2Outline The Acquired Immune Response Antigens Cellular Involvement in the Immune ResponseMajor Divisions of the Immune ResponseMemory and ImmunityTypes of ImmunityImmunopathologyOral Diseases with Immunologic PathogenesisAutoimmune Diseases that Affect the Oral Cavity
3The Acquired Immune Response (pg. 82)Defends the body against injuryHas the capacity to remember and respond more quickly the second time a foreign material enters the bodyWorks with the inflammatory response and a working repair processInvolves white blood cells, especially lymphocytes and their products
4Antigens Foreign substances Human cells that have been transformed (pg. 82)Foreign substancesMainly proteins, often microorganisms and their toxinsHuman cells that have been transformedMay be tumor cells, or cells infected with viruses
5Antigens (cont.) Human tissue Autoimmune diseases Organ transplants, tissue grafts, incompatible blood types during a transfusionAutoimmune diseasesTissue from the person’s own body becomes an antigen
6Cellular Involvement in the Immune Response B lymphocytesT lymphocytesMacrophagesCytokines
7Cellular Involvement in the Immune Response (cont.) (pg. 83)Cells that are able to recognize and respond to antigenDerived from precursor cells in bone marrow (stem cells)20% to 25% of the WBC (white blood cell) populationTwo main typesB lymphocytes (B cells)T lymphocytes (T cells)Also there are natural killer cells (NK cells)Can destroy cells recognized as foreign without recognizing specific antigens
8Cellular Involvement in the Immune Response (cont.)
9B Lymphocytes Mature and reside in lymphoid tissue (pgs )Mature and reside in lymphoid tissueLymph nodes, tonsils, and other body tissueB lymphocytes travel to the site of injury when stimulated by antigenTwo main typesPlasma cellsProduce specific antibodiesB memory cellRetains the memory of previously encountered antigen and will clone itself in the presence of antigen
11Plasma CellsProduce antibodies that are categorized into 5 classes of immunoglobulins, which are carried in blood serumAll have the same basic “Y” structure, but have an area with variable (V) structure at the tips of the YThe stem of the Y is constant (C) for all 5 types, and links the antibody to other components of the immune responseImmune complexAntigen combined with antibody
12T Lymphocytes Travel to the thymus and mature (pgs. 83, 85)Travel to the thymus and matureThe thymus is large in an infant, shrinks as the child maturesSeveral different types of T lymphocytesMemory cellsT-helper cellsIncrease functioning of B lymphocytesT-suppressor cellsTurn off functioning of B lymphocytesT-cytotoxic cellsAttack virally infected cells or tumor cells
14Macrophages Active in phagocytosis of foreign material (pg. 84)Active in phagocytosis of foreign materialProduce cytokines called monokinesHelp both B and T lymphocytesAfter phagocytosis, they process and present antigen to lymphocytesThis stimulates lymphocytes to travel from lymphoid tissue to the injury siteAmplify the immune response but do not remember the antigen like lymphocytes
16Cytokines (Cont.)(pgs ) (Table 3-2)Proteins made by cells that are able to affect the behavior of other cellsDifferent cytokines have different functions.
17Major Divisions of the Immune Response (pgs )Humoral responseB lymphocytes are the primary cells.Involves production of antibodiesCell-mediated responseT lymphocytes are the primary cells.Lymphocytes may work alone or be assisted by macrophages.The cell-mediated portion regulates both major responses.
19Memory and Immunity(pg. 86)The immune system has memory; the inflammatory system does not.Some lymphocytes retain memory of an antigen after an initial encounter.This means the immune response will be faster and stronger the next time an antigen enters the body.The retained memory is called immunity.
