Chapter 8: Alterations in Immunity

Question 1

Hypersensitivity: Allergy, Autoimmunity, and Alloimmunity

Answer 1

1. Hypersensitivity is an immune response misdirected against the host’s own tissues (autoimmunity) or directed against beneficial foreign tissues, such as transfusions or transplants (alloimmunity); or it can be exaggerated responses against environmental antigens (allergy).
2. Mechanisms of hypersensitivity are classified as type I (immunoglobulin E [IgE]–mediated) reactions, type II (tissue-specific) reactions, type III (immune complex–mediated) reactions, and type IV (cell-mediated) reactions.
3. Hypersensitivity reactions can be immediate (developing within seconds or hours) or delayed (developing within hours or days).
4. Anaphylaxis, the most rapid immediate hypersensitivity reaction, is an explosive reaction that occurs within minutes of re-exposure to the antigen and can lead to shock.
5. Type I (IgE-mediated) reactions occur after antigen reacts with IgE on mast cells, leading to mast cell degranulation and the release of histamine and other inflammatory substances.
6. Type II (tissue-specific) reactions are caused by four possible mechanisms: complement-mediated lysis, opsonization and phagocytosis, antibody-dependent cell-mediated cytotoxicity, and modulation of cellular function.
7. Type III (immune complex–mediated) reactions are caused by the formation of immune complexes that are deposited in target tissues, where they activate the complement cascade, generating chemotactic fragments that attract neutrophils into the inflammatory site.
8. Immune complex disease can be a systemic reaction, such as serum sickness (e.g., Raynaud phenomenon), or localized, such as the Arthus reaction.
9. Type IV (cell-mediated) reactions are caused by specifically sensitized T cells, which either kill target cells directly or release lymphokines that activate other cells, such as macrophages.
10. Allergens are antigens that cause allergic responses, usually a type I hypersensitivity response.
11. Autoimmune disease is loss of tolerance to self-antigens. There can be a genetic predisposition, and the diseases can be a type II or type III hypersensitivity reaction.
12. Alloimmunity is the immune system’s reaction against antigens on the tissues of other members of the same species.
13. Alloimmune disorders include transient neonatal disease, in which the maternal immune system becomes sensitized against antigens expressed by the fetus; and transplant rejection and transfusion reactions, in which the immune system of the recipient of an organ transplant or blood transfusion reacts against foreign antigens on the donor’s cells.

Question 2

Deficiencies in Immunity

Answer 2

1. Immunodeficiency is the failure of mechanisms of self-defense to function in their normal capacity
2. Immunodeficiencies are either primary or secondary. Congenital immunodeficiencies are caused by genetic defects that disrupt lymphocyte development, whereas acquired immunodeficiencies are secondary to disease or other physiologic alterations.
3. The clinical hallmark of immunodeficiency is a propensity to unusual or recurrent severe infections. The type of infection usually reflects the immune system defect.
4. The most common infections in individuals with defects of cell mediated immune response are fungal and viral, whereas infections in individuals with defects of the humoral immune response or complement function are primarily bacterial.
5. Severe combined immunodeficiency (SCID) is a total lack of T-cell function and a severe (either partial or total) lack of B-cell function.
6. Wiskott-Aldrich syndrome (WAS) is caused by decreased production of IgM antibody.
7. DiGeorge syndrome is characterized by complete or partial lack of the thymus (resulting in depressed T-cell immunity), frequently associated with diminished or absent parathyroid gland activity (resulting in hypocalcemia) and cardiac anomalies.
8. Antibody deficiencies result from defects in B-cell maturation or function and range from a complete lack of the human bursal equivalent, the lymphoid organs required for B-cell maturation (as in Bruton agammaglobulinemia), to deficiencies in a single class of immunoglobulins (e.g., selective IgA deficiency).
9. Phagocyte defects include inadequate numbers or alteration in function, such as inadequate adhesion to bacteria or ineffective killing.
10. Complement and mannose-binding lectin deficiencies also are rare causes of increased risk for infection.
11. Primary immunodeficiency syndromes are usually treated with replacement therapy. Deficient antibody production is treated by replacement of missing immunoglobulins with commercial gamma globulin preparations. Lymphocyte deficiencies are treated by the replacement of host lymphocytes with transplants of bone marrow, fetal liver, or fetal thymus from a donor. There are ongoing trials for gene therapy.
12. Acquired immunodeficiencies are caused by superimposed conditions, such as malnutrition, malignancy, medical therapies, physical or psychologic trauma, or infections.
13. Malignancy is associated with both local and generalized immune suppression that can result in life-threatening infections.
14. Treatments for hypersensitivity disorders, malignancy, and transplant rejection cause profound immune suppression and the benefits of these treatments must be carefully balanced with the risks.
15. Acquired immunodeficiency syndrome (AIDS) is acquired dysfunction of the immune system caused by a retrovirus (HIV) that infects and destroys CD4+ lymphocytes (T-helper cells).