Autoimmune disease.pptx

8/15/2019 Autoimmune disease.pptx

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INTRODUCTION

Self tolerance is lost

Specic adaptive immune responses

mounted against self antigens Inability to eliminate antigen leads to

cronic in!ammatory process

"rlic termed tis horror autotoxicus


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Autoimmune Diseases

Failure of autoantibodies and T cells torecognize own cells

Autoantibodies and T cells launch attackagainst own cells

Perhaps due to overactive or anoverabundance of helper T lymphocytes


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Examples of Autoimmune Diseases

Multiple sclerosis

Myasthenia gravis

Crohn’s disease

Grave’s disease

Type 1 Diabetes mellitus

Rheumatoid arthritis

PsoriasisScleroderma

Systemic lupus erythematosus


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Autoimmune diseases mediated

by cytoto#ic antibodies $Type II%


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Autoimmune diseases mediated

by immune comple#es $Type III%


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Autoimmune diseases

mediated by T&cells $Type I'%


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Autoimmune disease susceptibility

(enetic predisposition

› T)in studies $Diabetes* +,-

mono.ygotic vs/ 0- di.igotic%› 1amily studies

Association )it 23C genotype

›

34A genotyping


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Associationbet)een

34A andsusceptibility to

autoimmune disease


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Diagnosis: AutoimmuneDisease

Genetic predisposition

› coding for the variety of MHC molecules

Demographics› most common among middle aged women

Additional viral infections

Disease specific environmental factors Aging, stress, hormones, pregnancy


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Possible Causes:› Inefficient lymphocyteprogramming

› “Self proteins” circulate

without having been exposedto system(ex: sperm, eye lens, thyroid)

› Reactions between self-antigens and antibodyproduction against foreign

antigens

Potential Treatments:› Control inflammation

(ex: diabetes mellitus)

› Immunosuppressive Medication

(ex: corticosteriods,cyclosporin, methotrexate)

› Therapeutic Antibodies againstspecific T cell molecules

(with fewer side effects)


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S56gren7s Syndrome

Cronic autoimmune disorder

2a5or clinical manifestations resulting

from canges in e#ocrine glands


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1orms of S56gren7s

Syndrome

8rimary S56gren7s is caracteri.edby in!ammatory cell involvement ofbot te salivary and lacrimalglands

Secondary S56gren7s includes oter

dened connective tissue disease Causes are un9no)n


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1eatures of S56gren7s Syndrome

Glandular epithelial cells participate in the

autoimmune disease process

Epithelial cells produce a number ofimmunologically active mediators

May serve as antigen-presenting cells

Epithelial cell responses modulatemechanisms occurring in the salivary glands


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Is S56gren7s Syndrome anAutoimmune Disorder:

Described as an autoimmunee#ocrinopaty $Strand and Talal; ,%

(rouped )it oter connective tissuediseases

› Reumatoid artritis

› Systemic lupus erytematosis $S4"% ?at is te evidence tat it is an

autoimmune disease:


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"vidence tat S56gren7s Syndrome

is an Autoimmune Disease

A specic auto&immunogen andpatogenic antibodies ave not been

identied Autoantibodies tat ave been found

ave not been so)n to ave any directpatogenic e@ects on e#ocrine tissues

Tere is substantial circumstantialevidence tat tissue damage is te resultof autoimmunity


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8olyclonal 3ypergammaglobulinemia

&cell yper&responsiveness

2ar9ed elevations of Ig( 8roduction ofreumatoid factors

8resence of anti&nuclear antibodies› "#tractable nuclear antigens Anti&SS&A $Ro% and anti&

SS& $4a%

Antibodies are found directed against salivary

duct cells $=,- of patients%› 8rimarily against e#tractable nuclear antigens

› Concentration does not correlate )it glanddestruction


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Oter Caracteristics

"levated sedimentation rates anddecreased ?C counts; as seen in oterautoimmune connective tissue diseases

