Innate and Adaptive Immunity, Host-Microbe Interactions, and Biomedical Applications

Chapter 11: Innate Immunity

Overview of Innate and Adaptive Immunity

The immune system is divided into innate and adaptive branches, each with distinct mechanisms and roles in host defense.

• Innate Immunity: The body's first line of defense, providing rapid, non-specific responses to pathogens.

• Adaptive Immunity: Develops more slowly, is highly specific, and provides immunological memory.

• Comparison: Innate immunity includes barriers and cellular responses present from birth, while adaptive immunity involves lymphocytes (T and B cells) and is acquired after exposure to antigens.

Normal Microbiota and the Immune System

• Normal microbiota compete with pathogens for resources and stimulate immune system development.

• They can produce substances (e.g., bacteriocins) that inhibit pathogen growth.

First Line of Defense: Barriers

• Mechanical Barriers: Physical actions that remove microbes (e.g., cilia movement, flushing by tears, saliva, urine).

• Chemical Barriers: Substances that inhibit or destroy pathogens (e.g., lysozyme in tears, low pH in stomach).

• Physical Barriers: Structural features such as skin and mucous membranes that block pathogen entry.

Antimicrobial Peptides

• Short proteins that disrupt microbial membranes, leading to cell death.

• Examples include defensins and cathelicidins.

Lymphoid Tissues

• Primary lymphoid tissues: Sites of lymphocyte development (bone marrow, thymus).

• Secondary lymphoid tissues: Sites where immune responses are initiated (lymph nodes, spleen, MALT).

Leukocytes (White Blood Cells)

• Neutrophils: Phagocytosis and destruction of microbes.

• Macrophages: Phagocytosis, antigen presentation.

• Dendritic cells: Antigen presentation to T cells.

• Eosinophils: Defense against parasites.

• Basophils/Mast cells: Release histamine, involved in inflammation and allergy.

• Lymphocytes: T cells, B cells, and NK cells (bridge to adaptive immunity).

Cytokines

• Interleukins (ILs): Mediate communication between leukocytes.

• Interferons (IFNs): Antiviral responses, activate immune cells.

• Tumor Necrosis Factors (TNFs): Inflammation, apoptosis.

Interferons

• Produced in response to viral infection.

• Induce antiviral states in neighboring cells.

Iron-Binding Proteins

• Limit microbial access to iron (e.g., transferrin, lactoferrin).

• Essential for inhibiting microbial growth.

Complement System

• Series of plasma proteins that enhance immune responses.

• Activation leads to opsonization, inflammation, and lysis of pathogens.

Inflammation

• Local response to infection or injury.

• Four cardinal signs: redness, heat, swelling, pain.

• Results from increased blood flow, vascular permeability, and leukocyte recruitment.

Fever

• Systemic increase in body temperature.

• Enhances immune function and inhibits pathogen growth.

Chapter 12-13.1: Adaptive Immunity

Overview of Adaptive Immunity

• Involves T cells and B cells that recognize specific antigens.

• Provides long-lasting protection and immunological memory.

Antigens and Immunogenicity

• Antigen: Any substance that can elicit an immune response.

• Immunogenicity: The ability of an antigen to provoke an immune response.

T Cell Types

• Cytotoxic T cells (TC): Kill infected cells.

• Helper T cells (TH): Activate other immune cells.

• Regulatory T cells (TReg): Suppress immune responses to maintain tolerance.

Self-Tolerance Screening

• Elimination of self-reactive lymphocytes during development to prevent autoimmunity.

T Cells vs. B Cells

• T cells: Mediate cellular immunity, require antigen presentation.

• B cells: Produce antibodies, mediate humoral immunity.

Major Histocompatibility Complexes (MHCs)

• MHC I: Present on all nucleated cells, present endogenous antigens to CD8+ T cells.

• MHC II: Present on antigen-presenting cells, present exogenous antigens to CD4+ T cells.

Antigen Presentation

• Intracellular: Endogenous antigens presented via MHC I to cytotoxic T cells.

• Extracellular: Exogenous antigens presented via MHC II to helper T cells.

T Cell Activation, Proliferation, and Differentiation

• Requires antigen presentation and co-stimulatory signals.

• Activated T cells proliferate and differentiate into effector and memory cells.

Cytotoxic T Cell Action

• Recognize infected cells via MHC I and induce apoptosis.

B Cell Activation

• T-dependent: Require T cell help for activation.

