Chapter 17
Immune Disorders
17.1 Type I IgE-Mediated Hypersensitivity
• Type I Hypersensitivity Is Induced by Allergens
• The sensitizing dose is the first dose of antigen
• The immune system responds as it would a pathogen
• The person is sensitized as IgE antibodies attach to mast cells and
basophils
• On subsequent allergen exposure, IgE antibodies are cross-linked
• This causes degranulation, which releases mediator substances:
• Histamine is released into the blood and causes smooth muscle cell
constriction
• Leukotrienes are potent smooth muscle constrictors
• Prostaglandins can constrict bronchial tubes
• Cytokines can also stimulate inflammation
• Systemic Anaphylaxis Is the Most Dangerous Form of a Type I Hypersensitivity
• Allergens in the bloodstream can trigger mast cell degranulation that
contracts smooth muscle
• Small veins constrict and capillary pores expand, forcing fluid into the
tissues
• A drop in blood pressure, edema, and rash occur
• Contractions in the gastrointestinal tract and bronchial muscles cause
cramps and shortness of breath
• The lungs fill with carbon dioxide
• This can cause death by asphyxiation in 10–15 minutes
• Atopic Disorders Are the Most Common Form of a Type I Hypersensitivity
• Atopic disease is a common (seasonal) allergy caused by the inhalation of
pollen
• Year-round allergies can result from chronic exposure to allergens
• Food allergies can cause symptoms like:
• swollen lips
• abdominal cramps
• nausea
• diarrhea
• hives
• anaphylaxis
• Physical factors that can cause allergies include:
• extreme temperatures
• sunlight
• sweating
• Exercise can cause allergies in the form of an asthma attack
• Allergic Reactions Are Also Responsible for Triggering Many Cases of Asthma
• Asthma can be caused by airborne allergens, exercise, or cold temperature
• Degranulation of mast cells releases mediators in the lower respiratory
tract, causing:
• bronchoconstriction
• vasodilation
• mucus buildup
• Recruitment of eosinophils and neutrophils into the lower respiratory tract
can cause:
• tissue injury
• airway blockage
• Why Do Only Some People Have IgE-Mediated Hypersensitivities?
• Atopic people may lack sufficient IgA-secreting lymphocytes to block
antigen stimulation in IgE
• Atopic people may have defective suppressor T cells, allowing for more
IgE production
• Allergies may help expel pathogens through:
• sneezing
• gastrointestinal tract contractions
• Therapies Can Sometimes Control Type I Hypersensitivities
• Desensitization therapy involves a series of injections of allergens which
may:
• Cause gradual reduction of granules in sensitized mast cells
• Cause production of IgG antibodies that neutralize allergens
(blocking antibodies)
• Monoclonal antibodies can be used to dislodge IgE from mast cells and
basophils
• This prevents allergic reactions
• Antihistamines block the effect of histamine
• Corticosteroids are inhaled through the nose to relieve symptoms
• Some also block mediator release
17.2 Other Types of Hypersensitivity
• Type II Cytotoxic Hypersensitivity Involves Antibody-Mediated Cell Destruction
• It occurs when IgG reacts with antigens, often activating complement
• If incompatible blood types are mixed, agglutination occurs and
complement is activated
• Rh disease can lead to stillbirth or jaundice
• Type III Immune Complex Hypersensitivity Is Caused by Antigen-Antibody
Aggregates
• Serum sickness occurs when IgG is produced against residual proteins in a
serum
• This can cause:
– kidney damage
– symptoms of type I anaphylactic hypersensitivity
• In the Arthus phenomenon, very large amounts of IgC complex with
antigens
• This can lead to thromboses in blood vessels
• Type IV Cellular Hypersensitivity Is Mediated by Antigen-Specific T Cells
• Cellular hypersensitivity is an exaggeration of cell mediated immunity
• It is a delayed reaction characterized by:
• thickening and drying of skin tissue (induration)
• surrounding by erythema
• Infection allergy occurs when the immune system responds to certain
microbial agents
• Sensitized lymphocytes remain in the tissue to provide immunity
to subsequent infection
• Sensitivity can be determined by injection of a purified microbial
