Unit 4 Lec 6

Question 0

What are autoantigens?

Answer 0

Antigens that activate autoimmune response

Wheras autoantibodies are antibodies generated by autoimmune responses and autoimmune disease is caused by autoimmune responses

Question 1

What happens in autoimmunity?

Answer 1

Results from failure of tolerance to self antigens

Can occur at any of the steps of central or peripheral tolerance

Question 2

What do most autoimmune diseases involve?

Answer 2

Involve both B and T cells

• Antibodies (against tissues, or immune complex formation)
• T cells

Usually chronic and progressive and self perpetuating

• Constant supply of autoantigens that are not cleared from the body
• AMPLIFICATION and EPITOPE SPREADING

Question 3

What is epitope spreading?

Answer 3

Response initiated against one self antigen that injures tissues that may result in the release and alteration of other tissue antigens and activation of lymphocytes specific to these other antigens (leads to exacerbation of the disease)

Question 4

What are some amplification mechanisms?

Answer 4

Cytokines that promote activation of autoreactive lymphocytes

Question 5

What is a strong component of autoimmune disease?

Answer 5

Concordance in diabetes mellitus type I
35-50 monozygotic twins
5-6% dizygotic twins

Question 6

What has the strongest genetic association with autoimmune disease?

Answer 6

Associated with MHC genes

• HLA B-27 positive individual – 73 relative risk of developing Ankylosing Spondylitis
• Autoantigenic peptides to autoreactive T cells

Question 7

What is APECED?

Answer 7

Autoimmune PolyEndocrinopathy Candidiasis, Ectodermal dystrophy

• Autoimmune polyglandular syndrome type I (APS1)
• AiRE gene mutations (Autoimmune Regulator )– Failure to delete autoreactive T cells
• Hypoparathyroidism, adrenal insufficiency, hypogonadism

Question 8

What is IPEX?

Answer 8

Immune dysregulation, Polyendocrinopathy, Enteropathy, X linked

• FOXP3 gene mutations – Impaired regulatory T cells
• Neonatal type I diabetes, thyroiditis, chronic life-threatening diarrhea due to enteropathy, dermatitis

USUALLY FATAL within the first year

Question 9

What is ALPS?

Answer 9

Autoimmune Lymphoproliferative syndrome

• FAS gene mutations – impaired apoptosis
• Autoimmune disease: hemolytic anemia, thrombocytopenia (ITP) neutropenia
• Glomerulonephritis, autoimmune hepatitis, Guillain-Barré syndrome uveitis

Lymphadenopathy, hepatomegaly, splenomegaly: INCREASED risk of lyphoma

Question 10

What is bystander activation?

Answer 10

Infections induce local innate immune responses in tissues that recruit leukocytes and result in activation of tissue APCs, these APCs express costimulators and activate bystanders T Cells are not specific for infectious pathogen, result in breakdown of tolerance

Question 11

What is molecular mimicry?

Answer 11

Microbes may contain antigens that cross-react with self antigens, so immune response to the microbes may result in reactions against self antigens

• Examples include Rheumatic Fever following group A Streptococcus infection
• Hemolytic anemia following mycoplasma infection

Question 12

What is hashimotos thryoiditis?

Answer 12

Ab against thyroid peroxidase

Question 13

What is Grave’s disease?

Answer 13

Ab against TSH (thyroid stimulating hormone) receptor

Question 14

What happens in Type I diabetes?

Answer 14

Insulin producing pancreatic B cells

Question 15

What are examples of Systemic autoimmune?

Answer 15

Systemic Lupus Erythematous (SLE)– Ab to nuclear antigens (eg chromatin)
- Multiple organs: skins, joints, kidneys, heart, lungs, nervous system

Question 16

What happens in systemic lupus erythematosus (SLE)

Answer 16

Chronic remitting and relapsing multisystem autoimmune disease
Prevalence 20-150 cases per 100,000 
- Female to male ratio is 10:1
Age of onset is 15-55
- Genetic factors
50 loci predisposes to SLE
- Complement deficiencies (C1q, C4A, C4B, C2
- HLA-DR2, HLA-DR3

Question 17

What is the pathophysiology?

Answer 17

Immune complex deposition – Glomerulonephritis, arthritis, and vasculitis involving small arteries throughout the body
- Virtually every organ is effeted

Important autoantibodies in SLE

• ANA (anti-nuclear Ab) very sensitive for SLE
• Neg. AN excludes SLE
• Anti-dsDNA is very specific for SLE

Question 18

What is rheumatoid arthritis?

Answer 18

Most common inflammatory arthritis: 1 percent pop

Risk factors: HLA-DR4 and cigarette smoking

Question 19

What is the pathophysiology of RA?

Answer 19

T cell and Abs both contribute to joint inflammation

• 7 autoantigens are likely to be involved e.g. type II collagen, citrullinated peptides
• Citrullinate peptides are derived from proteins modified in the inflammatory environment by enzymatic conversion of arginine residues to citruillin

Synovial inflammation perpetuated by proinflammatory cytokines IL-17 and TNF and IL-1

Question 20

What are some rheumatoid factos?

Answer 20

Circulating IgM against Fc portion of patients own IgG
Antibodies against cyclic citruiillinated peptides (ANTI-CCP)
Treatment:
- Glucocorticoids
DMARDS
Biologic agents: Monoclonal Ab against: TNF, IL-1, IL-6, CD20 (B cells)