Specic e#tended 23C aplotype at aiger freBuency tan controls

23C&encoded proteins›

Induction of tolerance to self proteins› Selection of te T&cell repertoire

› inding and presentation of antigen to T&cells


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3istopatology

2ononuclear inltrate consistingprimarily of T&cells $primarily CD%

3ost of mediators

Altered cell adesion moleculese#pression

Increased 34A class II antigens

e#pression Immunosuppressive terapy often

e@ective


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Classical 3istopatological4esion

4ympo&epitelial lesion a@ecting te parotidgland

8rogressive replacement of te salivary tissue

by dense lympoid inltrates 1ormation of proliferating islands of ductal

epitelial cells

Creates )ell&formed lympoid follicles typical

of 2A4T and may give rise to lympomas of te2A4T type as an e#pansion of monoclonal &cells


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Salivary(landStructure


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Scleroderma(Systemic Sclerosis)


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Defnition


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Epidemiology


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Classifcation


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Classifcation o systemic sclerosis


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Classification of systemic

sclerosis

Classification of systemic

sclerosis

2. Limited cutaneous systemic sclerosis

1) symmetric restricted fibrosis

- affecting the distal extremities and face/neck

2) prolonged delay in appearance of distinctive internal

manifestation 3) prominence of calcinosis and telangiectasia

) good prognosis

! "#$%& syndrome

- calcinosis' #aynaud(s phenomenon' esophageal dysmotility' sclerodactyly' telangiectasia

2. Limited cutaneous systemic sclerosis

1) symmetric restricted fibrosis

- affecting the distal extremities and face/neck

2) prolonged delay in appearance of distinctive internal

manifestation 3) prominence of calcinosis and telangiectasia

) good prognosis

! "#$%& syndrome

- calcinosis' #aynaud(s phenomenon' esophageal dysmotility' sclerodactyly' telangiectasia


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Classifcation o systemicsclerosis

Overlap syndromes

– 1eatures of systemic sclerosis togeter)it tose of at least one oter

autoimmune reumatic disease; e/g/ S4";RA; or polymyositis


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"tiology

"nvironmental factors % 4&tryptopan =% silicone implant $:%

(enetic predisposition Defective immunoregulation ; cyto9ines

+% umoral immunity–

ypergammaglobulinemi

a

– autoantibody

production

– antinuclear antibody

$% J =0-


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PathogenesisPathogenesis

%usceptible host

$xogenous events

mmune systemactivation

$ndothelial cell

activation/damage*ibroblast activation

$nd stage pathology

+bliterative

vasculopathy

*ibrosis


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Pathogenesis


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Clinical eatures


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Raynaud7s penomenon


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Raynaud7s penomenon


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Raynaud7s penomenon

. Arteriogram

& narro)ing and

occlusion

of digital arteries

& pro#imal vessels;

arcades

and metacarpalvessels are

)idely patent


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Telangiectasia

. local disruption of

angiogenesis

. blanced by pressure


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Clinical featuresClinical features

2. %kin involvement ,1)

1) stage

- edematous phase

- indurative phase

- atrophic phase

2) firm' thickened bound to underlying soft tissue

3) decrease in range of motion' loss of facial expression' inability

to open mouth fully' contractures


1) stage

- edematous phase

- indurative phase

- atrophic phase

2) firm' thickened bound to underlying soft tissue

3) decrease in range of motion' loss of facial expression' inability

to open mouth fully' contractures


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"dematous pase


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S9in Induration


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Acrosclerosis


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1acial canges

&ight' thin lips ith vertical perioral furros


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ulceration' loss of soft tissue of finger tip' pigmentation' calcific

deposit' capillary change

3. usculoskeletal system

• olyarthritis and flexion contracture

• uscle eakness and atrophy ,primary /secondary)


ulceration' loss of soft tissue of finger tip' pigmentation' calcific

deposit' capillary change

3. usculoskeletal system

• olyarthritis and flexion contracture

• uscle eakness and atrophy ,primary /secondary)


