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287 Cards in this Set

  • Front
  • Back
What is Autoimmune Disease?
Autoimmune disease refers to a gourp of immunological disease caused by adaptive immunity that becomes misdirected at autologous (self) components of the body
What is the result of Autoimmune disease?
- Autoimmune diseases are the result of unwanted adaptive immune responses

- Results of failure of mechanisms that maintain self tolerance
What is the % of the population of the developed countried suffering from autoimmune disease with an increasing incidence?
5%
What is autoimmunity?
An immune response that causes an autoimmune disease is called an autoimmune response and it produces a state of autoimmunity
What organ does autoimmune disease affect?
Autoimmune disease may affect any particular organ (or cell type) or a whole (or multiple) system of the body.
What are autoantigens?
Autoantigens are aubsets of self antigen against which antibodies and effector T cells are generated during an autoimmune response.
In Autoantigens what are antibodies and effect T cells called?
These antibodies are called autoantibodies and the T cells are called autoimmmune T cells.
What is a defining characteristic of an autoimmune disease?
Presence of autoantibodies and autoimmune T cells specific for antigens exprssed by the target tissue is a defining characteristics of an autoimmune disease
Autoimmune Disease is NEVER caused by...
IgE
List the three types of Autoimmune Diseases
1. Autoimmune disease caused by antibodies directed against components of cell surfaces or the extracellular matrix (corresponding to type II hypersensitivity).

2. Autoimmune disease caused by the formation of soluble immune complexes that are deposited in tissues (corresponding to type III hypersensitivity)

3. Autoimmune disease caused by the effector T cells(corresponding to type IV hypersensitivity)
What is the Autoimmune hemolytic anemia Autoantigen?
Rh blood gorup antigens, I antigen
What is the consequence for Autoimmune hemolytic anemia?
Destruction of Red blood cells by complement and phagocytes anemia
What is the autoantigen for autoimmune thrombocytopenia purpura?
Platelet integrin gpllb:IIIa
What is the consequence for thrombocytopenia purpura?
Abnormal bleeding
What is the autoantigen for Goodpasture's syndrome?
Non-collegenous domani of basement membrane collagen type IV
What is the consequence for Goodpasture's syndrome?
Glomerulonephritis, pulmonary hemorrhage
What is the autoantigen for Pemphigus Vulgaris?
Epidermal cadherin
What is the cosequence for Pemphigus Vulgaris?
Blistering of skin
What is the Autoantigen for Acute rheumatic fever?
- Streptococcal cell wall antigens
- Antibodies cross react with cardiac muscle
What is the consequnce of Acute rheumatic faver?
Arthritis, myocarditis, late scarring of heart valves
What are the autoantigen of Grave's disease?
Thyroid stimulating hormone receptor
What are the consequence of Grave's disease?
Hyperthyroidism
What are the autoantigen of Myasthenia Gravis?
Acetylcholine receptor
What is the consequence of Myasthenia Gravis?
Progressive weakness
What is the Autoantigen of Insulin-resistent diabetes?
Insulin receptor (antagonist)
What is the consequence of Insulin-rsistent diabetes?
Hyperglycemia, ketoacidosis
What is the autoantigen of Hypoglycemia?
insulin receptor (agonist)
what is the Consequence of Hypoglycemia?
Hypoglycemia
How does Destruction in autoimmune hemolytic anemia occur?
- IgG and IgM antibodies binds to components of the erythrocyte surface

- Leading to complement activcation by classical pathway.

- Destruction of red blood cell.
What is a Autoimmune Disease?
Cause by antibodies directed against components of cell surfaces or the extracellular matriz (= type II hypersensitivity) --> Good Pastures Syndrome
What is Goodpasture Syndrome?
GPS is an uncommon autoimmune disease characterized by the presence of circulating autoanitbodies targeted against the noncollaagenour domain of teh a-3 chain of collagen IV
What specifically happens in Goodpasture Syndrome?
The Abs initiate an inflammatory destruction involving basement memrbanes of renal glomeruli.

- Proliferative and rapidly progressive glomerulonephritis (usualy) basement membranes of lung alveoli

- Necrotizing hemorrhagic interstitial pneumonitis
What age gets Goodpasture's Syndrome?
Age: Teen and twenties (most common) also occurs in 3rd and 4th decades of life.
Which sex common gets Goodpasture's Syndrome?
Men suffer more than females (approx 6 times higher)
What are the the Clinical Features?
Respiratory Symptoms (appears first in 20-60% cases)
- Cough
- Hemoptysis
- Dyspnea
- Diffuse bilaterla alveloar
- Hypoxemia
- Respiratory failure (if untreated)
What are the manifestations of Good Pasture's Syndrome?
- Hematuria (may be microscopic)
- Anemia (iron deficiency)
- Hypertension
- Edemia
- Uremia
- Renal Failure (in advanced and untreated cases)
What is the diagnosis of Goodpasture's Syndrome?
Characteristics linear IgG deposition on GBM and alveolar membrane, directed by immunofluorescence

- Presence of anti-basement membrane antibodies in the serum
What specifically happens with IgG in Goodpastures Syndrome?
Antibody deposition along glomerular basement membrane in Goodpasture's syndrome

-IgG is formed against type IV collagen of glomerular basement membrane and basement membrane of respiratory tract; giving rise to glomerulonephritis and pulmonary hemorrhage.

