ch3 immunity and immunologic

• Defends the body against injury

• Has memory capability

• Responds quicker than inflammatory response

• Involves complex network of white blood cells

• May result in increased level of tissue damage and disease as it fights

acquired (adaptive) immune response

• Foreign substances (bacteria, viruses) that have these which activates the immune system to defends the body.

• Components of our own cells, our immune system tolerates

• Tumor cells (may develop abnormal ____)

• Cells infected with viruses

• Organ transplant (may have different _____, that cause ur body to reject the organ)

• Tissue graft

• Incompatible blood transfusion

• Cells of own body: Autoimmune diseases

Antigens or Immunogens

• Develop from stem cells in bone marrow

• Mature and reside in lymphoid tissue

• Lymph nodes, tonsils, and other body tissue

• 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

B-cell lymphocytes

• Round, pinwheel-shaped nucleus with visible cytoplasm

• Produces and releases a protein (antibody) in response to presence of antigen

• Circulating antibodies: Immunoglobulins (Igs

• produces specific antibodies

b-cell lymphocytes: plasma cells

• Five different types of immunoglobulins:

• IgA

• IgD

• IgE

• IgG

• IgM

• Antibody titer: Level of a specific antibody

• Immune complex: Antibody + antigen

B-cell lymphocytes: Immunoglobulins

• Develop from bone marrow stem cell

• Travel to the thymus and mature

• Types:

• 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

T-cell lymphocytes

• Destroy foreign cells

• Located within the microcirculation

• Active against viruses and cancer cells

• Activity can be abnormal as in HIV infection

• releases substances that cause the target cell to destroy itself

Natural Killer Cells (lymphocytes)

• Accessory cells in immune response that amplify but do NOT have memory

• Located in connective tissue (CT) during inflammation

• Functions:

• Phagocytosis

• Assist B cells and T cells

• messenger between inflammatory response and immune response

• Activating factor: produce and secrete lysosomal (digestive) enzymes

macrophages

• Type of white blood cell found on skin, mucosa, and in blood

• Antigen-presenting cells (APCs): Process antigenic material and present it to other immune system cells such as T-lymphocytes to activate immune response)

• Messenger between innate immunity and acquired immunity

• Langerhans’ cell: Specialized dendritic cell (NOT isle of langerhans)

Dendritic cells

• Immunomodulating agents: Alter the immune response

• Communication system

• Interleukins (may regulate inflammation/immune activation)

• Macrophage chemotactic factor (attracts macrophages)

• Migration inhibitory factor (keeps macrophages at inflammation site, promotes inflammation)

• Macrophage-activating factor (activates macrophages, makes them better at killing/digesting pathogens)

• Lymphotoxin (contributes to inflammation/cell killing)

• Interferons (important for antiviral defense/immune signaling)

• Tumor necrosis factor (major proinflammatory, actives immune response and contribute to cell death)

Cytokines

1) B cells produce antibodies that bind to antigens

2) Remove from the body, key in extracellular bacteria & toxins.

3) Long term protection through memory B cells & the antibodies they produce

4) Faster response, antibodies produce quickly

humoral immunity

1) Kill cells or activate other immune cells

2) Role in destruction of intracellular viruses & bacteria

3) Long term protection through memory T cells to future infection

4) T cell response can take longer but are highly specific and effective intracellular pathogens.

cell-mediated immunity

Using antibodies created by another person to prevent infectious disease

• Natural: Mother to fetus

• Acquired: Injection

Passive Immunity

Antibodies created by the person himself or herself

• Natural: Microorganism causes the disease

• Acquired: Immunization, vaccination, booster

• Killed-type vaccine

• Live-attenuated vaccine

Active Immunity

• The study of immune reactions involved in disease; the study of diseases caused by the malfunctioning of the immune system

• Hypersensitivity

• Autoimmune diseases

• Immunodeficiency

immunopathology

• anaphylactic

• anaphylaxis, asthma, allergies

• Plasma cells → histamine (inflammation) → edema (dilation) → bronchoconstriction (smooth muscle)

ex. (hay fever, urticaria, asthma, anaphylaxis)

Type I Hypersensitivity

• cytotoxic

• binding

• Antibody/Antigen bind tissues cells → (RBC) → complement system, IgG and IgM → causes cell tissue destruction w/ antigen (foreign) attached.

