Autoimmune Diseases Part One

What are autoimmune diseases caused by

erroneous attack of the immune system on self-tissues

What are 5 common autoimmune diseases

• Rheumatoid arthritis

• multiple sclerosis

• Type 1 Diabetes

• Graves Disease

• Myasthenia gravis

What can cause/contribute to immune damage

pathogenic antibodies or immune cells (T cells, other immune cells)

What demographic do autoimmune diseases affect most?

Young people

Which gender do autoimmune diseases affect more

Women

Is there a cure for most autoimmune diseases

No

What are 10 issues with Glucocorticoids

• Immunosuppression

• hyperglycemia

• skin atrophy

• bruising 

• muscle atrophy

• osteoporosis

• weight gain

• glaucoma

• cataracts

• euphoria/psychosis

What are some TNF inhibitors

infliximab- remicade, adalimunab- Humira

What is an example of a glucocorticoids?

Prednisolone

What are 3 issues with TNF inhibitors

T cell lymphomas, opportunistic infections, Tb

What are some issues with Interferon beta

Flu like symptoms

What are 3 examples of Anti-B cell antibodies

CD20 Ab, Ocrelizumab, Rituximab

What are 5 issues with Anti B-cell antibodies?

Cardiac arrest, acute renal failure, infections, progressive multifocal leukoencephalopathy (PML), pulmonary problems

What is an example of Anti-VLA-4 antiobodies

Tysabri

What is an issue with Anti-VLA-4 antiobodies

progressive multifocal leukoencephalopathy (PML)

What are 2 issues with Fingolimod

skin cancer, hemorrhagic encephalitis

What is autoimmunity

immune response against self tissues

Autoimmune disease

Autoimmune response resulting in tissue damage

What are 4 ways autoimmune diseases arise

Molecular mimicry, failure of regulatory mechanisms, access to “forbidden sites,” Genetic and Environmental causes contribute to autoimmune diseases

What is molecular mimicry

sequence homology between microbial and self proteins. Immune system responds to microbes and cross-reactive autoimmunity to self-antigens

Failure of regulatory mechanisms

Failure of tolerance, lack of regulatory T cells, lack of regulatory B cells

Whatyare some examplesof Molecular mimicry

Rheumatic Fever, Guillain-Barre syndrome (GBS)

What are some examples of regulatory mechanisms

mutation in Foxp3 gene leads to IPEX syndrome (immune
dysregulation, polyendocrinopathy, enteropathy, X-linked)

What is access to forbidden sites

Antigens may be normally sequestered from the immune system (brain, testes, anterior chamber of the eye).Inflammation may give lymphocytes access to these sites

What are genetic and environmental causes that contribute to autoimmune diseases?

Certain genes like HLA, TNF and Environmental influences like smoking, infections, microbiome

What is the strongest link in the genetic base for an autoimmune disease

HLA (MHC)

Which Antigen does Multiple Sclerosis affect

Myelin peptide

What MHC Class II molecule is in Multiple Sclerosis

HLA-DR2

What antigen does Rheumatoid Arthritis have

Joint Proteins

What MHC Class II molecule is in Rheumatoid Arthritis

HLA-DR1-DR4

What antigen does Celiac Disease have

Gluten-derived peptides

What MHC Class II molecule is in Celiac Disease

HLA-DQ2-DQ8

What antigen does Type 1 Diabetes have

Islet antigen; insulin

What MHC Class II molecule is in Type 1 Diabetes

HLA-DQ8-DQ2

What percent of MS patients are DR2?

60%

What percent of RA patients are DR1 or DR$

80-90%

What percent of celiac patients are DQ2

98%

What are 6 other genes that play a role in autoimmune diseases

AIRE, Foxp3, Fas, Polymorphisms of TNF, TNF receptor genes, CTLA-4, IL-74

What does AIRE stand for

Autoimmune Regulator

What does AIRE do in autoimmune diseases?

failure to present self antigens in the thymus which leads to APS 1

What is APS 1

Autoimmune polyglandular syndrome

What do Foxp3 mutations do

affect Tregs; IPEX syndrome in humans

What does Fas do?

deficiency in death receptor; leads to ALPS

What is ALPS

Autoimmune lymphoproliferative syndrome

What does CTLA-4 do

lead to ALPS

What does IL-7R stand for

Interleukin-7 receptor

What are two ways autoimmune diseases are classified

organ-specific and systemic

What are the two types of organ-specific autoimmune diseases

Antibody-mediated and cell-mediated

What are 3 examples of antibody-mediated organ-specific autoimmune diseases

• Grave’s disease

• Myasthenia gravis

• Goodpasture’s syndrome

What are 2 examples of cell-mediated organ-specific autoimmune diseases

• Multiple sclerosis

• Type 1 diabetes

What are 2 examples of systemic autoimmune diseases

• systemic lupus erythematosus

• Rheumatoid Arthritis

What are the 8 clinical presentation markers for Graves’ Disease

• Tremor, nervousness, restlessness

• weight Loss despite increased appetite

• intolerance to heat

• Profuse swelling

• Tachycardia

• Cardiac arrhythmia

• Exophthalamus

• Diffuse goiter

What is Exophthalamus

eye bulging

What is Diffuse goiter

generalized smooth enlargement of the thyroid gland (Thyromegaly)

What does Graves’ Disease do 

stimulate autoantibodies

What does Myasthenia Gravis do

block autoantibodies

What does Goodpasture’s syndrome do

destroy autoantibodies

What is autoimmune hyperthyroidism

autoimmune-induced overactivity of the thyroid gland AKA diffuse toxic goiter or Basedow disease

T3 is what chemical

triiiodothyronine

T4 is what chemical

Thyroxine

What is the ratio of T4 to T3 release in the body

20:1

Which is more bioactive and by how much? T3 and T4

T3 is 3-4 times more bioactive than T4

What is the first step in the HPT axis?

Hypothalamus detects T4

What is the second step in the HPT axis?

releases TRH

What is TRH

Thyrotropin-releasing hormone

What is the third step in the HPT axis?

TRH induces TSH by the pituitary

What is TSH

Thyroid stimulating hormone

What is the fourth step in the HPT axis?

TSH induces T3/T4 by the thyroid gland