• Immunity

Immunity

Immunity is the body’s ability to resist infections and defend against foreign substances, pathogens, and harmful agents. It involves a complex network of cells, tissues, and molecules that work together to recognize and eliminate invaders while maintaining tolerance to self-antigens.

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Types of Immunity

1. Innate Immunity

• Definition:
  • The first line of defense, present at birth, non-specific, and immediate.
• Components:
  • Physical Barriers:
    • Skin, mucous membranes, cilia.
  • Chemical Barriers:
    • Acidic pH (stomach), lysozymes (tears, saliva).
  • Cellular Defenses:
    • Neutrophils, macrophages, dendritic cells, natural killer (NK) cells.
  • Molecular Defenses:
    • Complement system, cytokines, interferons.
• Features:
  • No memory.
  • Same response to repeated infections.

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2. Adaptive Immunity

• Definition:
  • Specific immunity developed after exposure to antigens; has memory.
• Types:
  1. Humoral Immunity:
     • Mediated by B lymphocytes and antibodies.
     • Effective against extracellular pathogens.
  2. Cell-Mediated Immunity:
     • Mediated by T lymphocytes (helper T cells, cytotoxic T cells).
     • Effective against intracellular pathogens and tumors.
• Features:
  • Specific response.
  • Memory for faster and stronger responses upon re-exposure.

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Classification of Adaptive Immunity

1. Active Immunity

• Definition:
  • Immunity acquired through direct exposure to antigens.
• Types:
  • Natural Active Immunity:
    • Infection by pathogens (e.g., chickenpox infection).
  • Artificial Active Immunity:
    • Vaccination (e.g., measles vaccine).
• Features:
  • Long-lasting.
  • Develops slowly.

2. Passive Immunity

• Definition:
  • Immunity acquired through transfer of preformed antibodies.
• Types:
  • Natural Passive Immunity:
    • Transfer of maternal antibodies through placenta or breast milk.
  • Artificial Passive Immunity:
    • Administration of antibodies (e.g., tetanus antitoxin).
• Features:
  • Short-lived.
  • Immediate protection.

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Key Components of the Immune System

1. Cells

• Lymphocytes:
  • B cells: Produce antibodies.
  • T cells:
    • Helper T cells (CD4+): Activate B cells and cytotoxic T cells.
    • Cytotoxic T cells (CD8+): Destroy infected or abnormal cells.
• Antigen-Presenting Cells (APCs):
  • Macrophages, dendritic cells, B cells present antigens to T cells.
• Phagocytes:
  • Neutrophils, macrophages engulf and destroy pathogens.
• NK Cells:
  • Destroy virus-infected cells and tumors.

2. Molecules

• Antibodies (Immunoglobulins):
  • Produced by plasma cells.
  • Classes: IgG, IgA, IgM, IgE, IgD.
• Cytokines:
  • Signaling molecules like interleukins, interferons, tumor necrosis factor (TNF).
• Complement System:
  • Enhances phagocytosis and destroys pathogens.

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Mechanisms of Immunity

1. Recognition of Antigens

• Immune cells recognize specific antigens using receptors.
• Example: T cells recognize antigens presented by MHC molecules.

2. Activation of Immune Cells

• Binding of antigen triggers activation and proliferation of immune cells.
• Example: Helper T cells activate B cells to produce antibodies.

3. Elimination of Pathogens

• Phagocytosis:
  • Engulfment of pathogens by macrophages and neutrophils.
• Cytotoxicity:
  • Cytotoxic T cells and NK cells kill infected cells.
• Neutralization:
  • Antibodies block pathogen attachment to host cells.

4. Immunological Memory

• Memory cells provide long-lasting immunity, leading to a quicker and stronger response upon re-exposure.

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Immune Disorders

1. Hypersensitivity

• Overreaction of the immune system to antigens.
• Types:
  • Type I (Immediate): Allergies, anaphylaxis.
  • Type II (Cytotoxic): Hemolytic anemia.
  • Type III (Immune Complex): Lupus.
  • Type IV (Delayed): Tuberculin reaction.

2. Autoimmune Diseases

• Immune system attacks self-antigens.
• Examples: Rheumatoid arthritis, Type 1 diabetes, multiple sclerosis.

