Immunity

Learning Objectives
Lesson 3.1: Immune Response,
Immunity Types, and Hypersensitivity
1. Define each of the words in the vocabulary list for this
chapter.
2. Describe the differences between an immune response and
an inflammatory response.
3. With regard to cellular involvement in the immune response:
• List the three main types of lymphocytes and their origins.
• Describe the different types of B-cell lymphocytes as well as their
formation of plasma cells in the production of antibodies.
• List and describe the different types of T-cell lymphocytes and their
functions.
• Describe the functions of natural killer cells.

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Learning Objectives
Lesson 3.1: Immune Response,
Immunity Types, and Hypersensitivity
4. Describe the origin of macrophages and dendritic cells
and list their activities in the immune response.
5. Describe where cytokines are produced and the roles
they play in the immune response.
6. Describe the differences between passive and active
immunity and give an example for each type of immunity.
7. Define herd immunity and describe how it may be
achieved.

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Learning Objectives
Lesson 3.1: Immune Response,
Immunity Types, and Hypersensitivity
8. Describe the differences between humoral immunity and
cell-mediated immunity and include the cells involved in
each.
9. List and describe four types of hypersensitivity reactions
and give an example for each type of hypersensitivity.

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Acquired Immune
Response
•Defends against injury
•Focuses on foreign substances, microorganisms
•The immune system differs from the inflammatory
response in that it has the capacity for memory and
responds more quickly to a foreign substance if
encountered again.
•Complex network of WBCs (lymphocytes)
•May result in an increased level of injury (tissue damage)
and disease
Acquired Immune
Response (Cont.)

From McCance K, Huether S: Pathophysiology, ed 7, St. Louis, Mosby/Elsevier, 2014.

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Antigens
Foreign substances versus body
◦ The body reacts to the introduction of an antigen in various ways

Components of self as antigen(immunogens):

◦ Tumor cells
◦ Cells infected with viruses
◦ Organ transplant
◦ Tissue graft
◦ Incompatible blood transfusion
◦ Cells of own body: autoimmune disease

Nonrecognition of foreign material as antigen: autoimmune disease

Overreaction to antigens: hypersensitivity
Major Histocompatibility
Complexes (MHC)
Major histocompatibility complexes (MHC)
Identify host cells as “self”

“Coding” process

Changes trigger immune system response.

Cell destruction

Organ and tissue transplantation

Cellular Involvement in
the
Immune Response
Cytokines
Lymphocytes - the primary WBCs involved
◦ B-cell lymphocytes
◦ T-cell lymphocytes
◦ Natural killer (NK) cells

Macrophages
Dendritic cells

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the
Immune Response
(Cont.)

10
B-Cell Lymphocytes
Develop from stem cells in bone marrow
Mature and reside in lymphoid tissue
◦ Lymph nodes, tonsils, and other body tissue

B cells travel to the site of injury when stimulated

by antigen
Two main types:
◦ Plasma cell: Produces specific antibodies
◦ B-memory cell: Retains the memory of previously
encountered antigen and will clone itself in the presence
of antigen
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B-Cell Lymphocytes:
Plasma Cells
Round, pinwheel-shaped nucleus
with visible cytoplasm
The plasma cell is a fully
differentiated descendant of B-cell
lymphocytes.
Produce and release a protein
(antibody) in response to presence
of antigen
Circulating antibodies:
Immunoglobulins (Ig)

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B-Cell Lymphocytes:
Plasma Cells (Cont.)
Five different types of immunoglobulins, all
variations of the same structure:
◦ IgA
◦ IgD
◦ IgE
◦ IgG
◦ IgM

Antibody titer: Level of a specific antibody

Immune complex: Antibody + antigen

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Known
Immunoglobulins
IgA Has two subgroups: serous in the blood and secretory in the
saliva and other secretions; aids in defense against
proliferation of microorganisms in body fluids; secreted by
plasma cells; found in breast milk; activation of alternative
pathway of complement system.

