4. Autoimmunity
Breakdown of mechanisms responsible for self tolerance and
induction of specific adaptive immune response against
components of the self.
Condition in which structural or functional damage is produced
by action of immunological component cells or antibodies
against the normal components of the body
Dr Nidesh mds pedodontics
5. Earliest example by
Metalnikoff(1900)
Ehrlich (1901)- “horror autotoxicus”
Donath and landsteiner-circulating auto antibodies in
paroxysomal cold hemaglobinema
This is first description of an auto immune disease in human
beings.
Dr Nidesh mds pedodontics
6. Dameshek and schwartz(1938) established the autoimmune
basis of acute hemolytic anemia
The term auto immune disease is to those where autoimmune
process , humoral or cellular are shown to be responsible for
pathogenesis.
Dr Nidesh mds pedodontics
7. Sequestered or Hidden antigens
Neo antigens
Cessation of Tolerance
It may result when tolerance to the self-Ag is aborted.
Causes of autoimmune diseases
Loss of Immunoregulation
Loss of Self tolerance - caused by over activity or lowered
activity of T and B- cells
Dr Nidesh mds pedodontics
8. Cross reacting Antigens
A foreign Ag which resembles self a ag
Many species share organ specific Ags.
E.g. Ag of Human brain & Ag of sheep brain, Streptococcal
M protein & Heart muscles, Nephritogenic strains of
Streptococci Ags & Renal glomeruli shares similar epiotes.
Dr Nidesh mds pedodontics
9. Contributing Factors
Defects in the immune system
Influence of hormones
Environmental conditions
Dr Nidesh mds pedodontics
10. Immunity
The lymho reticular system is a complex organisation of cells of
diverse morphology distrubuted widely in different organs and
tissues of the body responsible for immunity
Lymphoreticular cells consists of
Lymhoid
Reticuloendothelial component
Lymphoid cells-lymphocytes
Plasma cells
Specific immune response
Dr Nidesh mds pedodontics
11. Reticuloendothelial system
Phagocytic cells-
scavenger functions of eliminating effete cells
and foreign particles
Non specific immunity removal of microorganisms from
blood and tissues
The functional component of lymphoid system are
Humoral or antibody mediated immunity(AMI)
Cellular or cell mediated immunity(CMI)-
sensitized lymphocytes
Dr Nidesh mds pedodontics
12. Humoral immunity-mediated by plasma cells
Lymphoid system
lymphoid organs-
central(primary)-thymus
bone marrow
peripheral(secondary)-lymph nodes
Spleen
Lymphoid cells
Dr Nidesh mds pedodontics
14. Digeorge syndrome-
deficient cmi seen in congenital aplasia of thymus
T lymphocytes develop in thymus
B lympho cytes develop in bone marrow
RUNT disease-
Lymphopenia
deficient graft rejection
neonatally thymectomised mice
Dr Nidesh mds pedodontics
15. Lymphoid cells appear in spleen in 20th week of gestation
Then fetus produces igM and igD
It receives maternal igG
Dr Nidesh mds pedodontics
17. Lymph node functions:
As a filter for lymph , each of nodes draining a specific part of
body
Functions-
Phagocytose foreign materials including microorganisms
In proliferation and circulation of t and b cells
Dr Nidesh mds pedodontics
19. The resources such as iron hemoglobulin are recycled serving
as strong case for renaming this as green pulp
Functions
its graveyard
Reserve tank and settling bed for blood and as a systemic
filter for trapping circulating blood borne foreign particles
Primarly directed against blood borne antigens
Dr Nidesh mds pedodontics
20. Lympho-reticular system
According to their size-
Classified into
Small(5-8um)(numerous)
Medium(8-12)
Large(12-15)
Based on life span
Short lived-2 weeks
Long lived-3 years or more
Dr Nidesh mds pedodontics
21. B lymphocyte
T lymhocytes
B lymphocytes-
Differentiated by their synthesis and display of