3. Immunodeficiency

• Partial or complete failure of the immune system.
• Types:
  • Primary (genetic): Severe Combined Immunodeficiency (SCID).
  • Secondary (acquired): HIV/AIDS, chemotherapy-induced.

4. Transplant Rejection

• Immune system attacks transplanted organs or tissues.
• Prevented using immunosuppressive drugs.

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Vaccination

1. Principle:
   • Stimulates the immune system to produce memory cells without causing disease.
2. Types of Vaccines:
   • Live-attenuated (e.g., measles, mumps).
   • Inactivated (e.g., polio, hepatitis A).
   • Subunit (e.g., hepatitis B).
   • Toxoid (e.g., diphtheria, tetanus).
3. Importance:
   • Prevents infectious diseases, reduces morbidity and mortality.

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Applications of Immunology

1. Diagnostics:
   • ELISA, flow cytometry, immunofluorescence for detecting infections and immune disorders.
2. Therapeutics:
   • Monoclonal antibodies for cancer, autoimmune diseases.
3. Public Health:
   • Vaccination programs, herd immunity.
4. Research:
   • Understanding immune responses to develop better treatments and vaccines.

• Immunity and hypersensitivity –Skin test

Immunity, Hypersensitivity, and Skin Tests

Skin tests are diagnostic tools used to assess immune responses, particularly hypersensitivity reactions. These tests involve introducing antigens into the skin to evaluate the body’s immune reaction.

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Immunity and Hypersensitivity

1. Immunity

• The body’s ability to defend against pathogens and other harmful substances.
• Types:
  • Innate Immunity: Non-specific, first-line defense.
  • Adaptive Immunity: Specific, involves memory cells.

2. Hypersensitivity

• An exaggerated immune response to antigens (allergens) that can lead to tissue damage.
• Types of Hypersensitivity:
  1. Type I (Immediate Hypersensitivity):
     • Mediated by IgE antibodies.
     • Involves mast cells and histamine release.
     • Examples: Allergic rhinitis, asthma, anaphylaxis.
  2. Type II (Cytotoxic Hypersensitivity):
     • Mediated by IgG or IgM antibodies.
     • Targets host cells, leading to their destruction.
     • Examples: Hemolytic anemia, Goodpasture syndrome.
  3. Type III (Immune Complex-Mediated Hypersensitivity):
     • Involves antigen-antibody complexes deposited in tissues.
     • Examples: Lupus, post-streptococcal glomerulonephritis.
  4. Type IV (Delayed-Type Hypersensitivity):
     • T-cell-mediated response.
     • Examples: Tuberculin reaction, contact dermatitis.

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Skin Tests in Immunity and Hypersensitivity

Skin tests are used to evaluate immune responses, particularly hypersensitivity reactions. The results are interpreted based on the presence of erythema (redness) and induration (swelling).

1. Type I Hypersensitivity Skin Tests

• Purpose:
  • Diagnose immediate hypersensitivity reactions (allergies).
• Procedure:
  • Prick Test (Scratch Test):
    • A small amount of allergen is introduced into the skin using a needle or lancet.
    • Positive Reaction: Wheal and flare within 15–20 minutes.
  • Intradermal Test:
    • Small amounts of allergen injected intradermally.
    • Used for more sensitive testing.
• Common Allergens Tested:
  • Pollens, dust mites, animal dander, foods, insect venoms.
• Clinical Significance:
  • Used for diagnosing allergic conditions like asthma, rhinitis, or food allergies.

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2. Type IV Hypersensitivity Skin Tests

• Purpose:
  • Diagnose delayed hypersensitivity and cell-mediated immune responses.
• Procedure:
  • Tuberculin Skin Test (Mantoux Test):
    • Used to detect latent or active tuberculosis.
    • Procedure:
      • Inject 0.1 mL of purified protein derivative (PPD) intradermally on the forearm.
      • Read after 48–72 hours.
    • Interpretation:
      • Measure the diameter of induration (not erythema).
        • ≥5 mm: Positive in immunocompromised individuals.
        • ≥10 mm: Positive in healthcare workers, recent immigrants.
        • ≥15 mm: Positive in healthy individuals.
  • Patch Test:
    • Used to diagnose contact dermatitis.
    • Procedure:
      • Small amounts of allergens applied to the skin using adhesive patches.
      • Read after 48–96 hours.
    • Positive Reaction:
      • Erythema, vesicles, or induration.

