Autoimmune diseases

a condition in which damage to body organs results from the presence of:

• autoantibodies (B cells) and/or

• autoreactive (T cells) cells

what is autoimmunity disease?

clonal deletion of relevant effector cells

what is self-tolerance?

T regulatory cells

what actively regulates self-tolerance?

maintaining balance between Th1 and Th2 populations

what do T regulatory cells play a central role in?

there is no single theory or mechanism

what is unique about autoimmunity?

interacting factors: genetic factors, age, exogenous factors

what is antibody expression regulated by with autoimmunity?

certain HLAs associated with increased risk of certain autoimmune states

what are genetic factors?

the type of peptides that can be presented

what do MHC molecules determine?

Ankylosing spondylitis; Reiter syndrome

what disorder is B27 associated with?

Graves’ disease

what disorder is B08,C07,DR3 and DR7 associated with?

Hasimoto’s thyroiditis

what disorder is DR3 and DR4 associated with?

SLE

what disorder is DR3, DR8, and DR15 associated with?

Myasthenia Gravis and Addison’s disease

what disorders is DR3 associated with?

Rheumatoid Arthritis

what disorder is DR4 associated with?

incidence of autoantibodies increases with age

how does age correlate to autoimmunity?

• UV radiation

• drugs

• viruses

• chronic infectious diseases

what are exogenous factors associated with autoimmunity?

• release of sequestered antigens

• altered antigens as a result of chemical, physical, or biological processes

• molecular mimicry

what are immunopathogenic mechanisms?

shared immunologic epitope with a microbe and the host

what does molecular mimicry represent?

bulging eyes

what is a localized symptom of Graves’ disease?

butterfly rash

what is a systemic symptom of SLE?

synovial membrane of multiple joints

what does rheumatoid arthritis involve?

• joint stiffness

• swelling subcutaneous nodules around joints—can lead to permanent joint deformity

what are the clinical signs of rheumatoid arthritis?

it is directed against the Fc portion of IgG

what happens to IgM during rheumatoid arthritis?

anti-cyclic citrullinated peptides antibodies—doctors requests both RF (more sensitive) and anti-CCP (more specific)

what is the anti-CCP test?

• other antibodies may be present

• increased ESR

• elevated C-reactive protein

• complement component levels normal or increased

• associated with HLA DR4 alleles

what are the immunologic findings of rheumatoid arthritis?

a chronic systemic inflammatory disease—multisystem

what is systemic lupus erythematosus (SLE)?

• loss of tolerance leads to polyclonal B cell hyperactivity

• autoantibodies produced

• immune complexes formed in circulation and in tissues

• tissue injury

what is the pathogenesis of SLE?

Hargraves cells

what are SE cells also known as?

• autoantibodies

• complement levels affected

• macrophage or neutrophil engulfing antibody-coated nucleus of neutrophils

what are the immunologic findings of SLE?

• nonspecific symptoms

• joint problems

• skin manifestation

  • erythematous rash

  • classic butterfly rash on face

• renal disease

what are the clinical manifestations of SLE?

dry eyes and mouth

what are the clinical manifestations of Sjӧgren Syndrome?

exocrine glands—mainly salivary and lacrimal glands

what does Sjögren syndrome affect?

progressive systemic sclerosis

what is scleroderma also known as?

excessive collagen deposition in skin and internal organs

what does scleroderma cause?

• edema, tightening and thickening of skin, joint pain, internal organ complaints

• Raynaud phenomenon

• “Stone face”

what are symptoms of severe and progressive scleroderma?

discoloration of the fingers, toes, and occasionally other areas

what is the Raynaud phenomenon?

calcinosis, Raynaud’s phenomenon, esophageal dysmotility, sclerodactyly and telangiectasia

what are symptoms of the CREST variant of scleroderma?

features of SLE, scleroderma, polymyositis and rheumatoid arthritis

what does mixed connective tissue disease have?

multisystem (involves skin and muscle)

what does polymyositis/dermatomyositis affect?

hypothyroidism

what does Hashimoto’s Thyroiditis cause?

• anti-thyroid peroxidase antibodies

• anti-thyroglobulin

what is involved with Hashimoto’s Thyroiditis?

hyperthyroidism

what does Graves’ disease cause?

antibody to thyroid stimulating hormone receptor

what is involved in Graves’ disease?

islet beta cells in the pancreas

what are the autoantibodies of insulin-dependent diabetes mellitus to?

destruction of myelin sheath of CNS

what causes Multiple Sclerosis?

lesions in white matter in brain and spinal cord

what does Multiple Sclerosis lead to?

the nerves’ protective sheath

what is myelin?

CNS cell that builds myelin

what is oligodendrocyte?

• myelin

• oligodendrocyte

• glycoprotein

what comprises MOG disease?

autoantibody to acetylcholine receptor

what causes Myasthenia Gravis?

facial weakness, difficulty in chewing and swallowing

what are the symptoms of Myasthenia Gravis?

antibody to glomerular basement membrane

what is Goodpasture’s syndrome?

renal function

what does Goodpasture’s syndrome result in?

gluten

what triggers celiac disease?

antibodies against antitransglutimanase

what causes celiac disease?

small intestine and other organs

what does celiac disease affect?

• gastric parietal cells—lack of intrinsic factor

  • autoantibody made to gastric parietal cells, affects formation of intrinsic factor

  • absorption of vitamin B12 and intrinsic factor

  • decrease red blood cells because body cannot absorb vitamin B12

what are the characteristics of pernicious anemia?

• antibody to adrenal cells

  • low cortisol: hypoglycemia, hypercalcemia and anemia

  • low sex hormone: decreased secondary hormonal characteristics, muscle wasting

  • low aldosterone: low serum sodium and high potassium, dehydration, postural hypotension, weight loss

what are the characteristics of Addison’s disease?

antibody to RBCs

what is the characteristic of autoimmune hemolytic anemia?

antibody to platelets

what is the characteristics of autoimmune thrombocytopenic purpura?