Download Types of Immunity

Unit 3
Unit 3
Immunity
Unit 3 Objectives: Students will be able to:
1.
Describe the role of the immune system/response in controlling and causing disease.
Include the common cells of the immune system and their functions.
2.
Describe the clinical features of desquamative gingivitis and give examples of diseases in
which it may occur.
3.
Apply descriptive and histologic terminology to describe and differentiate the clinical and
histologic manifestations of each of the following autoimmune diseases:
a.
b.
c.
4.
Lupus erythematosus
Pemphigus vulgaris
Cicatricial pemphigoid
For each of the following infectious diseases a) name the organism causing it,
b)
summarize the route or routes of transmission of the organism and the oral manifestations
of the disease, and c) explain how the diagnosis is made:
a.
b.
c.
d.
e.
f.
Tuberculosis
Actinomycosis
Syphilis (primary, secondary, tertiary)
Verruca vulgaris
Condyloma acuminatum
Primary herpetic gingivostomatitis
5.
Compare the clinical features of intraoral herpes and minor aphthous ulcers.
6.
Differentiate between the humoral immune response and the cell-mediated immune
response.
7.
Differentiate between active and passive immunity.
8.
Describe, compare, and contrast the clinical features of each of the three types of
aphthous ulcers.
9.
Describe using correct descriptive terminology the clinical and histologic features of
lichen planus. Point out differences in the different types of lichen planus.
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10.
Describe the oral manifestations of each of the following autoimmune diseases:
a.
b.
c.
d.
e.
Sjogren’s syndrome
Lupus erythematosus
Pemphigus vulgaris
Cicatricial pemphigoid
Behcet’s syndrome
11.
List, describe and differentiate between the four forms of oral candidiasis listed in your
text.
12.
Describe the clinical features of herpes labialis. Distinguish between herpes labialis and
other forms of herpes.
13.
Compose a well thought out differential diagnosis for lesions and conditions that
resemble aphthous ulcers, lichen planus, desquamative diagnosis and herpes infections.
Be able to give reasons for your decisions by comparing clinical and histological features.
14.
Recognize from a slide those lesions reviewed in chapter 3.
The Immune Reaction
The immune reaction is designed to help the healthy body resist and defend against certain
injurious agents. The immune reaction plays a helping role in the cellular stage of acute
inflammation and a sustaining role in both nonspecific and granulomatous chronic inflammation.
These are very important functions. The immune system also functions to prevent injurious
agents such as certain microbes, toxins, parasites, and even altered cells (cancer, transplantation)
from becoming established, proliferating, and causing harm. Basically, four types of diseases can
result from immune system dysfunction.
1.
2.
3.
4.
Immune deficiency disorders
Hypersensitivity disorders
Autoimmune disorders
Immune cellular proliferative disorders (leukemia, lymphoma).
The normal immune system functions to destroy and isolate antigen-bearing injurious agents.
Remember that most body tissues are antigenic. However, the immune system learns to
recognize “self” during development and therefore usually does not attack the body’s own cells.
The immune system is composed of two distinct classes of lymphocytes: T Lymphocytes, and B
Lymphocytes. It is also composed of antigen-processing and antigen-presenting cells (APC’s),
which are most frequently macrophages.
The lymphocytes are memory cells. When a lymphocyte precursor is stimulated and becomes
sensitized to a specific nonself antigen--usually a protein on a microbe or cell--the sensitized
lymphocyte will react to that antigen. All progeny of the sensitized lymphocyte will also develop
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a memory for the specific antigen and will react (ATTACK) when the antigen (INJURIOUS
AGENT) reappears.
Example: If you were cheated in a business relationship, Mr. Jones stole all of your money from
the partnership you were in and left town. You now go home and tell your kids all about Mr.
Jones--He wore a silk tie, drove a big car, wore a Rolex watch and had a big silver cross around
his neck. This is the antigenic code, which your children pass on to their children and
grandchildren. Generations later a similar-appearing cheater wearing the silk tie, Rolex and
silver cross appears. He is instantly recognized by your great-grandchildren, who might tar and
feather him, and tie him up (the antibodies at work), tear his suit and tie it into shreds (cytolytic
cells), or call the police (the lymphokines). The antigen would be inhibited and the damage
prevented or restricted.
The lymphocytes are the primary WBC involved in immune
response...20 to 25% of WBC’s.