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Factors Influencing Skin Test Results

1. Immune Status:
   • Immunosuppression may cause false negatives.
2. Medication:
   • Antihistamines or corticosteroids can suppress reactions.
3. Technique:
   • Improper allergen preparation or administration may affect results.
4. Timing:
   • Immediate reactions (Type I) are read within minutes.
   • Delayed reactions (Type IV) are read after 48–96 hours.

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Comparison of Skin Tests

Feature	Prick Test	Intradermal Test	Mantoux Test	Patch Test
Type of Hypersensitivity	Type I	Type I	Type IV	Type IV
Purpose	Allergy diagnosis	Allergy diagnosis	TB diagnosis	Contact dermatitis diagnosis
Procedure	Allergen placed on pricked skin	Allergen injected intradermally	PPD injected intradermally	Allergen applied via patches
Timing of Results	15–20 minutes	15–20 minutes	48–72 hours	48–96 hours
Positive Reaction	Wheal and flare	Wheal and flare	Induration	Erythema or vesicles

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Applications of Skin Tests

1. Diagnosis:
   • Allergic diseases (Type I hypersensitivity).
   • Tuberculosis or latent TB infection (Type IV hypersensitivity).
   • Contact dermatitis (Type IV hypersensitivity).
2. Monitoring Immunity:
   • Assess immune status in diseases like leprosy or TB.
3. Vaccine Efficacy:
   • Evaluate immune response to certain vaccines.

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Advantages and Limitations

Advantages:

1. Rapid results (Type I tests).
2. Cost-effective and minimally invasive.
3. High sensitivity for specific conditions (e.g., allergies, TB).

Limitations:

1. Risk of anaphylaxis in Type I hypersensitivity tests.
2. False positives due to cross-reactivity.
3. False negatives in immunosuppressed patients.
4. Requires trained personnel for administration and interpretation.

• Antigen and antibody reaction

Antigen and Antibody Reaction

Antigen-antibody reactions, also known as immune reactions, are specific interactions between antigens (foreign substances) and antibodies (proteins produced by B cells). These reactions form the basis of the adaptive immune response and are fundamental to immunity, diagnostics, and vaccine development.

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Key Features of Antigen-Antibody Reactions

1. Specificity:
   • Antibodies bind specifically to their corresponding antigens.
2. Lock-and-Key Mechanism:
   • The antigen’s epitope fits into the antibody’s paratope.
3. Non-Covalent Interactions:
   • Include hydrogen bonds, ionic bonds, hydrophobic interactions, and van der Waals forces.

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Stages of Antigen-Antibody Reaction

1. Recognition:
   • Antigen binds to the specific antigen-binding site on the antibody.
2. Formation of Immune Complexes:
   • Multiple antigen-antibody molecules aggregate.
3. Outcome:
   • Neutralization, opsonization, agglutination, precipitation, or complement activation.

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Types of Antigen-Antibody Reactions

1. Precipitation

• Definition:
  • Soluble antigen reacts with its antibody to form an insoluble complex.
• Example:
  • Detection of fungal infections using precipitation tests.
• Clinical Application:
  • Double immunodiffusion (Ouchterlony test).

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2. Agglutination

• Definition:
  • Particulate antigens (e.g., cells, beads) react with antibodies to form visible clumps.
• Types:
  • Direct Agglutination: Uses natural antigens (e.g., ABO blood grouping).
  • Indirect (Passive) Agglutination: Uses coated particles like latex beads.
• Clinical Application:
  • Widal test for typhoid fever.

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3. Neutralization

• Definition:
  • Antibodies neutralize toxins or viruses by blocking their activity.
• Example:
  • Neutralization of diphtheria toxin by antitoxin.
• Clinical Application:
  • Assessing immunity to viruses like measles.

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4. Complement Fixation

• Definition:
  • Antigen-antibody complexes activate the complement system.
• Outcome:
  • Cell lysis or enhanced phagocytosis.
• Clinical Application:
  • Diagnosis of infections like syphilis (Wassermann test).

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5. Immunofluorescence

• Definition:
  • Antibodies are tagged with fluorescent dyes to visualize antigen-antibody binding.
• Types:
  • Direct Immunofluorescence: Antibody binds directly to the antigen.
  • Indirect Immunofluorescence: Secondary antibody binds to the primary antibody.
• Clinical Application:
  • Detection of autoimmune diseases (e.g., lupus).

