Immunology Exam 4: Chapter 7 Autoimmune Diseases

How many Americans are affected by autoimmune diseases?

20 million

Describe autoimmune diseases

chronic and irreversible, defect in mechanisms underlying recognition and definition of self

Who first conceptualized self and the concept of Immune Tolerance?

Sir Peter Medawar

What is tolerance? What is an example?

the ability to not regard body tissues as foreign, ignoring MHC antigens

When does tolerance usually occur?

during neonatal development

What is involved in B cell tolerance?

a lack of help from T cells, deletion of immature B cells in the bone marrow, deletion of autoreactive B cells in T cell zones, and a weak second signal

What mechanisms make up T cell tolerance?

central and peripheral tolerance

What is involved in T cell central tolerance?

elimination of self-reactive T cells before leaving the thymus, apoptosis in cells not showing the correct interaction with antigens linked to MHC in the thymus

What is involved in T cell peripheral tolerance?

sequestered antigens, anergic T cells produce cytokines inhibiting further activation, phenotypic skewing, fas ligand expressing cells are delated

What happens in phenotypic skewing?

cells expressing CD28 are more likely to react with APC than those without the molecule

What are the five symptoms typically seen in patients with autoimmune diseases?

elevation in serum gamma-globulin levels, diverse autoantibodies, depressed serum complement and T suppressor cells, presence of immune complexes in serum, detection of lesions on a biopsy from deposition of immune complexes

What mechanisms are involved in autoimmune disease?

excess of altered T helper cell activity, abnormal B cell triggering, T suppressor cell deficiency, release of sequestered antigens

What causes the excess of T-helper activity?

altered self-antigens induced by chemicals or drugs and molecular mimicry

What is involved in molecular mimicry?

cross-reactivity between self antigens and foreign antigens, common in viral infections

What viral infections are associated with molecular mimicry?

EBV, rheumatoid arthritis, measles, multiple sclerosis, cocksackie virus, IDDM, influenza, polio, Guellain-Barre

What is involved in abnormal B cell triggering?

overexpression of cell signaling molecules like CD45 or CD19 OR underexpression of regulatory molecules Fcg and CD22

What does abnormal B cell triggering prevent?

prevents the clearance of apoptotic particles

What do T suppressor cells usually do?

down-regulate immune response to self antigen

How are sequestered antigens released? Where from? Is it normally accessible by the immune system?

trauma or infection, from the lens of eyes or sperm, no

What increases a person’s predisposition to autoimmune disease?

association with HLA antigens, increases with age, many are more frequent in women, patients suffer from multiple autoimmune disease

When do most autoimmune disease appear?

20-40 age group

What is the ratio of women to men developing: rheumatoid arthritis, lupus, and Sjogren’s syndrome?

3:1, 4:1, 9:1

What autoimmune disease is more frequent in men than women? What is the ratio?

ankylosing spondylitis, 9:1

What percentage of patients with autoimmune thyroiditis also suffer from pernicious anemia?

10%

What percentage of patients with Sjogren’s syndrome also suffer from rheumatoid arthritis?

50%

Rheumatoid Arthritis: Antibody present? T cell present? What antigen is associated? What are the affected tissues?

yes, no, IgG, joints and vascular bed

SLE (lupus): Antibody present? T cell present? What antigen is associated? What are the affected tissues?

yes, no, various antigens, skin kidney and CNS

Sjogren’s Syndrome: Antibody present? T cell present? What antigen is associated? What are the affected tissues?

yes, no, salivary gland, lacrimal glands salivary glands and vagina

Guillian-Barre: Antibody present? T cell present? What antigen is associated? What are the affected tissues?

no, yes, myelin, PNS

Multiple Sclerosis: Antibody present? T cell present? What antigen is associated? What are the affected tissues?

yes, yes, myelin, CNS

Myasthenia gravis: Antibody present? T cell present? What antigen is associated? What are the affected tissues?

yes, no, acetylcholine receptors, CNS

Hashimoto’s disease: Antibody present? T cell present? What antigen is associated? What are the affected tissues?