• ex (blood transfusion incompatibilty, rhesus (Rh) incompatibility

Hypersensitivity Type 2

• immune complex

• complexes

• “serum sickness”

• Immune complexes form (antigen attaches to antibody) → deposit in tissues →( inflammation) → causes tissue destruction

• ex (autoimmune diseases like SLE)

hypersensitivity type 3

• cell mediated

• delayed response

• Delayed reaction 2-3 days to develop Cell Mediated (T Cells) rather than humoral response (B cells-antibodies) T cells cause tissue damage

• ex (TB test, granulomatosis, organ & tissue rejection)

hypersensitivity type 4

• Oral hypersensitive reaction

• Diffuse swelling of the lips (^ permeability of deeper blood vessels)

• Surface skin on affected area appears normal

• Not itchy usually

• Acute self limited episodes

• Type I hypersensitive reaction

• Acetylsalicylic Acid, NSAIDS (can cause vascular permeability)

• this condition involving the of larynx and pharynx can be fatal

• Dx: clinical appearance of lesion

• Tx: Antihistaminic drugs (Benadryl) or Epinephrine

Angioedema

• Hypersensitive reaction on oral mucosa

• Direct contact on the skin w/ an allergen.

• T cells w/ in a cell mediated response

• Type IV hypersensitive reaction

• Erythematous an edematous, burning, itching, smooth shiny appearance where the agent contacted the skin

• Small vesicles may appear in area

Contact Mucositis

• Skin hypersensitive reaction

• Multiple areas of well demarcated and erythema on the skin, itchy (pruritus)

• Cause can be difficult to pinpoint: infection, trauma, emotional stress, certain systemic diseases, ingested allergens

• Dx: clinical appearance of the lesion

• Tx: Antihistaminic Drugs (Benedryl)

Urticaria “hives”

• Skin hypersensitive reaction

• Erythematous, swelling and vesicles

• Later: crusted, scaly, white

• Common causes of allergic reaction:

LA preservatives, topical medications, acrylics, metal-based alloys, epoxy resins, flavoring agents, chewing gum, dentifrices, mouthwashes, cinnamon oil, latex

Contact Dermatitis

• Lesion that appears at the same site each time a drug is introduced.

• Single or multiple sl. Raised, reddish patches or clusters of macules on skin or oral mucosa (rare in oral)

• Appear after latent period of several days

• Subside when drug is discontinued

• Type III sensitivity reaction (immune complex type)

• Barbituates, chlorhexidine, lidocaine, penicillamine, sulfonamides, tetracycline all assoc. w. fixed drug eruptions

Fixed Drug Eruption

• Most common type

• Discrete, punched out round to oval ulcers, yellowish, fibrin center w/ a halo or erythema.

• up to 1cm in diameter, more common in anterior area of mouth

• small but painful, burning, tingling, soreness, prodromal period

• Single or multiple lesions, heal 7-10 days

• Tx: manage pain – kanka eeze, orabase

Minor Apthous Ulcer “canker sore”

• Smallest 1-2 mm ulcers, least common type

• Herpetiform is misnomer (look like lesions caused by herpes) not caused by herpes

• Do not have a known cause

• Painful and develop anywhere in the oral cavity

Herpetiform Apthous Ulcers

• larger than 1cm in diameter

• deeper and last longer than minor

• more painful, common in posterior area

• several weeks to heal, may result in

scarring

• HIV, Bechet Syndrome, Chron’s Disease, Reactive Arthritis: systemic conditions can typically be reported w/ this

Major Apthous Ulcer (Sutton Disease, Periadentis Muosa Necrotica Recurrens)

• acute self limited disease

• skin & mucous membrane lesions

• Cause not clear (hypersensitive reaction?)

• Young adults under 30, wide range of clinical disease

• minor: oral site, some skin sites

• major: 2 or more oral sites, widespread skin involvement

• Explosive onset, prodromal symptoms: fever, malaise, headache, cough, sore throat

• Oral Lesions: diffuse, large, superficial erythematous areas, frequently ulcers on lateral borders of the tongue, crusted bleeding lips

Erythema Multiforme “crusty lips & oral ulcerations”

• Skin lesions: target or bullseye lesions, concentric ring of alternating erythema and normal skin color, darkest color at the center

• Triggers: herpes simplex infection, Mycoplasm pneumoniae, drug therapy (antibiotic and analgesics)

• Wide range of skin lesions: macules, plaques, and bullae

• Oral lesions can occur alone or with skin lesions.