B-Lymphocytes: Developed from the stem cell in the bone marrow (B = Bone marrow). The B
lymphocyte precursor cells reside is in the lymphoid tissue, usually found in the lymph nodes.
The lymphocytes travel to the site of injury after stimulated by an antigen.
There are two types of B lymphocytes:
l.
Plasma cells: produce antibodies specifically directed against the antigen. The
antibody binds itself to the antigen material. Once the binding occurs, Ag is
inactivated: the Ag-Ab complex may be opsonized, agglutinated, or precipitated
for inflammatory phagocytosis. Antibodies, also called immunoglobulins, are
carried in blood serum. There are five different types, all with the same basic
structure; however, in each type of antibody, this structure is arranged differently:
IgM, IgA, IgD, IgG, IgE = MADGE.
2.
B memory cell: retains the memory of the previously encountered antigens.
T-Lymphocytes: The T lymphocytes develop from the bone marrow stem cell, travel to
the thymus, and mature, (are processed), (T = Thymus), and subsequently reside in the lymphoid
nodules that they share with B-lymphocyte precursors. They produce lymphokines. These T
cells develop a memory for a single specific foreign antigen associated with an injurious agent.
The antigenic memory is passed down through generations to numerous T-cell progeny. When
sensitized T cells encounter the “silk tie antigen,” they react by sending messages to other cells,
including T cells, B cells, and macrophages. These chemical messages are termed lymphokines
or cytokines, and they instruct the other cells to shred, club, punch, and generally disable the
antigenic agent. Some sensitized T cells (cytolytic) can directly destroy the agent, whereas some
simply call other cells to help. (Fig 4-2 p.41 Miller) The net result is that the silk tie bandit is
destroyed or at least inhibited.
AG-Processing Cells: The third series of cells to participate in the immune reaction is the
AG-processing cells. In many cases the T lymphocytes are quite farsighted and do not
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immediately recognize the antigenic substances. Antigen-processing cells such as macrophages
initially change or process the Ag until it is recognizable to the lymphocytes. Then the
lymphocytes can react and function.
Coordination of Cells: The three cell systems usually function as a team, and therefore,
communications are important.
The T-helper lymphocyte In many situations the t-helper functions as a team leader to call and
coordinate signals. They are also called the T4 lymphocytes. The T-helper cells are involved in
the activation of effector cells. Once the T4 lymphocyte has been presented with the Ag by the
APC, it sends chemical lymphokines, termed interleukins, to other T4 and T8 lymphocytes and
B lymphocytes, instructing them to proliferate and function.
Other lymphokines have effects on macrophages, such as initiation of macrophage chemotaxis,
activation of phagocytosis, and aggregation at the area of injury (antigen). (See table 3-1 in text,
page 110)
T8 lymphocytes = T-suppressor cells function to (1) directly destroy the antigenic agent and (2)
send messages back to T4 - helper cells (again via interleukins). Some of these messages inhibit
further immune response so that there is not an overreaction. Because T8 cells function to limit
the immune response, they are often referred to as suppressor cells.
Activated macrophages and B cells also communicate by interleukins.
Other types of lymphocytes (NK cells = Natural Killer) and macrophages participate in the
immune reaction with extensive communication and feedback by interleukins. The system
therefore is very complex, precise, and is easily distorted (Miller p.40).
Lymph Nodes and Lymphatics
Blood and lymphatic systems parallel each other throughout the body. Lymphocytes make up 70
- 80 % of nucleated cells in blood and more than 99% of nucleated cells in lymph.
Principal functions of lymphoid system:
Concentrate antigens into distinct structures
Circulate lymphocytes through tissues
Carry products of immune responses to bloodstream and tissues
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Major Divisions of the Immune Response
Humoral Response: Antibodies secreted by B lymphocytes. Associated with the fluid
phase of blood (plasma or serum--humoral means liquid). The humoral response is effective
against extracellular stages of bacterial and viral infections.
Cell-mediated Response: lymphocytes working alone (usually T lymphocytes) or
assisted by macrophages. Associated with lymphoid system. Primarily effective against
intracellular viruses, fungi, parasites, neoplastic cells, and foreign tissue.
Types of Immunity
Active Immunity: Occurs naturally when a disease is caused by a microorganism. This
type of immunity is also acquired by artificial means.
Vaccine: a person is injected with or ingests either altered pathogenic microorganisms or
products of those microorganisms = Vaccination. The immune system produces a
stronger, faster response next time the pathogen is encountered. This production of
acquired immunity is called immunization.