IgD Functions in the activation of B lymphocytes

IgE (important in inflammatory response) Involved in hypersensitivity reactions since it can bind to mast
cells and basophils and bring about the release of biochemical
mediators such as histamine; secreted by plasma cells;
anaphylactic reactions;

IgG (80% of circulating antibodies) Major antibody in blood serum; can pass the placental barrier
and forms the first passive immunity for the newborn; viruses,
bacteria, toxins; complement system

IgM (largest) Involved in early immune responses because of its involvement

with IgD in the activation of B cell lymphocytes; most efficient
at activation of complement system
T-Cell Lymphocytes
Develop from bone marrow stem cells
Travel to the thymus and mature
Types of T-cell lymphocytes
◦ Memory cells
◦ T-helper cells: Increase functioning of B cells
◦ T-suppressor cells: Turn off functioning of B cells
◦ T-cytotoxic cells: Attack virally infected cells or tumor cells

The T cell can be distinguished from other lymphocytes by

the presence of a special receptor on its cell surface that is
called the T-cell receptor (TCR).

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T-Cell Lymphocytes
(Cont.)

16
T-Cell Lymphocytes:
Function Review
Increase the function of B cells: Enhancing the
antibody response
◦ Similar to B-memory cells, the T-memory cell retains a
memory of the antigen.
Carry the CD8 marker
Active in surveillance against virally infected cells
Directly attack virally infected and neoplastic cells
Start, regulate, and coordinate the overall immune
response

17
Natural Killer (NK) Cells
Destroy foreign cells
Usually located within the
microcirculation, and not in the outlying
tissue.
Active against viruses and cancer cells
Activity can be abnormal as in HIV
infection

18
Macrophages
Accessory cells in immune response
Located in connective tissue (CT) during inflammation
The macrophage is a large tissue-bound mononuclear phagocyte
derived from monocytes circulating in the blood.
Functions
◦ Phagocytosis
◦ Assist B cells and T cells
◦ Messenger between inflammatory response and immune response
◦ Activating factor: Produce and secrete lysosomal enzymes
◦ Amplify the immune response but do not have memory of the encountered
antigen

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Dendritic Cells (DCs)
•Type of WBC found on skin, on mucosa, and in blood
•Main function is to process antigenic material and present it
on its surface to other cells of the immune system.
•The DC is present in tissue that is in contact with the
external environment.
•Antigen-presenting cells (APCs): Process antigenic material
and present it to other immune system cells
•Messenger between innate immunity and acquired
immunity
•Langerhans cell: Specialized dendritic cell

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Cytokines in the
Immune Response
Immunomodulating agents: Alter the immune response
Cytokines are produced by the cells of the immune system and play a
prominent role in the activation of the immune response.
Different cytokines have differing functions within the immune response;
refer to Table 3.2.
Communication system
◦ Interleukins
◦ Macrophage chemotactic factor
◦ Migration inhibitory factor
◦ Macrophage-activating factor
◦ Lymphotoxin
◦ Interferons
◦ Tumor necrosis factor

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 Cytokines and their
functions
Cytokine Function

Interleukins (ILs) Stimulates leukocyte proliferation and other functions

Macrophage chemotactic factor

(MCF)
Stimulates macrophage emigration

Migration inhibitory factor

Inhibits macrophage activity
(MIF)
Macrophage-activating Activates macrophages to produce and secrete lysosomal
factor (MAF) enzymes

Lymphotoxin (LT) Destroys fibroblasts

Various functions involving leukocytes, fibroblasts, and

Interferons (IFNs)
endothelial cells

Tumor necrosis factor (TNF) Various functions involving leukocytes and fibroblasts
Major Divisions of the
Immune Response
Humoral immunity
Cell-mediated immunity

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Major Divisions of the
Immune Response
(Cont.)
Humoral immunity
◦ Antibody-mediated immunity
◦ Production of antibodies
◦ Protection against bacteria and viruses
◦ B cells are the primary cells
Cell-mediated immunity
◦ Cellular immunity
◦ T cells are the primary cells
◦ Regulates both major immune responses

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Types of Immunity
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
◦ There are two types of immunity: passive and
active

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Types of Immunity
(Cont.)
Passive immunity: Using antibodies created by another person to prevent
infectious disease
◦ Natural: Mother to fetus
◦ Acquired: Injection of plasma Immunoglobulins

Active immunity: Antibodies created by the person themselves

◦ Natural: Microorganism causes the disease
◦ Acquired: Immunization, vaccination, booster
◦ Killed-type vaccine
◦ Live-attenuated vaccine
◦ An alternative approach to vaccination that is being studied is known
as DNA vaccination and involves genetically engineering a vaccine
from an infectious agent’s DNA.

