Chapter 16


Disorders in Immunity



Types of Immunological Disorders

  Hypersensitivity reactions

  Autoimmune disease




Hypersensitivity Reactions

  Hypersensitivity reactions to usually harmless substances are often called allergies or allergic reactions

  Allergens antigens that cause allergic reactions

  4 Types:

  Type I:  Immediate IgE-mediated

  Type II:  Cytotoxic

  Type III:  Immune complex-mediated

  Type IV:  Delayed cell-mediated



Type I Hypersensitivity

  Also called IgE Mediated Hypersensitivity

  First exposure:

  Allergen is taken up by APCs and merged with MHC molecules

  APC presents the allergen to T-cells

  Activated T-cells release cytokines that stimulate B-cells to become plasma cells which secrete IgE antibodies

  IgE antibodies bind to mast cells and the individual is now sensitized

Mast cells are derived from basophils

  Second exposure:

  allergens bind IgE on the mast cell causing it to degranulate

  histamine, leukotrienes, prostaglandins, bradykinin and serotonin are released

  these chemicals are the cause of hives, hay fever, asthma, and anaphylactic shock

  Reactions generally occur within 30 minutes of exposure



Type I Hypersensitivity: Atopy

  Localized allergic reaction

  Hives skin condition characterized by the formation of a wheal and flare pattern 

  frequently the result of food allergies

  due to the release of histamine

causes dilation of tiny blood vessels and leakage of plasma into the area

  treat with anti-histamines

  Allergic rhinitis (hay fever) also mediated by histamine

  itchy, teary eyes, sneezing, and runny nose, occurs when allergic person inhales an allergen rather than ingests it

  Atopic Dermatitis (eczema)

  itchy inflammatory reaction in the skin from ingestion, inhalation, or skin contact with allergens

  predisposed to bacterial infections

  Asthma leukotrienes and prostaglandins are responsible for bronchospasms

  inhaled allergen causes chemical mediators to stimulate increased mucus secretions and spasms of the bronchi 

  treated with bronchodilators by inhaler



Type I Hypersensitivity: Anaphylaxis

  Systemic allergic reaction

  Allergen enters the bloodstream and disrupts respiratory and circulatory systems

  Loss of fluid from the blood vessels into tissues causes swelling and possibly shock

  Reactions may be fatal within minutes

  Commonly caused by: bee stings, peanuts, and penicillin injections

  Can usually be controlled by epinephrine injections



Type I Hypersensitivity: Treatment

  Desensitization - often effective in decreasing the Type I hypersensitivity state

  Repeated injections of very small amounts of allergen are given over several months

  This regimen leads to the formation of specific IgG antibodies

  The IgG reacts with allergen before it can bind to IgE and therefore it blocks the IgE reaction that might result in allergic reactions

  Another approach is to use antibodies to IgE to counteract and remove the allergy-causing IgE (rhuMab)

  effective in treating asthma



Type II Hypersensitivity

  Cytotoxic - utilizes antibodies that can destroy normal cells by complement lysis

  Generally occurs within hours after exposure

  Transfusion Reactions - The ABO blood groups are the major cause of hemolytic anemia in blood transfusion patients

  Persons with A type blood possess the A antigen and the natural antibody anti-B

  Persons with B type blood possess the B antigen and the natural antibody anti-A

  Persons with O type blood lack both the A and B antigens but possess both the natural antibodies anti-A and anti-B (universal donor)

  Persons with AB type blood possess both the A and B antigens but possess no natural antibodies (universal recipient)

  In the case of ABO incompatibility, the antibodies cause reactions that include fever, jaundice, kidney failure, and shock

  Cross-matching blood from donor and recipient helps to ensure compatibility

  Hemolytic Disease of the Newborn - results when mother is Rh- and baby is Rh+

  Also called Erythroblastosis fetalis

  Upon delivery, Rh antigens enter the mothers bloodstream which causes her to produce anti-Rh antibodies

  If the mother becomes pregnant again with an Rh+ child, the antibodies cross the placenta, enter the circulation of the fetus, and cause extensive fetal erythrocyte damage

causes anemia, jaundice, and enlarged spleen and liver

  RhoGAM may be administered near birth to prevent this reaction

contains Rh antibodies and prevents the mothers natural production of them



Type III Hypersensitivity

  Caused by free-floating antigen-antibody complexes that deposit in tissues and cause inflammation and tissue damage