membrane bound immunoglobulin(antibody)which
serves as recepter for antigen
During binding of antigen to anyibody cells divide
rapidly into
Effector cells/plasma cells
Memory b cells
Plasma cells produce antibodies
Dr Nidesh mds pedodontics
22. T lymphocyte
During maturation t cells exhibit unique antigen antibody
molecule called t cell receptor
T cell receptor only recognize the antigen that is bound to
cell membrane called MHC
Proliferates and differentiate into effector t cells
Memory t cells
Dr Nidesh mds pedodontics
23. • Activate cells related to cell mediated
immunity , marcophages, natural
killer cells,Tc cells
T helper cells
• Destroys target cells on contact
Cytotoxic t
cells
• Regulates immune response and
helps maintain tolerance
T regulatory
cells
Dr Nidesh mds pedodontics
28. Diseases of auto immune origin usually exhibit the following
features:
An elevated level of immunoglobulins
Demonstrable autoantibodies
Accumulation of lymphocytes and plasma cells at the site of
lesions
The occurrence of more than one type of autoimmune lesion in
an individual
A genetic predisposition towards autoimmunity
Incidence higher among females
Chronicity. Usually non reversible
Benefit from corticosteroid or other immunosuppressive therapy
Dr Nidesh mds pedodontics
30. Altered Antigen
Surface antigens on host altered by chemical, biological
or physical means.
This new antigenic determinant may be recognized as
foreign by the host.
Loss of immunoregulation
Loss of Self tolerance –
caused by over activity or lowered activity of T and B-
cells
Dr Nidesh mds pedodontics
32. Systemic Lupus Erythematosus
Autoimmune disease characterized by
Autoantibodies
immune complex formation
immune dysregulation resulting in damage to kidney, skin, blood
cells and CNS.
Because of its protien manifestations lupus must be considered in
the differential diagnosis of many problems.
Dr Nidesh mds pedodontics
33. Etiology
Specific etiology is unknown
Genetics
Hormones
Environment
Greater production of auto
antibodies
• Immune complex formation
Tissue damage
Dr Nidesh mds pedodontics
34. Produce autoantibodies against DNA
Nuclear antigens
Ribosomes
Platelets
Erythrocytes
Leucocytes
Other tissue specific antigens
Dr Nidesh mds pedodontics
35. Clinical Manifestations
Serious cutaneous – systemic disorder with repeated remissions
and exacerbations.
Females – 30 years
Males – 40 years
Female to male ratio 2:1
Before and after puberty-4:1
Dr Nidesh mds pedodontics
36. Also involves neck
upper arms
shoulders
fingers
The generalized manifestations involve various organs including
kidney and heart.
Collagen diseasesDr Nidesh mds pedodontics
40. DIAGNOSIS
Anemia
Leukopenia
Thrombocytopenia
Elevated sedimentation rate
LE cell inclusion phenomenon
Formation of gamma globulin of serum
Elevation of ESR with normal C reactive protein levels
Detection of antinuclear antibodies (anas)
Dr Nidesh mds pedodontics
41. Treatment
Carefull and frequent clinical and laboratory evaluation –
corner stone of successful intervention.
Corticosteriods are Useful in controlling disease flares.
When symptomatic oral lesions present- potent topical
steroids such as
Clobetasol Propionate gel – 0.05%
Betamethasone dipropionate- 0.05% 2-3 times daily
Fluticazzone propionate spray – 50 microgms
Dr Nidesh mds pedodontics
42. For severe : a pulse IV Cyclophosphamide
Other less toxic agents such as Mycophenolate mofetil (MMF)
and Azathioprine has been shown to possess efficacy
equivalent to that of quaterly Cyclophosphamide with fewer
side effect.
NSAIDS are used for sympotomatic relief in arthritis.
Dr Nidesh mds pedodontics
43. A complete blood count(CBC) is obtained prior to treatment.
Elective oral surgical procedures with potential of Bacteremia
is delayed.