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Herd Immunity
◦ Type of indirect protection from an infectious disease that
occurs when a large percentage of the population
becomes immune to infection
◦ Can be achieved through vaccination or through exposure
to and recovery from infection
◦ Approximately 70% to 90% of a population needs
immunity to achieve
◦ When an individual gains immunity, they are no longer
able to contribute to disease transmission.
◦ The concept of herd immunity has recently gained
renewed attention in relation to the novel coronavirus
disease 19 (COVID-19) pandemic of 2020 (see Chapter 4).

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Major Divisions of the
Immune Response
These two divisions of the immune response differ in their reaction to
an antigen.
Humoral immunity
◦ Antibody-mediated immunity
◦ Production of antibodies
◦ Protection against bacteria and viruses
◦ B cells are the primary cells

Cell-mediated immunity
◦ Cellular immunity
◦ T cells are the primary cells
◦ Regulates both major immune responses

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Immunopathology
The study of immune reactions involved in disease;
the study of diseases caused by the malfunctioning
of the immune system
The immune response helps defend the body
against disease-producing antigens, but it can also
malfunction and cause tissue damage, resulting in
the production of lesions.
◦ Hypersensitivity
◦ Autoimmune diseases
◦ Immunodeficiency

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Hypersensitivity
Antigens that induce a hypersensitivity or allergic response are
also called allergens

Type of Reaction Examples

Type I (anaphylactic) Hay fever, asthma, anaphylaxis

Type II
Autoimmune hemolytic anemia
(cytotoxic)

Type III
Autoimmune disease (SLE)
(immune complex)

Type IV
Granulomatous disease (TB)
(cell mediated)
Type I Hypersensitivity
Immediate (anaphylactic type)
◦ The reaction occurs within minutes of 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, urticaria,
to asthma and life-threatening anaphylaxis

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Type I Hypersensitivity
Plasma
Previously cells
Produce IgE
encountered
Antigen
ex. Pollen or latex

Constrictio
IgE causes
n of
Mast Cells
bronchiole
to release
smooth
histamine
muscle

Increase
b.v. dilation
And
permeabilit
y
Urticaria
Superficial
Pruritic
May be localized or
generalized
Angioedema
Swelling

Severe manifestations
may impair breathing.

Affects other body parts

Clinically similar lesions

may not have an allergic
etiology.

Hereditary angioedema

TX antihistamines
Latex Hypersensitivity
Etiology: contact with natural rubber latex (NRL) proteins

Epidemiology: 1 to 5% of general population, at 17% of health care

workers

Pathogenesis: type I hypersensitivity

Contact with skin or mucus membranes

Extraoral: reactions are always systemic.

Intraoral: angioedema, burning, pruritus

Dental implications: name some of the implications

TX and prognosis: depends on severity, reactions can be fatal

Type II Hypersensitivity
Cytotoxic type
◦ Antibody combines with an antigen bound to the surface of tissue cells,
usually a circulating red blood cell (RBC)

Activated complement components and 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)

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Type II Hypersensitivity
Antibody +
antigen
Bind to surface
of IgG and
Tissue cells Tissue IgM
destructio Antibodies
n in
blood
react
Allergic Contact Dermatitis
(ACD)
ACD from a Henna Tattoo
ACD Associated with Latex Gloves
More common than type I
NRL
Not allergic to NRL but to
chemicals used in
producing glove
5 to 20% of DHCW
Repeated exposures
cause dry, cracked,
irritated skin.
Avoid contact with NRL.
Irritant Contact Dermatitis
Not an allergic
reaction
Inflammatory
reaction initiated
by caustic
chemicals or
mechanical skin
irritation
Type III Hypersensitivity
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 after phagocytosis by
neutrophils
◦ Neutrophils are attracted to the tissue in which the
complexes have been deposited.

42
Type IV Hypersensitivity
Cell-mediated type (delayed)
◦ T cells that previously were introduced to an
antigen cause damage to tissue cells or recruit
other cells
◦ Responsible for the rejection of tissue grafts and
transplanted organs
◦ Responsible for allergy to nickel found in some
jewelry and older dental restorations.

