1. Chapter 3
Immunity

2. Outline The Acquired Immune Response Antigens
Cellular Involvement in the Immune Response
Major Divisions of the Immune Response
Memory and Immunity
Types of Immunity
Immunopathology
Oral Diseases with Immunologic Pathogenesis
Autoimmune Diseases that Affect the Oral Cavity

3. The Acquired Immune Response
(pg. 82)
Defends the body against injury
Has the capacity to remember and respond more quickly the second time a foreign material enters the body
Works with the inflammatory response and a working repair process
Involves white blood cells, especially lymphocytes and their products

4. Antigens Foreign substances Human cells that have been transformed
(pg. 82)
Foreign substances
Mainly proteins, often microorganisms and their toxins
Human cells that have been transformed
May be tumor cells, or cells infected with viruses

5. Antigens (cont.) Human tissue Autoimmune diseases
Organ transplants, tissue grafts, incompatible blood types during a transfusion
Autoimmune diseases
Tissue from the person’s own body becomes an antigen

6. Cellular Involvement in the Immune Response
B lymphocytes
T lymphocytes
Macrophages
Cytokines

7. Cellular Involvement in the Immune Response (cont.)
(pg. 83)
Cells that are able to recognize and respond to antigen
Derived from precursor cells in bone marrow (stem cells)
20% to 25% of the WBC (white blood cell) population
Two main types
B 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

8. Cellular Involvement in the Immune Response (cont.)

9. B Lymphocytes Mature and reside in lymphoid tissue
(pgs )
Mature and reside in lymphoid tissue
Lymph nodes, tonsils, and other body tissue
B lymphocytes travel to the site of injury when stimulated by antigen
Two main types
Plasma cells
Produce specific antibodies
B memory cell
Retains the memory of previously encountered antigen and will clone itself in the presence of antigen

10. B Lymphocytes (cont.)

11. Plasma Cells
Produce antibodies that are categorized into 5 classes of immunoglobulins, which are carried in blood serum
All have the same basic “Y” structure, but have an area with variable (V) structure at the tips of the Y
The stem of the Y is constant (C) for all 5 types, and links the antibody to other components of the immune response
Immune complex
Antigen combined with antibody

12. T Lymphocytes Travel to the thymus and mature
(pgs. 83, 85)
Travel to the thymus and mature
The thymus is large in an infant, shrinks as the child matures
Several different types of T lymphocytes
Memory cells
T-helper cells
Increase functioning of B lymphocytes
T-suppressor cells
Turn off functioning of B lymphocytes
T-cytotoxic cells
Attack virally infected cells or tumor cells

13. T Lymphocytes (cont.)

14. Macrophages Active in phagocytosis of foreign material
(pg. 84)
Active in phagocytosis of foreign material
Produce cytokines called monokines
Help both B and T lymphocytes
After phagocytosis, they process and present antigen to lymphocytes
This stimulates lymphocytes to travel from lymphoid tissue to the injury site
Amplify the immune response but do not remember the antigen like lymphocytes

15. Cytokines (Cont.)

16. Cytokines (Cont.)
(pgs ) (Table 3-2)
Proteins made by cells that are able to affect the behavior of other cells
Different cytokines have different functions.

17. Major Divisions of the Immune Response
(pgs )
Humoral response
B lymphocytes are the primary cells.
Involves production of antibodies
Cell-mediated response
T lymphocytes are the primary cells.
Lymphocytes may work alone or be assisted by macrophages.
The cell-mediated portion regulates both major responses.

18. Major Divisions of the Immune Response (cont.)

19. Memory 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.

20. Types of Immunity
Passive Immunity
Active Immunity

21. Passive Immunity
(pg. 86)
Using antibodies created by another person to prevent infectious disease
Natural
When antibodies from the mother pass through the placenta to the developing fetus
Acquired
When antibodies are acquired through an injection
Short lived but fast acting

22. Active Immunity Antibodies created by the person themselves (pg. 86)
Natural
Protection conferred following survival from an infectious disease
Acquired
Injection or ingestion of either altered pathogenic microorganisms or products of those microorganisms – immunization with a vaccine

23. Immunopathology The study of immune reactions involved in disease
(pg. 86)
The study of immune reactions involved in disease
The immune system can malfunction and cause tissue damage.
Hypersensitivity
Autoimmune diseases

24. Hypersensitivity (Cont.)
(pgs ) (Table 3-3)
An allergic reaction
An exaggerated response
Tissue destruction occurs as a result of the immune response.
Four main types

25. Hypersensitivity (Cont.)

26. Type 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.

27. Type II Hypersensitivity
(pg. 87)
Cytotoxic type
Antibody 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).

28. Type 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.

29. Type 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

30. Hypersensitivity 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.

31. Autoimmune Diseases Immunologic tolerance Autoimmune disorder (pg. 88)
The body learns to determine self from nonself.
Autoimmune disorder
The recognition mechanism breaks down; some body cells are not tolerated and are treated as foreign antigens.