IgF and inflammatory cells accumulate and kidney function is progressively impaired.
What is the treatment of Goodpasture Syndrome?
- Plasma Exchange
- Immunosupporessive Drugs
Waht is Plasma Exchange?
Plasmapheresis is done daily for up to 2 weeks.

- Remove circulating antibasement membrane autoantibodies
- Chemical mediators of immunologic injury
What is Immunosuppressive Drugs?
Prevent formation fo new autoantibodies
- Prednisone or methyprednisolone
- Cyclophosphamide
Autoimmune Disease of Endocrine Glands: What disease is effected by Thyroid Gland?
-Hashimoto's thyroiditis (Hypothyroid condition)
-Graves' Disease (Hyperthyroid condition)
-Subacture thyroiditis
-Idiopathic hypothyroidism
Autoimmune Disease of Endocrine Glands: What disease is effected by the Islets of Langerhans (Pancreas)?
- Insulin-dependent diabetes
- Insulin-resisten diabetes
Autoimmune Disease of Endocrine Glands: What disease is effected by Adrenal Gland?
Addison's Disease
What is a insulin dependent diabetes?
(IDDM, juvenile onset diabetes) is an autoimmune disease causing destruction of insulin producing B cells in the pancreatic islets.
What is Insulitis?
Infiltration of islet with autoimmune lymphocytes,
Because of
What happens in IDDM? Juvenile onset diabetes
InIDDM antibodies and T cell responses are made against insulin, glutamic acid decarboxylase, adn other specialized protein antigen unique to B cells are believed to mediate B cell destruction.

- Infiltration of islets with autoimmune lymphocytes give rise to insulitis

Because of large number of B cells in excess, the symptoms of insulin deficiency does not appear until significant amount of destruction has occurred.
What is the tx of Juvenile Onset diabetes?
daily injection with insulin (pig or cattle pancreas origin or synthetic insulin)
What is Rhematic Fever?
Complication of streptococcal pharyngitis.
Antibodies generated against streptococcal antigens cross -react with antigenic epitopes on heart, joint and kidney (molecular mimicry)
What gets damaged in Rhematic Fever?
Mitral Valve amd aortic valves are damaged
-
What is sub-acute bacterial endocarditis?
results from infection of the damaged valves by normal flora of mouth (Streptococcus Viridans) and skin (Staphylococcus epidermis)
What is the basis of Rheumatic Fever Pathogenesis?
Molecular mimicry is the basis of rhematic fever pathogenesis
What is Molecular Mimicry?
Chance resemblance of pathogen and host antigen
What is ACUTE Rheumatic Fever?
Complication of untreated S. pyogenes throat infection
When does ACute Rheumatic Fever happen?
Usually begins 3 weeks post infection
What are the symptoms of Acute Rheumatic Fever
- Fever
- Joint Pain (salient feature, knee, ankle, elbow and wrist are commonly involved)
- Chest pain (d/t pancarditis)
Nodules under skin (over knee, elbow and spine; hard and nontender)
- Rash (pink splotches; erythema marginatum)
- Chorea (inovluntary jerky movements of arms and legs; Sydenham's chorea or St. Vitus' Dance
Diagnosis of Rheumatic Fever
Done on basis of Presence of the preset diagnostic criteria (Jones criteria).

* A patient can be diagnosed with RF if have either TWO major criteria (conditions), or one major and two minor criteria
In Diagnosis of Rheumatic Fever What is the MAJOR Criteria?
- Carditis
- Arthritis
- Chorea
- Subcutaneous nodules
- Erythema Marginatum
In Diagnosis of Rheumatic Fever What is the MINOR Criteria?
- Fever
- Joint Pain (without actual arthritis)
- evidence of electrical changes in the heart (EKG)
- blood test for presence of certain proteins= sign of inflammatory/infectious disease
What is the FIRST line of TX of Rheumatic Fever?
A ten day course of Penicillin or a single injection of Penicillin G is the first line of treatment
What is the maintinence dose of Rheumatic Fever?
Mainatinence dose of Penicillin (oral or injectable) is necessary to prevent relapse and complications

