AUTOIMMUNITY AND AUTO IMMUNE DISEASES.pdf

The immune system could go awry and, instead of reacting against foreign antigens, could focus its attack on self-antigens. Paul Ehrlich termed this condition “horror autotoxicus.”
Mechanisms of self-tolerance normally protect an individual from potentially self-reactive lymphocytes, there are failures. They result in an inappropriate response of the immune system against self-components termed autoimmunity.

1. AUTOIMMUNITY
AUTOIMMUNE DISEASES
Mrs. G, NITHYA M.Sc., M. Phil., SET.,
ASSISTANT PROFESSOR,
DEPARTMENT OF BIOCHEMISTRY,
D.K.M COLLEGE FOR WOMEN,
VELLORE –632001.

2. Theimmunesystemcouldgoawryand,instead
ofreactingagainstforeignantigens,couldfocus
itsattackonself-antigens.PaulEhrlichtermed
thiscondition“horrorautotoxicus.”
Mechanismsofself-tolerancenormallyprotect
anindividualfrompotentiallyself-reactive
lymphocytes,therearefailures.Theyresultinan
inappropriateresponseoftheimmunesystem
againstself-componentstermedautoimmunity.

3. TWO CATEGORIES
ORGAN SPECIFIC DISEASES
DIRECT CELLULAR DAMAGE
ANTIBODIES STIMULATE OR BLOCK THE TARGET
ORGAN
SYSTEMIC DISEASES

4. Organ-Specific Autoimmune Diseases
•Inanorgan-specificautoimmunedisease,the
immuneresponseisdirectedtoatargetantigen
uniquetoasingleorganorgland,sothatthe
manifestationsarelargelylimitedtothatorgan.
Thecellsofthetargetorgansmaybedamaged
directlybyhumoralorcell-mediatedeffector
mechanisms.
•Alternatively,theantibodiesmayoverstimulate
orblockthenormalfunctionofthetargetorgan.

5. Autoimmune Diseases Mediated by
Direct Cellular Damage
•Autoimmunediseasesinvolvingdirectcellular
damageoccurwhenlymphocytesorantibodies
bindtocell-membraneantigens,causingcellular
lysisand/oraninflammatoryresponseinthe
affectedorgan.
•Gradually,thedamagedcellularstructureis
replacedbyconnectivetissue(scartissue),and
thefunctionoftheorgandeclines

6. HASHIMOTO’S THYROIDITIS
•InHashimoto’sthyroiditis,whichismostfrequently
seeninmiddle-agedwomen,anindividualproduces
auto-antibodiesandsensitizedTH1cellsspecificfor
thyroidantigens.
•TheDTHresponseischaracterizedbyanintense
infiltrationofthethyroidglandbylymphocytes,
macrophages,andplasmacells,whichform
lymphocyticfolliclesandgerminalcenters
•Theensuinginflammatoryresponsecausesagoiter,
orvisibleenlargementofthethyroidgland,a
physiologicalresponsetohypothyroidism

7. •Antibodiesareformedtoanumberofthyroid
proteins,includingthyroglobulinandthyroid
peroxidase,bothofwhichareinvolvedinthe
uptakeofiodine.
•Bindingoftheauto-antibodiestotheseproteins
interfereswithiodineuptakeandleadsto
decreasedproductionofthyroidhormones
(hypothyroidism).

8. AUTOIMMUNE ANEMIAS
•Autoimmuneanemiasinclude
▫perniciousanemia,
▫autoimmunehemolyticanemia,and
▫drug-inducedhemolyticanemia.
•Perniciousanemiaiscausedbyauto-antibodies
tointrinsicfactor,amembrane-boundintestinal
proteinongastricparietalcells.Intrinsicfactor
facilitatesuptakeofvitaminB12fromthesmall
intestine.

9. •Bindingoftheauto-antibodytointrinsicfactor
blockstheintrinsicfactor–mediatedabsorption
ofvitaminB12.
•IntheabsenceofsufficientvitaminB12,which
isnecessaryforproperhematopoiesis,the
numberoffunctionalmatureredbloodcells
decreasesbelownormal.
•Perniciousanemiaistreatedwithinjectionsof
vitaminB12,thuscircumventingthedefectinits
absorption.

