1. Chapter 16
Topics
- Allergies
- Autoimmunity
- Immunodeficiency

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

3. Type I
Epidemiology
Allergens
Mechanisms
Syndromes

4. 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

5. 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)

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

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

8. 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

9. 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

10. 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

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

12. 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

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

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

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

16. Prostaglandins Vasodilation Increase vascular permeability
Increase sensitivity to pain
Bronchoconstriction

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

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

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

20. Syndromes Atopic diseases Food allergy Drug allergy Anaphylaxis
Treatment

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

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

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

24. 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

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

26. 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

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

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

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

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

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

32. 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

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

34. 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 The genetic/molecular basis for the A and B antigens
(receptors) on red blood cells.

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

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

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

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

39. 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

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

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

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

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

44. Type III
Mechanism
Immune complex reactions
Diseases

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

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

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

48. Diseases
Arthus reaction
Serum sickness

49. 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

50. 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

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

52. Delayed-type hypersensitivity
Infectious allergy
Contact dermatitis
Tissue rejection

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

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

55. 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

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

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

58. 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

59. 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

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

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

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

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

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

65. 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

66. 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

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

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

69. Secondary
Caused by
Infection
Organic disease
Chemotherapy
Radiation