• Skins lesion w/out presence of oral lesions.

• Dx: clinical features, exclude diseases, biopsy, micro

• Tx remove cause, topical and systemic corticosteroids, antiviral for reoccurring episodes

Erythema Multiforme “bullseye target lesions”

• Benign chronic condition affecting skin and oral mucosa

• Interconnecting white lines and circles (lace-like) does not wipe off, asymptomatic

• Slender white lines are called Wickham Striae

• small papular, pin-sized, domed or hemispheric glistening white nodule

• Most common site is buccal mucosa but can occur on the tongue, lips, floor of the mouth and gingiva

• 13-78 yrs old, most common middle aged female, can have skin lesions

• Cause unknown, some drugs and chemicals have been implicated

• Dx: Clinical, biopsy, micro, rule out epithelial dysplasia

• Tx: corticosteroids if symptomatic, antifungal if candidiasis results from tx.

Lichen Planus

Types of Lichen Planus

• Reticular Lichen Planus – most common, white lines lacelike,

2-4mm papules

• Erosive Lichen Planus – epithelium separated from ct, results

in erosions, ulcers, bullae, less common

• Bulbous Lichen Planus – same as above, w/ bullae (large

blisters

• Lichen Planus can occur with desquamative gingivitis

• Erosive as been linked to possible development of squamous

cell carcinoma

• Lichenoid mucositis – mixed inflammatory infiltrate rather

than lymphocytes, extends deeper into ct, may be cause by

response to something topical (amalgam, cinnamon), may

develop into malignancy.

• Rec 3-6 mnth intervals for eval and biopsy for premalignant

lesions

Skin Lesions and Desquamative Gingivitis assocaited w/ Lichen Planus

Chronic disease w/ triad of disease

1) Arthritis

2) Urethritis

3) Conjunctivitis

• Develops 1-6 weeks after an sexually transmitted or gastrointestinal infection: Chlamydia, Salmonella, Shigella, Yersinia and HIV, more common in men

• Inflammation of iris, arthritis w/ ankles and knees, TMJ has been reported

• Oral Lesions: anywhere, apthous like lesions erythematous lesions and depilation of the tongue (like erythema migrans)

• Dx: Clinical symptoms, HLA-B27 marker

• Lasts 3 months to a year, aspirin, NSAIDS, antibiotics, corticosteroids, physical therapy

Reactive Arthritis (Reiter Syndrome)

• rare disease

• w/ histiocytes and eosinophils present in lesions

1) Single cell disease (bone, most common site, skin, lymph node, lung)

2) Multisystem disease w/ or w/out organ dysfunction (bone, skin, liver, spleen, bone marrow)

• White children, of northern European ancestry

• Dx: biopsy histopathologic examination

• Young child: have lesions in skull and femur, organ involvement more common

• Over 20 yrs: ribs, shoulder girdle, and mandible

• Punched out radiolucencies , similar to perio, may result in tooth loss

tx: single lesions- radiation

widespread disease – chemotherapy

Eosinophilic Granuloma of bone – localized form, surgical excision needed

Langerhans Cell Histiocytosis (Langerhans Cell Disease)

• chronic systemic, autoimmune disease that affects the salivary and lacrimal glands

• Combo of dry eye and dry mouth (sicca syndrome)

• Cause not known genetic? virus?