20Types of ImmunityPassive ImmunityActive Immunity
21Passive Immunity(pg. 86)Using antibodies created by another person to prevent infectious diseaseNaturalWhen antibodies from the mother pass through the placenta to the developing fetusAcquiredWhen antibodies are acquired through an injectionShort lived but fast acting
22Active Immunity Antibodies created by the person themselves (pg. 86) NaturalProtection conferred following survival from an infectious diseaseAcquiredInjection or ingestion of either altered pathogenic microorganisms or products of those microorganisms – immunization with a vaccine
23Immunopathology The study of immune reactions involved in disease (pg. 86)The study of immune reactions involved in diseaseThe immune system can malfunction and cause tissue damage.HypersensitivityAutoimmune diseases
24Hypersensitivity (Cont.) (pgs ) (Table 3-3)An allergic reactionAn exaggerated responseTissue destruction occurs as a result of the immune response.Four main types
26Type I Hypersensitivity (pg. 87)Immediate (anaphylactic type)The reaction occurs within minutes after exposure to an antigen.Plasma cells produce IgE.IgE causes mast cells to release histamine, causing increased dilation and permeability of blood vessels and constricting smooth muscle in bronchioles of the lungs.The reaction may range from hay fever to asthma and life-threatening anaphylaxis.
27Type II Hypersensitivity (pg. 87)Cytotoxic typeAntibody combines with an antigen bound to the surface of tissue cells, usually a circulating RBC (red blood cell).Activated complement components, IgG and IgM antibodies in blood, participate in this type of hypersensitivity reaction.This destroys the tissue that has the antigens on the surface of its cells (e.g., Rh incompatibility).
28Type III Hypersensitivity (pg. 87)Immune complex type (serum sickness)Immune complexes are formed between microorganisms and antibody in circulating blood.These complexes leave the blood and are deposited in body tissues, where they cause an acute inflammatory response.Tissue destruction occurs following phagocytosis by neutrophils.
29Type IV Hypersensitivity (pg. 87)Cell-mediated type (delayed)T lymphocytes that previously have been introduced to an antigen cause damage to tissue cells or recruit other cells.Responsible for the rejection of tissue grafts and transplanted organs
30Hypersensitivity to Drugs (pgs )Drugs can act as antigens.Topical administration may cause a greater number of reactions than oral or parenteral routes.But the parenteral route may cause a more widespread and severe reaction.
31Autoimmune Diseases Immunologic tolerance Autoimmune disorder (pg. 88) The body learns to determine self from nonself.Autoimmune disorderThe recognition mechanism breaks down; some body cells are not tolerated and are treated as foreign antigens.
32Immunodeficiency An immunopathologic condition (pg. 88) A deficiency in number, function, or interrelationships of the involved WBC’s and their productsMay be congenital or acquiredInfections and tumors may occur as a result of the deficiency.
33Oral Diseases with Immunologic Pathogenesis Aphthous ulcersUrticaria and angioedemaContact mucositis and dermatitisFixed drug eruptionsErythema multiformeLichen planusReactive arthritis (Reiter syndrome)Langerhans cell disease
34Aphthous Ulcers Painful oral ulcers with an unclear cause (pgs. 88-91) Occur in about 20% of the populationTrauma is the most common precipitating factor.May be caused by emotional stress or certain foodMay be associated with certain systemic diseasesThought to have an immunologic pathogenesisOccur in three forms: minor, major, and herpetiform
35Minor Aphthous Ulcers Discrete, round or oval ulcers (pg. 89) Occur on movable mucosaUp to 1 cm in diameter with a erythematous halo surrounding a yellowish-white fibrin surfaceMay have single or multiple lesionsMay have a prodrome of 1 to 2 days
37Major Aphthous Ulcers(pgs )Larger (>1 cm), deeper, and longer lasting than minor aphthous ulcersVery painfulOccur in the posterior of the mouth more often than minor aphthous ulcersMay require several weeks to healMay require a biopsy
41Diagnosis of Minor Aphthous Ulcers (Cont.) (pgs ) (Table 3-4)Clinical appearanceLocationHerpetic lesions appear on mucosa fixed to bone, aphthous lesions appear on movable tissueClinical historyAphthous ulcers do not produce systemic signs or symptoms as do herpetic lesions
42Treatment of Minor Aphthous Ulcers (pg. 91)TreatmentThere are several OTC medications such as Orabase and Zilactin.Topical or systemic steroids may help.Topical anesthetic may help.