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Drug Hypersensitivity
Drugs can act as antigens
◦ Topical administration may cause a greater number of
reactions than oral or parenteral routes
◦ Parenteral route may cause more widespread/severe
reaction
Multifactorial
◦ Route of administration
◦ Infection
◦ Multiple allergies
Serum sickness
Autoimmune Diseases
Connective tissue diseases
Bodies immune system differentiates between own cells
and tissues and foreign substances
Immunologic tolerance
Recognition mechanism breaks down and certain body cells
no longer tolerated
Single cell type or an organ
Genetic or viral?
Learning Objectives:
Lesson 3.2: Autoimmune Diseases,
Oral Lesions, and Reiter Syndrome
10. Define autoimmunity and describe how it results in disease.
11. Define immunodeficiency and describe how it results in disease.
12. With regard to aphthous ulcers:
• Describe and contrast the clinical features of each of the three types of aphthous
ulcers.
• Describe the diagnosis, treatment, and prognosis of aphthous ulcers.
• List systemic diseases associated with aphthous ulcers.

46
Learning Objectives:
Lesson 3.2: Autoimmune Diseases,
Oral Lesions, and Reiter Syndrome
13. Describe and compare the clinical features of urticaria, angioedema, contact
mucositis, and fixed drug eruption.
14. Describe the clinical features of erythema multiforme and Stevens-Johnson
syndrome.
15. With regard to lichen planus
• Describe the clinical and microscopic features of lichen planus.
• Name and describe the types of lichen planus.
• Discuss the diagnosis, treatment, and prognosis of lichen planus.

16. List the triad of systemic signs that comprise reactive arthritis (Reiter
syndrome) and describe the oral lesions that occur in this condition.

47
Autoimmune Diseases
Immunologic tolerance
◦ The body learns to distinguish self from nonself
early in embryologic development.
Autoimmune disorder
◦ The recognition mechanism breaks down; some
body cells are not tolerated and are treated as
foreign antigens

48
Immunodeficiency
Immunopathologic condition
Deficiency in number, function or interrelationships of the
involved WBCs and their products
Congenital or acquired
Genetically inherited or result of other factors
Infections and tumors may occur as a result of the
deficiency
When a person’s immune system is not functioning
adequately, infections and neoplasms may develop
undeterred by any defense mechanisms.
Oral Immunologic
Lesions and Diseases
Aphthous ulcers
Urticaria and angioedema
Contact mucositis and contact dermatitis
Fixed drug eruptions
Erythema multiforme
Lichen planus
Reactive arthritis (Reiter syndrome)
Langerhans cell disease

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 Aphthous Ulcers
Painful oral ulcers with an unclear cause
◦ Reported incidence ranges from 5% to 56%
◦ Trauma is the most common precipitating factor
◦ May be caused by emotional stress or certain foods
◦ The highest incidence was found in school students and the
lowest in male hospitalized patients.
◦ May be associated with certain systemic diseases
◦ Thought to have an immunologic pathogenesis
◦ Occur in three forms
◦ Minor
◦ Major
◦ Herpetiform
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Recurrent Aphthous Ulcers
(Canker Sores, Aphthous
Stomatitis)
Trauma
◦ The most commonly reported precipitating factor in the
development of aphthous ulcers.

Perceived food associations

Menstruation
Systemic diseases
Tobacco cessation
Stress

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 Aphthous Ulcers
Minor Aphthous Ulcers
 Minor Aphthous Ulcers
Minor aphthous ulcers are the most commonly occurring type, affecting
about 80% of patients with recurrent aphthous ulcers.
Discrete, round or oval ulcers
Occur on movable mucosa
Up to 1 cm in diameter
Erythematous halo surrounding a yellowish-white fibrin surface
May have single or multiple lesions
May have a prodrome of 1 to 2 days

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Apthous Ulcers
Canker sores or aphthous stomatitis (ex. Of Major Aphthous Ulcer)
Major Aphthous Ulcers (Sutton Disease,
Periadenitis Mucosa Necrotica Recurrens)
Larger than minor aphthous ulcers (>1 cm)
Deeper and longer lasting than minor aphthous ulcers
Very painful, and are less common than minor aphthous ulcers.
Occur in the posterior of the mouth more often than do minor aphthous
ulcers
May require several weeks to heal
May require a biopsy

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 Aphthous Ulcers
Major Aphthous Ulcers
Aphthous Ulcers
Herpetiform Aphthous
Ulcers
◦ Very tiny (1 to 2 mm)
◦ Resemble herpes simplex
virus
◦ Painful, occur in clusters,
anywhere in the mouth
◦ No systemic involvement
◦ Image on page 94
 Aphthous Ulcers and
Systemic Disease
Chronic gastrointestinal symptoms
Crohn disease
Gluten-sensitive enteropathy/celiac disease
Inflammatory bowel syndrome
Intestinal lymphoma
Ulcerative colitis
Arthritis
Skin lesions (Behçet syndrome)
Childhood periodic fevers
Know Table 3.4 to discuss the clinical features of the three types of recurrent
aphthous ulcers.