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6. Enzyme-Linked Immunosorbent Assay (ELISA)

• Definition:
  • Uses enzyme-labeled antibodies to detect antigens or antibodies.
• Types:
  • Direct ELISA: Detects antigen.
  • Indirect ELISA: Detects antibody.
  • Sandwich ELISA: Detects specific antigens between two antibodies.
• Clinical Application:
  • HIV testing, hepatitis detection.

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7. Western Blotting

• Definition:
  • Antigen-antibody reaction is visualized after separating proteins via gel electrophoresis.
• Clinical Application:
  • Confirmatory test for HIV.

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8. Radioimmunoassay (RIA)

• Definition:
  • Uses radioactively labeled antibodies or antigens.
• Clinical Application:
  • Hormone level detection (e.g., insulin, thyroid hormones).

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Factors Influencing Antigen-Antibody Reactions

1. Affinity:
   • Strength of binding between a single antigenic epitope and an antibody’s paratope.
2. Avidity:
   • Overall strength of binding between multivalent antigens and antibodies.
3. Antigen-Antibody Ratio:
   • Optimal ratio enhances reaction efficiency.
4. Environmental Conditions:
   • pH, temperature, and ionic strength affect binding.

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Applications of Antigen-Antibody Reactions

1. Diagnostics:
   • Detection of infectious diseases (e.g., malaria, syphilis).
   • Identification of autoimmune diseases (e.g., rheumatoid arthritis).
2. Vaccines:
   • Development of vaccines relies on understanding antigen-antibody interactions.
3. Research:
   • Studying immune mechanisms.
4. Therapeutics:
   • Monoclonal antibodies for cancer, autoimmune diseases, and infections.

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Differences Between Precipitation and Agglutination

Feature	Precipitation	Agglutination
Antigen Type	Soluble antigens	Particulate antigens
Visualization	Formation of a precipitate	Visible clumping
Sensitivity	Lower	Higher
Examples	Double immunodiffusion	Widal test, latex agglutination

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Key Points in Antigen-Antibody Reactions

• Specificity ensures accurate targeting of pathogens or antigens.
• Immune responses can be harnessed in various diagnostic tests and therapies.
• Advancements like ELISA and RIA have revolutionized medical diagnostics.

• Immunization in disease.

Immunization in Disease Prevention

Immunization is a process by which an individual’s immune system is fortified against specific diseases. This is achieved by administering vaccines, which stimulate the body’s immune response to recognize and fight pathogens effectively.

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Types of Immunization

1. Active Immunization

• Definition:
  • The process of inducing immunity by exposing the body to antigens, which stimulates the production of antibodies and memory cells.
• Types:
  • Natural Active Immunization:
    • Immunity developed after infection (e.g., chickenpox).
  • Artificial Active Immunization:
    • Immunity developed through vaccination (e.g., measles vaccine).
• Duration:
  • Long-lasting, often for years or a lifetime.

2. Passive Immunization

• Definition:
  • Transfer of pre-formed antibodies to an individual.
• Types:
  • Natural Passive Immunization:
    • Transfer of maternal antibodies via placenta or breast milk.
  • Artificial Passive Immunization:
    • Administration of immunoglobulins or antitoxins (e.g., rabies immunoglobulin).
• Duration:
  • Short-lived, usually weeks to months.