Prophylactic antibiotics is often recommended if neutrophilic
count falls below 500-1000cells/mm3.
Platelet transfusion recommended in surgical patients with
platelet count <50000cells/mm3 .
Dental management
Dr Nidesh mds pedodontics
44. Systemic sclerosis
Scleroderma, Dermatosclerosis, Hidebound disease
Is a systemic connective tissue disease characterized by
vasomotor disturbances
Fibrosis
Subsequent atrophy of the skin
Sub cutaneous tissue
Muscle
Internal organs including alimentary tract,heart , lungs, kidney,
gastrointestinal tract.
Dr Nidesh mds pedodontics
45. Etiology
Unclear etiology.
Genetic
Environmental
vascular factors
Human leukocyte antigens likeHLA-B8, HLA-DR5, HLA-DR3,HLA-
DR52 and HLA-DQB2.
Dr Nidesh mds pedodontics
46. Apoptosis and generation of free radicals may be involved in
pathogenesis
Increased collagen deposition in tissues is a characteristic
feature of systemic sclerosis
Dr Nidesh mds pedodontics
47. Clinical features
begin in children or young adults.
30 and 50 years
Females>males
Ultimate induration of the skin and fixation of the epidermis
to the deeper subcutaneous tissues.
Dr Nidesh mds pedodontics
48. Usually begins on the face
Hands or trunk simultaneously with the development of the
early typical indurated oedema of the skin
Neuralgia
Paresthesia
Arthritis
Pigmention of skin
Erythema accompaines these cutaneous changes
Skin takes on yellow,gray/ivory white waxy appearnce
Deposition of calcium in affected areas is also found.
Dr Nidesh mds pedodontics
49. Involves many internal organs by fibrosis most frequently
involving GIT, lungs, CVS, muscoskeletal system and CNS.
One variant of systemic sclerosis is crest syndrome.
Dr Nidesh mds pedodontics
50. Circumscribed scleroderma / morphea
Circumscribed scleroderma
on sides of chest and thighs
Linear scleroderma
Coup de sabre
One or more slightly elevated
Depressed cutaneous patches
White or yellowish
Surrounded by violaceous haloDr Nidesh mds pedodontics
51. Oral manifestations:
Tongue, soft palate and larynx are mostly involved.
Early mild edema followed by atrophy and induration of
mucosa and muscular tissues
Microstomia , “mouse fascies”
Dr Nidesh mds pedodontics
52. •Gingival recession
•Dysphagia
•hypomobile (board like ) tongue
•Reduced mouth opening and fixation of jaw
•Xerostomia
Alarcon-segovia-sjorgen disease with
Lymphocyte infiltration
Duct cell proliferation
Collagen infiltration
Weisman and calcatena-alterations in salivary gland
functions-sicca syndrome
Dr Nidesh mds pedodontics
53. Radiographic findings
Extreme widening of periodontal ligament space
Bilateral bone resorption of the angle of mandibular ramus.
Partial or complete resorption of condyles or coronoid process.
Dr Nidesh mds pedodontics
54. Early diagnosis and treatment are advised.
Calcium channel blockers
D- penicillamine
Cyclophosphamide
Angiotensins
Treatment
Dr Nidesh mds pedodontics
55. Dental management
Most common problem is physical limitation of oral aperture.
Stretching Exercises
Tongue Blades
Bilateral Commissurotomy
Customized tooth brush handles should be provided for patients
who cannot grip.
Dr Nidesh mds pedodontics
56. Rheumatoid Arthritis
Commonly begins in early adult life
Women>men 2:1
Hypersensitivity reaction to bacterial toxins
specifically streptococci
Poly articular disease
Its symptoms include fatigue
Weight loss
Morning stiffness
Low grade fevers
Anemia.
Dr Nidesh mds pedodontics
57. Subtypes:
Juvenile rheumatoid arthritis
children < 16 years
Joint stiffness
Decreased range of motion,
Pain on range of motion
Joint warmth for atleast 6 weeks without another cause.