Antibacterial:
1.
Low skin surface pH and its general dryness inhibit bacterial growth.
2.
Epithelial desquamation, mucus barrier, ciliary activity, pH of the lumen, and
fluid flow of mucous membranes limit bacterial colonization.
3.
Bactericidal agents include lysozyme, lactoferrin, leukin and plakin.
4.
Phagocytosis is the most important element in host resistance to infectious
disease.
Antiviral:
1.
Interferons inhibit viral infection of healthy cell
Antifungal
Passive Immunity: using antibodies produced by another person to protect against
infectious disease.
Natural: mother to fetus
Acquired: short-lived but active immediately (HBiG: hepatitis B immunoglobulin)
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Immunopathology
Hypersensitivity (allergic reaction) is an immune response to a harmless substance
(Langlais, p88).
Type I (IgE mediated immediate hypersensitivity) Histamine mediated. Can be life
threatening because tissues swell and bronchioles constrict. Occurs immediately after exposure
to a previously encountered antigen (e.g., penicillin).
1.
2.
Local allergic reactions: (hay fever--allergic rhinitis, asthma, and allergic dermatitis)
Systemic (termed anaphylaxis) involves several organs, may be triggered by insect
venom, drugs, or certain foods.
Type II Hypersensitivity (Cytotoxic): (Hemolytic anemia of the newborn, aka erythroblastosis
fetalis), also includes transfusion reactions, and Rh incompatibility).
Type III Hypersensitivity (complex-mediated) Autoimmune type, e.g. lupus.
Type IV (Delayed) Cell-mediated --initiated by T cell lymphocytes-- of no benefit (ex. tissue
rejection, tuberculin test, and poison ivy allergy).
Drug Hypersensitivity (Types I, II, III, and IV)
Route of administration:
Topical causes more reactions
Parenteral reaction is severe and widespread--increased risk if :
 infection present
 multiple allergies
 autoimmune diseases present
 adults more than children
Immediate localized hypersensitivity is managed with antihistamines, whereas delayed
hypersensitivity is best treated with corticosteroids.
Autoimmune Diseases: In autoimmune diseases (connective tissue diseases) certain
body cells are no longer tolerated, and the immune system treats them as antigens. Autoimmune
disease may involve a single cell type, single organ, or multiple organs. Genetic factors may play
a role as may viral infection.
Immunodeficiency: A condition involving a deficiency in number, function, or
interrelationships of the involved white blood cells and their products. Can be congenital
(present at birth) or acquired (developing after birth).
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Oral Diseases with Immunologic Pathogenesis
1.
Aphthous Ulcers (aka canker sores, recurrent aphthous
stomatitis-RAS) (Langlais, p. 94). Painful recurrent ulcers usually on vestibular and
buccal mucosa, tongue, soft palate, fauces, and floor of the mouth (movable mucosa).
Prevalence tends to be higher in professional persons and those in upper socioeconomic
groups. Affects about 20% of the population.
Unknown etiology, but possibly defect in the immune system--see higher levels of Ab’s
to oral mucous membranes--. Other causes that may have a triggering role include trauma
(most common), food allergy (nuts, chocolate, gluten), stress, hormonal alterations, and
nutritional factors (deficiencies of vitamin B12, folic acid, iron). Familial patterns have
been demonstrated. Non-smokers are more frequently affected than smokers. Not
caused by the herpesvirus.
Peridex has been used to treat with some success. Patients with severe aphthous may be
given steroids (due to relation to immunologic defect).
Three forms of aphthous ulcers have been classified according to size; all are believed to
be part of the same disease spectrum. Differences are essentially clinical and correspond
to degree of severity.
a.
b.
Minor aphthae: most commonly occurring type. On movable mucosa-mucosa not covering bone--and occasionally on gingiva. Yellow membrane
surrounded by erythematous halo, less than 1 cm in size. Often a 1 to 2 day
prodromal period. Generally lasts 7 to 10 days. Invariably recurrent. Minor
ulcers usually heal spontaneously without scar formation within 14 days. Occurs
as single ulcer usually, occasionally in crops but not more than 5. They are more
common in the anterior of the mouth.