10. •Anindividualwithautoimmunehemolytic
anemiamakesauto-antibodytoRBCantigens,
triggeringcomplementmediatedlysisor
antibody-mediated opsonization and
phagocytosisoftheredbloodcells.
•Oneformofautoimmuneanemiaisdrug-
induced:whencertaindrugssuchaspenicillin
ortheanti-hypertensiveagentmethyldopa
interactwithredbloodcells,thecellsbecome
antigenic.

11. GOODPASTURE’S SYNDROME
•InGoodpasture’ssyndrome,auto-antibodiesspecific
forcertainbasement-membraneantigensbindto
thebasementmembranesofthekidneyglomeruli
andthealveoliofthelungs.
•Subsequentcomplementactivationleadstodirect
cellulardamageandanensuinginflammatory
responsemediatedbyabuildupofcomplementsplit
products.
•Damagetotheglomerularandalveolarbasement
membranesleadstoprogressivekidneydamageand
pulmonaryhemorrhage

12. INSULIN-DEPENDENT DIABETES MELLITUS
•Adiseaseafflicting0.2%ofthepopulation,
insulin-dependentdiabetesmellitus(IDDM)is
causedbyanautoimmuneattackonthe
pancreas.
•Theattackisdirectedagainstspecialized
insulin-producingcells(betacells)thatare
locatedinsphericalclusters,calledtheisletsof
Langerhans,scatteredthroughoutthepancreas.
•Theautoimmuneattackdestroysbetacells,
resultingindecreasedproductionofinsulinand
consequentlyincreasedlevelsofbloodglucose.

13. Autoimmune Diseases Mediated by Stimulating or
Blocking Auto-Antibodies
Insomeautoimmunediseases,antibodiesactas
agonists,bindingtohormonereceptorsinlieuof
thenormalligandandstimulatinginappropriate
activity.Thisusuallyleadstoanoverproduction
ofmediatorsoranincreaseincellgrowth.
Conversely,auto-antibodiesmayactas
antagonists,bindinghormonereceptorsbut
blockingreceptorfunction.Thisgenerallycauses
impairedsecretionofmediatorsandgradual
atrophyoftheaffectedorgan.

14. GRAVES’ DISEASE
•Theproductionofthyroidhormonesiscarefully
regulatedbythyroid-stimulatinghormone
(TSH),whichisproducedbythepituitarygland.
•BindingofTSHtoareceptoronthyroidcells
activatesadenylatecyclaseandstimulatesthe
synthesisoftwothyroidhormones,thyroxine
andtriiodothyronine.

15. •ApatientwithGraves’diseaseproducesauto-
antibodiesthatbindthereceptorforTSHand
mimicthenormalactionofTSH,activating
adenylatecyclaseandresultinginproductionof
thethyroidhormones.
•UnlikeTSH,however,theautoantibodiesarenot
regulated,andconsequentlytheyoverstimulate
thethyroid.Forthisreasontheseauto-
antibodiesarecalledlong-actingthyroid-
stimulating(LATS)antibodies.

17. MYASTHENIA GRAVIS
•Myastheniagravisistheprototypeautoimmune
diseasemediatedbyblockingantibodies.
•Apatientwiththisdiseaseproducesauto-
antibodiesthatbindtheacetylcholinereceptors
onthemotorend-platesofmuscles,blockingthe
normalbindingofacetylcholineandalso
inducingcomplementmediatedlysisofthecells.
•Theresultisaprogressiveweakeningofthe
skeletalmuscles

19. Systemic Autoimmune Diseases
•Insystemicautoimmunediseases,theresponse
isdirectedtowardabroadrangeoftarget
antigensandinvolvesanumberoforgansand
tissues.

20. Systemic Lupus Erythematosus
•Systemic Lupus ErythematosusAttacks Many
Tissues One of the best examples of a systemic
autoimmune disease is systemic lupus
erythematosus(SLE),which typically appears in
women between 20 and 40 years of age
•the ratio of female to male patients is 10:1. SLE
is characterized by fever, weakness, arthritis,
skin rashes, pleurisy, and kidney dysfunction.