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Types of Vaccines

1. Live-Attenuated Vaccines:
   • Contain weakened forms of the pathogen.
   • Examples:
     • Measles, Mumps, Rubella (MMR) vaccine.
     • Oral Polio Vaccine (OPV).
   • Advantages:
     • Strong and long-lasting immunity.
   • Disadvantages:
     • Not suitable for immunocompromised individuals.
2. Inactivated Vaccines:
   • Contain killed pathogens.
   • Examples:
     • Hepatitis A vaccine, Rabies vaccine.
   • Advantages:
     • Safe for immunocompromised individuals.
   • Disadvantages:
     • Requires booster doses.
3. Subunit, Recombinant, or Conjugate Vaccines:
   • Contain specific parts of the pathogen (e.g., protein, polysaccharide).
   • Examples:
     • Hepatitis B vaccine, Human Papillomavirus (HPV) vaccine.
   • Advantages:
     • Fewer side effects.
   • Disadvantages:
     • May require multiple doses.
4. Toxoid Vaccines:
   • Contain inactivated toxins produced by bacteria.
   • Examples:
     • Diphtheria and Tetanus vaccines.
   • Advantages:
     • Targets toxin-mediated diseases.
   • Disadvantages:
     • Requires booster doses.
5. mRNA Vaccines:
   • Deliver genetic material encoding for pathogen proteins.
   • Examples:
     • COVID-19 vaccines (Pfizer-BioNTech, Moderna).
   • Advantages:
     • Rapid production.
   • Disadvantages:
     • Requires cold chain storage.
6. Vector-Based Vaccines:
   • Use a harmless virus to deliver genetic material.
   • Examples:
     • Johnson & Johnson COVID-19 vaccine.
   • Advantages:
     • Effective delivery system.
   • Disadvantages:
     • Immune interference by pre-existing vector immunity.

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Mechanism of Immunization

1. Antigen Introduction:
   • The vaccine introduces antigens (weakened, killed, or part of a pathogen).
2. Immune Activation:
   • Antigens are recognized by antigen-presenting cells (APCs).
   • APCs present antigens to T and B cells, activating them.
3. Antibody Production:
   • B cells produce specific antibodies against the antigen.
4. Memory Formation:
   • Memory cells are formed, enabling a faster and stronger immune response upon re-exposure to the pathogen.

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Immunization Schedule

• Purpose:
  • To ensure timely protection against vaccine-preventable diseases.
• Examples of Key Vaccines in Routine Immunization:
  1. BCG: Administered at birth to prevent tuberculosis.
  2. Hepatitis B: Administered at birth and subsequent doses.
  3. Pentavalent Vaccine: Protects against Diphtheria, Pertussis, Tetanus, Hepatitis B, and Hib.
  4. Oral Polio Vaccine (OPV): Administered at birth and subsequent doses.
  5. Measles, Mumps, Rubella (MMR): Administered at 9–12 months and a second dose later.

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Benefits of Immunization

1. Prevention of Diseases:
   • Reduces morbidity and mortality from infectious diseases.
   • Examples: Polio eradication, reduction in measles deaths.
2. Herd Immunity:
   • Protects unvaccinated individuals by reducing the spread of infectious agents in a population.
3. Cost-Effectiveness:
   • Prevents the economic burden of treating preventable diseases.
4. Control of Outbreaks:
   • Vaccination during outbreaks (e.g., cholera, Ebola) limits the spread of the disease.

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Challenges in Immunization

1. Vaccine Hesitancy:
   • Misinformation and fear of side effects lead to refusal or delay in vaccination.
2. Cold Chain Maintenance:
   • Many vaccines require specific storage conditions.
3. Global Inequity:
   • Unequal distribution of vaccines, especially in low-income countries.
4. Emerging Diseases:
   • Need for rapid development of vaccines for new pathogens (e.g., COVID-19).

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Adverse Effects of Immunization

1. Common Side Effects:
   • Mild fever, redness, or swelling at the injection site.
2. Severe Reactions:
   • Anaphylaxis (rare).
   • Managed by immediate administration of epinephrine.
3. Vaccine-Associated Diseases:
   • Rare cases of disease caused by live-attenuated vaccines (e.g., vaccine-associated paralytic polio).

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Examples of Vaccine-Preventable Diseases

Disease	Causative Agent	Vaccine Type	Example of Vaccine
Tuberculosis	Mycobacterium tuberculosis	Live-attenuated	BCG
Measles	Measles virus	Live-attenuated	MMR
Diphtheria	Corynebacterium diphtheriae	Toxoid	DPT
Hepatitis B	Hepatitis B virus	Subunit	Hepatitis B vaccine
COVID-19	SARS-CoV-2	mRNA, Vector-based	Pfizer-BioNTech, AstraZeneca

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Future of Immunization

1. Development of Universal Vaccines:
   • Vaccines that target multiple strains or pathogens.
2. Therapeutic Vaccines:
   • Vaccines for non-infectious diseases (e.g., cancer, Alzheimer’s).
3. Needle-Free Vaccines:
   • Oral or nasal vaccines to improve compliance.
4. Personalized Vaccines:
   • Tailored to individual genetic profiles.