43Urticaria (Hives)(pg. 91)Appears as multiple areas of well-demarcated swelling of skinMay have itching (pruritis)Lesions caused by localized areas of vascular permeability in superficial connective tissue
44Angioedema(pg. 91)Lesions caused by diffuse swelling due to increased permeability of deeper blood vesselsThe skin covering the swelling appears normalUsually do not have itching
45Urticaria and Angioedema (pgs )Often idiopathic causeMay be due to infection, trauma, emotional stress, and certain systemic diseasesMay be due to ingested allergens
46Contact Mucositis and Dermatitis (pg. 92)Lesions resulting from contact of an allergen with skin or mucosaInvolves CMI (cell-mediated immunity)The mucosa initially becomes erythematous and edematous.Often there is burning and pruritusLater, the area becomes white and scaly.TreatmentTopical and/or systemic corticosteroids
48Fixed Drug Eruptions(pgs )Lesions that appear in the same site each time a drug is introducedGenerally appear suddenly after a latent period and subside when the drug is discontinuedMay be single or multiple slightly raised, reddish patches or clusters of macules on the skin, or sometimes the mucous membranesMay have pain or pruritis
49Fixed Drug Eruptions (cont.) A type of allergic reaction (Type III)Immune complexes are deposited along the endothelial walls of blood vessels.Inflammation causes vasculitis with damage to the vessel wall.This creates erythema and edema in superficial layers of skin or mucosa.TreatmentThe drug causing the reaction should be identified and discontinued.
50Erythema Multiforme(pgs )Cause is not clear; may be a hypersensitivity reactionMost commonly occurs in young adults, affects men more commonly than womenTarget lesionCharacteristic skin lesion with concentric erythematous rings alternating with normal skin color
52Erythema Multiforme (cont.) (pgs )Skin lesions can range from macules to papules to bullae.Oral lesions are usually ulcersFrequently form on lateral borders of the tongueCrusted and bleeding lips are frequently seen.Gingival involvement is rare.May be chronic or may have recurrent acute episodes
54Erythema Multiforme (cont.) (pgs )Stevens-Johnson syndromeThe most severe formMore extensive and painful oral lesionsGenital mucosa and mucosa of eyes may be involved.Lips generally are encrusted and bloody.
55Erythema Multiforme (cont.) (pg. 93)DiagnosisBased on clinical features and by exclusion of other diseasesTreatment and prognosisTopical or systemic corticosteroidsEye lesions may lead to blindness.
56Lichen Planus A benign, chronic disease affecting skin and oral mucosa (pgs )A benign, chronic disease affecting skin and oral mucosaUnknown causeLesions have characteristic Wickham striaeMost commonly on buccal mucosaLesions may be on the tongue, lips, floor of mouth, and gingiva.Present in about 1% of the U.S. populationMost common in middle ageSlightly more common in women
58Types of Lichen Planus Reticular lichen planus (pgs )Reticular lichen planusMost common formErosive and bullous lichen planusEpithelium separates from connective tissueDesquamative gingivitis can be caused by lichen planus.Skin lesions2 to 4 mm papules most commonly in lumber region, flexor surfaces of the wrist, anterior ankle
60Diagnosis of Lichen Planus (pgs )Based on clinical appearance and possibly biopsyEpithelial atypia and dysplasia may occur in lesions that clinically appear to be lichen planus.These lesions may be premalignant.
61Treatment and Prognosis of Lichen Planus (pg. 96)A chronic diseaseTreated when symptomaticRegular oral examination and biopsy of suspicious lesions are necessary as these patients may be at increased risk of development of squamous cell carcinoma.