59
Aphthous Ulcers:
Treatment
Topical corticosteroids
Topical nonsteroidal anti-inflammatory drugs
(NSAIDs)
◦ Topical corticosteroids and nonsteroidal anti-
inflammatory agents are most effective when applied
very early in the development of the ulcer.
Pain relief: Lidocaine, benzocaine
Systemic steroids
Nicotine replacement therapy

60
Urticaria Angioedem
(Hives) a
Appear as multiple areas Lesions caused by
of well-demarcated diffuse swelling as a
swelling of skin result of increased
permeability of deeper
May include itching
blood vessels
(pruritus)
◦ The skin covering the
Lesions are caused by swelling appears
localized areas of normal
vascular permeability in ◦ Usually does not itch
superficial connective
tissue
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 Causes
◦ Idiopathic
◦ Infection
◦ Trauma
◦ Emotional stress
Uticaria ◦ Systemic diseases
and ◦ Ingested allergens
Angioede
ma Diagnosis - based on clinical
appearance of the lesions, the
patient’s history, and the
history of the lesion.
Treatment
◦ Antihistaminic drugs
◦ Epinephrine 62
Uticaria and
Angioedema
Allergic Contact
Mucositis
and Dermatitis
Lesions result from contact
of an allergen with skin or
mucosa
Involves T cells in a cell-
mediated immune response
Type IV hypersensitivity

A, Courtesy Dr. Edward V. Zegarelli.

64
Contact Mucositis
and Contact Dermatitis
Possible causes
◦ Preservatives in local anesthetics
◦ Topical medications
◦ Acrylics
◦ Metal-based alloys
◦ Epoxy resins
◦ Flavoring agents
◦ Gloves

Treatment
◦ Topical corticosteroids
◦ Systemic corticosteroids
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Fixed Drug Eruptions
Lesions that appear in the same site each time a drug is
introduced
Generally appear suddenly after a latent period
Disappear when stop drug and reappear when reintroduced
Single or multiple slightly raised, reddish patches or clusters
of macules on skin, or rarely the mucous membranes in the
oral cavity.
Pain and pruritus may be associated
Type III hypersensitivity reaction
Fixed Drug Eruptions
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 the
skin or mucosa
◦ Some medications associated with fixed drug eruptions are
barbiturates, chlorhexidine, lidocaine, penicillamine,
sulfonamides, and tetracycline.
Treatment
◦ The drug causing the reaction should be identified and
discontinued

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 Acute, self-limited disease
that affects skin and mucous
membranes
Most commonly occurs in
adults younger than 30
Erythema years.
Multiforme
Cause: Not clear; may be a
hypersensitivity reaction
Target or bull’s-eye lesion
◦ Concentric erythematous
rings alternating with normal
skin color
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Erythema Multiforme
Erythema Multiforme
 Erythema Multiforme
Diagnosis
◦ Based on clinical features and by
exclusion of other diseases
◦ Eye lesions may lead to blindness

Treatment
◦ Remove cause, if possible
◦ Topical or systemic corticosteroids
◦ Topical corticosteroids may be helpful in
mild cases of erythema multiforme, but
systemic corticosteroid treatment is usually
needed.
◦ Systemic antiviral medications
Stevens-Johnson
Syndrome
Used to be considered a very severe
form of erythema multiforme; now
classified as a variant of toxic
epidermal necrolysis (TEN)
Extensive and painful oral lesions
Genital mucosa and mucosa of eyes
may be involved
Lips generally are encrusted and
bloody

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Lichen Planus
 Lichen Planus
A benign, chronic disease affecting the skin and oral
mucosa
Unknown cause
Lesions have characteristic Wickham striae (lacelike)
The classic appearance of lichen planus affecting the
oral mucosa is an arrangement or interconnecting
white lines and circles.
Most commonly on buccal mucosa
◦ Lesions may be on the tongue, lips, floor of mouth,
and gingiva
Present in about 2% of the U.S. population
◦ Most common in middle age
◦ Slightly more common in women
Types of Lichen Planus
Reticular lichen
planus
◦ Most common form
Erosive and bullous
lichen planus
◦ Epithelium separates
from connective
tissue

75
Types of Lichen Planus
(Cont.)
Desquamative gingivitis can be
associated with lichen planus
Skin lesions
◦ Papules (2 to 4 mm) most commonly
in lumbar region, flexor surfaces of
the wrist, anterior ankle Courtesy Dr. Edward V. Zegarelli.

