Immune Disorders and Diagnosing Infections

Learning Objectives

Hypersensitivities:
Identify the 4 major categories of hypersensitivities and explain their immunologic features.

Type I: Allergy
Type II: Antibody-mediated
Type III: Immune-complex
Type IV: Cell-mediated (T-cell)

Autoimmunity:
Explain the basis of autoimmune diseases and list examples and features related to them.

Hyposensitivities:
Define hyposensitivity and distinguish between primary and secondary immunodeficiencies.

Immunopathology

Definition:
Disease states caused by overreactivity or underreactivity of the immune system.

Key Terms:
Hypersensitivity: Immune overreaction
Autoimmunity: Immune self-reaction
Hyposensitivity: Immune underreaction (immunodeficiency)

Hypersensitivity: Four Types

  1. Type I: Common allergies and anaphylaxis

  2. Type II: Antibody-mediated

  3. Type III: Immune complex-mediated

  4. Type IV: T-cell response

Type I Hypersensitivity

Overview: Rapid reaction to an antigen (allergens) mediated by Immunoglobulin E (IgE). This hypersensitivity is an exaggerated immune response which can vary in intensity from mild reactions, like sneezing, to severe life-threatening events, such as anaphylaxis.

Examples:

  • Allergies: Exaggerated immune responses to antigens, characterized by symptoms like itching, swelling, and rashes.

  • Atopy: Chronic local allergies, such as allergic rhinitis (hay fever) or asthma, which are often hereditary.

  • Anaphylaxis: Extreme, systemic reactions that obstruct airways and may lead to circulatory collapse, requiring immediate medical intervention.

Mechanism of Action:

  • Sensitization: Initial exposure to allergens causes B cells to produce IgE antibodies, which bind to mast cells and basophils.

  • Subsequent Exposure: Upon later contact with the same allergen, it binds to these IgE antibodies, triggering mast cell degranulation and the release of mediators like histamine, prostaglandins, and leukotrienes that contribute to allergic symptoms.

Role of Immunoglobulins (Ig)

Types of Immunoglobulins:

  • IgG: Most prevalent antibody in blood and serum, important for long-term immunity.

  • IgA: Found in mucosal areas, such as the gut and respiratory tract, as well as in breastmilk, playing a crucial role in mucosal immunity.

  • IgM: The first antibody produced in response to an antigen, indicating recent infection.

  • IgD: Functions primarily as a receptor on B cells, playing a critical role in the activation and differentiation of B cells.

  • IgE: Primarily involved in allergic reactions and protection against parasitic infections, associated with hypersensitivity responses.

Allergens

Definition: Antigens that provoke abnormally strong immediate responses from the immunological system.

Types of Allergens:

  • Inhaled: Pollen, dust mites, mold spores, and animal dander.

  • Ingested: Common food allergens including peanuts, tree nuts, eggs, soy, milk, and shellfish.

  • Injected: Allergens from antibiotics, vaccines, and insect venoms, presenting increased risk of systemic reactions.

  • Contact: Substances like latex, lotions, and certain metals that can provoke dermatological reactions.

Treatment of Type I Hypersensitivity

  1. Blocking Allergens:

    • Medications such as antihistamines (e.g., loratadine), corticosteroids, and leukotriene receptor antagonists to minimize immune response.

    • Epinephrine for severe reactions such as anaphylaxis, counteracting symptoms rapidly.

  2. Avoidance:

    • Detailed patient histories to identify allergens; implementation of allergen-free environments when possible.

  3. Desensitization:

    • Immunotherapy involving gradually injecting specific amounts of allergens to shift the immune response towards IgG production, which competes with IgE, thus reducing the allergic symptom severity over time.

Type II Hypersensitivity

Overview: Antibody-mediated response (IgG and IgM) that activates the complement system and leads to cell lysis.

Examples:

  • Transfusion reactions: Occur when mismatched blood types lead to hemolysis of red blood cells.

  • Autoimmune diseases (e.g., Graves' disease) wherein antibodies target self-antigens, leading to tissue damage.

Key Concept: Alloantigens are self-antigens that differ among individuals (e.g., ABO blood groups).

Rh Factor

  • Blood Types: Distinguished by the presence of antigens on red blood cells: A, B, O, and Rh (Rhesus).

  • Rh Factor: Present in 85% of humans (Rh+) and absent in 15% (Rh-).

  • Antibodies against the Rh antigen only develop through transfusions, pregnancy exposure to Rh+ blood, making Rh incompatibility a concern in pregnancy.

Rh Incompatibility in Pregnancy
Mechanism:

  • First pregnancy with Rh+ fetus may sensitize Rh- mother to produce anti-Rh antibodies, potentially causing hemolytic disease of the newborn (HDN) in subsequent pregnancies.

  • RhoGAM Treatment: Administering anti-Rh antibodies to the mother during and after the first pregnancy helps prevent antibody production.

Type III Hypersensitivity

Overview: Occurs when soluble antibodies react with soluble antigens to form immune complexes that precipitate and cause tissue damage.

