1. Chapter 16
Disorders in Immunity

2. The Immune Response - A Two- Sided Coin
Humans possess a powerful and intricate system of defense, which by its nature also carries the potential to cause injury and disease
Abnormal or undesirable immune functions are actively involved in certain debilitating or life-threatening diseases
asthma, anaphylaxis, rheumatoid arthritis, graft rejection

3. Immunopathology
Immunopathology is the study of disease states associated with overreactivity or underreactivity of the immune response
Allergy, hypersensitivity – a condition of altered reactivity or exaggerated, misdirected immune responsiveness that is manifested by inflammatory symptoms
Involves the same types of immune reactions as those at work in protective immunities
Autoimmunity – abnormal responses to self Ag
Immunodeficiency diseases – immune function is incompletely developed, suppressed or destroyed
Cancer – a cause and an effect of immune dysfunction

6. Type I Hypersensitivity
Two levels of severity:
Atopy – any chronic local allergy such as hay fever or asthma
Anaphylaxis – a systemic, often explosive reaction that involves airway obstruction and circulatory collapse

7. Contact With Allergens
Allergic and hypersensitive individuals are acutely sensitive to repeated contact with antigens called allergens, that do not noticeably affect nonallergic individuals
Allergy can be affected by age, infection, and geographic area
Atopic allergies may be lifelong or may be “outgrown”; may also develop later in life

8. Nature of Allergens and Their Portals of Entry
Allergens have immunogenic characteristics
Typically enter through epithelial portals – respiratory, gastrointestinal, skin
Organ of allergic expression may or may not be the same as the portal of entry

11. Mechanism of Type I Allergy
Develop in stages:
Sensitizing dose – on first contact with allergen, specific B cells form IgE which attach to mast cells and basophils; generally no signs or symptoms
Provocative dose - subsequent exposure with the same allergen binds to the IgE-mast cell complex
Degranulation releases mediators with physiological effects such as vasodilation and bronchoconstriction
Symptoms are rash, itching, redness, increased mucous discharge, pain, swelling, and difficulty breathing

13. Role of Mast Cells and Basophils
Mast cells are located in the connective tissue of virtually all organs; high concentration in lungs, skin, GI and genital tract
Basophils circulate in blood and migrate into tissues
Each cell can bind 10,000-40,000 IgE
Cytoplasmic granules contain physiologically active cytokines, histamine, etc.
Cells degranulate when stimulated by allergen

14. Insert figure 16.3
Cellular reactions

15. Chemical Mediators and Allergic Symptoms
Act alone or in combination; account for scope of allergic symptoms
histamine, serotonin, leukotriene, platelet-activating factor, prostaglandins, bradykinin
General targets include: skin, upper respiratory tract, GI tract, and conjunctiva
responses: rashes, itching, redness, rhinitis, sneezing, diarrhea, shedding tears
Systemic targets: smooth muscles, mucous glands, and nervous tissue
responses: vascular dilation and constriction resulting in change in blood pressure and respiration

17. Histamine – most profuse and fastest acting; stimulator of smooth muscle, glands, and eosinophils
response to chemical depends on the muscle location: constricts smooth muscles of small bronchi, intestines; relaxes vascular smooth muscles

18. Specific Diseases Associated with IgE- and Mast Cell-Mediated Allergy
Atopic disease – hay fever (allergic rhinitis) is a seasonal reaction to inhaled plant pollen or molds, or a chronic year-round reaction to a wide spectrum of airborne allergens or inhalants
The targets are typically respiratory membranes, and the symptoms include nasal congestion, sneezing, coughing, profuse mucous secretion, itchy red teary eyes, and mild bronchoconstriction
asthma – severe bronchoconstriction; inhaled allergen
eczema – dermatitis; ingestion, inhalation, skin contact

20. Food and Drug Allergy
Food allergy – intestinal portal can affect skin and respiratory tract
vomiting, diarrhea, abdominal pain; possibly severe
eczema, hives, rhinitis, asthma, occasionally anaphylaxis
Drug allergy – common side effect of treatment; any tissue can be affected; reaction from mild atopy to fatal anaphylaxis

21. Systemic Anaphylaxis
Sudden respiratory and circulatory disruption that can be fatal in a few minutes
Allergen and route are variable
Bee stings, antibiotics or serum injection

22. Diagnosis of Allergy
Important to determine if a person is experiencing allergy or infection
Skin testing

24. Treatment and Prevention of Allergy
General methods include:
Avoiding allergen
Use drugs that block the action of the lymphocytes, mast cells, chemical mediators – antihistamines
Desensitization therapy – injected allergens may stimulate the formation of high-levels of allergen-specific IgG that act to block IgE; mast cells don’t degranulate

27. Type II Hypersensitivity
Reactions that lyse foreign cells
Involve antibodies, complement, leading to lysis of foreign cells
Transfusion reactions
ABO blood groups
Rh factor – hemolytic disease of the newborn

28. Human ABO Antigens and Blood Types
4 distinct ABO blood groups
Genetically determined RBC glycoproteins; inherited as 2 alleles of A, B, or O
4 blood types: A, B, AB, or O
named for dominant antigen(s)
type O persons lack both A and B antigens
tissues other than RBCs also carry A and B antigens.

