Immunity and Host Defense against Infectious Diseases

Related resources:

• Understanding Infectious Diseases: A Comprehensive Guide
• Common Infectious Diseases: Pathophysiology and Clinical Presentations
• Transmission Mechanisms of Infectious Diseases
• Prevention and Control of Infectious Diseases
• Diagnosis and Management of Infectious Diseases

Introduction

The human immune system serves as the body's defense against infectious agents. Understanding how immunity works is essential for comprehending both the pathogenesis of infectious diseases and the principles behind their prevention and treatment. This guide explores the complex relationship between pathogens and host immunity, with particular relevance to topics covered in NEET and other medical entrance examinations.

Layers of Host Defense

The human body employs multiple layers of defense against infectious agents:

Physical and Chemical Barriers

The first line of defense prevents pathogens from entering the body:

• Skin: Intact epidermis forms a physical barrier
• Mucous membranes: Line respiratory, gastrointestinal, and urogenital tracts
• Chemical defenses:
  • Sweat and sebaceous secretions (pH, fatty acids)
  • Gastric acid
  • Lysozyme in tears, saliva
  • Defensins and other antimicrobial peptides

Clinical Relevance:

• Breakdown of these barriers (burns, wounds, intubation) significantly increases infection risk
• Many pathogens specifically target mucosal surfaces (e.g., Neisseria gonorrhoeae adheres to urethral epithelium)

Innate Immunity

Provides immediate but non-specific defense against pathogens:

Cellular Components

• Neutrophils: Phagocytose bacteria and release antimicrobial substances
• Macrophages: Phagocytose pathogens and present antigens to T cells
• Natural Killer (NK) cells: Recognize and destroy infected cells
• Dendritic cells: Capture antigens and present them to lymphocytes

Molecular Components

• Complement system: Cascade of proteins that enhance phagocytosis and directly lyse pathogens
• Acute-phase proteins: C-reactive protein, mannose-binding lectin
• Interferons: Inhibit viral replication and enhance immune responses
• Pattern recognition receptors (PRRs): Recognize pathogen-associated molecular patterns (PAMPs)

Clinical Relevance:

• Defects in neutrophil function (chronic granulomatous disease) lead to recurrent bacterial infections
• Complement deficiencies are associated with increased susceptibility to encapsulated bacteria

Adaptive Immunity

Provides specific, memory-based responses to pathogens:

Cell-Mediated Immunity

• T lymphocytes:
  • CD4+ (helper) T cells: Coordinate immune responses
  • CD8+ (cytotoxic) T cells: Kill infected cells
  • Regulatory T cells: Control immune responses

Humoral Immunity

• B lymphocytes:
  • Produce antibodies (immunoglobulins)
  • IgM: Primary response, complement activation
  • IgG: Memory response, opsonization, neutralization
  • IgA: Mucosal immunity
  • IgE: Parasitic infections, allergic responses
  • IgD: B cell activation

Clinical Relevance:

• HIV targets CD4+ T cells, leading to progressive immunodeficiency
• X-linked agammaglobulinemia (defect in B cell development) increases susceptibility to encapsulated bacteria

Immune Responses to Different Pathogens

Different types of pathogens elicit distinct immune responses:

Bacterial Infections

Extracellular Bacteria:

• Primarily controlled by:
  • Neutrophils and macrophages (phagocytosis)
  • Complement (opsonization, membrane attack complex)
  • Antibodies (neutralization, opsonization)

Examples:

• Enteric fever (Typhoid): Neutrophils and macrophages attempt to clear Salmonella, but some bacteria survive intracellularly
• Diphtheria: Antitoxin antibodies neutralize the exotoxin

Intracellular Bacteria:

• Primarily controlled by:
  • Cell-mediated immunity (CD4+ Th1 cells, CD8+ cytotoxic T cells)
  • Activated macrophages

Examples:

• Tuberculosis: Cell-mediated immunity forms granulomas to contain Mycobacterium tuberculosis
• Leprosy: The spectrum of disease (tuberculoid to lepromatous) correlates with the strength of cell-mediated immunity

Viral Infections

• Primarily controlled by:
  • Interferons (inhibit viral replication)
  • NK cells (kill virus-infected cells)
  • CD8+ cytotoxic T cells (kill virus-infected cells)
  • Antibodies (neutralize viruses, prevent cell entry)

Examples:

• Measles: Causes temporary immunosuppression by affecting dendritic cells and T cells
• Herpes zoster: Reactivation occurs when cell-mediated immunity wanes with age or immunosuppression

Fungal Infections

• Primarily controlled by:
  • Neutrophils and macrophages
  • Cell-mediated immunity (Th17 response)

Examples:

• Candidiasis: Common in immunocompromised hosts, especially those with defects in cell-mediated immunity
• Cryptococcosis: Serious fungal infection in HIV patients due to impaired T cell responses

Parasitic Infections

• Primarily controlled by:
  • Eosinophils (against helminths)
  • IgE antibodies
  • Th2 immune responses

Examples:

• Malaria: Protective immunity develops slowly and is incomplete
• Filariasis: Eosinophils and IgE mediate defense against filarial worms

Evasion of Host Defenses

Pathogens have evolved various mechanisms to evade or subvert host immunity:

Antigenic Variation

Mechanism: Changing surface antigens to avoid recognition by antibodies or T cells.

Examples:

• Influenza virus: Antigenic drift (minor changes) and shift (major changes)
• Plasmodium falciparum: Varies surface antigens (PfEMP1) to evade antibody recognition
• Trypanosoma brucei: Sequential expression of variant surface glycoproteins (VSGs)

Immunosuppression

Mechanism: Direct suppression of immune responses.