Mechanism:

  • Immune complex reaction involving IgG or IgM antibodies which activate the complement pathway, initiating inflammation and recruiting neutrophils to the site of accumulation.

Diseases:

  • Arthus reaction: Localized acute response that manifests after the second exposure to an antigen such as vaccine during which immune complexes deposit in tissues.

  • Serum sickness: Systemic immunological response when immune complexes form after exposure to certain medications or antigens, resulting in widespread inflammation.

Type IV Hypersensitivity

Overview: Delayed-type hypersensitivity which involves T-cell mediated immune responses against antigens that may be self or from transplanted foreign cells.

Examples:

  • Infectious allergy: T cell-mediated response following sensitization to specific antigens (e.g., Tuberculosis skin test reactions).

  • Contact dermatitis: Manifestation of T-cell recruitment to contact allergens, resulting in delayed rashes (e.g., poison ivy).

Autoimmune Disorders

Definition: Conditions where the immune system mistakenly attacks the body’s own tissues due to dysregulation.

Causes:

  • Genetic Factors: Certain MHC (Major Histocompatibility Complex) gene variants are associated with increased autoimmune susceptibility.

  • Molecular Mimicry: Occurs when microbial antigens share similarities with self-antigens, leading to cross-reactive immune responses.

  • Infection: Some viral and bacterial infections can modify host proteins creating new epitopes that the immune system recognizes as foreign.

  • Microbiome Changes: Shifts in gut microflora due to diet or antibiotics can influence immune system training and regulation.

Examples of Autoimmune Diseases

  • Systemic lupus erythematosus (lupus): A complex disorder characterized by autoimmunity affecting multiple body systems and causing symptoms including fatigue, joint pain, and rashes.

  • Rheumatoid arthritis: Chronic inflammation results from immune complexes binding to joints, leading to erosion of cartilaginous structures.

Neuromuscular Autoimmunity:

  • Myasthenia gravis: Autoantibodies disrupt communication between nerves and muscles by blocking acetylcholine receptors, leading to muscle weakness.

  • Multiple sclerosis: Autoimmune condition characterized by immune-mediated damage to the myelin sheath of neurons, causing motor and cognitive dysfunctions.

Hyposensitivities (Immunodeficiency)

Definition: A state of weakness in the immune system, leading to increased vulnerability to infections and diseases.

Primary Immunodeficiency: Deficiencies present from birth due to genetic mutations affecting various components of the immune system.

Secondary Immunodeficiency: Aquired later in life due to external factors such as age, malnutrition, chronic stress, or immunosuppressive treatments that decrease the immune response.

Primary Immunodeficiency Examples

B-cell defects:

  • Conditions such as Agammaglobulinemia, hypogammaglobulinemia, and selective immunoglobulin deficiencies which impair antibody production leading to recurrent infections.

T-cell defects:

  • Examples include thymic aplasia (DiGeorge syndrome) and Severe combined immunodeficiency (SCID), affecting T cell functioning or development.

Complement defects:

  • Anomalies in the complement system impair phagocytosis and inflammation, leading to increased susceptibility to infections.

Secondary Immunodeficiency

Causes: Result from various factors including viral infections (e.g., HIV), age-related decline in immune efficacy, malnutrition leading to diminished immune response, stress provoking the release of glucocorticoids, and medical treatments like chemotherapy or long-term corticosteroid therapy.

Example: Acquired Immunodeficiency Syndrome (AIDS) caused by HIV infection.

Human Immunodeficiency Virus (HIV)

Type: Enveloped retrovirus specifically infecting CD4+ helper T cells, crucial for orchestrating the immune response.

Enzymes:

  • Reverse Transcriptase: Converts viral RNA into DNA, allowing integration into the host cell genome.

  • Integrase: Facilitates the integration of viral DNA into the host's chromosomes, enabling replication during cell division.

AIDS Overview

Mechanism: HIV targets CD4+ T cells, leading to their destruction and progressive immune system failure. A CD4 count of below 200 cells/µl is a diagnostic criterion indicating severe immunodeficiency or AIDS status.

Concept Review

Hypersensitivities: Overreactive immune response characterized by exaggerated responses to antigens.

  • Type I: Immediate reactions (appointments and anaphylaxis).

  • Type II: Antibody-mediated responses, implicated in blood type reactions.

  • Type III: Immune complex-mediated responses causing tissue inflammation.

  • Type IV: Delayed type pathologies primarily involving T-cell responses.

Autoimmunity: Self-reactive immune system processes leading to tissue damage.

Hyposensitivities: Underreactive immune responses characterized by an inability to mount adequate defense, with primary forms present from birth and secondary forms developed later in life.

