dental microbiology #211 immunology lecture 6 adverse immune reactions and immune deficiencies
TRANSCRIPT
Dental Microbiology #211IMMUNOLOGY
Lecture 6
Adverse Immune Reactions and Immune Deficiencies
Topics
• Hypersensitivity reactions• IgE-mediated hypersensitivity (Allergy)• T cell-mediated reactions (Delayed-type hypersensitivity)• Autoimmune disorders• Inherited and acquired immunodeficiency disorders• Impact on the oral cavity
Hypersensitivity (Allergy)
Definition:Altered capacity of the body to react to a foreign substance The hypersensitivity states or allergies can be divided into four categories: Type I (IgE antibody-mediated)Type II (IgG and IgM-mediated)Type III (Immune complex-mediated)Type IV (T cell-mediated)
Over 30% of individuals in the western hemisphere have the tendency to produce IgE-and suffer from IgE-mediated reactions. They are called atopic individuals. The atopic state is influenced by both genetic and environmental factors.
The prevalence of atopic allergy and bronchial asthma is affected by air pollution and exposure to infectious diseases of the respiratory tract
Type I (IgE-mediated hypersensitivity reactions)
There are certain antigens and routes of Ag exposure that favour IgE Ab production
Antigens that evoke IgE responses are collectively called allergens
The symptomatology is different depending on whether the Ag is injected, inhaled or ingested i.e. depending on the tissue where the pharmacologic mediators of allergy i.e histamine and serotonin are released (the target tissue) .
IgE-mediated reactions Fig 1
The IgE molecule Fig 2
Properties of IgE
IgE is present in low concentrations in the plasma (<50 nannograms/ml) Has a very potent biological effect: The Fc segment of IgE binds with extremely high affinity to an Fc receptor, called FcRI, on mast cells and basophils. Basophils are circulating polymorphonuclear leukocytes. Mast cells reside in tissues
IgE has a half life of only two days in the plasma but over 30 days when bound to a basophil or mast cell surface.
Mediator release Fig 3
The biological effector mechanism is triggered when mast cell- (or basophil-) bound IgE molecules are cross-linked by multivalent Ag .The cross-linking induces membrane modifications resulting in the release of granules containing powerful pharmacologic mediators such as histamine and serotonin
Allergens
Most allergens are relatively small molecular weight soluble proteins carried on desiccated particles (pollen, dander, dried animal saliva, house mite faeces, etc) which become released from the particles, and penetrate the respiratory or the gastro-intestinal mucosa, depending on whether they are air-borne or ingested.
House-dust Mites Fig 4
Fecal pellets
Consequences of mediator release Fig 5
Two major pathological consequences: contraction of smooth muscles and increase in vascular permeability.
All symptoms of IgE-mediated allergic reactions can be explained based on these two effects
Oral Allergy Syndrome
In the oral cavity a specific condition called Oral Allergy Syndrome appears when an allergen (from foods or drugs) makes contact with the oral cavity in sensitive patients.
This syndrome is characterized by a rapid swelling of the lips, tongue, gums, palate and pharynx.
Early and Late phases
An IgE allergic reaction is divided into an immediate response (seconds to minutes) and a late-phase response (8-10 hr).
IgE-mediated reactions have also been termed Immediate-type hypersensitivity reactions.
The intradermal injection of a minute amount of allergen into an allergic (atopic) individual gives rise to a local reaction called cutaneous anaphylaxis and characterized by the immediate appearance of a blister full with histamine called a wheal, and redness around it called erythema or flare
The Wheal and Flare, and the Late-phase responses Fig 6
Immediate: appearance of a blister containing histamine called a wheal, surrounded by redness called erythema or flare Late: Only erythema
Systemic anaphylaxis
Allergen given in high doses and reaching the circulation, or given intravenously, triggers the sudden release of large quantities of mediators from the mast cells, and by the basophils in the circulation, and may causes a generalized or systemic reaction called systemic anaphylaxis or anaphylactic shock. These reactions can be fatal: insect venoms or drugs (antibiotics, sulphonamides or even foods)Dentists beware!!Anaphylactic shock to local anaesthetics such as lidocaine or novocaine although rare, are encountered in dental practice
Treatment
Allergy can be treated:
a) by inhibiting IgE production through immune deviation, called also desensitization therapy or
b) by interfering with the release of mediators or with their pharmacologic effects, such as administration of anti-histamines and topical steroids (Fluticasone propionate), or of drugs that prevent mast cell/basophil degranulation (cromolyn sodium).
c) Epinephrine injection (against anaphylactic shock)
Type-II Hypersensitivities
Triggered by IgG or IgM Ab directed against cells and tissues. These Ab activate the complement cascade which in turn induces target cell death.