32. Immunodeficiency An immunopathologic condition (pg. 88)
A deficiency in number, function, or interrelationships of the involved WBC’s and their products
May be congenital or acquired
Infections and tumors may occur as a result of the deficiency.

33. Oral Diseases with Immunologic Pathogenesis
Aphthous ulcers
Urticaria and angioedema
Contact mucositis and dermatitis
Fixed drug eruptions
Erythema multiforme
Lichen planus
Reactive arthritis (Reiter syndrome)
Langerhans cell disease

34. Aphthous Ulcers Painful oral ulcers with an unclear cause (pgs. 88-91)
Occur in about 20% of the population
Trauma is the most common precipitating factor.
May be caused by emotional stress or certain food
May be associated with certain systemic diseases
Thought to have an immunologic pathogenesis
Occur in three forms: minor, major, and herpetiform

35. Minor Aphthous Ulcers Discrete, round or oval ulcers (pg. 89)
Occur on movable mucosa
Up to 1 cm in diameter with a erythematous halo surrounding a yellowish-white fibrin surface
May have single or multiple lesions
May have a prodrome of 1 to 2 days

36. Minor Aphthous Ulcers (cont.)

37. Major Aphthous Ulcers
(pgs )
Larger (>1 cm), deeper, and longer lasting than minor aphthous ulcers
Very painful
Occur in the posterior of the mouth more often than minor aphthous ulcers
May require several weeks to heal
May require a biopsy

38. Major Aphthous Ulcers (cont.)

39. Herpetiform Aphthous Ulcers
(pgs )
Tiny (1 to 2 mm)
Resemble herpes simplex ulcers
Painful, generally occur in groups

40. Diagnosis of Minor Aphthous Ulcers (Cont.)

41. Diagnosis of Minor Aphthous Ulcers (Cont.)
(pgs ) (Table 3-4)
Clinical appearance
Location
Herpetic lesions appear on mucosa fixed to bone, aphthous lesions appear on movable tissue
Clinical history
Aphthous ulcers do not produce systemic signs or symptoms as do herpetic lesions

42. Treatment of Minor Aphthous Ulcers
(pg. 91)
Treatment
There are several OTC medications such as Orabase and Zilactin.
Topical or systemic steroids may help.
Topical anesthetic may help.

43. Urticaria (Hives)
(pg. 91)
Appears as multiple areas of well-demarcated swelling of skin
May have itching (pruritis)
Lesions caused by localized areas of vascular permeability in superficial connective tissue

44. Angioedema
(pg. 91)
Lesions caused by diffuse swelling due to increased permeability of deeper blood vessels
The skin covering the swelling appears normal
Usually do not have itching

45. Urticaria and Angioedema
(pgs )
Often idiopathic cause
May be due to infection, trauma, emotional stress, and certain systemic diseases
May be due to ingested allergens

46. Contact Mucositis and Dermatitis
(pg. 92)
Lesions resulting from contact of an allergen with skin or mucosa
Involves CMI (cell-mediated immunity)
The mucosa initially becomes erythematous and edematous.
Often there is burning and pruritus
Later, the area becomes white and scaly.
Treatment
Topical and/or systemic corticosteroids

47. Contact Mucositis and Dermatitis (cont.)

48. Fixed Drug Eruptions
(pgs )
Lesions that appear in the same site each time a drug is introduced
Generally appear suddenly after a latent period and subside when the drug is discontinued
May be single or multiple slightly raised, reddish patches or clusters of macules on the skin, or sometimes the mucous membranes
May have pain or pruritis

49. Fixed 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.
Treatment
The drug causing the reaction should be identified and discontinued.

50. Erythema Multiforme
(pgs )
Cause is not clear; may be a hypersensitivity reaction
Most commonly occurs in young adults, affects men more commonly than women
Target lesion
Characteristic skin lesion with concentric erythematous rings alternating with normal skin color

51. Erythema Multiforme (cont.)

52. Erythema Multiforme (cont.)
(pgs )
Skin lesions can range from macules to papules to bullae.
Oral lesions are usually ulcers
Frequently form on lateral borders of the tongue
Crusted and bleeding lips are frequently seen.
Gingival involvement is rare.
May be chronic or may have recurrent acute episodes

53. Erythema Multiforme (cont.)

54. Erythema Multiforme (cont.)
(pgs )
Stevens-Johnson syndrome
The most severe form
More extensive and painful oral lesions
Genital mucosa and mucosa of eyes may be involved.
Lips generally are encrusted and bloody.

55. Erythema Multiforme (cont.)
(pg. 93)
Diagnosis
Based on clinical features and by exclusion of other diseases
Treatment and prognosis
Topical or systemic corticosteroids
Eye lesions may lead to blindness.