- Penicillin is given for 5 years or till the age of 18 years (whichever comes first)
What other drugs are used for the TX of Rheumatic Fever?
- Aspirin is given for pain and inflammation

- Steroids, sometime used for Carditis

-Diazepam or haloperidol used for Chorea
In the TX of Rheumatic Fever, who should continue the use of Pencillin?
Penicilin is continues in patients who are regularly exposed (teachers and medical workers) or patients with cardiac complications
What is Grave's Disease?
- A hyperthyroid state due to autoimmune response towards the TSH receptors

* The autoimmune response is biased towards a TH2 response

* Little tissue destruction and fewer lymphocyte infiltration
Who commonly get Graves Disease?
Much more common in women than in men (8:1)
What is the age onset for Grave's Disease?
20-40 years
What other high risk does patient with Grave's Disease can get?
Grave's disease patients have a high risk of developing other autoimmune diseases including
- Penicious anemia
- Myastenia Gravis
- Diabetes Mellitus type 1
- Addison's Disease
- Celiac Disease
What anitbodies that Grave's Disease involve?
It has a familial tendency
- Histocompatibility studies shown an association with HLA-B8 and HLA-DR3

-80% patients have TSH-R Ab in the plasma

Other antibodies:
- Antinuclear antibody (ANA)
- Antithyroperoxidase antibody
- Antithyroglobulin antibody
What is the Pathophysiology of Grave's Disease?
- Autoantibody binds to THS receptors
- Receptors recognize it as TSH
- Leading to chronic overproductio of thyroid hormones
- Resulting in hyperthyroid condition
What do you see in Microcopy of Thyroid Gland in Grave's Disease?
Tall columnar thyroid epithelium with Grave's disease lines the hyperplastic infoldings into the colloid
What are the symptoms of Graves disease?
Heat intolerance
Nervousness
Irritability
Warm moist skin
weight loss
Bulging eyes (infiltrative opthalmopathy: exophthalmost)
enlargement of thyroid (goiter; typical)
Pretibila myxedema (infiltrative dermopathy; less common)
What is Exopthalmous and goiter in Grave's Disease?
Increased volume of retro-orbital connective tissue and extraocular muscles
How is Exopthalmous and goiter in Grave's Disease caused?
Due to accumulation of proteoglycans and hyaluronic acid push eyeball forward

- sympathetic overtimulation also causes wide eye, staring gaze
What is the major finding in Grave's disease?
Diffuse enlarged thyroid gland associated with hyperthyroidism
What labs are increased in Grave's Disease?
increased:
T3/T4
TSH-R levels
serum ANA levels without evidence of SLE or other collagen-vascular disease
antithyroglobulin and antithyroperoxidase antibody (nonspecific)
What labs are diffuse in Grave's disease?
diffuse uptake of radioactive iodine
What is decreased in labs of Grave's disease?
TSH
What are the treatment of Grave's disease?
Propranolol
Thyourea drugs
Thyroidectomy OR
Ablation with radioactive followed w/thyroid hormones
What are the two types of Thyurea drugs?
(not given more than 1-2 years)
Methimazole
Propylthiouracil
What is Hashimoto's Thyroiditis?
Autoimmune reaction against thyroid cells leading to a hypothyroid condition
What is the most common thyroid disorder in the US?
Hasimoto's Thyroiditis
What race commonly gets Hashimoto's Thyroiditis?
White Americans. Mexican Americans.African Americans
What sex commonly gets Hashimoto's Thyroiditis?
6 times more common in females than males
What causes Hashimoto's Thyroiditis?
Familial predisposition exists
May be drug induced
What are the drugs that cause Hashimoto's Thyroiditis?
Amioderone
IFN-a
IFN-b
IL-2
G-CSF
What are the immune reaction of (chronic thyroiditis) Hashimoto's Thyroiditis?
autoantibody production (TH2 response) as well as production of effector T cells specific for thyroid antigens (TH1 response)
Microscope: What happens in Hashimoto's Thyroiditis?
Lymphocutes infiltrate into glands cause destruction of normal architecture and a consquent loss of functio leading to a hypothyroid state.
What is the symptoms of Hashimoto's Thyroiditis?
Thyroid gland is diffusely enlarged.
Firm and finely nodular
What ar the systemic manifestations of Hashimoto's Thyroiditis?
-mostly related to ambient levels of thyroid hormone
Depression
Chronic fatgue
Dry mouth (xerostomia)
Dry eyes (keratoconjunctivitis sicca)
What other autoimmune condition is associated with Hashimoto's Thyroiditis?
IBD
Celiac disease
Patients of Turner's syndrome have a 15% incidence of signifcant thyroid dysfunction by age of 40 years
What are the lab findings of Hashimoto's Thyroiditis?
Thyroid autoantibodies=
Antithyroid peroxidase 90%
Antithyroglobulin 40%