Major aphthous (aka Sutton’s disease, periadenitis mucosa
necrotica recurrens--PMNR, major scarring aphthous
stomatitis, scarifying stomatitis) (Langlais, p. 96). Regarded as the
most severe expression of aphthous stomatitis. Lesions are larger, deeper, more
painful and persist longer (up to 6 weeks with immediate recurrence) than minor
aphthae. Lesions heal with scarring. Pain may result in difficulty in eating and
psychological stress and systemic health may be compromised. Young female
adults with anxious personality traits are most commonly affected.
(Aphthous ulcers usually occur as single lesions located on oral mucous
membranes that contain minor salivary glands. These locations include all oral
mucosa except gingiva, anterior and lateral surfaces of the hard palate.
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c.
Herpetiform are tiny (1-2mm) recurrent crops of small ulcers. Mostly on
movable mucosa but also see on gingiva, palate and tip of tongue. Smaller than
aphthae. Very painful. May be clinically confused with primary herpes.
Recurrent history of aphthous and lack of gingival involvement (usually) in
aphthous help make the distinction between this and primary herpes.
2.
Urticaria: (hives) (Langlais, p. 88) Immediate allergic responses are histaminemediated and occur within minutes of exposure to Ags (ex. anaphylaxis)..Individual
wheals (aka urticaria, hives) arise following ingestion of certain foods such as shellfish,
citrus fruits, chocolate, or systemically administered drugs. Managed with
antihistamines.
3.
Angioedema: (Langlais, p. 88) Swelling is the most prominent feature. It appears
rapidly and lasts for 24 to 36 hours. Sensations of warmth and tenseness. Commonly
perioral and periorbital tissues. May occur with urticaria. Managed with antihistamines.
4.
Contact Mucositis (aka allergic mucositis): (Langlais p88) Delayed
(Type IV) reaction. (ex. flavoring ingredients, topical anesthetics, mouthwashes, cast
alloy restorations)
5.
Contact Dermatitis: ex. Latex glove allergy, reaction to lipstick or sunscreen.
Treat delayed hypersensitivity with corticosteroids.
6.
Fixed Drug Eruptions: These are lesions that appear in the same site each time a
drug is introduced. A complex-mediated allergic reaction (type III).
7.
Erythema Multiforme (EM, aka ectodermosis erosiva
pluriorificialis) (Langlais, p. 90).
Unknown etiology but in about half the cases precipitating factors (infections--esp. herpes
simplex, stress, and drugs) can be identified. Malaise, headache and low-grade fever
typically precede lesions by 3 to 7 days.
Characteristic skin lesion is called a target, iris, or bull’s eye. It consists of concentric
erythematous rings separated by rings of near-normal color. Lesions rapidly appear on
arms and legs. Oral lesions can occur with or without skin lesions and are usually painful
ulcers. Oral lesions frequently form on the lateral borders of the tongue. Dark, redbrown, hemorrhagic crusts are characteristically present on the lips.
8.
Stevens-Johnson syndrome: the most severe form of EM. “If eye, mouth and
genital lesions are involved it is usually Steven Johnson syndrome” (Dr. Wooley). More
widespread involvement, and more systemic signs (fever, malaise, headache, cough, chest
pain, diarrhea, vomiting, arthralgia). Hemorrhagic lip lesions are intensely painful.
Topical corticosteroids for mild EM, systemic corticosteroid treatment usually needed.
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9.
Lichen Planus: (Langlais) Benign, chronic disease affecting the skin and oral
mucosa. Frequently misdiagnosed. Disease of middle age; often severity parallels stress
level.
The most common oral pattern of presentation is termed reticular lichen planus. It is so
named because of the presence of a lace-like pattern of intersecting, somewhat angular to
curved white striations--Wickham’s striae. These are present to some extent in all forms
of lichen planus.
Oral lesions occur most commonly on buccal mucosa, often bilateral and symmetrical. A
single patient may have more than one form:
a.
b.
c.
d.
e.
Reticular form = striated form: Most common type with numerous interlacing
keratotic lines (striae of Wickham) producing a lacy pattern. Most commonly on
buccal mucosa but may be on almost any mucosal tissue.
Plaque-like lichen planus looks like leukoplakia and is usually on buccal mucosa
and dorsum of tongue. Asymptomatic. Least common type.
Atrophic form comes with burning or pain complaints. Attached gingiva is
frequently involved; keratotic striae radiate from atrophic dark areas. When the
attached gingiva is affected the term “desquamative gingivitis” has been used.
Erosive form shows granular and brightly erythematous surface. A pseudomembrane covers areas of significant erosion. Intermittently painful. Erosive
lichen planus shows striations, as well as irregular painful ulcers (Miller p. 270).