56. Lichen Planus A benign, chronic disease affecting skin and oral mucosa
(pgs )
A benign, chronic disease affecting skin and oral mucosa
Unknown cause
Lesions have characteristic Wickham striae
Most commonly on buccal mucosa
Lesions may be on the tongue, lips, floor of mouth, and gingiva.
Present in about 1% of the U.S. population
Most common in middle age
Slightly more common in women

57. Lichen Planus (cont.)

58. Types of Lichen Planus Reticular lichen planus
(pgs )
Reticular lichen planus
Most common form
Erosive and bullous lichen planus
Epithelium separates from connective tissue
Desquamative gingivitis can be caused by lichen planus.
Skin lesions
2 to 4 mm papules most commonly in lumber region, flexor surfaces of the wrist, anterior ankle

59. Types of Lichen Planus (cont.)

60. Diagnosis of Lichen Planus
(pgs )
Based on clinical appearance and possibly biopsy
Epithelial atypia and dysplasia may occur in lesions that clinically appear to be lichen planus.
These lesions may be premalignant.

61. Treatment and Prognosis of Lichen Planus
(pg. 96)
A chronic disease
Treated when symptomatic
Regular oral examination and biopsy of suspicious lesions are necessary as these patients may be at increased risk of development of squamous cell carcinoma.

62. Reactive 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 antigen
Skin and mucous membrane lesions may be observed.
May see aphthous ulcers, erythematous lesions, and geographic tonguelike lesions

63. Reactive Arthritis (Reiter Syndrome) (cont.)

64. Reactive Arthritis Diagnosis Treatment and prognosis
Clinical signs and symptoms
HLA-B27 antigenic marker
Treatment and prognosis
Disease lasts for weeks to months.
Recurrent attacks are common.

65. Langerhans Cell Disease (Histiocytosis X)
(pgs )
Includes three entities
Letterer-Siwe disease
Hand-Schuller-Christian disease
Solitary eosinophilic granuloma
All have Langerhans cells and eosinophils.

66. Langerhans Cell Disease (Histiocytosis X) (cont.)

67. Langerhans Cell Disease
A type of macrophage
An immunocompetent cell of the mononuclear phagocyte series and participates in CMI
Treatment
Eosinophilic granuloma is treated by conservative surgical excision.
Low-dose radiation may be used

68. Autoimmune Diseases that Affect the Oral Cavity
Sjögren Syndrome
Systemic Lupus Erythematosus
Pemphigus Vulgaris
Mucous Membrane Pemphigoid
Bullous Pemphigoid
Behçet Syndrome

69. Autoimmune 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.

70. Autoimmune Diseases that Affect the Oral Cavity (cont.)

71. Sjögren Syndrome Affects the salivary and lacrimal glands
(pgs )
Affects the salivary and lacrimal glands
Results in a decrease in saliva and tears causing a dry mouth (xerostomia) and dry eyes (xerophthalmia)
The combination may be called sicca syndrome.

72. Sjögren Syndrome (cont.)
(pg. 99)
May be associated with other autoimmune disorders
Primary Sjögren syndrome – when it occurs alone
Secondary Sjögren syndrome - when it occurs with other autoimmune disorders
Patient may complain of oral discomfort due to dry mouth.
May see loss of filiform and fungiform papillae on the dorsum of the tongue

73. Sjögren Syndrome (cont.)
(pg. 99)
Affects both major and minor salivary glands
Parotid gland enlargement occurs in about 50% of patients.
Biopsy reveals a characteristic appearance.
Major salivary glands
Replacement with lymphocytes and the presence of islands of epithelium called epimyoepithelial islands
Minor salivary glands
Aggregates of lymphocytes surrounding the salivary gland ducts

74. Sjögren Syndrome (cont.)

75. Sjögren 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 phenomenon
20% of these patients will have this disorder affecting fingers and toes
Initial pallor and subsequent cyanosis of skin due to cold or stress
Hyperemia when blood vessels are warmed

76. Sjögren Syndrome (cont.)
90% of these patients have a positive response to rheumatoid factor, an antibody to IgG present in serum
It is an antibody to an antibody.
Other autoantibodies, anti-Sjögren syndrome A, and anti-Sjögren syndrome B are also present.

77. Diagnosis and Management of Sjögren Syndrome
(pg. 100)
Diagnosis is made when two of three components are present.
Xerostomia
Measurement of salivary flow and biopsy can help
Keratoconjunctivitis sicca
Confirmed with eye examination
Rheumatoid arthritis
For 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.