Hypersensitivities Overview

  • Hypersensitivities: Overreactive immune responses

    • Type I: Immediate (e.g., allergies, anaphylaxis)

    • Type II: Antibody-mediated (e.g., blood types)

    • Type III: Immune complexes

    • Type IV: Cell-mediated (e.g., transplant rejections, delayed allergies)

  • Autoimmunity: Self-reactive immune system

  • Hyposensitivities: Underreactive immune responses

    • Primary: Immunodeficiency from birth

    • Secondary: Acquired immunodeficiency

Learning Objectives

  1. Sample Collection

    • Recognize common sample types and factors affecting identification.

  2. Phenotypic Testing

    • Explain phenotypic tests and their relation to previous lab knowledge.

  3. Immunological Testing

    • Explain principles of immunologic testing (selectivity vs. sensitivity) and provide examples.

  4. Genotypic Testing

    • Describe benefits of genotypic methods in diagnosing infectious diseases.

Diagnosing Infections

  • Methods to identify unknown organisms:

    1. Phenotypic Testing: Microscopic and macroscopic analysis (morphology, physiology, and biochemistry).

    2. Immunologic Testing: Serological analysis (antigens and antibodies).

    3. Genotypic Testing: Genetic techniques for diagnosis.

Sample Collection Practices

  • Specimen Collection:

    • Aseptic technique is critical to avoid contamination by normal flora.

    • Common Sample Types:

    • Saliva and Sputum:

      • Saliva: collected by spitting into a container.

      • Sputum: collected by coughing into a container or using a catheter.

      • Note: Normal bacteria in saliva can hinder identification.

    • Urine Samples:

      • Two methods: clean catch and catheter.

      • Clean catch involves collecting midstream urine after cleaning the urethra.

      • Catheter collection is aseptic and minimizes contamination.

    • Skin Samples:

      • Obtained by swabbing or scraping the skin to reach deeper layers.

    • Body Fluids:

      • Collected from the bloodstream, CSF, or tissue fluids, with aseptic technique crucial.

  • Proper labeling and transport of samples are essential for accurate diagnosis.

Specimen Analysis

  • Clinical lab results are documented in patient charts, including:

    • Gram stain and morphology.

    • Growth information.

    • Antibiotic susceptibility.

  • Nurses must understand and effectively communicate lab results.

Phenotypic Methods

  • Phenotypic Identification: Observing organism traits (appearance and behavior).

  • Examples:

    • Shape, morphology, cell wall composition, presence/absence of enzymes.

    • Biochemical properties and antibiotic susceptibility.

  • Advantages:

    • Traditional methods; tools widely available; valuable information from tests even without species identification.

  • Disadvantages:

    • Issues with culturing or isolating organisms; can be time-consuming.

Modern Phenotypic Techniques

  • Direct Examination: Microscopy and staining of specimens without cultivation.

  • Growth Techniques:

    • Selective and Differential Growth: Specialized media reveal identifying characteristics (colony appearance, motility).

  • Biochemical Testing:

    • Tests that identify specific enzymes producing a metabolic fingerprint.

  • Susceptibility Testing:

    • Patterns of antimicrobial susceptibility can indicate microbial identity.

Immunologic Methods

  • Antigen presence leads to an antibody response, allowing for diagnostic exploitation.

  • Advantages:

    • Easier than culturing microbes; immediate results; commercially available kits.

  • Disadvantages:

    • Potential for false positives/negatives; limited by available antibodies/antigens.

Serological Principles

  • Antibodies:

    • Collect serum to test for antibodies against antigens.

    • Antibodies indicate previous exposure and immune response.

  • Antigens:

    • Sample collection to test for pathogen antigens using lab-grown or commercial antibodies.

    • Presence of antigen implies active infection.

Testing Specifics of Immunologic Methods

  • Best Tests Needed: High specificity and sensitivity.

    • Specificity: Focus on a specific antigen/antibody; low specificity leads to false positives.

    • Sensitivity: Ability to detect small quantities; low sensitivity increases false negatives.

Immunologic Diagnostic Techniques

  • Agglutination/Precipitation:

    • Mediated clumping of cells (agglutination) or smaller antibody-antigen complexes (precipitation).

  • Immuno-chromatography:

    • Lateral flow systems available in kits producing colored results.

  • Western Blot:

    • Electrophoresis separates proteins for detection with labeled antibodies.

  • ELISA:

    • Sandwich technique using antigen, antibody, and secondary antibody for color change.

  • In Vivo Tests:

    • Antigen introduced to elicit a reaction (e.g., TB skin test).

Genotypic Methods

  • Unique genetic sequences in organisms allow diagnosis by detection of specific genes.

  • Advantages:

    • Avoids culturing; rapid results; high precision accuracy.

  • Disadvantages:

    • Not widely available; sometimes costly.

Genotypic Techniques

  • PCR (Polymerase Chain Reaction):

    • Rapidly copies DNA sequences using thermal cycling in labs, producing millions of copies.

    • Highly specific due to targeted primers.

  • Whole-Genome Sequencing (WGS):

    • Analysis of entire genomes, useful for identifying organisms and virulence factors.

    • Costs are decreasing annually, paving the way for broader applications in medicine.