Autoimmune Disease

Question 1

What are autoimmunity diseases?

Answer 1

Dysregulated specific immune response to self-antigen resulting in clinical disease

Initially a hypersensitivity reaction

Question 2

What is autoimmune polyendocrinopathy, chronic mucocutaneous candidiasis and extodermal dystrophy (APCED)?

Answer 2

AIRE protein defect causing no negative selection in the thymus

Autosomal recessive

Question 3

What are the resulting autoimmune diseases from APCED?

Answer 3

Hypoparathyroidism

Primary adrenocortical failure

Insulin dependent diabetes

Question 4

What is immune dysregulation polyendocrinopathy enteropathy X-linked (IPEX)?

Answer 4

Lack of Treg development, increase in Th17 effector cells

Question 5

What does IPEX lead to?

Answer 5

Skin disease

Insulin dependent diabetes

Hypothyroidism

Diarrhea

Autoimmune blood disorders

Question 6

What is autoimmune lymphoproliferative syndrome (ALPS)?

Answer 6

Fas, FasL, caspase deficiencies

Autosomal dominant gene defect

Question 7

What does ALPS result in?

Answer 7

Evan’s syndrome - self attack on red cells, neutrophils, platelets

Autoimmune liver and kidney disease

Large lymph nodes, lymphoma

Question 8

What is the therapy for ALPS?

Answer 8

Rituximab - anti B cells

Sirolimus - stop T cell proliferation

Bone marrow transplantation

Question 9

What is intramolecular spreading?

Answer 9

The immune recognition of additional new epitopes on the same protein

Question 10

How does pemphigus vulgaris develop as an autoimmune disease?

Answer 10

First autoantibody response to domain 5 of desmoglein - no disease

Spreading identification of B cell to other domains of the same molecule - causes protein dysfunction

Type II hypersensitivity*

Question 11

What is the pathogenesis of lupus?

Answer 11

Inflammation-apoptosis

Nuclei inadequately cleared, becomes autoantigen

Self reactive T and B cells start antibody production against nuclear antigens

DC activation with INF production amplifies immune response

Question 12

How dos multiple sclerosis develop?

Answer 12

Genetic risk causts T cell recognizing neuroantigen escape the thymus

Inflammation in CNS (EBV) allows BBB to be breached by T cells

Immune response destroys nerves

Question 13

What are the therapies for MS?

Answer 13

Target T cells:

Alemtuzumab

Fingolimod

Natalizumab

Question 14

What is molecular mimicry?

Answer 14

Lymphocyte recognizes microbial antigen which is identical to self-antigen, responds to both

E.g. Rheumatic Fever

Question 15

What is rheumatic fever?

Answer 15

Anti-streptococcal cell wall antibody also binds to identical antigen on heart causing carditis

Question 16

What types of diseases are transferrable from mother to fetus and why?

Answer 16

Type II hypersensitivity diseases

IgG antibody crosses the placenta

E.g. Myasthenia gravis, Graves, TP

Question 17

What is IVIG?

Answer 17

Donor IgG saturates Fc receptor, causing patient IgG to not bind and be degraded instead of recycled via endosome

FcyR becomes saturated with donor IgG on macrophage, reducing autoimmune response

B cell inhibition

Attenuates complement activation