sample and observation for induration
• Contact dermatitis develops after exposure to a variety of allergens
• Repeated exposures cause drying to skin with erythema and
scaling
17.3 Autoimmune Disorders and Transplantation
• An Autoimmune Disorder Is a Failure to Distinguish Self from Nonself
• There are several theories explaining the development of self-tolerance
• The clonal deletion theory says that self-reactive lymphoid cells are
destroyed during immune system development
• The clonal anergy theory says that self-reactive T or B cells are
inactivated and cannot differentiate into effector cells
• The Regulatory T cell theory says that regulatory T cells suppress
exaggerated immune responses
• Autoimmune disorders can be triggered in several ways:
• Gene mutations can affect cell division and apoptosis
• If the immune system gains access to privileged sites, an immune
response will be mounted
• An antigen can mimic a body substance, causing the immune
system to attack “self” substances
• Treatment usually involves suppressing the immune system
• In myasthenia gravis, antibodies react with receptors on muscle fiber
membranes,
• This causes a loss of muscle activity
• In Graves disease, antibodies bind onto thyroid gland cells
• This causes overproduction of thyroxine
• In type I diabetes, pancreatic beta cells are destroyed
• A lack of insulin production results
• In systemic lupus erythematosus (a.k.a. SLE, lupus), nuclear components of
disintegrating white blood cells elicit IgG production
• Immune complexes aggregate in the skin and organs, causing rash and
lesions
• Rheumatoid arthritis (RA) is an inflammatory condition resulting in accumulation
of immune complexes in joints
• Transplantation of Tissues or Organs Is an Important Medical Therapy
• An autograft is a graft taken from one part of the body and transplanted to
another part of the same body
• An isograft is a graft from one identical twin to the other twin
• Allografts are grafts between genetically different members of the same
species
•
Xenografts are grafts between members of different species (rarely
successful)
• Rejection of transplants becomes more vigorous as the difference in
genetic makeup of donor and recipient increases
• If the recipient body sees the transplanted tissue as “nonself,” the tissue is
rejected
• Cytotoxic T cells attack and destroy transplanted cells
• Phagocytes secrete lysosomal enzymes that digest the tissue
• In bone marrow transplants, the transplanted marrow can form immune
products against the host’s suppressed immune system
• Graft-versus-host-reaction (GVHR) can be fatal to the host
• Rejection is stimulated by recognition of MHC proteins on the surface of
graft cells
• The closer the match between donor and recipient MHC proteins 
the greater the chance of successful transplantation
• Rejection is inhibited by immunosuppression in the host using:
• steroids that suppress the inflammatory response
• antilymphocyte antibodies
• antimitotic drugs
• drugs to suppress cell mediated immunity, monoclonal antibodies
• radiation
17.4 Immunodeficiency Disorders
• Immunodeficiencies Can Involve Any Aspect of the Immune System
• Primary immunodeficiency is the result of a genetic abnormality
• Secondary immunodeficiency is acquired later in life
• X-linked (Bruton) agammaglobulinemia is a congenital humoral
immunodeficiency
• B cells fail to develop, so patients lack mature B cells, plasma
cells, and antibodies
• It is a sex-linked trait, more common in males than females
• In DiGeorge syndrome, the thymus fails to mature in the embryo, so T
cells do not develop
• Patients with ataxia-telangiectasia:
– have malfunctioning B and T cells
– are deficient in IgA and IgE
• Paralysis and dementia lead to death by age 30
• Severe combined immunodeficiency disease (SCID) involves lymph nodes
deficient in B and T cells
• One form is caused by an enzyme deficiency that can be corrected using
gene therapy
• In Chédiak-Higashi syndrome, lysosomes within phagocytes cannot release their
contents to kill microbes
• In chronic granulomatous disease, phagocytes do not produce substances to kill
microbes