9.3 Recorded Lecture - Immunity and Inflammation Alterations

• Alterations in immunity and inflammation involve abnormal immune responses that can damage the host.

Hypersensitivity

• An altered immunological response to an antigen that damages the host.
• Divided into four types, although multiple mechanisms can be active in a hypersensitivity reaction:
  • Type I: IgE mediated
  • Type II: Tissue-specific
  • Type III: Immune complex mediated
  • Type IV: Cell-mediated
• Sensitivity can develop rapidly in some individuals, while others require multiple exposures over years.
• Immediate reactions occur within minutes to hours, whereas delayed reactions may take hours to days to reach maximum severity.

Allergy

• Deleterious effects from hypersensitivity to environmental antigens.

Autoimmunity

• Disturbance in immunological tolerance of self-antigens.
• The immune system reacts against self-antigens, producing antibodies against its own tissues.

Alloimmunity

• The immune system reacts against tissues from another individual.
• Commonly occurs after transfusions, transplanted tissues, or during pregnancy against the fetus.

Type I Hypersensitivity

• IgE mediated and antigen-specific.
• Often involves common allergies like pollen or hay fever, which are allergic reactions to environmental antigens.
• Histamine is the most potent mediator, acting on histamine receptors:
  • H1 stimulation: bronchial smooth muscle contraction, increased vascular permeability, edema, vasodilation, and increased blood flow.
  • H2 stimulation: increased gastric acid secretion and decreased histamine release, acting as a self-limiting reaction.
• Blocking histamine receptors can control some Type I responses.

Mast Cells

• Products modulate almost all aspects of acute inflammatory response.
• Immediate response: histamine is released
• Long-term response: leukotrienes, prostaglandins, cytokines, and growth factors are released

Type II Hypersensitivity

• Characterized by immune response targeting a specific cell or tissue.
• Symptoms depend on which tissue or organ expresses the antigen.
• Mechanisms:
  • Cell destruction via the complement cascade through the classical pathway
  • Phagocytosis by macrophages
  • Neutrophil attraction and release of toxic products that damage tissue
  • Antibody-dependent cell-mediated cytotoxicity, where cytotoxic cells release toxic substances
  • Antibody binding to target cell receptors, preventing normal ligand interactions, causing inappropriate stimulation or destruction (e.g., myasthenia gravis).
• In myasthenia gravis, antibodies bind to acetylcholine receptors at the neuromuscular junction, disrupting signaling.

Type III Hypersensitivity

• Caused by antigen-antibody complexes formed in circulation that deposit in vessel walls or extravascular tissue.
• Damage results from complement system activation
• Neutrophils are attracted and release enzymes that damage the inflammatory site.
• Raynaud phenomenon, a type of Type III reaction, involves temperature-dependent deposition of immune complexes in capillary beds, causing localized pallor, numbness, cyanosis, and potential gangrene.

Type IV Hypersensitivity

• Mediated by T lymphocytes, without involvement of antibodies.
• Tissue destruction occurs through direct killing by T cells or release of factors from macrophages, such as lysosomal enzymes and reactive oxygen species.
• Typically involved in graft rejections and contact reactions, like poison ivy.

Autoimmunity (in depth)

• Breakdown of tolerance where the body's immune system recognizes self-antigens as foreign.

Alloimmunity (in depth)

• Immune system reacts against antigens on tissues of other members of the same species.
• Occurs in neonatal diseases where the maternal immune system is sensitized against fetal antigens, as well as in transplant rejection and transfusion reactions.

Systemic Lupus Erythematosus (SLE)

• Chronic, multisystem inflammatory disease involving production of antibodies against various self-components.
• Treatment includes steroids, anti-malarial drugs, intravenous immune globulin (IVIg), and immunosuppressive agents.

Transfusion Reactions and Blood Types

• Antigens on red blood cells determine blood type.
• Type A blood has anti-B antibodies.
• Type B transfusions will cause reaction.
• Type O individuals have both anti-A and anti-B antibodies (agglutinins) but have neither A nor B antigens.
• The Rh system includes five major antigens, with RHD determining Rh positivity or negativity.

Disorders Resulting from Immune Deficiency

• Impaired function of immune or inflammatory response components.
• Leads to increased susceptibility to infections.
• Primary deficiencies are caused by genetic anomalies.
• Secondary deficiencies are caused by other illnesses.
• Pregnancy decreases immune reactivity, but not severely altered.

Secondary Immune Deficiencies

• Caused by various factors including other illnesses.

Treatments for Primary Immune Deficiency Diseases

• Treatment options are available for primary immune deficiency diseases.