Bullous lichen planus is a severe

form of erosive lichen planus that
involves the formation of large
blisters (bullae) that occur when
the epithelium separates from the
connective tissue.

76
 Diagnosis of
Lichen Planus
Epithelium is generally parakeratotic
Either hyperplastic or atrophic
Degeneration of basal cell layer of epithelium
Broad band of lymphocytes in CT
Separation of epithelium from CT = erosive areas
May be premalignant
The diagnosis of lichen planus is made on the basis of both the
distinctive clinical features and the microscopic appearance of
the tissue obtained through scalpel biopsy.
77
Treatment and
Prognosis
for Lichen Planus
This is a chronic disease, treated when symptomatic
Topical corticosteroid medications
Meticulous oral hygiene
Discontinuation of drugs causing condition
Regular oral examination
Biopsy of suspicious lesions is necessary because these patients may be
at increased risk of development of squamous cell carcinoma (but this is
controversial)

78
Reiter Syndrome
Classic syndrome includes the triad of
arthritis, urethritis, and conjunctivitis,
Polyarthritis is generally the most prominent
component of the syndrome
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
May see aphthous ulcers, erythematous
lesions, and geographic tongue–like lesions
Diagnosis is made on basis of clinical signs
and symptoms, along with identification of
HLA-B27 antigenic marker
• Reactive arthritis lasts from 3 months to 1
year.
• Aspirin or other NSAIDs are generally used
for treatment.
Learning Objectives
Lesson 3.3: Langerhans, Oral
Manifestations, and Immunodeficiency

17. With regard to autoimmune diseases with oral manifestations:

• Describe the oral manifestations, diagnosis, treatment, and prognosis of each of the
following autoimmune diseases: Sjögren syndrome, lupus erythematosus,
pemphigus vulgaris, mucous membrane pemphigoid, bullous pemphigoid, and
Behçet syndrome.
• Define desquamative gingivitis, describe the clinical features, and list three diseases
in which desquamative gingivitis may occur.
• Describe the clinical features of Behçet syndrome.

18. With regard to immunodeficiency:

• Describe the difference between primary and secondary immunodeficiency.
• List and describe three examples of primary immunodeficiency.
• List four causes of secondary immunodeficiency.

80
Autoimmune Diseases
with Oral Manifestations
(Table 3.5)
Sjögren syndrome
Systemic lupus erythematosus
Pemphigus vulgaris
Mucous membrane pemphigoid
Bullous pemphigoid
Behçet syndrome

81
Sjögren Syndrome
Specific cause is unknown, although
there is evidence of a genetic
influence
Affects the salivary and lacrimal
glands
Results in a decrease in saliva and
tears, causing a dry mouth
(xerostomia) and dry eyes
(xerophthalmia)
Keratoconjunctivitis sicca (KCS):
Damage to eyes
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Sjögren
Syndrome
May be associated with other
autoimmune disorders
◦ Primary Sjögren syndrome: When it
occurs alone
◦ Secondary Sjögren syndrome: When it
occurs with other autoimmune
disorders
Affects both major and minor
salivary glands
◦ Parotid gland enlargement occurs in
about 50% of patients

83
Sjögren Syndrome
Oral discomfort caused by dry
mouth
Lips: Cracked and dry
May see loss of filiform and
fungiform papillae on the
dorsum of the tongue
High risk for caries, periodontal
disease, and oral candidiasis

84
Sjögren Syndrome
(Cont.)
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 salivary gland ducts
◦ Biopsy of the minor salivary glands
is sometimes performed to assist in
diagnosis.

Courtesy Dr. Harry Lumerman.