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Terminal digit resorption


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Acrolysis


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Digital pitting scars


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Calcinosis and acrolysis


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. intestinal involvement

1) esophagus0 hypomotility and retrosternal pain'

reflux esophagitis' stricture

2) stomach0 delayed emptying

3) small intestine0 pseudo-obstruction' paralytic ileus'

malabsorption' eight loss' cachexia

) large intestine0 chronic constipation and fecal impaction

diverticula

. intestinal involvement

1) esophagus0 hypomotility and retrosternal pain'

reflux esophagitis' stricture

2) stomach0 delayed emptying

3) small intestine0 pseudo-obstruction' paralytic ileus'

malabsorption' eight loss' cachexia

) large intestine0 chronic constipation and fecal impaction

diverticula


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Abnormal motility


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Diverticula

. arium enema study

& multiple )ide&

mouted

diverticula of colon

& broad base and

nec9

& usuallyasymptomatic


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Diverticula


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. lungs

1) 2/3 of patients affected

- leading cause of mortality and morbidity in later stage

of systemic sclerosis

2) pathology

- interstitial fibrosis

- intimal thickening of pulmonary arterioles

,pulmonary hypertension)

3) "omplains - dry cough' breathlessness

. lungs

1) 2/3 of patients affected

- leading cause of mortality and morbidity in later stage

of systemic sclerosis

2) pathology

- interstitial fibrosis

- intimal thickening of pulmonary arterioles

,pulmonary hypertension)

3) "omplains - dry cough' breathlessness


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8ulmonary brosis


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. heart ,14)

1) pericarditis

2) heart failure

3) arrhythmia

) myocardial fibrosis

. heart ,14)

1) pericarditis

2) heart failure

3) arrhythmia

) myocardial fibrosis


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5. kidney

1) diffuse scleroderma in association ith

rapid progression of skin involvement

2) pathology

- intimal hyperplasia of the interlobular artery - fibrinoid necrosis of afferent arterioles

- glomerulosclerosis

3) proteinuria' abnormal sediment' a6otemia'

microangiopathic hemolytic anemia' renal failure

5. kidney

1) diffuse scleroderma in association ith

rapid progression of skin involvement

2) pathology

- intimal hyperplasia of the interlobular artery - fibrinoid necrosis of afferent arterioles

- glomerulosclerosis

3) proteinuria' abnormal sediment' a6otemia'

microangiopathic hemolytic anemia' renal failure


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Midney arteriogram

Midney Intimal arterial


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Midney; Intimal arterialbrosis


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Clinical eatures

"#ocrine glands

– erostomia

– #eroptalmia


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Laboratory fndings


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Diagnosis


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TreatmentTreatment

7 ide spectrum of clinical manifestations and severity- spontaneous improvement occurs fre8uently

• 9isease modifying interventions ,:)

- penicillamine

- methotrexate- immunosuppressive agent0 cyclosporin' *;-γ

- recombinant human relaxin

• %ymptomatic ,organ-specific) treatment

7 ide spectrum of clinical manifestations and severity- spontaneous improvement occurs fre8uently

• 9isease modifying interventions ,:)

- penicillamine

- methotrexate- immunosuppressive agent0 cyclosporin' *;-γ

- recombinant human relaxin

• %ymptomatic ,organ-specific) treatment


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Treatment

Raynaud7s penomenon and iscemia


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TreatmentTreatment

ulmonary

1) nterstitial fibrosis

- corticosteroid

- cyclophosphamide' a6athioprine

2) pulmonary artery hypertension

- calcium channel blocker

- prostacyclin

- transplantation

ulmonary

1) nterstitial fibrosis

- corticosteroid

- cyclophosphamide' a6athioprine

2) pulmonary artery hypertension

- calcium channel blocker

- prostacyclin

- transplantation


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Treatment

Renal


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Prognosis

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Autoimmune disease.pptx