Chapter 16 Topics - Allergies - Autoimmunity - Immunodeficiency

Allergies Allergens (antigens) cause an exaggerated immune response or hypersensitivity Type I Type II Type III Type IV

Type I Epidemiology Allergens Mechanisms Syndromes

Epidemiology 10% - 30% of population suffer from allergies Hereditary – generalized susceptibility to allergies Allergic antibody (IgE) production Increased reactivity of mast cells Age, infection, and geographic locale can also determine risk for allergies

Allergens Protein Hapten (must combine with a larger carrier molecule) Entry Respiratory tract Inhalants (pollen, mold spores) Gastrointestinal tract Ingestants (food, water) Skin Injectants (bites)

Example of dust mites and pollen, which are a source of allergies. Fig. 16.2 Monitoring airborne allergens

Common allergens for the respiratory tract, gastrointestinal tract, and skin. Table 16.2 Common allergens, classified by portal of entry

Mechanisms First exposure Mast cells and basophils Reexposure Sensitizing dose - elicits no symptoms Memory B cells are produced Small amount of IgE antibodies are produced Mast cells and basophils Reexposure Second expoure

Mast cells and basophils Contain receptors that bind IgE antibodies Ubiquitous location (connective tissue for most organs) Secrete chemical mediators from cytoplasmic granules Release contents of granules by degranulation

Second exposure Allergens bind to memory B cells B cells produce large amounts of IgE antibodies (high titer) IgE bind to mast and basophil cells Release chemical mediators Degranulation

Chemical mediators Responsible for allergic symptoms Histamine Serotonin Leukotriene Platelet-activating factor Prostaglandins Bradykinin

Histamine Fast-acting allergic mediator Constricts smooth muscle layers – small bronchi, intestine Relaxes vascular smooth muscle, dilates arterioles and venules Stimulator of glands and eosinophils Wheal and flare reactions in the skin Pruritis (itching) Headache Anaphylaxis

Serotonin Complements histamine Increases vascular permeability, capillary dilation, smooth muscle contraction, intestinal peristalsis, respiratory rate Diminishes central nervous system activity

Leukotriene Different types Prolonged bronchospasm Vascular permeability Mucous secretions Stimulate polymorphonuclear leukocyte activity

Platelet-activating factor Lipid Produced by basophils, neutraphils, monocytes, and macrophages Response similar to histamine

Prostaglandins Vasodilation Increase vascular permeability Increase sensitivity to pain Bronchoconstriction

Bradykinin Prolonged smooth muscle contractions of the bronchioles Dilatation of peripheral arterioles Increase capillary permeability Increase mucous secretion

The mechanism of action of chemical mediators. Fig. 16.4 The spectrum of reactions to inflammatory cytokines

Summary of the Type I allergic response. Fig. 16.3 A schematic view of cellular reactions during the Type I allergic response.

Syndromes Atopic diseases Food allergy Drug allergy Anaphylaxis Treatment

Atopic diseases Atopy – chronic local allergy Hay fever (allergic rhinitis) Asthma Dermatitis

Hay fever Reaction to pollen or molds Targets respiratory membranes Symptoms Nasal congestion Sneezing Coughing Mucous secretions Itchy, red and teary eyes Mild bronchoconstriction

Asthma Severe bronchoconstriction Symptoms Shortness of breath to suffocation Wheezing Cough Inflamed respiratory tract

Atopic dermatitis Intense itchy inflammatory condition of the skin (eczema) Can begin in infancy and progress to adulthood Symptoms Dry, scaly, thickened skin Face, scalp, neck, inner surface of limbs and trunk

An example of atopic dermatitis in an infant. Fig. 16.5 Atopic dermititis

Anaphylaxis Cutaneous Systemic Wheal and flare inflammatory reaction to the local injection of an allergen Systemic Rapid immune response that can disrupt respiratory and circulatory systems Can result in death

Treatment Diagnosis Drug Desensitizing Skin testing Antiallergy medications Desensitizing IgG antibodies block IgE function

An example of a typical skin test to determine sensitivity to certain allergens. Fig. 16.6 A method for conducting an allergy skin test.

The method of desensitization. Fig. 16.8 The blocking antibody theory for allergic desensitization.

Type II Interaction of antibodies, foreign cells, and complement, which then leads foreign cell lysis ABO blood groups Rh factor Other RBC antigens

ABO blood groups RBC markers (glycoproteins) Genetically determined Alleles – A, B, O Blood types

Blood types Each individual will have antibodies against another antigenic type (environmental sensitization). Type A will have anti-b antibodies Type B will have anti-a antibodies Type O will have anti-b and anti-a antibodies Universal donor Type AB will has no anti-b or a antibodies Universal recipient

Major characteristics of the four bloods types. Table 16.3 Characteristics of ABO blood groups

Specific genes that encode for enzymes that add a unique sugar to the RBC receptor are the basis for the A and B antigens. Fig. 16.9 The genetic/molecular basis for the A and B antigens (receptors) on red blood cells.