Examples:

• HIV: Depletes CD4+ T cells, impairing overall immunity
• Measles virus: Suppresses cell-mediated immunity
• Mycobacterium tuberculosis: Inhibits phagosome-lysosome fusion in macrophages

Molecular Mimicry

Mechanism: Expressing molecules that resemble host components to avoid recognition as foreign.

Examples:

• Group A Streptococcus: M protein shares epitopes with human cardiac myosin
• Campylobacter jejuni: Lipooligosaccharides mimic gangliosides (associated with Guillain-Barré syndrome)

Biofilm Formation

Mechanism: Bacteria form structured communities within a protective matrix.

Examples:

• Staphylococcus epidermidis: Forms biofilms on medical devices
• Pseudomonas aeruginosa: Biofilms in cystic fibrosis lungs resist immune clearance and antibiotics

Immunopathology in Infectious Diseases

Sometimes immune responses themselves contribute to disease pathology:

Hypersensitivity Reactions

Type I (Immediate):

• IgE-mediated responses
• Examples: Allergic bronchopulmonary aspergillosis

Type II (Antibody-dependent):

• IgG or IgM against cell surface antigens
• Examples: Hemolytic anemia in malaria

Type III (Immune complex):

• Antigen-antibody complexes deposit in tissues
• Examples: Post-streptococcal glomerulonephritis, serum sickness after antitoxin therapy

Type IV (Delayed-type):

• T cell-mediated inflammation
• Examples: Tuberculin reaction, leprosy (especially tuberculoid form)

Cytokine Storm

Excessive proinflammatory cytokine production leading to systemic inflammation.

Examples:

• Severe dengue
• Toxic shock syndrome
• Severe malaria

Persistent Inflammation

Examples:

• Chronic hepatitis
• Post-kala-azar dermal leishmaniasis

Immunity and Leprosy: A Case Study

Leprosy perfectly illustrates the spectrum of immune responses to infection:

Tuberculoid Leprosy (TT)

• Strong cell-mediated immunity
• Few bacilli (paucibacillary)
• Well-formed granulomas containing the infection
• Limited disease with few, well-demarcated lesions

Lepromatous Leprosy (LL)

• Poor cell-mediated immunity
• Numerous bacilli (multibacillary)
• Minimal granuloma formation
• Widespread disease with multiple, poorly demarcated lesions

Borderline Forms (BT, BB, BL)

• Intermediate immune responses with features of both polar forms
• Can shift toward either end of the spectrum

Clinical Relevance: Understanding this spectrum is crucial for diagnosis, classification, and treatment decisions in leprosy.

Immunological Memory and Vaccination

Adaptive immunity generates memory cells that provide long-term protection:

Primary vs. Secondary Immune Response

Primary Response:

• Slow development (days)
• Initially IgM predominates
• Lower affinity antibodies
• Short-lived

Secondary Response:

• Rapid development (hours)
• IgG predominates
• Higher affinity antibodies (due to somatic hypermutation)
• Long-lasting

Principles of Vaccination

Vaccination stimulates protective immunity by mimicking natural infection without causing disease:

Types of Vaccines:

• Live attenuated: Weakened pathogens (MMR, oral polio, yellow fever)
• Inactivated: Killed pathogens (injectable polio, rabies)
• Toxoid: Inactivated toxins (diphtheria, tetanus)
• Subunit: Specific pathogen components (hepatitis B, acellular pertussis)
• Conjugate: Polysaccharide antigens linked to carrier proteins (Hib, pneumococcal)
• Recombinant: Antigens produced through genetic engineering (HPV)

Herd Immunity: When a sufficient proportion of a population is immune, pathogen transmission is interrupted, protecting even unvaccinated individuals.

Clinical Relevance: Understanding vaccine types helps explain their efficacy, safety profiles, and contraindications in different populations.

Clinical Applications and NEET Relevance

Diagnostic Applications

Serological Tests:

• Detecting antibodies to specific pathogens
• Examples: Widal test for typhoid, VDRL/RPR for syphilis

Cell-Mediated Immunity Tests:

• Tuberculin skin test
• Lepromin test in leprosy
• Interferon-gamma release assays for TB

Therapeutic Applications

Passive Immunization:

• Administration of preformed antibodies
• Examples: Diphtheria antitoxin, rabies immunoglobulin, tetanus immunoglobulin

Immunomodulation:

• Corticosteroids in certain infections with excessive inflammation
• Cytokine inhibitors in specific scenarios

NEET Examination Focus

For NEET preparation, focus on:

• Immune responses to specific pathogens (TB, leprosy, malaria)
• Immunological basis of diagnostic tests
• Hypersensitivity reactions in infectious diseases
• Types of vaccines and their mechanisms
• Immune evasion strategies of major pathogens

Practice Questions

1. Which of the following is characteristic of tuberculoid leprosy but not lepromatous leprosy? a) Strong cell-mediated immunity b) High bacterial load c) Multiple skin lesions d) Negative lepromin test
2. The primary immunological defense against viral infections is: a) Neutrophils b) Antibodies c) Cell-mediated immunity d) Complement system
3. Which type of hypersensitivity reaction is responsible for the tuberculin skin test? a) Type I b) Type II c) Type III d) Type IV

Conclusion

Understanding the complex interplay between pathogens and host immunity is essential for comprehending infectious disease pathogenesis, diagnosis, and management. This knowledge forms a critical foundation for medical students preparing for competitive examinations like NEET and for future clinical practice.

The spectrum of immune responses seen in diseases like leprosy highlights how the same pathogen can produce dramatically different clinical presentations based on the host's immune response. By mastering these concepts, students can better understand not only infectious diseases but also immune-mediated disorders and vaccination principles.