Dr Nidesh mds pedodontics
58. Systemic (still’s disease): characterized by joint swelling, fever,
rash, and organ involvement
Early stages may be manifested by slight fever, loss of weight
and fatigability.
The joints affected are swollen.
Movement of the jaw as during mastication or talking causes
pain and may be limited because of stiffness.
Clinical features
Dr Nidesh mds pedodontics
59. Severe cases ankylosis of tmj
Stills disease : class ii div i malocclusion, anterior open bite
Deformation of the mandible characterized by shortening of the
body and reduction in the height of the ramus due to failure of
growth center in the condylar area
Dr Nidesh mds pedodontics
60. Radiographic findings: flattening and stunting of condyle
Haziness about joint-periarticular fibrosis
Dr Nidesh mds pedodontics
61. Is a symmetrical polyarthritis often involving proximal inter
phalangeal joints of the fingers and metacarpophalengeal joints
of the hands: the wrists, elbows, knees and ankles also can be
affected.
Dr Nidesh mds pedodontics
62. The treatment of causes oral manifestations, the long term use
of Methotrexate and other anti rheumatic agents such as D-
pencillamine and NSAIDS can cause Stomatitis.
Minocycline may cause hyperpigmentation intraorally,
Oral manifestations
Dr Nidesh mds pedodontics
63. Gingival overgrowth in patients taking Cyclosporine,
Prednisone and TNFa blocking therapy may predispose
patient to development of opportunistic infections.
Dr Nidesh mds pedodontics
64. Dental management
When treating RA patient it is important to understand the
Mechanism of action
Side effects
Drug interactions of the current medications
Dr Nidesh mds pedodontics
66. Etiology
Genetic
Hormonal
Infectious
immunological or combination of factors play a role in the
etiology of this condition.
Most consider an altered immunological response to be the main
intrinsic factor which is responsible for the disease.
Primary form-HLA-DR3,HLA-B8
Hla-drw52 for both
Sera anti salivary duct antibody
Dr Nidesh mds pedodontics
67. Clinical manifestations:
Predominantly in women over 40 years of age.
Female to male ratio is 10:1
Typical features are dryness of the mouth and eyes
Various secretory glands of the nose, larynx, pharynx,
tracheobronchial tree are involved with this dryness
Xerostomia
Elevated levels of IgA,Potassium,sodium in saliva
80% primary Sjogrens syndrome have parotid enlargement
14% secondary Sjogrens syndrome have parotid enlargement
Lymphadenopathy
Dr Nidesh mds pedodontics
68. Radiographic findings
Sialography may be of diagnostic value in Sjogrens syndrome.
They demonstrate ‘cherry blossom’ or ‘ branchless fruit laden
tree’ effect.
Dr Nidesh mds pedodontics
69. Treatment
Most patients are treated symptomatically
Occular lubricants – methylcellulose – to treat keratoconjunctivitis
sicca
Saliva substitutes – to treat xerostomia
Extensive dental caries and poor oral hygiene – frequent fluoride
application.
Surgery and radiation therapy has been recommended to treat
enlarged salivary glands.
Dr Nidesh mds pedodontics
70. A major complicating factor is development of the
pseudolymphoma and malignant lymphoma.
The risk of lymphoma [non hodgkins] in sjogrens syndrome
patients is 6.4 cases for 100 cases.
Dr Nidesh mds pedodontics
71. Reiter’s syndrome
Unknown etiology associated with urethritis
Calanitis
Conjuctivitis
Mucocutaneous lesions
It is a complication of nonspecific urethritis and clinically mimics
gonorrhea.
Pleura-pneumonia like organisms have been implicated and
Mycoplasmal and Chlamydial species have also been suspected.
HLA-B27
Recent evidence suggests that this condition is also seen
frequently in HIV patients.