Increase TSH
What is the treatment of Hashimoto's Thyroiditis?
Synthetic Thyroid hormone
When do you give T4 tx to a Hashimoto's Thyroiditis pt?
T4 given to large goiter pt or increased serum TSH levels
What is Myasthenia Gravis?
Severe muscle weakness;
myo= muscle
asthenia = weakness
gravis = severe
What cause muscle weakness in Myasthenia Gravis?
autoimmune disease= signaling from nerve to muscle across neuromuscular junction is impaired due to blockade of acetycholine receptor by autoantibodies, resulting in progressive muscle weakness.
What is the EARLY symptoms of Myasthenia Gravis?
droopy eyelids
double vision
What will eventually happen after EARLY symptoms in Myasthenia Gravis?
weakness of facial muscle
weakness of upper/lower extremities
involvement of chest muscle cause breathing difficulty and make these patietns prone to respiratory infections
What is the diagnosis suggest Myasthenia Gravis?
Improvement of weakness after adrophonium (cholinesterase inhibitor) adminsitration suggest Myasthenia Gravis?
How is diagnosis of Myasthenia Gravis confirmed?
detect antibody to ACH receptor
What is the treatment of Myasthenia Gravis?
Pyridostigmine
Azathioprine
What is does the drug pyridostigmine do?
Inhibitor of enzyme cholinesterase, which normally cleaves and inactivates acetylcholine
What does azathioprine drug do?
inhibits DNA synthesis; growth of rapidly dividing cells: B and T cells is ihibited and immune response is supressed.
What are the Autoantigen in Systemic Lupus Erthematosus?
DNA
histones
ribosomes
snRNP
scRNP
What are the consequence of Systemic Lupus Erthematosus (SLE)?
Glomerulonephritis
Vasculitis
arthritis
SLE is common in which sex
Women of African or Asian
What will you see in SLE?
Butterfly shaped skin rash (erythema) on face = wolf's head appearance

Lupus= wolf (latin)
What cause the rash in SLE?
deposition of immune complexes in the skin (similiar to type III hypersensitivity
What is the treatment of Myasthenia Gravis?
Pyridostigmine
Azathioprine
In SLE, immune complex can also deposit where?
blood vessels
kidneys
joints
other tissues
hence: Systemic lupus erythematosous
What eventually happens to SLE patients?
die from failure of vital organs (kidney/brain)
What is does the drug pyridostigmine do?
Inhibitor of enzyme cholinesterase, which normally cleaves and inactivates acetylcholine
What does azathioprine drug do?
inhibits DNA synthesis; growth of rapidly dividing cells: B and T cells is ihibited and immune response is supressed.
What are the Autoantigen in Systemic Lupus Erthematosus?
DNA
histones
ribosomes
snRNP
scRNP
What are the consequence of Systemic Lupus Erthematosus (SLE)?
Glomerulonephritis
Vasculitis
arthritis
SLE is common in which sex
Women of African or Asian
What will you see in SLE?
Butterfly shaped skin rash (erythema) on face = wolf's head appearance

Lupus= wolf (latin)
What cause the rash in SLE?
deposition of immune complexes in the skin (similiar to type III hypersensitivity
In SLE, immune complex can also deposit where?
blood vessels
kidneys
joints
other tissues
hence: Systemic lupus erythematosous
What eventually happens to SLE patients?
die from failure of vital organs (kidney/brain)
What is the treatment of Myasthenia Gravis?
Pyridostigmine
Azathioprine
What is does the drug pyridostigmine do?
Inhibitor of enzyme cholinesterase, which normally cleaves and inactivates acetylcholine
What does azathioprine drug do?
inhibits DNA synthesis; growth of rapidly dividing cells: B and T cells is ihibited and immune response is supressed.
What are the Autoantigen in Systemic Lupus Erthematosus?
DNA
histones
ribosomes
snRNP
scRNP
What is the treatment of Myasthenia Gravis?
Pyridostigmine
Azathioprine
What are the consequence of Systemic Lupus Erthematosus (SLE)?
Glomerulonephritis
Vasculitis
arthritis
What is does the drug pyridostigmine do?
Inhibitor of enzyme cholinesterase, which normally cleaves and inactivates acetylcholine
SLE is common in which sex
Women of African or Asian
What does azathioprine drug do?
inhibits DNA synthesis; growth of rapidly dividing cells: B and T cells is ihibited and immune response is supressed.
What will you see in SLE?
Butterfly shaped skin rash (erythema) on face = wolf's head appearance