31. Antibodies Against A and B Antigens
Serum contains pre-formed antibodies that react with blood of another antigenic type-agglutination; potential transfusion complication
Type A contains Abs that react against B antigens
Type B contains Abs that react against A antigens
Type O contains Abs that react against A and B antigens
Type AB contains no Abs that react against A or B antigens

34. Rh Factor and Hemolytic Disease of the Newborn
RBC antigen – type results from combination of 2 alleles
Inheriting one dominant gene results in the production of the Rh antigen; no pre-formed antibodies exist; must have exposure
Hemolytic Disease of the Newborn (HDN) – an Rh- mother forms antibodies to her Rh+ fetus; usually requires subsequent exposure to the antigen to be hemolytic
Prevention requires the use of passive immunization with antibodies against the Rh antigen; prevents sensitization of mother

35. Development and control of Rh
Insert figure 16.12
Development and control of Rh

36. Type III Hypersensitivity
A large quantity of soluble foreign Ag stimulates Ab that produce small, soluble Ag-Ab complexes
Immune complexes become trapped in tissues and incite a damaging inflammatory response
arthus reaction – local reaction to series of injected Ag to same body site
serum sickness – systemic disease resulting from repeated injections of foreign proteins
they depend upon IgG, IgM, or IgA rather than IgE
they require large doses of antigen
their symptoms are delayed (a few hours to days)

38. Type IV Hypersensitivity
T cell-mediated
Delayed response to Ag involving activation of and damage by T cells
Delayed allergic response – skin response to allergens – tuberculin skin test, contact dermititis from plants, metals, cosmetics
Graft rejection – reaction of cytotoxic T cells directed against foreign cells of a grafted tissue; involves recognition of foreign HLA

40. T Cells and Organ Transplantation
Graft/transplantation rejection – host may reject graft; graft may reject host
MHC markers of donor tissue (graft) are different; T cells of the recipient recognize foreignness
Release interleukin-2 which amplifies helper and cytotoxic T cells which bind to donor tissue and release lymphokines that begin the rejection

41. Classes of Grafts
Classified according to the degree of MHC similarity between donor and host:
autograft – recipient also serves as donor
isograft – tissue from identical twin is grafted
allograft – genetically different individuals but of the same species (humans)
xenograft – individuals of different species
Rejection can be minimized by tissue matching HLA antigens, immunosuppressive drugs, and use of tissue that does not provoke a type IV response

43. Autoimmunity
In certain type II & III hypersensitivities, the immune system has lost tolerance to autoantigens and forms autoantibodies and sensitized T cells against them
More common in females
Disruption of function can be systemic or organic specific:
systemic lupus erythematosus
rheumatoid arthritis
endocrine autoimmunities
myasthenia gravis
multiple sclerosis

48. Immunodeficiency Diseases
Components of the immune response system are absent. Deficiencies involve B and T cells, phagocytes, and complement
2 general categories:
primary immunodeficiency diseases – congenital; usually genetic errors
secondary immunodeficiency diseases – acquired after birth; caused by natural or artificial agents

49. Primary Immunodeficiency Diseases
Primary immunodeficiency - lack of B-cell and/or T cell activity
B cell defect – agammaglobulinemia – patient lacks antibodies
T cell defect – thymus is missing or abnormal
severe combined immunodeficiency (SCID) - both limbs of lymphocyte system are missing or defective; no adaptive immune response

50. Secondary Immunodeficiency Diseases
Secondary diseases - due to damage after birth
caused by: infection, organic disease, chemotherapy, or radiation
AIDS most common – T helper cells are targeted; numerous opportunistic infections and cancers

53. The Immune System and Cancer
Overgrowth of abnormal tissue arises due to malfunction of immune surveillance
Tumors may be benign (nonspreading) self-contained; or malignant that spreads from tissue of origin to other sites
Cancers occur in nearly every cell type
Appear to have genetic alteration that transforms a normal cell
Possible causes include: errors in mitosis, genetic damage, activation of oncogenes, or retroviruses