Dr Nidesh mds pedodontics
72. Clinical features
More prevalent in young adult men , usually between 20-30
years of age.
The male to female ratio is 9:1
Tetrad of manifestations
Non Gonococcal urethritis
Arthritis
Conjunctivitis
Mucocutaneous Lesions
Dr Nidesh mds pedodontics
73. Oral manifestations
Lesions are painless, red , slightly elevated areas, sometimes
granular or even vesicular with a white circinate border on the
buccal mucosa, lips,and gingiva.
Lesions on the tongue closely resemble Geographic tongue
Dr Nidesh mds pedodontics
74. Diagnosis
Mild leucocytosis
Elevated sedimentation rate
pyuria
Treatment:
The disease may undergo spontaneous remission but has
been treated by antibiotics and corticosteroids.
Dr Nidesh mds pedodontics
75. Oral Lichen Planus
lichen ruber planus
It is a common mucocutaneous disease.
Effects skin or mucosa or both
It can cause bilateral white striations, papules, or plaques on
the buccal mucosa, tongue and gingiva.
The involvement of the oral mucous membrane is so frequent
Dr Nidesh mds pedodontics
76. Etiology:
T cell mediated autoimmune disease in which cytotoxic CD8+T
cell trigger the apoptosis of oral epithelial cells.
The expression of the lichen planus antigen may be induced by
drugs - Lichenoid Drug Reaction
Association of lichen planus, diabetes mellitus and vascular
hypertension has been described as Grinspans Syndrome.
Dr Nidesh mds pedodontics
77. Clinical manifestations
Female-male 1.4:1
At 40 years
Skin lesions-small
Angular
Flat toped papules few mm to cm
Early stages-red-reddish purpule or viloceous hue
Later dirty brownish colour develops
Dr Nidesh mds pedodontics
78. Oral manifestations:
Radiating white or gray velvety threadlike papules in a linear,
annular or retiform arrangements forming typical lacy reticular
patches , rings and streaks.
Tiny white elevated dot is frequently present at the intersection
of white lines known as Wickhams Straie
Dr Nidesh mds pedodontics
79. These oral lesions produce no significant symptoms, although
some patients complain of burning sensation.
Different forms are
Plaque like,
Bullous form
Erosive form
Atropic form – chronic desqumative gingivitis
Hypertropic form
Oral manifestations occur weeks or months before the
appearance of the skin lesions.
Dr Nidesh mds pedodontics
80. Differential diagnosis:
Lichenoid reaction
Leukoplakia
Candidiasis
Pemphigus
Cicatrial pemphigoidsyphilis
Lupus erythematosus
Malignant transformation
Higher incidence of oral squamous cell carcinoma
0.3% to 3%
Erosive and atropic forms mostly undergo malignant
transformation.
Dr Nidesh mds pedodontics
81. Treatment:
At present there is no cure,
Potential for malignant transformation is minimal, these
patients kept on long term follow-up.
Principal aim is resolution of the painful symptoms, the lesion,
reduction of risk of cancer, and maintenance of good oral
hygiene.
Corticosteroids are recommended
Dr Nidesh mds pedodontics
82. Psoriasis
Noncontagious skin disorder
Inflamed
edematous skin lesions covered with a silvery white scale.
Most common type is plaque psoriasis
Nails are pitted/thickened
Dr Nidesh mds pedodontics
83. The trigger event is unknown, but is an immunological event,
significant evidence of autoimmunity is present.
Genetic predisposition
Lesions of psoriasis are associated with increased activity of T
cells in underlying skin.
Perceived stress
Etiology
Dr Nidesh mds pedodontics
84. Clinical features:
Of skin, is characterized by occurrence of small sharply defined
delineated dry papules each covered by a delicate silvery scale .
If the deep scale is removed , tiny bleeding point is disclosed a
characterstic feature termed – Auspitz’s sign
Dr Nidesh mds pedodontics
85. Oral manifestations
Involvement of oral mucosa is rare.