Lupus= wolf (latin)
What are the Autoantigen in Systemic Lupus Erthematosus?
DNA
histones
ribosomes
snRNP
scRNP
What cause the rash in SLE?
deposition of immune complexes in the skin (similiar to type III hypersensitivity
What are the consequence of Systemic Lupus Erthematosus (SLE)?
Glomerulonephritis
Vasculitis
arthritis
In SLE, immune complex can also deposit where?
blood vessels
kidneys
joints
other tissues
hence: Systemic lupus erythematosous
SLE is common in which sex
Women of African or Asian
What eventually happens to SLE patients?
die from failure of vital organs (kidney/brain)
What will you see in SLE?
Butterfly shaped skin rash (erythema) on face = wolf's head appearance

Lupus= wolf (latin)
What cause the rash in SLE?
deposition of immune complexes in the skin (similiar to type III hypersensitivity
In SLE, immune complex can also deposit where?
blood vessels
kidneys
joints
other tissues
hence: Systemic lupus erythematosous
What eventually happens to SLE patients?
die from failure of vital organs (kidney/brain)
What can provoke SLE and cause relapse and should be avoided?
sunlight, UV light.
What are the two most common symtpoms of SLE?
glomerulonephritis and arthritis
In SLE, what give rise to glomerulonephritis and arthritis?
Immune complexes deposit on various tissues, kidney and synovial tissue of joints.
In SLE what happens specifically to cells?
Hypercellularity
cellular proliferation
thickening basement membrane
In SLE, What causes Hypercellularity?
proliferation of mesengial cells and endothelial cells
infilatration of neutrophils
In SLE, what causes cellular proliferation?
reposne to cellular injury mediated by deposition of antigen-antibody complex on mesengium and basement membrane
In SLE, what cause thickening of basement?
immune complex deposition on the basement membrane
What clinical labs are seen in SLE?
Proteinurea
Microscopic hematuria
What is seen in SLE serum level?
40-60% has:
serum have antibody to double stranded DNA (anti-DNA antibody)
What specific antibody is seen in SLE patients?
95% anti-nuclear antibody (ANA); less specific

20-30% Smith antigen (anti-Sm)
In SLE patients, anti-nuclear antibody (ANA) is also seen in what type of disease?
drug induces LE
systemic sclerosis
scleroderma
Sjogren syndrome
Inflammatory myopathies
In SLE, What is Smith Antigen (anti-Sm) composed of?
Core protein of small nuclear ribonucleoprotein particle
In SLE pt, what lab levels are high?
IgG
In SLE patients, What lab levels are LOW?
C3 7 C4
What at the diagnostic tool for SLE?
Smith (SM) antigen
Antibodies to double stranded DNA
In SLE, what test make a false positive for VDRL?
Antibodies to cardiolipin make SLE patients FALSE POSTIVE for VDRL, a test for syphilis patients
What are the 3 converging lines of evidence of the Mechanism of Emergence of Autoanitbodies (SLE)?
Genetic Prediposition
Non-genetic (environmental) factors
Fundalmental abnormality in immune system
Do families of patients with SLE pt have risk?
Family members of SLE patients have increased risk of SLE

Higer for monzygotic twins when compared to dizygotic twins
What is linked to production of anti-double stranded DNA, anti-SM, and antiphospholipid antibodies (SLE)?
HLA-DQ locus
What inherited deficiencies is seen in Lupus patient (6% SLE pt)?
C2, C4, C1
In animal models, what has been identified (SLE)?
non-MHC susceptibility loci
What are the non-genetic (environmental) factors of SLE?
Drugs
Exposure to UV light
Sex hormones
What drugs induce SLE-like responses?
Hydrallazin
Procainamide
D-penicillamine
Isoniazid
What does sunlight cause in SLE pt?
induce IL-1 production by keratinocytes
Apoptosis in cells
Alter DNA= immunogenic
What does sex homrones do to SLE pt?
mostly in women in reproductive years
--exacerabation in normal menses and pregnancy
What is the treatment of SLE?
high dose Steroids Prednisone 60 mg/day
After treatment with Steroids, what happens to SLE patient?
improve in few weeks
decrease urine protein loss
return of BUN and serum creatinine to N/L
What is the MOST common cause of DEATH from SLE?
Renal failure
Intercurrent infections
What Drugs cause Lupus like syndrome? (Drug induced lupus erythematosus)
Hydrallazine
Procainamide
Isoniazid
D-penicillamine
Who are postive for ANA in Drug induced Lupus Erythematosus?
80% pt tx w/procainamide are positive for ANA. & have symptoms of
Arthralgias
Fever
Serositis
What is uncommon organs affected in Drug induced lupus erythematosus?
renal
CNS
What antibodies are seen in Drug induced lupus erythematosus?
high anti-histone antibody
What is RAREly seen in Drug induced lupus erythematosus?
DNA antibodies
What allelle is found in Drug induced lupus erythematosus?
HLA-DR4
What stops Drug induced lupus erythematosus?
Withdrawl from DRUG
What is rhematic disease?
a group of dsiease characterized by inflammation and pain in muscles or joints
Rheumatic Disease cause by autoimmunity
SLE
Rheymatoid arthritis
Sjogrens Syndrome
Junvenile Arthritis
Scleroderma
Polymyositis-dermatomyositis
Behcet's disease
Ankylosing spondylitis
Reiter's syndrome
Psoriatic arthritis
Auto-immune diseases due to cell-mediated immune responses
-Insulin dependent diabetes mellitus
Rheumatoid arthritis
Multiple sclerosis
Celiac disease
What autoantigen occur in insulin dependent diabetes mellitus?
Pancreatic
B cell antigen
What autoantigen occur in Rheumatoid arthritis?
Unknonw synovial joint antigen
What autoantigen occur in Mutliple sclerosis?
Muelin basic protein
Proteolipid protein
What autoantigen occur in
Celiac disease?
Gluten modified by tissue translgutaminase
What is the consequence of Insuline dependent diabetes mellitus?
B cell destruction
What consequence occur in Rheumatoid Arthritis?
Joint inflammation and destruction
What consequence occur in Multiple sclerosis?
Brain degeneration
Paralysis
What consequence occur in Celiac disease?
Malabsorption of nutrients
Atropy of intestinal villi
What is Rheumatoid Arthritis (RA)?
chronic systemic inflammatory disorder
affer tissue and organs
What organs are affecfed in Rheumatoid Arthritis (RA)?
skin, blood vessels, heart, lungs, muscles
What organ is principally attacked in Rheumatoid Arthritis (RA)?
joints producing nonsupportive proliferative and inflammatory synovitis --