62Reactive Arthritis (Reiter Syndrome) (pgs )Classic syndrome includes arthritis, urethritis, and conjunctivitis, but all components may not be present.An antigenic marker called HLA-B27 is present in most patients, meaning there may be a genetic influence.Probably an abnormal immune response to a microbial antigenSkin and mucous membrane lesions may be observed.May see aphthous ulcers, erythematous lesions, and geographic tonguelike lesions
67Langerhans Cell Disease A type of macrophageAn immunocompetent cell of the mononuclear phagocyte series and participates in CMITreatmentEosinophilic granuloma is treated by conservative surgical excision.Low-dose radiation may be used
68Autoimmune Diseases that Affect the Oral Cavity Sjögren SyndromeSystemic Lupus ErythematosusPemphigus VulgarisMucous Membrane PemphigoidBullous PemphigoidBehçet Syndrome
69Autoimmune Diseases that Affect the Oral Cavity (cont.) (pgs ) (Table 3-5)Several autoimmune diseases affect the oral cavity.The immune system treats the person’s own cells and tissues as antigens.
70Autoimmune Diseases that Affect the Oral Cavity (cont.)
71Sjögren Syndrome Affects the salivary and lacrimal glands (pgs )Affects the salivary and lacrimal glandsResults in a decrease in saliva and tears causing a dry mouth (xerostomia) and dry eyes (xerophthalmia)The combination may be called sicca syndrome.
72Sjögren Syndrome (cont.) (pg. 99)May be associated with other autoimmune disordersPrimary Sjögren syndrome – when it occurs aloneSecondary Sjögren syndrome - when it occurs with other autoimmune disordersPatient may complain of oral discomfort due to dry mouth.May see loss of filiform and fungiform papillae on the dorsum of the tongue
73Sjögren Syndrome (cont.) (pg. 99)Affects both major and minor salivary glandsParotid gland enlargement occurs in about 50% of patients.Biopsy reveals a characteristic appearance.Major salivary glandsReplacement with lymphocytes and the presence of islands of epithelium called epimyoepithelial islandsMinor salivary glandsAggregates of lymphocytes surrounding the salivary gland ducts
75Sjögren Syndrome (cont.) Patient may complain of burning and itching of eyes and photophobia.Severe eye involvement may lead to ulceration and opacification of the eyes.Raynaud phenomenon20% of these patients will have this disorder affecting fingers and toesInitial pallor and subsequent cyanosis of skin due to cold or stressHyperemia when blood vessels are warmed
76Sjögren Syndrome (cont.) 90% of these patients have a positive response to rheumatoid factor, an antibody to IgG present in serumIt is an antibody to an antibody.Other autoantibodies, anti-Sjögren syndrome A, and anti-Sjögren syndrome B are also present.
77Diagnosis and Management of Sjögren Syndrome (pg. 100)Diagnosis is made when two of three components are present.XerostomiaMeasurement of salivary flow and biopsy can helpKeratoconjunctivitis siccaConfirmed with eye examinationRheumatoid arthritisFor most patients, the course of the disease is chronic and benign but these patients are at risk for the development of other more serious diseases.
78Diagnosis and Management of Sjögren Syndrome (cont.)
79Treatment of Sjögren Syndrome (pg. 100)SymptomaticNonsteroidal antiinflammatory agents for arthritisMay need corticosteroids and immunosuppressive drugs for severe casesSaliva substitutes for xerostomiaHumidifier, sugarless gum, or lozengesPilocarpineGlasses and/or artificial tears to protect eyes
80Systemic Lupus Erythematosus (SLE) (pgs )An acute and chronic inflammatory autoimmune diseaseNo known causeAffects women 8 times more frequently than men, predominantly during childbearing yearsThree times more frequent in black women than in white women
81Systemic Lupus Erythematosus (SLE) (cont.) A syndrome with a wide range of disease activityUsually chronic and progressivePeriods of remission and exacerbationAutoantibodies to DNA are present in serumMay have a genetic component
82Clinical Features of Systemic Lupus Erythematosus (SLE) (pgs )Skin lesions occur in 85% of individuals“Butterfly” rash on bridge of noseMay be erythematous lesions on fingertipsArthritis and arthralgia are common.Oral lesions accompany skin lesions in about 25% of patients with discoid LE.Erythematous plaques or erosionsMay have white striae; resemble lichen planus but are less symmetric
83Clinical Features of Systemic Lupus Erythematosus (SLE) (cont.)