yes, yes, thyroglobulin, thyroid

Grave’s disease: Antibody present? T cell present? What antigen is associated? What are the affected tissues?

yes, no, TSH, thyroid

Pernicious anemia: Antibody present? T cell present? What antigen is associated? What are the affected tissues?

yes, no, gastric cells, stomach

What are 8 representative autoimmune disease?

rheumatoid arthritis, lupus, Sjogren’s syndrome, Guillian-Barre syndrome, multiple sclerosis, myasthenia gravis, Hashimoto’s thyroiditis, Grave’s disease

Describe rheumatoid arthritis

HLA-DR4, common in women, rheumatoid factor produced, forms large complexes that activate complement, chronic inflammation of synovial membrane occurs that produce the blue areas, damaged hyaline cartilage is replaced by pannus

What is pannus?

vascular fibrocartillagenous tissue

What are the seven features of RA defined by the American Rheumatism Association?

morning stiffness lasting more than one hour, arthritis in 3 joints, arthritis of the hand, arthritis on both sides of the body, positive test for rheumatoid factor, presence of rheumatic nodules, xrays showing presence of arthritis

What are symptoms of rheumatoid arthritis?

weight loss, malaise, fever, fatigue, weakness

What other organs are affected by rheumatoid arthritis?

cardiovascular, pulmonary, liver, eyes, skin

What is the treatment for RA?

exercise, diet, pain reduction using medication, DMARDs, joint replacement

What medication are used to reduce RA pain?

NSAIDs, steroids, TNF blocking agents

What DMARD medications are used to treat RA?

actemra, xeljanz, methotrexate

Describe Systemic Lupus Erythematosus aka lupus (SLE)

HLA-DRA2, HLA-DR3, common in young women, butterfly rash on nose and cheeks

What are the symptoms of lupus?

weight loss, fever, malaise, lethargy

What happens during lupus cellularly?

decreased- T cells, immunoglobulins, complement levels, presence of- antinuclear antibodies, anti-red cells, presence of platelets, mitochondria

What is the criteria for lupus?

arthritis, renal involvement, hematologic disease, immunological disorder

What is the treatment for SLE?

NSAIDS, sunscreen, hydroxychloroquine, steroids, DMARD therapy

What DMARD therapy is used for SLE?

benlysta, azathiaprine, methotrexate

Describe Sjogren’s syndrome

women, ages 40-50, HLA8, HLA-DR52, affects exocrine glands like lacrimals and salivary, overstimulation of innate immune system interferon production

What are the symptoms of Sjogren’s syndrome?

dry eyes, mouth, and vagina

What are viral triggers for Sjogren’s syndrome?

EBV, human T cell leukemia virus, and hepatitis C

What antibodies are assocaited with Sjogren’s syndrome?

ANA, rheumatoid factor

What do 50% of patients with Sjogren’s syndrome also suffer from?

rheumatoid arthritis

What is the treatment of Sjogren’s syndrome?

restasis- artificial tears, pilocarpine- for dry mouth, good dental hygiene, vaginal lubricants

What complications can accompany Sjogren’s syndrome?

non-hodgkin’s lymphoma, primary biliary cirrhosis

Describe Guillain-Barre Syndrome

occurs following viral infectious diseases like measles and hepatitis, influenza vaccination, connection with bacterial gastrointestinal infection

What are the symptoms of Guillain-Barre Syndrome?

progressive muscle weakness, possible paralysisW

What is Guillain-Barre Syndrome known for? think President

ascending paralysis

What is the treatment of Guillain-Barre Syndrome?

plasmapheresis and intravenous immunoglobulin

What is the prognosis of Guillain-Barre Syndrome?

poor, rapid progression of symptoms, advanced aging, prolonged ventilation and serve reduction of action potentials

What do publish reports say about recovery?

full recovery may be expected in 50-95% of cases by 6-10 months

Describe multiple sclerosis (MS)

relapsing neuromuscular disease, T cells adhere to and penetrate brain, microglia participate in destruction of CNS myelin, B cells generate anti-myelin antibodies to also damage

What are the symptoms of MS?

motor weakness, impaired vision, mental aberrations

What does demyelination of CNS lead to in MS?

leads to areas of demyelination or plaques in the brain and spinal cord

What do the plaques in the brain and spinal cord do in MS?

disrupt the transmission of information in the CNS and leads to MS symptoms

What part of the brain is commonly affected by MS?

cerebellum- balance and fine motor coordination

Where can lesions appear in MS?

mostly spinal region, some optic region

What are the risk factors of MS?

