Escolar Documentos
Profissional Documentos
Cultura Documentos
OF ORAL DISEASES
BY
DR. FAMUREWA B.A.
OUTLINE
Introduction
Review of basic Immunology
Oral cavity and immune system
Immunopathology of common oral lesions
Conclusion
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Introduction
systems:
1. The innate system, or first line of defense.
2.
Acquired immunity
Inborn
Adaptive
non-specific: Body
responds
Specific
involved
Constantly evolves
Basis of vaccination
as
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B.A. BChDetc.
lysozyme, FAMUREWA
lactoferrin
IMMUNE SYSTEM
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Complement system
Complement system is a biochemical cascade
that attacks the surfaces of foreign cells.
It contains at least 20 different proteins and is
Complement system
Pathway of complement activation:
Classical pathway
Alternate pathway
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IMMUNE SYSTEM
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IMMUNE SYSTEM
The adaptive immune system consists of:
Cellular immunity (lymphocytes and their products).
Humoral immunity (Antibodies).
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Immune cells
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13
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IMMUNE EFFECTOR
CELLS
B-lymphocytes
T-lymphocytes
Natural
killer cells
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T-lymphocytes
Mediate cellular immunity.
60-70% of circulating peripheral lymphocytes.
Thymus-derived. Found in paracortex of lymph
TCR.
Divided into:
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Tumour cells
Virus-infected cells
Some normal cells
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NB
without prior
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Immunological memory
When B cells and T cells are activated and begin to
passive
short-term
memory or active long-term
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FAMUREWA B.A. BChD
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IMMUNOGLOBULINS
Immunoglobulins, or antibodies, are a
complex, heterogeneous mixture of
proteins that exhibit two fundamental
types of structural variation.
Subtle structural differences in their
antigen combining sites, or
variable regions, account for their
unique antigen binding specificities.
Structural differences outside their
antigen combining sites, in the socalled constant regions, correlate with
the different effector functions
mediated by antibodies.
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IgA
IgD
IgE
IgM
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FUNCTIONS OF
IMMUNOGLOBULINS
Antigen binding
Effector Functions
1. Fixation of complement
2. Binding to various cell
types
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Fab
Fc
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IgG
Most versatile immunoglobulin because it is
capable of carrying out all of the functions of
immunoglobulin molecules.
IgG is the major Ig in serum - 75% of serum Ig
is IgG
IgG is the major Ig in extra vascular spaces
Placental transfer
Fixes complement
Binding to cells.
Opsonisation: The antibody has prepared the
antigen for eating by the phagocytic cells.
Binding of IgG to Fc receptors on other types of
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IgM
Pentamer
Third most common serum Ig.
First Ig to be made by the fetus & by a
lysis of microorganisms.
As a consequence of its structure, IgM
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IgA
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IgE
Very low concentration in serum
Membrane bound to mast cells & basophils
Antiparasitic in function
Important in type hypersensitivity(allergic or
atopic) diseases.
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IgD
Low serum level
Function uncertain.
Present on B lymphocytes
Levels are high in B cell activation seen in SLE,
HIV infection and Hodgkins disease.
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squames.
Membrane-coating granules discharged
extracellularly in the granular layer.
Transudation of antibody through the mucosa.
Intraepithelial dendritic Langerhans cells (APC)
process antigen.
Oral epithelial cells produce a range of cytokines
including IL-I , IL-6, TNF-alpha, GM-CSF, TGF-beta
and IL-8
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Activity
Lactoferrin
Iron-binding. Bacteriostatic.
Lysozyme
Agglutinins
Myeloperoxidase system
Bactericidal in presence of
thiocyanate/halide-H202.
Salivary peroxidase
system
Enzyme-thioycyanate-H202
Complement (trace
amounts)
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Leukocytes
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Immunopathology
Branch of immunology that deals with
pathologies of the immune system.
Defect or malfunction in innate and or adaptive
immune response can initiate disease process.
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Immunopathology
3 aspects:
Immonodeficiency
Hypersensitivity reactions
Autoimmunity
Hypersensitivity and autoimmune disorders are
hyperactive immune disorders.