• T-independent: Activated directly by certain antigens.

• Leads to proliferation and differentiation into plasma cells (antibody production) and memory B cells.

Antibody Structure and Function

• Y-shaped molecules with variable (antigen-binding) and constant regions.

• Functions: neutralization, opsonization, complement activation, agglutination, antibody-dependent cellular cytotoxicity.

Antibody Types

• IgG: Most abundant, crosses placenta.

• IgM: First produced, pentameric.

• IgA: Found in mucosal areas, dimeric.

• IgE: Involved in allergy and parasitic defense.

• IgD: B cell receptor.

Immunological Memory

• Faster and stronger response upon re-exposure to the same antigen.

Categories of Humoral Immunity

• Natural active: Infection-induced immunity.

• Natural passive: Maternal antibody transfer.

• Artificial active: Vaccination.

• Artificial passive: Antibody therapy.

Immunodeficiencies and Autoimmunity

• Primary immunodeficiencies: Genetic defects affecting immune function.

• Secondary immunodeficiencies: Acquired due to infection, malnutrition, or therapy.

• Autoimmunity: Immune response against self-antigens.

Chapter 14.1-14.3: Biomedical Applications

Smallpox Eradication

• Achieved through global vaccination campaigns.

• Possible due to lack of animal reservoir and effective vaccine.

Jenner’s Vaccination

• Edward Jenner used cowpox to protect against smallpox, coining the term "vaccine" from vacca (cow).

Herd Immunity

• Occurs when a high proportion of the population is immune, reducing disease spread.

Vaccine Categories

Type	Example	Benefits	Risks
Live attenuated	MMR, Varicella	Strong, long-lasting immunity	Risk in immunocompromised
Inactivated	Polio (IPV)	Safe for most	Weaker immunity, boosters needed
Subunit/conjugate	Hepatitis B	Very safe	May require adjuvants
Toxoid	Tetanus	Targets toxins	Boosters needed

Agglutination Reactions and Blood Typing

• Agglutination: Clumping of particles by antibodies, used in blood typing and pathogen detection.

ELISA (Enzyme-Linked Immunosorbent Assay)

• Direct ELISA: Detects antigens using labeled antibodies.

• Indirect ELISA: Detects antibodies using a secondary labeled antibody.

• Sandwich ELISA: Captures antigen between two antibodies.

Western Blotting

• Detects specific proteins using antibody binding after gel electrophoresis.

Chapter 10: Host-Microbe Interactions and Pathogenesis

Tropism

• Pathogen preference for specific host tissues or cells.

Virulence Factors

• Molecules that enhance pathogen ability to cause disease (e.g., toxins, adhesins, invasins).

ID50 and LD50

• ID50: Infectious dose for 50% of the population.

• LD50: Lethal dose for 50% of the population.

Basic Reproduction Number (R0)

• Average number of secondary cases generated by one case in a susceptible population.

• Higher R0 indicates greater transmissibility.

Endotoxins and Exotoxins

• Endotoxin: Lipopolysaccharide (LPS) from Gram-negative bacteria, causes systemic effects.

• Exotoxins: Secreted proteins with specific targets and effects.

Steps to Infection

1. Entry

2. Adhesion

3. Invasion

4. Immune evasion

5. Exit

Portals of Entry and Exit

• Entry: Mucous membranes, skin, parenteral route.

• Exit: Respiratory droplets, feces, urine, blood, etc.

Adhesion Factors

• Molecules (e.g., pili, fimbriae) that allow pathogens to attach to host cells.

Biofilm and Quorum Sensing

• Biofilm: Community of microbes attached to a surface, protected by extracellular matrix.

• Quorum sensing: Cell-to-cell communication regulating gene expression in response to population density.

Invasins

• Enzymes or proteins that help pathogens invade host tissues (e.g., hyaluronidase, collagenase).

Immune Evasion Mechanisms

• Antigenic variation, capsule formation, inhibition of phagocytosis, intracellular survival.

Transmission Modes and Precautions

Mode	Description	Precautions
Contact	Direct or indirect physical contact	Hand hygiene, gloves
Droplet	Large respiratory droplets	Masks, distance
Airborne	Small particles suspended in air	N95 respirators, ventilation

Additional info: Where diagrams are referenced (e.g., Figs 12.2, 12.9, 12.10, 12.16), students should review textbook figures for visual understanding of processes such as antigen presentation and lymphocyte activation.