Natural and Acquired Resistance to Infection

Natural and Acquired Resistance to Infection

Introduction

Resistance to infection refers to the ability of the body to prevent, combat, or eliminate pathogenic organisms that may cause disease. This resistance can be classified into:

• Natural (Innate) resistance
• Acquired (Adaptive) resistance

Both play critical roles in protecting the body from bacterial, viral, fungal, and parasitic infections. Natural (Innate) Resistance to Infection

Natural or innate resistance is the non-specific defense mechanism that an individual is born with. It provides the first line of defense against infection and does not require previous exposure to the pathogen.

Characteristics of Innate Resistance:

Feature	Description
Present from birth	Exists before exposure to pathogens
Non-specific	Acts against a wide variety of pathogens
Immediate response	Provides rapid defense
No memory	Does not improve with repeated exposure

Components of Innate Resistance:

A. Physical and Mechanical Barriers

• Skin: Intact skin forms a physical barrier against microbial invasion.
• Mucous membranes: Trap microbes in the respiratory, gastrointestinal, and genitourinary tracts.
• Cilia: Sweep away trapped particles in the respiratory tract.
• Tears and saliva: Wash away pathogens.

B. Chemical Barriers

• Acidic pH: Stomach acid (pH ~2) kills many ingested pathogens.
• Lysozyme: Enzyme in saliva, tears, and mucus that breaks down bacterial cell walls.
• Sebum and sweat: Contain antimicrobial substances.

C. Cellular Defenses

• Phagocytes:
• Neutrophils: First responders that engulf bacteria.
• Macrophages: Engulf and digest pathogens; present antigens to T cells.
• Natural Killer (NK) cells: Destroy virus-infected and cancerous cells.

D. Inflammatory Response

• Characterized by redness, heat, swelling, and pain
• Increases blood flow and brings immune cells to the site of infection.

E. Complement System

• A group of plasma proteins that enhance inflammation and promote pathogen lysis.

F. Interferons

• Proteins released by virus-infected cells that inhibit viral replication in neighboring cells.

Acquired (Adaptive) Resistance to Infection

Acquired or adaptive resistance is specific defense developed by the body after exposure to a particular pathogen or antigen. It involves immunological memory and provides long-term protection.

Characteristics of Acquired Resistance:

Feature	Description
Develops after exposure	Requires contact with antigen
Specific	Targets specific pathogens
Slow onset	Takes days to develop
Immunological memory	Responds faster and stronger on re-exposure

Types of Acquired Resistance:

A. Active Immunity

• Naturally acquired: Through infection (e.g., recovering from measles)
• Artificially acquired: Through vaccination (e.g., tetanus vaccine)

B. Passive Immunity

• Naturally acquired: From mother to child (e.g., IgG across placenta, IgA in breast milk)
• Artificially acquired: Injection of antibodies (e.g., antivenom, hepatitis B immunoglobulin)

Components of Acquired Resistance:

A. Humoral Immunity (B-lymphocytes)

• Involves antibody production by B cells
• Antibodies neutralize toxins, opsonize bacteria, and activate the complement system
• Major classes: IgG, IgA, IgM, IgE, IgD

B. Cell-Mediated Immunity (T-lymphocytes)

• Helper T cells (CD4+): Stimulate B cells and cytotoxic T cells
• Cytotoxic T cells (CD8+): Destroy infected or cancerous cells
• Regulatory T cells: Suppress immune response to prevent overreaction

C. Memory Cells

• B and T cells that remain after infection and respond quickly upon re-exposure

Factors Affecting Host Resistance

Factor	Impact
Age	Neonates and the elderly have weaker immune systems
Nutrition	Malnutrition impairs immunity
Genetics	Certain genes influence susceptibility (e.g., sickle cell trait vs malaria)
Chronic diseases	Diabetes, cancer, HIV weaken immune response
Stress	High stress suppresses immunity
Medications	Immunosuppressants reduce resistance
Vaccination status	Enhances acquired resistance

Comparison Table: Innate vs Acquired Resistance

Feature	Innate Resistance	Acquired Resistance
Specificity	Non-specific	Highly specific
Time to develop	Immediate	Delayed (days)
Memory	None	Present
Main cells involved	Neutrophils, macrophages, NK cells	B cells, T cells
Response to repeat exposure	Same each time	Stronger and faster

 

Importance of Resistance in Disease Prevention

• Prevents colonization and multiplication of pathogens
• Reduces severity and duration of disease
• Forms the basis for vaccination programs
• Protects immunocompromised individuals through herd immunity
• Determines susceptibility and response to infectious diseases

Examples Illustrating Resistance

Example	Type of Resistance	Description
Skin barrier	Natural	Prevents microbial entry
Hepatitis B vaccination	Acquired (active)	Produces antibodies against the virus
Breast milk antibodies	Acquired (passive)	Protects infant from pathogens
HIV infection	Weakens acquired immunity	Leads to opportunistic infections
TB infection and memory response	Acquired	Forms basis of tuberculin skin test (memory T cells)

Determination of Innate Immunity – Detailed Discussion

Introduction to Innate Immunity

Innate immunity is the body's first line of defense against infections. It is non-specific, present from birth, and acts immediately or within hours of a pathogen's appearance in the body. The determination (or assessment) of innate immunity refers to the evaluation of its functional components to understand how well the body can resist infection before adaptive immunity is activated.