  Occurs within hours or days after exposure

  When there is an overabundance of antigen, the antigen-antibody complexes activate complement and stimulate neutrophil and basophil degranulation

  The mediators released from the leukocyte granules cause vasodilation, increased vascular permeability and inflammation

  Arthus reaction - localized tissue death in previously immunized individuals at the site of injection

  Serum sickness - systemic reaction in individuals immunized with animal serum

  immune complexes are deposited in blood vessels of kidney, heart, skin, and joints



Type IV Hypersensitivity

  Also called Delayed Cell-Mediated Hypersensitivity

  Occurs within days after exposure

  T-cells rather than antibodies are involved with this type

  Tuberculin skin test a positive reaction to antigens of Mycobacterium tuberculosis introduced under the skin

  peaks 2-3 days after exposure

  there is no wheal formation

  redness results mainly from sensitized T-cell reactions, the release of cytokines and the influx of leukocytes to the injection site

  Contact Dermatitis mediated by sensitized T-cells that release cytokines when they come into contact with the same antigen 

  the cytokines cause inflammation which attracts macrophages to the site, causing local tissue damage

  caused by: poison ivy, poison oak, nickel reactions, and latex reactions

  Delayed hypersensitivity to infectious diseases as T-cells destroy macrophages and infected body cells, tissue damage results

  Ex.  leprosy, tuberculosis, and herpes simplex



Transplant Immunity

  There are 4 types of transplants:

  Autografts grafts from the same person

  Isografts grafts from a genetically identical twin

  Allografts grafts between genetically non-identical humans

  Xenografts transplantation of tissue from a non-human organism

  Transplantation rejection of allografts and xenografts involves cytolysis by cytotoxic T cells and NK cells

  Transplant success is dictated by the similarity of the MHC antigens on the surface of human cells

  MHC antigens are abundant on human leukocytes and are frequently called HLAs (human leukocyte antigens)

  MHC tissue typing - ensures that no major tissue incompatibilities exist between patient and donor   

  also Mixed Lymphocyte Reaction to see if lymphocytes are incompatible

  Immunosuppressive drugs - taken to reduce rejection

  these drug treatments however, make the patient susceptible to opportunistic infections and cancer

  Graft Versus Host Disease (GVHD) lymphocytes in graft attack host cells



Autoimmune Diseases

  Occur when the immune system responds to its own tissues as if they were foreign

  Involve autoantibodies and/or T cells

  Cluster in families and may result from normal reactions to antigens that are similar to the hosts normal antigens



Origins of Autoimmune Disease

  Molecular mimicry - some microbes express proteins similar to host antigens

  Sequestered Antigen Theory cellular antigens hidden from the immune system during development become exposed after tissue injury or infection

  Clonal Selection Theory clones that react to self antigens are not eliminated



Autoimmune Diseases: Organ-specific Reactions

  Graves disease thyroid

  autoantibodies cause overstimulation of thyroid gland and hyperthyroidism

  Type I diabetes pancreas

  cytotoxic T cells destroy insulin-producing beta cells

  Myasthenia gravis muscle

  autoantibodies to acetylcholine receptors on muscle membranes prevent muscle contraction

  first affects eye and throat, then can lead paralysis and death

  Multiple sclerosis (MS) myelin

  T cells and autoantibodies cause lesions in the myelin sheath that surrounds neurons

  muscle weakness, tremors, difficulties in speech and vision, and paralysis



Autoimmune Diseases: Systemic Reactions

  Rheumatoid arthritis

  autoantibodies form immune complexes that cause chronic inflammation in joints

  Systemic lupus erythematosus (SLE)

  autoantibodies against nuclear proteins of nearly all body cells

  involves kidneys, bone marrow, skin,nervous system, joints, muscle, heart, and GI tract

  Butterfly-shaped rash forms across the nose and cheeks




Autoimmune Diseases: Treatment

  Involves immunosuppressive and anti-inflammatory drugs

  Replacement therapy is possible sometimes




Immunodeficiency Disorders

  A condition in which there is a deficiency or defect in immune cells

  Primary immunodeficiencies present at birth from genetic abnormalities   

  Agammaglobulinemia deficient antibody production

   IgA deficiency

   DiGeorge Syndrome thymus doesnt develop so no cell-mediated immunity

  Severe combined immunodeficiencies (SCIDs) no functional B or T cells

  Secondary immunodeficiencies acquired after birth  

  malignancies, age, infections, radiation, chemotherapy, and immunosuppressive drugs

  Patients susceptible to repeated infections