21. •Affectedindividualsmayproduceautoantibodiesto
avastarrayoftissueantigens,suchasDNA,
histones,RBCs,platelets,leukocytes,andclotting
factors;interactionoftheseauto-antibodieswith
theirspecificantigensproducesvarioussymptoms.
•Auto-antibodyspecificforRBCsandplatelets,for
example,canleadtocomplement-mediatedlysis,
resultingin hemolytic anemia and
thrombocytopenia,respectively.
•Whenimmunecomplexesofauto-antibodieswith
variousnuclearantigensaredepositedalongthe
wallsofsmallbloodvessels,atypeIIIhypersensitive
reactiondevelops.

23. Multiple Sclerosis
•AttackstheCentralNervousSystem.Multiple
sclerosis(MS)isthemostcommoncauseof
neurologicdisabilityassociatedwithdiseasein
Westerncountries.
•Thesymptomsmaybemild,suchasnumbness
inthelimbs,orsevere,suchasparalysisorloss
ofvision.MostpeoplewithMSarediagnosed
betweentheagesof20and40.
•Individualswiththisdiseaseproduce
autoreactiveTcellsthatparticipateinthe
formationofinflammatorylesionsalongthe
myelinsheathofnervefibers.

24. •The cerebrospinal fluid of patients with active
MS contains activated T lymphocytes, which
infiltrate the brain tissue and cause
characteristic inflammatory lesions, destroying
the myelin.
•Since myelin functions to insulate the nerve
fibers, a breakdown in the myelin sheath leads to
numerous neurologic dysfunctions.

25. Rheumatoid Arthritis
•AttacksJointsRheumatoidarthritisisa
commonautoimmunedisorder,mostoften
affectingwomenfrom40to60yearsold.
•Themajorsymptomischronicinflammationof
thejoints,althoughthehematologic,
cardiovascular,andrespiratorysystemsarealso
frequentlyaffected.
•Manyindividualswithrheumatoidarthritis
produceagroupofauto-antibodiescalled
rheumatoidfactorsthatarereactivewith
determinantsintheFcregionofIgG.

26. •TheclassicrheumatoidfactorisanIgMantibody
withthatreactivity.Suchauto-antibodiesbindto
normalcirculatingIgG,formingIgM-IgG
complexesthataredepositedinthejoints.
•Theseimmunecomplexescanactivatethe
complementcascade,resultinginatypeIII
hypersensitivereaction,whichleadstochronic
inflammationofthejoints.

27. Scleroderma
•Sclerodermaisagroupofdiseaseswitha
commonsymptom:hardeningandtighteningof
theskin.Therearetwotypesofscleroderma:
localizedandsystemic.
Localizedsclerodermaonlyaffectstheskin
systemicsclerodermaaffectstheskin,theblood
vesselsandinternalorgans.

28. •Sclerodermaisarheumaticdisease,which
meanspatientsmayhaveinflammation,pain,
swellingandstiffnessinthejoints,tendons,
ligaments,bones,musclesand/ortissues.
•Sclerodermaaffectsmanymorewomenthan
men,andit’stypicallyfoundinpeoplebetween
theagesof30and50.
•Thereisnocureforscleroderma.Thegoalof
treatmentistorelievesymptomsandstopthe
progressionofthedisease.Earlydiagnosisand
ongoingmonitoringareimportant.

29. •Scleroderma is an autoimmune disease that
causes inflammation and fibrosis (thickening) in
the skin and other areas of the body. When an
immune response tricks tissues into thinking
they are injured, it causes inflammation, and the
body makes too much collagen,leading to
scleroderma.
•Too much collagen in your skin and other tissues
causes areas of tight, hard skin..

30. •There are two major types of scleroderma:
▫Localized scleroderma only affects the skin and
the structures directly under the skin
▫Systemic scleroderma, also called systemic
sclerosis, affects many systems in the body. This is
the more serious type of scleroderma and can
damage your blood vessels and internal organs,
such as the heart, lungs, and kidneys.

32. REFERENCES:
KUBY IMMUNOLOGY 4
th
EDITION

33. THANK YOU