lead to destruction of articular caritilage and ankylosis of joints = joint deformity and loss of function
What is the cause of Rheumatoid Arthritis (RA)?
unknown
What plays a role in chronicity (chronic) and progression?
autoimmunity
What is the % of US population suffer from RA?
1-3%
What sex is mostly affected by Rheumatoid Arthritis (RA)?
Women
What in seen in Rheumatoid Arthritis (RA) serum?
Rhematoid factor
What is Rheumatoid factor?
anti-immunoglobulin autoantibodies (UgG, IgM, IgA) produced against Fc portion of human IgG
What inflammatory cells affect the joints of Rheumatoid Arthritis (RA)?
Affeted joints show infiltration of synovium w:
CD4
CD8 T cells
C cell
lymphoblast
plasma cells
neutrophils
macrophages
What does the inflammatory cells produce?
inflammatory mediators (eg:)
prostaglandin
leukotriends
proteinase
collagenase
What does the inflammatory mesiators cause?
tissue damage
Classic presentation of Acute Rheumatoid Arthritis (RA).
-Affected joints in hand
polyarthritic
affects procimal inter-phalangial joints
fusiform swelling of soft tissue
symmetrical
Clinical freature of Chronic Rheumatoid Arthritis (RA)
All interphalangeal joints & metacarpophalangeal joints involved.
What happens to the thumb of a Chronic Rheumatoid Arthritis (RA)?
flexed at metacarpophalangeal joint
Hyperextend interphalangeal joints
What happens to th hand od degenerative arthritis?
distal interphalangeal joints invovled, involvement is bony, not symmetrical
Major changes in joint of Rheumatoid Arthritis (RA)
infiltration of synovium by inflammatory cells
increased vascularity d/t vasodilation and angiogenesis
aggregation of organized fibrin
accumulation of neutrophils in synovial fluid
oteoclastic activity=bone destruction
Pannus formation
What is Pannus --found in Rheumatoid Arthritis (RA)?
mass of synovium and synovial stroma sconsiting of inflammatory cells, granulation tissue, fibroblasts growing over articular cartilage
What triggers Rheumatoid Arthritis (RA)?
exposure of genetically susceptible person to unknow arthritogenic antigen
What causes the destructive features of Rheumatoid Arthritis (RA)?
-Continuing autoimmune reaction with activation of
- CD4 T cells
- Lymphocytes
- Release of cytokines/inflammatory antigen
Key considerationd in the pathogenesis of Rheumatoid Arthritis (RA)
Nature of Autoimmune Reaction
Mediators of Tissue Injury
Genetic Susceptibility
Arthitogenic Antigen
What does the autoimmune reacion consist of in Rheumatoid Arthritis (RA)?
CD4 and T cells
B cells
What is the mechanism of intial activation of Rheumatoid Arthritis (RA)?
unknown
What are the targe antigens of the lymphoctyes in Rheumatoid Arthritis (RA)?
unknonwn
What Cytokines play a pivotal role in Rheumatoid Arthritis (RA)?
IL-1 and THF-a
Where are the cytokines of Rheumatoid Arthritis (RA)produced?
macrophages and synovidal lining cells activated by T cells
What does TNF and IL-1 do in Rheumatoid Arthritis (RA)?
stimulate synovial cells to proliferate and make mediators of inflammation (eg. prostaglandin) and matrix mealloproteinases that contribute to cartilage damage
What does T cells and synovial fibroblast also produce (in Rheumatoid Arthritis (RA)?
RANKL
What does RANKL do?
activates osteoclases and promote bone destruction
What is rich in inflammatory cells and becomes adherent to and grows over the artcular surface, forming a pannus, adn stimulates resorption of the adjavent cartilage in Rheumatoid Arthritis (RA)?
Hyperplastic synovium
What does the pannus produce in Rheumatoid Arthritis (RA)?
sustained, irreversible cartilage destruction adn erosion of subchondral bone
What are the antigens of Rheumatoid Arthritis (RA)?
unknown
What are the microbial organism in Rheumatoid Arthritis (RA)?
no microbial organism identified
What are the tx of Rheumatoid Arthritis (RA)?
1. Anti-inflammatory drugs
2. Immnuo-suppressive drugs
3. Antibody against TNF-a
4. Physiotherapy
What is Multiple Sclerosis (MS)?
autoimmune disease
autoimmune response against myelin sheath of nerve cells causes demyelination of neuronal tissue in the white matter of central nervous system.
What sex commonly has Multiple Sclerosis (MS)?
women
What is Multiple Sclerosis (MS) associated with?
HLADR2
What are the autoantigens of Multiple Sclerosis (MS)?
structural protein of myelin:
bastic protein
proteolipid protein
myelin oligodendrocyte
glycoprotein
What is presumed to provoke presentations of CNS antigens to lumphocytes in Multiple Sclerosis (MS), resulting in exapnsion of clones of autoreative T cells and their differentiation into IFN-g secreting TH1 cells?
unknonw injurious event
What does the TH1 cells do in Multiple Sclerosis (MS)?
home to CNS and initiate inflammation
True or False:
90% of MS patients the sclerotic plaque contain plasma cells taht secrete oligoclonal IgG into CSF
True
What is the INITIAL tx of Multiple Sclerosis (MS)?
Immunosuppressive drugs
Corticosteroids
Injection of IFN-B
What does injection of IFN-B in Multiple Sclerosis (MS) do?
prevent progression od dz. Mechanism unknown
What is the LATE stage tx in Multiple Sclerosis (MS)?
aggressive immunosuppressive drugs eg: cycophosphamide w/ corticosteroids
What does GALT respond to?
pathogenic invasion
What does GALT do NOT respond to?
commensal organisms and everyday food stuff
WAvoiding autoimmune response to antigens entering into the system via gastrointestinal tract is called?
oral tolerance
An autoimmune condition where oral tolerance is broken and individuals suffereing from celiac disease develops immune response to gluten protein of wheat flour or related proteins of barley or rye
Celiac Disease
What is the cause when the patient suffer from chronic infalmmation fo the gut? in Celiac Disease?
CD4 T cell infiltration and activated tissue macrophages
What autoantibodies specific for tissue transglutaminase is also present in Celiac Disease?
IgG or IgA
Chronic inflammation of Celiac Disease cause what?
atrophy of intestinal villi
Malabsorption
Diarrhea
What happens to children who has Celiac Disease?
fail to thrive
What happens to adults who has Celiac Disease?
anemia
depressed
prine to other disease including intestinal cancer
How to do stop/treat Celiac Disease?
stop gluten diet
Celiac disease is associated with what HLA?
HLA DQ2
HLA DQ8
WAvoiding autoimmune response to antigens entering into the system via gastrointestinal tract is called?
oral tolerance
What is immunologic tolerance?
normal human immune system is unresponsive to self antigens. "unresponsive"
An autoimmune condition where oral tolerance is broken and individuals suffereing from celiac disease develops immune response to gluten protein of wheat flour or related proteins of barley or rye
Celiac Disease
What is the cause when the patient suffer from chronic infalmmation fo the gut? in Celiac Disease?
CD4 T cell infiltration and activated tissue macrophages
What autoantibodies specific for tissue transglutaminase is also present in Celiac Disease?
IgG or IgA
Chronic inflammation of Celiac Disease cause what?
atrophy of intestinal villi
Malabsorption
Diarrhea
What happens to children who has Celiac Disease?
fail to thrive
What happens to adults who has Celiac Disease?
anemia
depressed
prine to other disease including intestinal cancer
How to do stop/treat Celiac Disease?
stop gluten diet
Celiac disease is associated with what HLA?
HLA DQ2
HLA DQ8
What is immunologic tolerance?
normal human immune system is unresponsive to self antigens. "unresponsive"
When does autoimmune disease develop?
immune system of a person fails to discriminate between self and no-self
List the two factors in the development of autoimmunity
inheritance of susceptibility genes of defective genes