85
Sjögren Syndrome and
Raynaud Phenomenon
20% of patients with Sjögren syndrome will have this
disorder affecting the fingers and toes
Both cold and emotional stress tend to trigger the reaction,
which is characterized by an initial pallor and cyanosis of
the skin that results from vasoconstriction and reduced
blood flow
Hyperemia when blood vessels are warmed
Myalgia
Arthralgia
Chronic fatigue

86
Sjögren Syndrome
(Cont.)
90% of these patients have a positive response to
rheumatoid factor (RF), an antibody to IgG present
in serum
◦ Rheumatoid factor is an antibody to an antibody
Other autoantibodies, anti–Sjögren syndrome A
and anti–Sjögren syndrome B, are also present

87
Diagnosis and
Management
of Sjögren Syndrome
Diagnosis is made when two of three components are
present:
◦ Xerostomia
◦ Measurement of salivary flow and biopsy can help
◦ Keratoconjunctivitis sicca
◦ Confirmed by 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

88
 Treated symptomatically
◦ Nonsteroidal antiinflammatory agents for
arthritis
◦ May need corticosteroids and
immunosuppressive drugs for severe
cases
◦ Saliva substitutes for xerostomia
Treatment ◦ Humidifier, sugarless gum, or lozenges
of Sjögren ◦ Pilocarpine
Syndrome ◦ Glasses to protect from air flow and/or
artificial tears to protect eyes
◦ Good oral hygiene
◦ Fluoride
◦ Frequent re-care appointments

For most patients, the course of the

disease is chronic and benign
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 Systemic Lupus
Erythematosus (SLE)
An acute and chronic inflammatory autoimmune disease
◦ No known cause, but Genetics and environmental influences have been
implicated in the pathogenesis of the disease.
Affects women eight times more frequently than men, predominantly during
childbearing years
◦ Three times more frequent in black women than in white women
A syndrome with a wide range of disease activity
Both cellular and humoral immunity are impaired
◦ Usually chronic and progressive
◦ Periods of remission and exacerbation
Autoantibodies to DNA are present in serum
May have a genetic component
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 Systemic Lupus
Erythematosus (SLE)
Clinical Features: Skin lesions occur in 85% of individuals
“Butterfly” rash on bridge of nose
There may be erythematous lesions on fingertips
Arthritis and arthralgia are common
Systemic Lupus
Erythematosus (SLE)
(Cont.)
Oral lesions accompany skin lesions
in about 25% of patients with discoid
lupus erythematosus
◦ Erythematous plaques or erosions
◦ May have white striae; resemble
lichen planus but are less
symmetric
Medical consultation may be needed
before dental treatment

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Systemic Lupus Erythematosus
(SLE)
Diagnosis: Classic multi-organ involvement and presence of
antinuclear antibodies in serum
Treatment and Prognosis: based on degree of disease activity
◦ NSAIDS, aspirin, hydroxychloroquine, and corticosteroids
◦ Kidney involvement and severe hypertension, rapid renal
failure
◦ Hemorrhage secondary to thrombocytopenia, CNS
involvement, and infection
SLE is extremely complex – physician consultation
 Pemphigus Vulgaris

• A severe, progressive autoimmune disease affecting the skin and mucous

membranes
• No gender predilection exists. A broad age range has been reported as well.
• Characterized by intraepithelial blister formation resulting from
acantholysis, a breakdown of cellular adhesion between epithelial cells
• The first signs of disease occur in the oral cavity in more than 50% of cases
• There may be shallow ulcers, to fragile vesicles, to bullae
• Nikolsky sign
Rubbing with a finger can produce a bulla
Pemphigu
s Vulgaris
Microscopic
appearance
• Acantholytic
cells - The loss of
attachment
between
epithelial cells
leads to cells
that appear
rounded
• Tzanck cells
Treatment and
Prognosis
for 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
Courtesy Dr. Fariba Younai.

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Mucous Membrane Pemphigoid
(Benign Mucous Membrane
Pemphigoid; Cicatricial Pemphigoid)
A chronic autoimmune disease
Affects oral mucosa, conjunctiva, genital mucosa, and
skin
Not as severe as pemphigus vulgaris
Will see positive Nikolsky sign
This is twice as common in women and most
frequently diagnosed in women older than 50.

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Benign Mucous Membrane
Pemphigoid; Cicatricial
Pemphigoid
Gingival lesions have been called desquamative gingivitis, but this
condition may be seen with lichen planus and pemphigus as well
Will see positive Nikolsky sign

Courtesy Dr. Victor M. Sternberg.