Bullous variant is the most unusual form. Bullae rupture and leave ulcerated,
painful surface. Commonly on posterior buccal mucosa and lateral margin of
tongue.
Corticosteroids are used to treat symptomatic lesions. Stress reduction can bring about
abrupt and dramatic resolution of the lesions. Lichen planus is a chronic condition.
Erosive and atrophic forms may rarely transform to malignancy if associated with tobacco
use, so patients should be observed periodically (especially with history of tobacco or
alcohol abuse).
The etiology of lichen planus is not understood. However, considerable attention has
been directed toward the identification of predisposing factors. While it should be
emphasized that metallic restorations only rarely induce lichen planus, two mechanisms
are known. It is recognized that certain amalgam alloys in rare cases will induce
development of lichen planus in the adjacent buccal or lingual mucosa. Even less
common is lichen planus arising under the influence of galvanic currents flowing between
metallic restorations composed of dissimilar metals (Miller, p. 271)
Different drugs are a common and important predisposing factor in lichen planus. Beta
blockers used to treat hypertension are in this group.
Because it is the oral expression of an important dermatologic condition, it would be
reasonable to anticipate that oral lichen planus would usually occur with concurrent skin
disease. In like manner, lichen planus of the skin would be expected to typically include
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oral disease. Interestingly, neither pattern is frequently observed. Paradoxically, oral
lichen planus usually occurs in patients without cutaneous disease, and the majority of
patients with lichen planus of the skin are free of oral disease. However, concurrent oral
and cutaneous lichen planus do occur with some frequency. The finding of typical
cutaneous lichen planus in a patient with suspected oral lichen planus provides additional
support for the oral diagnosis.
10.
Reiter’s Syndrome: Unknown etiology but possibly genetic influence. Major
components (triad) are arthritis, urethritis, and conjunctivitis. Oral lesions are relatively
painless aphthous type ulcers occurring almost anywhere in the mouth. If on tongue,
looks like geographic tongue.
Abnormal immune response to microbial antigen(s) is now regarded as a likely
mechanism for the multiple manifestations of this syndrome. Predominantly in white
males in their third decade. Self-limiting: It lasts weeks to months; recurrence is
common.
11.
Histiocytosis X (aka idiopathic histiocytosis, Langerhans-cell
granulomatosis, Langerhans cell disease) Associated primarily with an
abnormal histiocyte. A condition of children and young adults. Oral changes may be the
initial presentation in all forms of this disorder. Classic presentation in the jaws often
results in loosening or premature exfoliation of teeth. Tenderness, pain and swelling are
frequent patient complaints. Loosening of teeth in the area of the affected alveolar bone
is a common occurrence. The gingival tissues are frequently inflamed, hyperplastic, and
ulcerated.
Three disorders grouped because of similar microscopic appearance but clinical
manifestations are diverse. There are debates on the appropriateness of this classification
scheme. In all 3 diseases, the proliferating cell is the macrophage. Also present are
eosinophils.
a.
b.
Letterer-Siwe Disease (aka acute disseminated histiocytosis) shows
rapidly progressive, usually fatal clinical course. Widespread, proliferative organ,
bone, and skin involvement in infants. Most likely represents a malignant
neoplastic process. Significant oral involvement is rare due to rapid and usually
fatal course.
Hand-Schuller-Christian Disease (aka multifocal eosinophilic
granuloma, chronic disseminated histiocytosis) Presents with a clinical triad of
single to multiple, well-defined or “punched-out” radiolucent areas in the skull
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c.
(may occur in jawbones); unilateral or bilateral exophthalamos (abnormal
protrusion of the eyeball), and diabetes insipidus. (Triad seen in about 25% of
cases). Usually in children younger than 5. Oral manifestations include: 1) sore
mouth with or without ulcerative lesions, 2) loose and sore teeth, 3) early
exfoliation of teeth, 4) nonhealing extraction sites, and 5) loss of alveolar bone
mimicking periodontal disease is characteristic.
Eosinophilic Granuloma refers to patients with solitary or multiple bone
lesions only. More localized form of the disease. Patient may complain of
redundant gingival tissue, pain, swelling of focal areas of the gingiva, or a
loosening of isolated teeth. Be especially suspicious of the presence of a single
loose tooth without apparent cause. Radiographically: “teeth floating in air.”
Treated with conservative surgical excision or radiation therapy... recurrence is
rare.
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