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Immunity- A two-edged
sword
Immune system
Immunodeficien
cy
Hyperactive immune
system
allergy
Infection
s
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Bacterial
Fungal
Viral
Neoplasia
Pemphigu
s
pemphigoi
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d
Erythema
multiforme
etc
autoimmunit
y
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Immunodeficiency
Could be primary(congenital) or secondary.
1 immunodeficiency- intrinsic failure of
development of one/ more component of the
immune system. This can involve :
Phagocytes
Complements
B cells
T cells
Combined T & B cells
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C) Phagocyte
disorders:
Disorder
Inheritance
Clinical Features
Therapy
1) Chronic
granulomatous
disease
X-linked
(66%);
autosomal re
cessive (33%)
Antibiotics;
-interferon
2)Myeloperoxida Autosomal
se deficiency
Recessive
3)Leukocyte
adhesion
deficiency
Antibiotics
Antibiotics
Autosomal
recessive
4)Abnormal
Variable
chemotaxis
-Hyper IgE
-chediak-Higashi
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Clinical Features
Therapy
Immune serum
globulin; antibiotics
Antibiotics; immune
serum globulin
(selected patients)
Antibiotics; immune
serum globulin (IgG
subclass deficiencies
only)
4-Immunoglobulin defi
ciency with increased IgM
(and IgD)
Immune serum
globulin; antibiotics
5-Common variable
immunodeficiency
Immune serum
globulin; antibiotics
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Clinical Features
Therapy
*Chronic mucocutaneous
candidiasis
*Ataxia-telangiectasia
*Wiskott-Aldrich syndrome
*Short-limbed dwarfism
Caltilage hair hypoplasia
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Secondary
immunodeficiency
Modification or suppression of immune system
components by exogenous factors. These are:
Infection
Malignancy
Malnutrition
Drug
Trauma
Ageing -thymus deterioration no new T
cells also affects antibody production.
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Secondary
immunodeficiency
Infections
Bacterial e.g. Mycobacterium leprae
Tuberculoid leprosy: antibody deficiency
Lepromatous leprosy: severe T-cell deficiency
Viral
Measles transient suppression of NK, T & B cells
Herpes (Epstein Barr, HSV,cytomegalovirus)
Influenza
HIV
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Secondary
immunodeficiency
Malignancy
Immunodeficiency caused by lymphoid tumours
e.g
leukaemia, lymphoma, plasma cell dyscrasias
Hodgkins lymphoma: causes classic example
of
T-cell deficiency
Chronic lymphocytic leukaemia: causes classic
example of B-cell deficiency.
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Secondary
immunodeficiency
Drugs
Cytotoxic drugs
e.g. azathioprine and cyclophosphamide kill
tumour cells but also lymphocytes
Corticosteroids
Down regulate lymphocytic genes
Mimic action of glucocorticoids
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Secondary
immunodeficiency
Trauma
Glucocorticoids released naturally in response
to burns,surgery and any other stressor
induce
Immunodeficiency.
Systemic diseases like diabetis mellitus,
nephrotic syndrome
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Secondary
immunodeficiency
Malnutrition
Most common cause of 2 immune deficiency
Protein-Calorie malnutrition can lead to
abnormalities of T cells, B cells & phagocytes
Atrophic and fibrotic thymus
Reduced lymphocyte proliferation in response
to antigens.
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HYPERSENSITIVITY REACTION
A state of altered reactivity in which the body reacts
with an exaggerated immune response to what is
perceived as a foreign substance (exogenous
allergen) or an endogenous antigen.