78. Diagnosis and Management of Sjögren Syndrome (cont.)

79. Treatment of Sjögren Syndrome
(pg. 100)
Symptomatic
Nonsteroidal antiinflammatory agents for arthritis
May need corticosteroids and immunosuppressive drugs for severe cases
Saliva substitutes for xerostomia
Humidifier, sugarless gum, or lozenges
Pilocarpine
Glasses and/or artificial tears to protect eyes

80. Systemic Lupus Erythematosus (SLE)
(pgs )
An acute and chronic inflammatory autoimmune disease
No known cause
Affects women 8 times more frequently than men, predominantly during childbearing years
Three times more frequent in black women than in white women

81. Systemic Lupus Erythematosus (SLE) (cont.)
A syndrome with a wide range of disease activity
Usually chronic and progressive
Periods of remission and exacerbation
Autoantibodies to DNA are present in serum
May have a genetic component

82. Clinical Features of Systemic Lupus Erythematosus (SLE)
(pgs )
Skin lesions occur in 85% of individuals
“Butterfly” rash on bridge of nose
May be erythematous lesions on fingertips
Arthritis and arthralgia are common.
Oral lesions accompany skin lesions in about 25% of patients with discoid LE.
Erythematous plaques or erosions
May have white striae; resemble lichen planus but are less symmetric

83. Clinical Features of Systemic Lupus Erythematosus (SLE) (cont.)

84. Diagnosis of Systemic Lupus Erythematosus (SLE)
(pgs )
Usually based on multiorgan involvement and presence of antinuclear antibodies in serum
Inflammatory infiltrate is around blood vessels in connective tissue.

85. Treatment and Prognosis of Systemic Lupus Erythematosus (SLE)
Aspirin and antiinflammatory drugs for mild signs and symptoms
Hydroxychloroquine and corticosteroids along with immunosuppressive agents may be used.
The text recommends consultation with the patient’s physician before initiating dental treatment.

86. Pemphigus Vulgaris
(pgs )
A severe, progressive autoimmune disease affecting skin and mucous membranes
Characterized by intraepithelial blister formation resulting from acantholysis, a breakdown of cellular adhesion between epithelial cells
Genetic and ethnic factors have been reported.
Often seen in Ashkenazic Jews

87. Pemphigus Vulgaris (cont.)
(pg. 103)
Oral lesions
The first signs of disease occur in the oral cavity in more than 50% of cases.
May be shallow ulcers, to fragile vesicles, to bullae
Nikolsky sign
Rubbing with a finger can produce a bullae.

88. Pemphigus Vulgaris (cont.)

89. Pemphigus Vulgaris (cont.)
(pgs )
Skin lesions
Erythema, bullae, erosions, ulcers
Microscopic appearance
Acantholytic cells
The loss of attachment between epithelial cells leads to cells that appear rounded.
Tzanck cells

90. Diagnosis of Pemphigus Vulgaris
Made by biopsy and microscopic examination
Direct immunofluorescence
Identifies autoantibodies present in tissue
Indirect immunofluorecence
The patient’s serum is used to detect circulating autoantibodies.

91. Treatment and Prognosis of Pemphigus Vulgaris
High doses of corticosteroids
May include immunosuppressive drugs
Mortality rate of 8% to 10% in 5 years is related to complications of corticosteroid treatment.

92. Mucous Membrane Pemphigoid (Cicatricial Pemphigoid) (BMMP)
(pgs )
A chronic autoimmune disease
Affects oral mucosa, conjunctiva, genital mucosa, and skin
Not as severe as pemphigus vulgaris
Gingival lesions have been called desquamative gingivitis, but this may be seen with lichen planus and pemphigus as well.
Will see positive Nikolsky sign

93. Mucous Membrane Pemphigoid (Cicatricial Pemphigoid) (BMMP) (cont.)

94. Diagnosis of Mucous Membrane Pemphigoid
(pg. 104)
Made by biopsy and histologic examination
No degeneration of epithelium occurs
An inflammatory infiltrate, usually with predominant plasma cells and eosinophils, is seen in connective tissue.

95. Treatment and Prognosis of Mucous Membrane Pemphigoid
A chronic disease with a benign course
Topical corticosteroid for mild cases
Systemic corticosteroids may be required for more severe cases.
Eye lesions can lead to eye damage.

96. Bullous 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.
Treatment
Systemic corticosteroids and nonsteroidal antiinflammatory drugs

97. Behçet Syndrome A chronic, recurrent autoimmune disease
(pg. 105)
A chronic, recurrent autoimmune disease
Primarily oral ulcers, genital ulcers, ocular inflammation
No sex predilection; mean onset is 30 years
Autoantibodies to human mucosa may be found.
Oral ulcers are similar in appearance to aphthous ulcers.

98. Behçet Syndrome (cont.)

99. Diagnosis 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.

100. Treatment and Prognosis of Behçet Syndrome
(pg. 105)
Systemic and topical corticosteroids
Chlorambucil is used for ocular lesions.

101. Discussion 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?