• Xerostomia, oral discomfort, erythematous mucosa, mouth feels sticky, dry cracked lips, angular chelitis, loss of papillae on the tongue, difficulty eating, swallowing, taste change (dysgeusia), bilateral parotid enlargement

• High risk of caries, perio disease, oral candidiasis

• Affects major and minor salivary glands

• Dx: 2 of 3 are present dry mouth, dry eye, arthritis or another autoimmune disorder

• Tx: Saliva substitutes, eye drops/meds, NSAIDS, corticosteroid, meticulous homecare, oral lubricants, xylitol, MI paste (Recaldent) fluoride rinses, electric tb, more frequent recall

• Pt should be monitored closely by physician

Sjogrens’ Syndrome “Lack of papillae & bilateral parotid enlargement”

• Severe progressive autoimmune disease affects skin and mucous membranes

• Vesicle formation due breakdown of epithelial cell to epithelial cell adhesion (acantholysis)

• Pt have circulating autoantibodies that react against the epithelial attachment (desmosomal attachment) mechanism

• Most common form “vulgaris” means common

• No gender or age predilection, some genetic and ethic factor reported

• Shallow painful ulcers, vesicles, bullae, size can vary, positive Nikolsky sign

• Tzanck Cells – breakdown of desmosomal cells, found on exam

• Dx: biopsy and micro

• Tx: high does of systemic corticosteroids, disease was once fatal.

Pemphigus Vulgaris

Chronic autoimmune disease that causes blistering and peeling (desquamation) of the gingiva, leaving red, painful, raw areas; may also affect the eyes and other mucous membranes.

Desquamative Gingivitis w/ Mucous Membrane Pemphigoid

• Older than 70 yrs.

• Variant of a single disease? w/ MMP

• Oral lesions are less common than MMP, more extensive and painful

• Dx: circulating auto antibodies detectable, autoantibodies do not always correlate to disease activity.

• Chronic disease w/ periods of remission, not life threating

• Tx: High doses of Systemic corticosteroids, NSAIDS, immunosuppressant medications

Bullous Pemphigoid

• Benign, chronic autoimmune disease affects oral mucosa, conjunctiva, genital mucosa and skin

• 2x more common in women, 50 + yrs of age, not as severe as pemphigus vulgaris

• “cicatricial” means healing w/ scarring (oral scarring is rare)

• Cleavage of the epithelial layer from the underlying ct

• Oral lesions limited to gingiva, marginal and attached gingiva, vesicles, bullae, ulcers are thicker and least longer than pemphigus vulgaris , episodic remission and exacerbation

• Dx: biopsy, microscopic examination

• Tx: chronic disease, topical and systemic corticosteroids, immunosuppressant agents

Mucous Membrane Pemphigoid Benign Mucous Membrane Pemphigoid, Cicatricial Pemphigoid

• Acute and chronic inflammatory autoimmune disease

• Unknown cuase – Genetics ? Environmental influences?

• 8x more frequently affects women, 3x more common in black women than white women

• Chronic and progressive w/ periods of remission and exacerbation (syndrome)

• Wide spectrum of disease activity skin lesion→ organ involvement → Kidney involvement

• Antiuclear antibodies (ANA’s ) present – autoantibodies to the pt DNA

• “Butterfly rash” across the face over the bridge of the nose w/ erythematous lesions on the fingertips

• Oral Lesions: erythematous plaques or erosions involving buccal mucosa, palate, gingiva, may resemble lichen planus but less symmetric, petechiae and gingival bleeding (due to thrombocytopenia)

• Develop other auto immune diseases: Sjogrens’, Rheumatoid Arthritis

• Dx: Circulating ANA, multiorgan involvement

• Tx: once fatal, aspirin, NSAIDS, Hydroxychloroquine (antimalarial), systemic corticosteroids, immunosuppressive agents, topical corticosteroids for oral lesions.

Systemic Lupus Erythematosus

• Toxic epidermal necrolysis (TEN)

• Rare & severe reaction to drugs

• Mucosal lesions, more severe and painful than erythema multiforme

• Lips more crusty & bloody than ER

• Can occur in older and females

• Genital and eye mucosa may be involved

• Tx: removing the drug or agent IV hydration, and corticosteroids

Steven Johnson Syndrome

• Chronic, recurrent multisystem autoimmune disease

• Due to systemic vasculitis

• Possible infectious or environmental antigen

• Oral ulcers (common), genital ulcers, ocular inflammation

• Emerges 30-40 yrs of age

• Oral lesions similar to apthous ulcers, larger red area than aphthous ulcers

• Dx: recurrent oral lesions w/ one or 2 other , pos. pathergy test

• Tx: Systemic, topical corticosteroids, and immunosuppressive drugs

Aphthous- like Ulcer on Tongue in Bechet

Syndrome (Bechet Disease)