A study by buchner found none with oral lesions of dermal
psoriasis patients, however they did note 11%had angular
cheliosis, 6% fissured tongue, 5% benign migratory glossitis.
They are yellowish-white plaques, as silvery white scaly lesions
with erythematous base .Or as multiple papular eruptions which
may be ulcerated
Dr Nidesh mds pedodontics
87. Treatment:
Lesions are benign but few cases are refractory to treatment.
Treatment include UV-light , Psoralen plus UV-A light(PUVA),
Retinoids, methotrexate, cyclosporine.
Dr Nidesh mds pedodontics
88. Pemphigus vulgaris
Is an autoimmune intraepithelial blistering disease
Skin and mucous membrane
Mediated by circulating IgG autoantibodies directed against
keratinocyte cell surface.
Effects all races with equal gender prediction and mean age of
onset is 50-60 years
Dr Nidesh mds pedodontics
89. Oral lesions – 1st sign of this disease
Characterized by rapid appearance of the vescicles and bullae,
varying in diameter from milimetrs to several centimetres.
These lesions contain thin watery fluid shortly after
development, but may soon become purulent
Nikolsky’s Sign
Clinical features
Dr Nidesh mds pedodontics
90. The disease involves mucosa in 50-70% of patients
Patients have ill defined irregularly shaped gingival buccal or
palatine erosions which are painful and slow to heal.
Erosions extend peripherally with shedding of epithelium, and
may spread to involve larynx with subsequent hoarseness.
Other mucosal surfaces may be involved including conjunctiva,
oesohagus, cervix.
Oral manifestations
Dr Nidesh mds pedodontics
92. Diagnosis:
Tzanck cells
Immunofluroscense testing demonstrate IgG with
combinations of C3
IgM in intercellular spaces
Differential diagnosis:
Dermatitis herprtiformis
Erythema multiforme
Bullous lichen planus
Bullous pemphigoid
Dr Nidesh mds pedodontics
93. Treatment:
Systemic Corticosteroids – main stay of treatment- 1-
2mg/kg/day
Adjuvants – immunosuppresive drugs- mycofenolate mofetil,
azathioprine, cyclophosphamide
Dr Nidesh mds pedodontics
94. WEGNER’ S GRANULOMATOSIS
Immunologically mediated multisystem disorder
Vascular, renal and respiratory systems.
It involves nose
paranasal air sinuses
lower respiratory tract
Gut
Joints
Nervous system and kidneys.
Etiology:
It may be caused by an abnormal immune reaction secondary to
a nonspecific infection or a hyper sensitivity reaction to an
unknown antigen.
Dr Nidesh mds pedodontics
95. Clinical features
Classic type renal + respiratory lesions
Limited type only respiratory lesions
Superficial type only skin and mucosal lesions
At any age
4th and 5th decades
Male>females
Rhinitis
Sinusitis
Otitis
Occular symptoms
Straw berry gingivitis
Dr Nidesh mds pedodontics
96. Oral manifestations:
Ulcerative
Friable
Granular lesions
Simple enlargments of gingiva
Inflammation starts in interdental
papilla,spreads to periodontal structure
Leads to bone loss and tooth mobility
Dr Nidesh mds pedodontics
98. Treatment
Majority of cases of wegners granulomatosis formerly
terminated fatally.
However to prevent long term remissions cyclophosphamide
and prednisolone are recommended.
Dr Nidesh mds pedodontics
99. CONCLUSION
An autoimmune disease develops when our immune system,
which defends our body against disease, decides our healthy cells
are foreign. As a result, our immune system attacks healthy cells.
Dr Nidesh mds pedodontics
100. Basics and clinical immunology-peakman,vergani-2nd edition
Kuby immunology-6th edition
Ananthanarayan and paniker text book of microbiology – 7th
edition
Shafers textbook of oral patholgy -6th edition
Burkitts oral medicine -11th edition
References
Dr Nidesh mds pedodontics