84Diagnosis of Systemic Lupus Erythematosus (SLE) (pgs )Usually based on multiorgan involvement and presence of antinuclear antibodies in serumInflammatory infiltrate is around blood vessels in connective tissue.
85Treatment and Prognosis of Systemic Lupus Erythematosus (SLE) Aspirin and antiinflammatory drugs for mild signs and symptomsHydroxychloroquine and corticosteroids along with immunosuppressive agents may be used.The text recommends consultation with the patient’s physician before initiating dental treatment.
86Pemphigus Vulgaris(pgs )A severe, progressive autoimmune disease affecting skin and mucous membranesCharacterized by intraepithelial blister formation resulting from acantholysis, a breakdown of cellular adhesion between epithelial cellsGenetic and ethnic factors have been reported.Often seen in Ashkenazic Jews
87Pemphigus Vulgaris (cont.) (pg. 103)Oral lesionsThe first signs of disease occur in the oral cavity in more than 50% of cases.May be shallow ulcers, to fragile vesicles, to bullaeNikolsky signRubbing with a finger can produce a bullae.
89Pemphigus Vulgaris (cont.) (pgs )Skin lesionsErythema, bullae, erosions, ulcersMicroscopic appearanceAcantholytic cellsThe loss of attachment between epithelial cells leads to cells that appear rounded.Tzanck cells
90Diagnosis of Pemphigus Vulgaris Made by biopsy and microscopic examinationDirect immunofluorescenceIdentifies autoantibodies present in tissueIndirect immunofluorecenceThe patient’s serum is used to detect circulating autoantibodies.
91Treatment and Prognosis of Pemphigus Vulgaris High doses of corticosteroidsMay include immunosuppressive drugsMortality rate of 8% to 10% in 5 years is related to complications of corticosteroid treatment.
92Mucous Membrane Pemphigoid (Cicatricial Pemphigoid) (BMMP) (pgs )A chronic autoimmune diseaseAffects oral mucosa, conjunctiva, genital mucosa, and skinNot as severe as pemphigus vulgarisGingival lesions have been called desquamative gingivitis, but this may be seen with lichen planus and pemphigus as well.Will see positive Nikolsky sign
94Diagnosis of Mucous Membrane Pemphigoid (pg. 104)Made by biopsy and histologic examinationNo degeneration of epithelium occursAn inflammatory infiltrate, usually with predominant plasma cells and eosinophils, is seen in connective tissue.
95Treatment and Prognosis of Mucous Membrane Pemphigoid A chronic disease with a benign courseTopical corticosteroid for mild casesSystemic corticosteroids may be required for more severe cases.Eye lesions can lead to eye damage.
96Bullous Pemphigoid(pg. 105)Some investigators believe bullous and mucous membrane pemphigoid are variants of a single disease, but 80% of these patients are older than 60.Oral lesions are less common than in cicatricial pemphigoid.TreatmentSystemic corticosteroids and nonsteroidal antiinflammatory drugs
97Behçet Syndrome A chronic, recurrent autoimmune disease (pg. 105)A chronic, recurrent autoimmune diseasePrimarily oral ulcers, genital ulcers, ocular inflammationNo sex predilection; mean onset is 30 yearsAutoantibodies to human mucosa may be found.Oral ulcers are similar in appearance to aphthous ulcers.
99Diagnosis of Behçet Syndrome Requires that two of three types of lesions (oral, genital, and ocular) be present.A pustular lesion after needle puncture suggests Behçet syndrome.
100Treatment and Prognosis of Behçet Syndrome (pg. 105)Systemic and topical corticosteroidsChlorambucil is used for ocular lesions.
101Discussion Questions What is an autoimmune disorder? What is the difference between an antigen and an antibody?What are the differences between active and passive immunity?What oral diseases have an immunologic pathogenesis?What are the oral symptoms of Sjögren syndrome?What are differences between pemphigus and pemphigoid?