Importance of Determining Innate Immunity

Determining innate immunity is crucial for:

• Evaluating susceptibility to infections
• Diagnosing immunodeficiencies
• Assessing the effectiveness of immunotherapies
• Studying host-pathogen interactions
• Understanding inflammatory or autoimmune diseases

Components of Innate Immunity to Be Evaluated

A. Physical and Mechanical Barriers

These are usually assessed indirectly:

• Skin integrity: Inspected for wounds, burns, or lesions
• Mucous membranes: Evaluated for inflammation or damage

B. Chemical Barriers

• Gastric acidity: Measured using pH testing
• Lysozyme: Activity tested in tears, saliva, or secretions using biochemical assays

C. Cellular Components

These are key players in innate immune defense and can be directly measured.

Cell Type	Role	Method of Evaluation
Neutrophils	Phagocytosis, killing of bacteria	Full blood count (CBC), neutrophil oxidative burst test
Macrophages	Phagocytosis, cytokine production	Flow cytometry, ELISA for cytokines
Natural Killer (NK) cells	Killing virus-infected and tumor cells	Flow cytometry (CD16/CD56 markers), cytotoxicity assays
Dendritic cells	Antigen presentation	Flow cytometry, functional activation assays
Eosinophils and basophils	Defense against parasites, allergic responses	CBC with differential, enzyme assays (e.g., eosinophil peroxidase)

 

Laboratory Methods for Determining Innate Immunity

A. Complete Blood Count (CBC) and Differential

• Measures the number and proportion of white blood cells:
• Neutrophils
• Monocytes
• Eosinophils
• Basophils
• Neutropenia or monocytopenia may indicate weakened innate immunity.

B. Phagocytic Function Tests

• Nitroblue Tetrazolium (NBT) Test:
• Measures oxidative burst activity in neutrophils.
• Defective in diseases like chronic granulomatous disease (CGD).
• Dihydrorhodamine (DHR) Assay:
• Flow cytometry-based test for reactive oxygen species production by neutrophils.

C. Natural Killer (NK) Cell Activity Assays

• Cytotoxicity assays:
• Assess the ability of NK cells to kill target cells (e.g., K562 cell line).
• Flow cytometry:
• Measures NK cell surface markers (e.g., CD56+, CD16+).

D. Complement System Assessment

• CH50 Assay (Total Complement Activity):
• Measures the ability of serum to lyse sheep red blood cells coated with antibodies.
• Deficiencies in complement components reduce CH50.
• C3 and C4 Levels:
• Quantitative measurement of individual complement proteins using ELISA or nephelometry.
• AH50 Assay:
• Measures activity of the alternative complement pathway.

E. Cytokine Profiling

• Measures levels of pro-inflammatory cytokines (e.g., IL-1, IL-6, TNF-α, IFN-α, IFN-γ)
• Done via:
• ELISA
• Luminex
• RT-PCR

F. Pattern Recognition Receptor (PRR) Studies

• Toll-like receptors (TLRs) are key PRRs involved in innate immune signaling.
• Detection methods include:
• Flow cytometry
• RT-PCR for gene expression
• Western blot for protein levels

Functional Tests of Innate Immunity

Test	Purpose
Skin Window Test	Evaluates local recruitment of neutrophils and monocytes
Delayed-type Hypersensitivity (DTH)	Assesses interaction between innate and adaptive immunity
Inflammatory markers	CRP and ESR levels indicate innate immune activation

Genetic and Molecular Testing

Some individuals have inherited defects in innate immunity pathways:

Condition	Defective Component
Chronic Granulomatous Disease (CGD)	NADPH oxidase (defective respiratory burst)
Leukocyte Adhesion Deficiency (LAD)	Defect in integrins (neutrophil migration impaired)
IRAK-4/MyD88 Deficiency	Defective TLR signaling
Complement Deficiencies	Missing classical/alternative pathway proteins

Diagnosis of such conditions involves:

• Gene sequencing
• Western blotting
• Functional assays

In Vivo Animal Models (Research Use Only)

• Mouse knockout models: Used to study genes involved in innate immunity.
• Challenge experiments: Assess immune responses to known pathogens or TLR agonists.

Limitations and Considerations

• Innate immunity is dynamic; responses may vary with time, disease status, or age.
• Many tests are complex and require specialized labs.
• Some components (e.g., skin, mucosa) are difficult to measure directly in clinical settings.

9. Clinical Relevance of Innate Immunity Assessment

• Primary Immunodeficiencies: Early detection in children with recurrent infections.
• Autoimmune and inflammatory diseases: Dysregulated innate responses are common.
• Cancer and transplant patients: Monitoring innate function helps guide immunosuppressive therapy.
• COVID-19 and viral infections: Excessive or inadequate innate responses determine severity.

Summary Table: Key Tests in Innate Immunity Determination

Component	Test	Application
Neutrophils	CBC, NBT, DHR assay	Phagocytic and oxidative activity
NK cells	Flow cytometry, cytotoxicity assay	Cell-mediated cytotoxicity
Complement	CH50, C3, C4, AH50	Complement function and deficiency
Cytokines	ELISA, PCR	Inflammatory response profiling
PRRs	PCR, flow cytometry	TLR and innate receptor expression

The determination of innate immunity involves evaluating multiple cellular, molecular, and biochemical factors that act as the body’s first responders to infection. Understanding the integrity and function of innate immunity is essential for diagnosing immunodeficiencies, monitoring immune function, and tailoring therapies in immunocompromised individuals. While often less specific than adaptive immunity, innate immunity is critical for immediate protection and orchestrates the activation of long-lasting immune responses.