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Diagnosis of
Mucous
Membrane
Pemphigoid
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
◦ Indirect immunofluorescence is
usually not helpful in the
diagnosis of mucous membrane
pemphigoid.

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Treatment and Prognosis for
Mucous Membrane Pemphigoid
A chronic disease with a benign course
◦ Topical corticosteroid for mild cases
◦ Systemic corticosteroids may be required for
more severe cases
◦ Disease may be difficult to control and slow to
respond to therapy.
◦ Eye lesions can lead to eye damage

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Bullous Pemphigoid
Some investigators believe bullous and mucous
membrane pemphigoid are variants of a single
disease
Most patients are older than 70, No gender
predilection exists.
Oral lesions are less common than in cicatricial
pemphigoid
Treatment
◦ Systemic corticosteroids and NSAIDs

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Bullous Pemphigoid

Image courtesy of

www.histopathology-india.net/BuPem.htm
Behçet Chronic, recurrent autoimmune disease
Primarily oral ulcers, genital ulcers, and ocular
Syndrome
inflammation
Mean age of onset 30 years, male = female
Identification of antibodies to human mucosa
Painful, recurrent aphthous ulcers ranging
from a few mm to several cm in size
Diagnosis: 2 of 3 principal manifestations
(oral, genital, and ocular) be present; a
pustular or erythematous lesion after needle
puncture
Treatment and Prognosis: Systemic and
topical corticosteroids. Chlorambucil for eye
lesions. Other immunosuppressive drugs may
be needed.
Sarcoidosi Multisystem granulomatous
s disease of unclear etiology
Women aged 20 to 50 are most
frequently seen involving the
lungs and the lymph nodes
Erythema nodosum: Type of skin
inflammation seen in the lower
extremities
Most common sites for oral
sarcoidosis: Jawbones, buccal
mucosa, gingiva, floor of mouth,
tongue, and palate
The manifestations of sarcoidosis
vary based on the affected body
site.
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 Diagnosis
◦ Made based on correlation of the
patient’s clinical presentation with
the biopsy findings
Treatment and prognosis
Sarcoidosi ◦ Chronic condition with no cure
s ◦ Most cases produce only mild
symptoms that will resolve on
their own after several months
without treatment
◦ Corticosteroids are the primary
treatment modality, if needed.

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Immunodeficiency
Can involve various components of the immune system
Immunodeficiency diseases are divided into primary and
secondary immunodeficiencies
Signs and symptoms that occur in a person with
immunodeficiency depend on the degree of deficiency and
type of immune response involved

106
Immunodeficiency
Can involve various components of the immune system
Immunodeficiency diseases are divided into primary and secondary
immunodeficiencies
Signs and symptoms that occur in a person with immunodeficiency
depend on the degree of deficiency and type of immune response
involved
The most common complication arising in persons with either primary
or secondary immunodeficiency is infection.

107
 Primary
Immunodeficiencies
Primary immunodeficiencies are immunodeficiencies of genetic
or developmental origin and can involve B cells, T cells, or both.
Isolated IgA deficiency
◦ Most common primary immunodeficiency
◦ Characterized by low levels of both serum and secretory IgA
X-linked congenital agammaglobulinemia (Bruton disease)
◦ Disorder in which B-cell precursors stop maturing before they
complete immunoglobulin gene development
Thymic hypoplasia (DiGeorge syndrome)
◦ Disorder in which the thymus is deficient or lacking
◦ Infants and children with this syndrome are extremely
susceptible to fungal and viral infections, and bacterial
infections that require T-cell and B-cell cooperation
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Primary
Immunodeficiencies

Severe combined immunodeficiency

◦ Group of genetically inherited syndromes that have
defects in both humoral and cell-mediated immune
responses
Leukocyte adhesion deficiency
◦ Primary immunodeficiency characterized by defects
in function of neutrophils
Bone marrow transplants have dramatically increased
survival of severe combined immunodeficiency.

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Secondary
Immunodeficiencies
Those that occur because of an underlying disorder
or by medication (See Table 3.6)
Much more common than primary
immunodeficiency disorders
Disorders that can have accompanying
immunodeficiency include:
◦ Malnutrition
◦ Renal diseases
◦ HIV infection

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