E.g. IgG or IgM Antibodies against red blood cells Haemolytic anemia
Type-III Hypersensitivities
Soluble Antigen reacting with soluble Ab in the circulation activate the complement cascade leading to powerful inflammatory reactions due to the release of anaphylatoxins.
E.g. glomerulonephritis (the immune complexes are deposited on the glomerular basement membrane of the kidney)
Type-IV Hypersensitivities
Due to the activation of Th-1 cells. The typical type-IV reaction is called also delayed-type hypersensitivity (DTH) The intradermal administration of antigen recognized by an effector CD4+ Th-1 cell local cutaneous reaction. “delayed”: takes 12-24 hr to appear. The aspect of the lesion is different from the wheal and flare of IgE.
Typical examples of DTH reactions are cutaneous reactions to tuberculin in individuals that were in previous contact with tubercle bacilli (Mycobacterium tuberculosis), and reactions to poison ivy
DTH Reaction to Poison Ivy Fig 7
Autoimmune diseases
Chronic inflammatory conditions that arise as a result of either Ab- or T cell-mediated responses to self-antigens (auto-antigens).Typical examples:Juvenile Diabetes: Target tissue: Beta islets (produce insulin) of the pancreas Multiple Sclerosis. Target tissue: CNS white matter (Myelin)Systemic Lupus Erythematosus (SLE): anti-DNA Ab. Target tissue: Kidney, Joints, LeukocytesGraves disease. Target tissue: Thyroid gland.Rheumatoid arthritis. Target tissue (joints).
Immune deficiencies
Occur when one or more components of the immune system are defective.
Immune defects can be inherited or acquired.
The immune defects can involve the T cell, the B cell or both compartments of the immune system, the Complement or the APC.
Inherited (Genetic) Immune defects
Genetic defects can occur in almost any molecule involved in the immune response.
T cell defects:DiGeorge syndrome: Failure of the thymus to be formed (thymic aplasia).
Patients suffer from general susceptibility to infections since the absence of T lymphocytes impacts also on the ability of B cells to synthesize antibodies (see Lecture on T cells)
Inherited B cell defects
X-linked agammaglobulinemia:
X-chromosome-linked inability to produce B lymphocytes, leads to absence of Ig. Patients suffer mainly from infectious diseases with bacteria and viruses that require antibodies for their disposal.
Mixed Immunodeficiencies
Inherited mixed T and B cell defects: Severe combined immune deficiencies (SCID). Patients suffer from total susceptibility to infections since neither T nor B cells are generated.
Inherited defects of phagocytic function.
Inherited defects of complement: Loss of specific complement components. Inability to form the MAC and/or to produce anaphylatoxins.
Acquired immune deficiencies.
Acquired immune deficiency syndrome (AIDS). The immune response becomes defective as a result of exposure to the Human Immunodeficiency Virus (HIV).The HIV infects selectively CD4+ T cells and macrophages. The disease is usually lethal due to loss of CD4+ T cells.
B cell and T cell tumours (myelomas and lymphomas).The uncontrolled growth either B or T lymphocyte tumours encroaches on the ability of normal T and B cells to divide and perform their function.
Consequences of immunodeficiencies in dental
patients Increased incidence of infections in the oral cavity, even with organisms that are usually non-pathogenic such as Candida species (candidiasis) in AIDS patientsCancer patients undergoing chemotherapy, and with AIDSUlcerationsXerostomiaSialadenitisOsteomyelitisPapillary atrophy of the tongueHerpes virus infectionsPeriodontal diseaseIncreased plaque formation.