Immunization, Immune Testing, Hypersensitivities, Autoimmunity, and Immunodeficiency

Immunization and Immune Testing

Types of Vaccines

Vaccines are biological preparations that provide acquired immunity to specific infectious diseases. They can be classified based on their composition and method of production.

• Attenuated (Live) Vaccines: Contain live, but weakened, pathogens. These stimulate strong immune responses but may cause disease in immunocompromised individuals.

• Inactivated Vaccines: Contain whole agents (entire killed microbes) or subunits (antigenic fragments). Examples include rabies and hepatitis A vaccines. These are antigenically weaker and require booster doses.

• Toxoid Vaccines: Use chemically or thermally modified toxins to stimulate active immunity. Multiple doses are required for lasting protection (e.g., tetanus toxoid).

• Combination Vaccines: Combine multiple antigens, such as MMR (measles, mumps, rubella) and Pentacel.

• Vaccines Using Recombinant Gene Technology: Involve inserting genes coding for antigens into cells (e.g., bacteria or yeast) to produce large quantities of pure antigen.

Vaccine Manufacture: Bacteria are grown in lab cultures, while viruses are cultured in chicken eggs or cell cultures. Egg-free vaccines are available for those with allergies.

Herd Immunity: Achieved when a high percentage of the population is immune, preventing the spread of pathogens.

Vaccine Safety

• Mild Toxicity: Includes swelling, redness, and pain at the injection site; general malaise.

• Severe Reactions: Rarely, anaphylactic shock may occur; patients should be monitored post-vaccination.

• Residual Virulence: Attenuated vaccines may rarely revert to a virulent form (e.g., oral polio vaccine).

• Regulatory agencies (CDA, FDA) confirm that vaccine risks are much lower than the risks of disease.

Passive Immunotherapy

Passive immunotherapy involves administering preformed antibodies to provide immediate protection.

• Antitoxins: Antibodies against toxins.

• Antivenoms: Used for venomous bites or stings.

• Antisera: Serum containing antibodies, usually from human or large animal donors. Provides immediate, but short-lived, immunity.

• Limitations: Can cause serum sickness (allergic reactions), rapid antibody degradation, and do not induce memory B cells.

• Monoclonal Antibodies: Produced by hybridomas (fusion of plasma cells and myelomas), providing large quantities of identical antibodies.

Serology and Immune Testing

Serology is the analysis of blood to detect antigens or antibodies, useful for diagnosing infections and monitoring disease spread.

• Precipitation Tests: Detect antigen-antibody complexes (precipitates) in optimal ratios. Immunodiffusion is a common method.

• Turbidimetric and Nephelometric Tests: Measure solution cloudiness or light reflection due to immune complex formation.

• Agglutination Tests: Detect clumping of insoluble particles (e.g., blood typing, hemagglutination).

• Neutralization Tests: Assess the ability of antibodies to neutralize pathogens or toxins (e.g., viral neutralization, hemagglutination inhibition).

• Complement Fixation Test: Detects antibodies too small for agglutination; largely replaced by ELISA.

• Labeled Immunoassays: Use labeled antibodies for detection (e.g., fluorescent dyes, enzymes in ELISA).

• ELISA (Enzyme-Linked Immunosorbent Assay): Highly sensitive, automated, and inexpensive test for detecting antigens or antibodies.

• Immunoblots (Western Blot): Detect specific proteins or antibodies, used for confirming infections like HIV or Lyme disease.

• Point of Care Testing: Rapid tests performed at the bedside (e.g., immunofiltration, immunochromatographic assays).

Hypersensitivities and Immune Disorders

Type I Hypersensitivity (Immediate)

Type I hypersensitivity, or allergy, is an exaggerated immune response to environmental antigens (allergens) mediated by IgE antibodies.

• Sensitization: Initial exposure leads to IgE production, which binds to mast cells and basophils.

• Degranulation: Re-exposure causes allergen binding to IgE, triggering release of inflammatory mediators (histamine, kinins, proteases, leukotrienes, prostaglandins).

• Clinical Manifestations: Localized (runny nose, rash, asthma) or systemic (anaphylactic shock).

• Diagnosis: CAP testing for allergen-specific IgE.

• Prevention and Treatment: Allergen avoidance, antihistamines, corticosteroids, epinephrine for anaphylaxis, and immunotherapy (allergy shots).

Type II Hypersensitivity (Cytotoxic)

Type II hypersensitivity involves antibody-mediated destruction of cells, often involving the complement system.

• ABO Blood Group System: Mismatched transfusions cause hemolysis due to antibody binding.

• Rh System: Hemolytic disease of the newborn occurs when Rh-negative mothers develop antibodies against Rh-positive fetal blood cells.

Type III Hypersensitivity (Immune Complex-Mediated)

Type III hypersensitivity results from immune complex deposition in tissues, causing inflammation and tissue damage.

• Examples: Hypersensitivity pneumonitis (e.g., "farmer's lung"), glomerulonephritis, rheumatoid arthritis, systemic lupus erythematosus (SLE).

• Mechanism: Immune complexes escape phagocytosis, deposit in tissues, and trigger complement activation and neutrophil-mediated damage.

Type IV Hypersensitivity (Delayed or Cell-Mediated)

Type IV hypersensitivity is mediated by T cells and occurs 24–72 hours after antigen exposure.

• Tuberculin Response: Skin test for tuberculosis exposure, mediated by memory T cells.

• Allergic Contact Dermatitis: T cell-mediated response to substances like poison ivy.

• Graft Rejection: Immune response against transplanted tissues (autograft, isograft, allograft, xenograft).

• Graft-versus-Host Disease: Donor immune cells attack recipient tissues, especially after bone marrow transplantation.

Immunosuppressive Drugs

Immunosuppressive drugs are used to prevent graft rejection and treat autoimmune diseases by inhibiting various aspects of the immune response.

Class	Examples	Action
Glucocorticoids	Prednisone, methylprednisolone	Anti-inflammatory, kill T cells
Cytotoxic drugs	Cyclophosphamide, azathioprine, mycophenolate mofetil, leflunomide, methotrexate	Block cell division nonspecifically
Cyclosporine	Cyclosporine	Block T cell responses
Lymphocyte-depleting therapies	Antithymocyte globulin, monoclonal antibodies	Kill T cells nonspecifically, or all activated T cells, or inhibit IL-2 reception

Autoimmunity and Immunodeficiency

Autoimmunity

Autoimmune diseases occur when the immune system attacks self-antigens, leading to tissue damage.

• Causes: Hormonal influences (e.g., estrogen), fetal-maternal cell exchange, environmental and genetic factors, exposure of hidden antigens, molecular mimicry by pathogens, and failure of immune regulation.

• Examples:

  • Hemolytic anemia: Antibodies against RBCs cause anemia.

  • Type 1 diabetes: Immune attack on pancreatic beta cells.

  • Graves disease: Autoantibodies stimulate thyroid hormone production.

  • Multiple sclerosis: Cytotoxic T cells attack myelin in the CNS.

  • Rheumatoid arthritis: Immune complexes deposit in joints.

Immunodeficiency Diseases

Immunodeficiency diseases are conditions where the immune system's ability to fight infections is compromised.

• Primary Immunodeficiency: Genetic or developmental defects present at birth or early childhood.

• Acquired (Secondary) Immunodeficiency: Develops later in life due to factors such as malnutrition, severe stress, or infectious diseases (e.g., HIV/AIDS).