2. Expression of tissue specific proteins in the thymus

3. No lymphocyte access to some tissues

4. Suppression of autoimmune responses by regulatory T cells

5. Induction of anergy in autoreactive B and T cells

What are mechanisms that contribute to immunological self tolerance? (5)

A

T or F: Under normal conditions weakly stimulating self antigens can lead to a low level of immune stimulation - just enough to keep the cells primed for an invader BUT not enough to stimulate a response against those self antigens

Transient

____________ autoimmune reactions can occur during an infection or inflammatory response but control mechanisms should terminate them

Molecular mimicry

Antigenic cross reactivity between microbe and self

1. Failure of central tolerance

2. Exposure of previously hidden antigens

3. Inappropriate display of CD80/86 (inappropriate co-stimulation)

4. Antigens cross reactivity between microbe and self (molecular mimicry)

5. Genetics

What are the main factors that can lead to autoimmune reactions? (5)

Failure of central tolerance

Self reactive lymphocytes get release from thymus and can affect individual systemically

Self reactive

Failure of mechanisms that delete _____________ lymphocytes can lead to autoimmunity

Autoreactive B cells

__________________ that bind their autoantigen are retained in the T cell area of secondary lymphoid tissue and, lacking T cell help, die by apoptosis

AIRE protein

Autoimmune regulator protein; allows for the translation and presentation of all types of self antigens to be used for negative selection in the thymus

A

T or F: In the absence of AIRE, T cells reactive to tissue specific antigens mature and leave the thymus

1. Brain

2. Eye

3. Testis

4. Uterus (fetus)

5. Hamster cheek pouch

What are the immunologically privileged sites that with exposure of them to lymphocytes through trauma or inflammation can lead to autoimmune reactions

Sympathetic opthalmia

Trauma in one eye results in effector T cells return via bloodstream to both eyes leading to injury/blindness in originally unaffected eye

Antigen presenting cells

Microbes can activate _________ so they will stimulate self reactive T cells

B-7

APC expressed co-stimulatory molecule required for activation of T cells

CTLA-4

High-affinity inhibitory cell-surface receptor on T cells that interacts with B7 co-stimulatory molecules

CD28

CTLA-4 antagonizes the activity of what?

Dampens T cell responses and reduces their proliferation

What is the effect of CTLA-4?

Autoimmunity

Deficiency in CTLA-4 causes widespread ______________________

Bystander activation

An infection may result in the activation of T cells that are not specific for the pathogen

A

T or F: Certain breeds of animals are predisposed to autoimmune disease

II

Autoimmune hemolytic anemia is what type of hypersensitivity?

III

Grave's disease is what type of hypersensitivity?

III (she also said II in class so not entirely sure which she wants)

Systemic Lupus Erythematosus (SLE) is what type of hypersensitivity?

IV

Type I diabetes is what type of hypersensitivity?

IV

Rheumatoid arthritis is what type of hypersensitivity?

A

T or F: Autoimmune diseases are NOT type I

Endocrine and skin

What two systems are commonly impacted by autoimmune diseases in vet med?

Endocrine

Most T cell mediated autoimmune diseases impact what system?

Grave's disease

Autoimmune hyperthyroidism

Lymphocytic thyroiditis (Hashimoto's thyroiditis)

Autoimmune hypothyroidism

Grave's disease

Mediated by antibodies that bind the thyroid stimulating hormone (TSH) receptor and cause chronic over production of thyroid hormones that are not responsive to regulation by TSH

Autoimmune hemolytic anemia (AIHA)

Extrinsic hemolytic anemias with intravascular or extravascular hemolysis

Extravascular hemolysis

Destruction of red blood cells outside of a blood vessel

Intravascular hemolysis

Destruction of red blood cells within blood vessels

Autoagglutination

The clumping or agglutination of an individual's cells by that individual's own serum, usually because of the presence of autoantibodies

TLR7 and TLR9

Infectious agents bind to what leading to systemic lupus erythematosus (SLE)?

Antinucleic acid antibodies

What type of antibodies are produced from systemic lupus erythematosus (SLE)?

LE cell

Mature neutrophil/macrophages with a phagocytized the denatured nuclear material of another cell; it is used as a marker of autoimmune diseases such as systemic lupus erythematosus

LE body

Denatured material associated with an LE cell

Immune complexes

SLE causes the deposition of what?

A. Typical skin lesions, polyarthritis, positive Coombs test (hemolytic anemia), thrombocytopenia, proteinuria

B. Positive ANA test OR positive LE cell test

There are certain diagnostic criteria for SLE:

A. List clinical signs that are present that you must have at least 2

B. What other diagnostic criteria is required

II

Pemphigus is what type of hypersensitivity?

Desmosomes

Pemphigus autoantibodies attack what structures of the epidermis?

Hemidesmosomes

Pemphigoid autoantibodies attack what structures of the epidermis?

Pemphigus vulgaris

Blisters in mucous membranes between basal and immediate suprabasal keratinocytes

Pemphigus foliaceus

Blisters within granular layers of superficial epidermis

Bullous pemphigoid

Blisters beneath basal layer

Desmoglein 3

Pemphigus vulgaris antibodies attack what?

Desmoglein 1

Pemphigus foliaceus antibodies attack what?

"Bullous pemphigoid antigens" (Collagen) at lamina lucida

Bullous pemphigoid antibodies attack what?

II

Myasthenia gravis is what type of hypersensitivity?

Myasthenia gravis

Autoimmune neuromuscular disorder characterized by weakness of voluntary muscles

Acetylcholine

Myasthenia gravis is due to the blockage of what receptors?