environmental triggers, such as infection, trauma (sympathetic opthalmia) or toxic irritants (eg. tobacco smoke)
Define Sympathetic Opthalmia
condition where following injury to one ye is undamaged eye suffer from impaired vision or even blindness
What are the two mechanisms of immunologic tolerance of T cells?
Central tolerance
Peripheral tolerance
What cause the loss of vision? in Sympathetic Opthalmia
Immune response developed against the proteins of damaged eye gain access to the undamaged eye and this autoimmen reactio cause loss of vision
Define Central Tolerance (Mechanisms of immunologic tolerance of T cells)
refers to development of tolerance to self antigens when lymphocytes encounter these antigens in the primary (site of maturation) lymphoid organs
What is the negative selection for Central intolerance? (Mechanisms of immunologic tolerance of T cells)
negative selection: of developing lymphocytes in the thymic medulla
What is peripheral tolerance?
development of tolerance when mature lymphocytes encounter self antigen in peripheral tissues
Exampel of Peripheral Tolerance of (Mechanisms of immunologic tolerance of T cells)
delection or anergy of lymphocytes that recognize self antigens in peripheral tissues
What is AIRE?
encodes a protein that is a transcription factor that normally induces seceral hundreds of genes in the cells of peripheral tissue
Where does AIRE also do transcribe?
AIRE also transcribe peripheral cellular proteins in subpopulations of epithelial cells in the medulla of thymus
What does defective AIRE genes give rise to?
autoimmune disease called inherited
Autoimmune poluglandular disease (APD) or
Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED)
Where is APECED common?
Finns, Sardinians, Iranian Jews APECED is not uncommon due to defective inheritance of AIRE gene
What are the two types of B cell tolerance?
Cental B cell tolerance
Peripheral B cell tolerance
what is Central B cell tolerance?
When immature B lymphocytes interact strongly with self antigens in the bone marrow, the B cells either deleted (clonal deletion) or change their antigen specificity
What is Peripheral B cell tolerance?
Mature B lymphocytes encounter high concentrations of self antigens in peripheral tissues become anergic and cannot again respond to that self antigen
What is the dominant genetic factor that affect susceptibility to autoimmune disease?
HLA
True or False
Susceptibility to IDDM correlated with shared HLA type between the siblings
True
What gene is associated with the disease Autoimmune lymphoproliferative syndrome (ALPS)?
Fas, FasL
What is the Mechanism of Action of Fas, FasL?
Defective elimination of self-reactive T an B lymphocytes by AICD (activcation induced cell death)
Who develops Autoimmune lymphoproliferative syndrome (ALPS)?
pt who do not have Fas molecule
What does the interaction of Fas and Fas ligand do in a normal person?
interaction of Fas and Fas ligand induce apoptosis of unwanted lymphocytes during development.
A Autoimmune lymphoproliferative syndrome (ALPS) patient cannot control what in their body?
size of lumphocyte population or remove autoimmune cells
What happens to the secondary lymphoid organs during absence of infection Autoimmune lymphoproliferative syndrome (ALPS)??
secondary lymphoid organs become swollen in absence of an infection
What happens to the blood cells including platelets and liver cells in Autoimmune lymphoproliferative syndrome (ALPS)?
autoimmune reaction against listed.
List the infections that give rise to autoimmune conditions
Group A streptococcus
Chlamydia trachomatis

