Chapter 3sreddy/DH180/Chapter 3.pdf · Involves white blood cells, ... Mature and reside in lymphoid tissue ... an imprint of Elsevier Inc. 11 Plasma Cells

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1Elsevier items and derived items © 2009 by Saunders, an imprint of Elsevier Inc.

Chapter 3

Immunity


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


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


Antigens

(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


Antigens (cont.)

Human tissue Organ transplants, tissue grafts, incompatible

blood types during a transfusion Autoimmune diseases

Tissue from the person’s own body becomes an antigen


Cellular Involvement in the Immune Response

B lymphocytes T lymphocytes Macrophages Cytokines

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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


Cellular Involvement in the Immune Response (cont.)


B Lymphocytes

(pgs. 83-84) 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


B Lymphocytes (cont.)


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


T Lymphocytes

(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

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T Lymphocytes (cont.)


Macrophages

(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


Cytokines (Cont.)


Cytokines (Cont.)

(pgs. 84-85) (Table 3-2) Proteins made by cells that are able to

affect the behavior of other cells Different cytokines have different functions.


Major Divisions of the Immune Response

(pgs. 85-86) 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.


Major Divisions of the Immune Response (cont.)

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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.


Types of Immunity

Passive Immunity Active Immunity


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


Active Immunity

(pg. 86) Antibodies created by the person

themselves 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


Immunopathology

(pg. 86) The study of immune reactions involved in

disease The immune system can malfunction and

cause tissue damage.• Hypersensitivity• Autoimmune diseases


Hypersensitivity (Cont.)

(pgs. 87-88) (Table 3-3) An allergic reaction

An exaggerated response Tissue destruction occurs as a result of the

immune response. Four main types

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Hypersensitivity (Cont.)


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.


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).


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.


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


Hypersensitivity to Drugs

(pgs. 87-88) 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.

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Autoimmune Diseases

(pg. 88) Immunologic tolerance

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.


Immunodeficiency

(pg. 88) An immunopathologic condition

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.


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


Aphthous Ulcers

(pgs. 88-91) Painful oral ulcers with an unclear cause

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


Minor Aphthous Ulcers

(pg. 89) Discrete, round or oval ulcers

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


Minor Aphthous Ulcers (cont.)

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Major Aphthous Ulcers

(pgs. 89-90) 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


Major Aphthous Ulcers (cont.)


Herpetiform Aphthous Ulcers

(pgs. 89-90) Tiny (1 to 2 mm)

Resemble herpes simplex ulcers Painful, generally occur in groups


Diagnosis of Minor Aphthous Ulcers (Cont.)


Diagnosis of Minor Aphthous Ulcers (Cont.)

(pgs. 89-91) (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


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.

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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


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


Urticaria and Angioedema

(pgs. 91-92) Often idiopathic cause

May be due to infection, trauma, emotional stress, and certain systemic diseases

May be due to ingested allergens


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


Contact Mucositis and Dermatitis (cont.)


Fixed Drug Eruptions

(pgs. 92-93) 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

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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.


Erythema Multiforme

(pgs. 93-94) 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


Erythema Multiforme (cont.)



(pgs. 93-94) 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





(pgs. 93-94) 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.

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(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.


Lichen Planus

(pgs. 93-96) 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


Lichen Planus (cont.)


Types of Lichen Planus

(pgs. 95-96) 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


Types of Lichen Planus (cont.)


Diagnosis of Lichen Planus

(pgs. 95-96) 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.

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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.


Reactive Arthritis (Reiter Syndrome)

(pgs. 96-97) 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


Reactive Arthritis (Reiter Syndrome) (cont.)


Reactive Arthritis

Diagnosis Clinical signs and symptoms HLA-B27 antigenic marker

Treatment and prognosis Disease lasts for weeks to months. Recurrent attacks are common.


Langerhans Cell Disease (Histiocytosis X)

(pgs. 97-98) Includes three entities

Letterer-Siwe disease Hand-Schuller-Christian disease Solitary eosinophilic granuloma

All have Langerhans cells and eosinophils.


Langerhans Cell Disease (Histiocytosis X) (cont.)

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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


Autoimmune Diseases that Affect the Oral Cavity

Sjögren Syndrome Systemic Lupus Erythematosus Pemphigus Vulgaris Mucous Membrane Pemphigoid Bullous Pemphigoid Behçet Syndrome


Autoimmune Diseases that Affect the Oral Cavity (cont.)

(pgs. 98-105) (Table 3-5) Several autoimmune diseases affect the oral

cavity. The immune system treats the person’s own

cells and tissues as antigens.


Autoimmune Diseases that Affect the Oral Cavity (cont.)


Sjögren Syndrome

(pgs. 99-100) 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.


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

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(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





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



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.


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.


Diagnosis and Management of Sjögren Syndrome (cont.)

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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


Systemic Lupus Erythematosus (SLE)

(pgs. 100-102) 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


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


Clinical Features of Systemic Lupus Erythematosus (SLE)

(pgs. 101-102) 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


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


Diagnosis of Systemic Lupus Erythematosus (SLE)

(pgs. 101-102) Usually based on multiorgan involvement

and presence of antinuclear antibodies in serum Inflammatory infiltrate is around blood vessels

in connective tissue.

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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.


Pemphigus Vulgaris

(pgs. 102-104) 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


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.





(pgs. 103-104) 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


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.

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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.


Mucous Membrane Pemphigoid (Cicatricial Pemphigoid) (BMMP) (pgs. 104-105)

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


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


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.


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.


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

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Behçet Syndrome

(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.


Behçet Syndrome (cont.)


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.


Treatment and Prognosis of Behçet Syndrome

(pg. 105) Systemic and topical corticosteroids

Chlorambucil is used for ocular lesions.


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 is an autoimmune disorder? What are the oral symptoms of Sjögren

syndrome? What are differences between pemphigus and

pemphigoid?

Documents

Chapter 3sreddy/DH180/Chapter 3.pdf · Involves white blood cells, ... Mature and reside in lymphoid tissue ... an imprint of Elsevier Inc. 11 Plasma Cells