HLA-DRB1, decreased vitamin D, decreased sunlight exposure, prior infection with measles or EBV

What is the prognosis of MS?

30% of untreated patients develop disability within 25 years, higher incidence of spinal cord lesions has poor prognosis, being male with rapidly progressive disease has poor prognosis, death from secondary cardiac and respiratory complications

What is the treatment of MS?

methotrexate, azothiaprine, immunomodulators

What immunomodulators are used to treat MS?

betaseron, extavia, avonex, rebif, ampyra, lemtrada, gilenya

What do betaseron, extavia, avonex, and rebif do?

decrease inflammatory cytokines, decrease incidence of disease exacerbations

What does ampyra do?

improves walking ability

What does lemtrada do?

prevents antibody driven cell lysis

What does gilenya do?

may prevent lymphocytes migrating into the CNS

What is the new hope for MS patients?

second generation antihistamine clemastine was shown in a mouse MS model to remyelinate nerves

Describe myasthenia gravis

HLA-DR3, depletion of ACH receptors at myoneural junction, symptoms start when 30% of ACH receptors are not functional, only impacts skeletal muscle

What are the symptoms in myasthenia gravis?

muscles weakness and fatigue, ptosis, muscle weakness spreading from the face to the trunk, enlarged thymus, thymic tumor, antibodies against ACH receptors

What is ptosis?

drooping of eyelid

What disease may co-present with myasthenia gravis?

RA, SLE

What is the treatment of myasthenia gravis?

anticholinesterases, azathiaprine, other immunomodulators

What do anticholinesterases do?

maintain bioavailability of neurotransmitter

What is the prognosis of myasthenia gravis patients?

fewer than 5% patients die of the disease, may require thymus removal, late onset of disease associated with other cancers and has a poor outcome

Describe Hashimoto’s thyroiditis

familial, more common in females, occurs between 40-50 years, inheritance of HLA-DR5

What are symptoms of Hashimoto’s thyroiditis?

weight gain, slow pulse, thinning hair, hoarse voice, enlarged thyroid, sleep apnea

What is the pathophysiology of Hashimoto’s thyroiditis?

autoimmune thyroiditis, presence of antithyroid peroxidase, presence of antithyroglobulin antibodies

What other disease is Hashimoto’s thyroiditis associated with?

RA, IDDM, SLE

How is Hashimoto’s thyroiditis diagnosed?

low T4 and T3 levels, nodules, histology, needle biopsy of thyroid

What are the complications of Hashimoto’s thyroiditis?

complications associated with therapy, bone issues-weakening, increased heart rate and thickening- arrhythmia

Describe Graves’ disease

familial, common in females, seen in the 20-40 age group

What autoimmune diseases is Graves’ disease seen in conjunction with?

pernicious anemia and SLE

What are the clinical signs of Graves’ disease?

weight loss, tremor, rapid pulse, and exophthalmos

What does exophthalmos mean?

bulging eyes

What are the risk factors for Graves’ disease?

HLA-DR4, CTLA-4, bacterial infection

What is the pathophysiology of Graves’ disease?

increase in thyroid epithelial cell numbers, production of prohormone thyroxine and T3, inhibition of pituitary release of TSH

What are the two components of the ocular symptoms of Graves’ disease?

peripheral monocytes become fibroblasts and accumulate in the eye tissue resulting in inflammation, antiorbital antibodies increase inflammation and cause eye to protrude

What is the treatment of Graves’ disease?

ocular lubricants, radioactive iodine to shrink thyroid, thioamides to block thyroid stimulation

What is the treatment of Hashimoto’s thyroiditis?

synthroid to replace thyroid hormone, avoid antacids and iron-containing vitamins for 4 hours after ingestion

High levels of what are found in patients with MS?

measles antibodies