Agglutination test will confirm the blood type of an individual. Fig. 16.10 Interpretation of blood typing.

Incompatible blood will result in agglutination, complement activation, and cell lysis. Fig. 16.11 Microscopic view of a transfusion.

Rh factor Another RBC antigen Placental sensitization At least one dominant allele = Rh+ Two recessive alleles = Rh- Placental sensitization Hemolytic disease Prevention

Hemolysis Rh- mother and Rh+ fetus First birth Second birth Little anti-Rh antibody produced Memory cells Second birth Larger immune response Hemolysis

Prevention Passive immunity using anti-Rh factor immunoglobulin (Rhogam) 28-38 weeks Immediately after delivery Administer for each pregnancy that involves Rh+ fetus Ineffective if mother is already sensitized

Placental sensitization can cause hemolysis, but this can be prevented by immunoglobulin treatments. Fig. 16.12 Development and control of Rh incompatibility.

Type II Autoimmune Diseases and tissue targeted Hashimoto’s Disaese – Thyroid Grave’s Disease – Thyroid Myasthenia Gravis – Acetylcholine Receptors Goodpasture Syndrome – Kidney

The autoimmune reaction of myasthenia gravis, in which antibodies block the attachment of acetylcholine. Fig. 16.19 Mechanism for involvement of autoantibodies in myasthenia gravis.

An example some major autoimmune diseases. Table 16.4 Selected autoimmune diseases.

Type III Mechanism Immune complex reactions Diseases

Mechanisms Similar to Type II, except antibodies react with free- antigens, no fixed antigens Ab-Ag complexes deposit in tissue causing immune complex reactions

Steps associated with the formation of immune complexes. Fig. 16.13 Pathogenesis of immune complex disease.

Type III Autoimmune Diseases Systemic Lupus Erythematosis antigen/antibody complexes settle in the skin Rheumatoid Arthritis antigen/antibody complexes settle in the joints

Diseases Arthus reaction Serum sickness

Arthus reaction Injected antigen (eg. Vaccine, drug) Localized dermal injury due to inflamed blood vessels Acute response to a second similar antigen injection Severe cases result in necrosis and loss of tissue

Serum sickness Injection of serum, hormones, drugs Systemic injury Ag-Ab complexes circulate in the blood and eventually settle into membranes (kidney, heart, skin) Chronic – enlarged lymph nodes, rashes, painful joints, swelling, fever, and renal dysfunction

Type IV Cell-mediated (delayed) reactions Primary a T cell response Delayed-type hypersensitivity

Delayed-type hypersensitivity Infectious allergy Contact dermatitis Tissue rejection

An example of an infectious allergy would be an individual that is sensitized by a tuberculosis infection. Fig. 16.14 Positive tuberculin test.

Contact dermatitis can result from poison oak. Fig. 16.15 Contact dermatitis

Tissue rejection T cell mediated recognition of foreign MHC receptors Cytotoxic T cells Host rejection of graft Graft rejection of host Classes of grafts Types of transplants

Two possible reactions that can occur due to transplantation. Fig. 16.16 Potential reactions in transplantation.

Classes of transplants Autograft - from self Isograft – from twin Allograft – from another organism from same species Xenograft – from another organixm from a different species

Types of transplants Live donors – skin, liver, kidney, bone marrow Fetal donors – pancreas, brain tissue Cadaver donors – heart, kidney, cornea Stem cells – bone marrow, blood, umbilical cord

Autoimmunity Antibodies, T cells or both, mount an immune response against self antigens Systemic or organ-specific Type II or III reactions Cause Genetic Gender Origins Diseases

Origins Sequestered antigen theory Clonal selection theory Theory of immune deficiency Inappropriate expression of MHC II Molecular mimicry Viral infections

Diseases Systemic autoimmunities Endocrine Neuromuscular Systemic lupus erythematosus Rheumatoid arthritis Endocrine Graves disease Hashimoto thyroiditis Diabetes mellitus Neuromuscular Myasthenia gravis Multiple sclerosis

An example of systemic lupus and rheumatoid arthritis. Fig. 16.17 Common autoimmune diseases.

The autoimmune response in Type I diabetes mellitus. Fig. 16.18 The autoimmune component in diabetes mellitus.

Immunodeficiency A person can be born with or develop a weakened immune system Primary Secondary

Primary Affects antibody production and phagocytosis Inherited abnormality Deficiencies in B-cell or T-cell and development and expression Combined B- and T-cell deficiency

Primary Immune Disorders Agammaglobinemia – Lack of B-cells DeGeorge Syndrome – Lack of T-cells Severe Combined Immune Deficiency – Lack of B and T cells Chediak-Higashi Syndrome – Phagocyte Defect

Deficiencies in B and T cell development can reduce the level of protection by the immune system. Fig. 16.20 The stages of development and the function

Example of DeGeorge syndrome, which is a T cell development deficiency. Fig. 16.21 Facial characteristics of a child with DiGeorge syndrome

Secondary Caused by Infection Organic disease Chemotherapy Radiation