Shigella flexneri. Salmonella typhimurium, Salmonella enteritidis, Yersinia Enterocoltica, Campylobacter jejuni

Borrelia burgdorferi

Coxsackie A virus/Coxsackie B virus/exhoviruses/rubella
What HLA association does Group A Strep have?
unknown
What is the consequence of Group A Strep?
Rheumatic fever
What HLA association does Chlamydia trachomatis have?
HLA B 27
What consequence does Chlamydia trachomatis have?
Rheymatic fever (carditis, polyarthritis)
What HLA assocaition does
Shigella flexneri. Salmonella typhimurium, Salmonella enteritidis, Yersinia Enterocoltica, Campylobacter jejuni
have?
HLA B 27
What consequence does
Shigella flexneri. Salmonella typhimurium, Salmonella enteritidis, Yersinia Enterocoltica, Campylobacter jejuni
have?
Reactive arthritis
What HLA association does Borrelia burgdorferi have?
HLA-DR2, DR 4
What is the consequence of Borrelia burgdorferi?
Chronic arthritis in Lyme Disease
What HLA association does
Coxsackie A virus
Coxsackie B virus
echoviruses
Rubella
have?
HLA-DQ2
HLA-DQ8
DR4
What consequence does
Coxsackie A virus
Coxsackie B virus
echoviruses
Rubella
have?
IDDM