NURS 212: Week 15 - Alterations in Immune Function

• Hypersensitivity reactions


  Altered immunologic response to an antigen that results in disease or damage to the host
• Ways hypersensitivity reactions are classified


  • The source of the antigen (allergy, autoimmunity, alloimmunity)
  • The mechanism that causes disease (Types I-IV)
• Alloimmunity (isoimmunity)


  A response to antigens from members of the same species
• Hypersensitivity reactions


  1. Sensitization against a particular antigen

  2. Primary immune response - first encounter forms memory cells

  3. Secondary immune response - memory cells rapidly activated
• Sensitization


  When adequate antibodies or T cells are available to cause a noticeable reaction on re-exposure
• Immediate hypersensitivity


  Reaction within minutes to a few hours of re-exposure
• Delayed hypersensitivity


  Reaction several hours later, maximum severity days after re-exposure
• Anaphylaxis


  The most rapid and severe immediate hypersensitivity reaction (a type I reaction)
• Types of hypersensitivity reactions

  • Type I - IgE mediated
  • Type II - Tissue-specific
  • Type III - Immune complex mediated
  • Type IV - Cell-mediated
• Type I hypersensitivity


  • Mediated primarily by sensitized mast cells (and basophils)
  • Initiated by cross-linking of IgE on mast cells
  • Reaction within 15-30 mins
  • Release of histamines, kinins, prostaglandins, interleukins and leukotrienes
• Type I hypersensitivity


  • Bee sting, drug reactions, asthma
• Type II hypersensitivity


  • Antibody-mediated destruction of target cells
  • Antibodies bind to specific tissue antigens and mark the cell for destruction
  • Mediated by complement system and/or phagocytosis
  • Immediate, within 15-30 mins or can happen over time
• Type II hypersensitivity


  • ABO transfusion reactions
  • Hemolytic disease of the newborn
  • Hyperacute graft rejection
  • Graves' disease
  • Myasthenia gravis
  • Type 1 diabetes
• Type III hypersensitivity

  • Antibody-antigen complexes deposit in tissues and activate complement leading to tissue inflammation and destruction
  • Failure of immune and phagocytic systems to effectively remove antigen-antibody complexes
  • Not tissue-specific, caused by chronic circulating antigens
• Type III hypersensitivity


  • Serum sickness
  • Immune complex glomerulonephritis
  • Arthus reaction
• Type IV hypersensitivity


  • T-cell mediated (no antibodies produced)
  • Slow to react (~24 hrs), last longer (14 days)
  • Inflammation initiated when T-cells react to altered or foreign cells
  • Lymphocytes and macrophages are principle effector cells
• Type IV hypersensitivity


  • Tuberculin skin test
  • Poison ivy
  • Contact dermatitis
  • Transplant rejection
• Type IV hypersensitivity - contact hypersensitivity

  • An epidermal phenomenon
  • Peaks in 48 to 72 hours
  • Dendritic cells present antigen to lymph nodes and activate T cells, leading to inflammatory response
• Type IV hypersensitivity - contact hypersensitivity

  • Poison ivy
  • TB skin test
• Latex allergies


  Can be type 1 (anaphylactic reaction) or type 4 (contact dermatitis)
• Primary immunodeficiency disorders are congenital, caused by genetic defects
• Primary immunodeficiency disorders


  Functional deficiency can affect all cell types depending on which stage of development is interrupted
• Secondary immunodeficiency can be caused by a number of factors including neuroendocrine, poor nutrition, medications/drugs, and acquired immunodeficiency like HIV/AIDS
• Severe Combined Immune Deficiency (SCID)


  Combined absence of T-lymphocyte and B-lymphocyte function, extreme susceptibility to serious infections
• Secondary (acquired) immunodeficiencies are much more common than primary immunodeficiencies
• Acquired Immunodeficiency Syndrome (AIDS)


  A secondary immune deficiency caused by the human immunodeficiency virus (HIV)
• HIV


  • Blood borne RNA virus present in body fluids
  • Transmission in blood, IV drug abuse, sexual activity, maternal-child
  • Infects and depletes T helper cells (CD4+), leaving individuals susceptible to infections and malignancies
• HIV infection


  Retrovirus with RNA genetic information, contains reverse transcriptase to convert RNA to DNA
• HIV structure


  gp120 protein binds to CD4 molecule on helper T cells, destroys CD4+ T cells
• HIV infection stages


  Serologically negative, serologically positive but asymptomatic, early stages, or AIDS
• AIDS diagnosis


  CD4+ T cells < 200 cells/mm3 and presence of opportunistic infections and cancers
• Individuals can be infected with HIV but seronegative for 6-14 months (window period)
• Opportunistic infections associated with AIDS

  • Pneumocystis jiroveci pneumonia (PCP)
  • Mycobacterium avium complex (MAC)
  • Mycobacterium tuberculosis
  • Cytomegalovirus (CMV)
  • Kaposi's sarcoma
  • Candidiasis
• CD4+ cell count and AIDS

  • Above 500 - no unusual conditions likely
  • 200-500 - increased risk of some infections
  • 50-200 - increased risk of opportunistic infections, preventative treatment needed
  • Below 50 - increased risk of MAC, CMV, invasive fungal infections
• Without treatment, people with AIDS typically survive about 3 years
• AIDS treatment


  Antiretroviral therapy (ART) - combination of reverse transcriptase inhibitors, protease inhibitors, integrase inhibitors, fusion inhibitors, and CCR5 antagonists
• ART has significantly reduced death from AIDS, but is not curative
• T-lymphocytes (T-cells) have two subsets: helper/inducer T-cells and suppressor/cytotoxic T-cells.
• Lymphocytes are produced by bone marrow stem cells and mature into T-cells or B-cells.
• The spleen is the largest lymphoid organ, located on the left side of the abdomen.