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REACTION
Type
Prototype Immune
Disorder
Mechanis
ms
Pathologi
c Lesions
Immediate (type
I)
hypersensitivity
Anaphylaxis;
allergies;
bronchial asthma
(atopic forms)
Production of IgE
antibody immediate
release of
vasoactive
amines and other
mediators from
mast cells;
recruitment of
inflammatory
cells (late-phase
reaction
Vascular dilation,
edema,
smooth muscle
contraction,
mucus
production,
inflammation
Autoimmune
hemolytic
anemia;
Goodpasture
FAMUREWA B.A. BChD
syndrome
Production of IgG,
IgM - binds to
antigen on target
cell or tissue phagocytosis or
Cell lysis;
inflammation
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HYPERSENSITIVITY REACTION
Type
Prototype Immune
Patholo
Disorder
Mechanisms gic
Lesions
Immune complexmediated
(type III)
hypersensitivity
Systemic lupus
erythematosus;
some forms of
glomerulonephriti
s; serum
sickness; Arthus
reaction
Necrotizing
vasculitis
(fibrinoid
necrosis);
inflammation
Cell-mediated
(type IV)
hypersensitivity
Contact
dermatitis;
multiple sclerosis;
type I, diabetes;
FAMUREWA B.A. BChD
transplant
Activated T
lymphocytes - release
of cytokines and
macrophage
activation; T cell-
Perivascular
cellular
infiltrates;
edema; cell
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destruction;
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Autoimmune diseases
Involve the loss of normal immune homeostasis
such as that body produces an abnormal
response to its own tissues
Presence of self-reactive T cells, autoantibodies
and inflammation.
Examples Celiac disease, Graves disease,
Addisons disease.
Failure of tolerance or incomplete tolerance
results in autoimmune diseases
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Autoimmune
diseases
Clinical features
1.Commoner in females
2.Onset is middle age(>45years)
3.Family history is frequently positive
4.Raised level of Ig autoantibodies
5.Circulating antibody is frequently detectable in
unaffected family members
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Autoimmune diseases
Clinical features:
6.Presence of circulating autoantibodies to several
tissues
7.Increase risk of other autoimmune diseases
8.Immunoglobulin complement is often detectable
9.Immunosupressive treatment frequently limits
tissue damage
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Autoimmune oral
diseases
Pemphigus vulgaris
mediated by autoantibodies that target the extracellular
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Mucous Membrane
Pemphigoid
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Autoimmune oral
diseases
Epidermolysis bullosa acquisita
Autoimmune form of EB.
Ig G directed against basement membrane
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Autoimmune oral
diseases
Lupus erythematosus
Circulating serum antibodies against cell nucleus
components- antinuclear antibody(ANA).
ANA includes- antihistones, anti-DNA,
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Oral hypersensitivity
disorders
Erythema multiforme
Acquired angioedema
Contact stomatitis
Allergic drug reaction(stomatitis
medicamentosa).
Urticaria (anaphylactic shock)
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Oral hypersensitivity
disorders
Erythema multiforme
Type hypersensitivity reaction
Antigenic peptides form complex with Ig(IgG & IgM).
The immune complex fixes complements(C3)
This initiates leukocytic infiltrates(PMN & Macrophages)
Necrosis of epithelium(skin and or oral mucosa) by
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EM
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Oral hypersensitivity
disorders
Acquired angioedema
Ig E mediated hypersensitivity reaction
There is normal functioning C1 esterase
inhibitor.
Precipitated by :
Drugs- ACE inhibitors, NSAIDS.
Stress(emotional), food,dust,plant,heat/cold
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Oral hypersensitivity
disorders
Contact stomatitis
Synonyms- allergic contact reaction,contact mucositis, stomatitis
venenata
Analogous reation on the skin is contact dermatitis
It is an allergic reaction of the oral mucosa to the exposed allergen. This
could be:
Foods nuts, cinnamon, shellfish, fruits, some vegetables
Metals- amalgam,
Chemicals- acrylic, denture cleansers, ingredients in toothpastes,
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Oral hypersensitivity
disorders
Allergic drug reaction
(stomatitis medicamentosa)
o Allergic oral mucosa reaction to administration
of systemic drugs.
o Drugs- penicilline, sulfa containing drugs
o Mimics lichen planus , Lupus Erythematosus &
Pempigus
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Behets Syndrome
Genetic aspects of Behcets disease
The strongest association of BD is with HLA-
B51.
Factor V Leiden mutation and the thrombotic
tendency in BD.
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Oral malignancies
Tumour Specific Transplantation Antigen (TSTA)-
against TSTA
Immune surveillances: minute tumours arise
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ORAL CANCERS
Abnormalities in cell mediated
immune responses in patients with
head and neck carcinoma
1
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Conclusion
A sound knowledge of the
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Reference
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