MCB 100 Exam 3 Study Guide: Infection, Immunity, and Pathogen Evasion

Infection and Disease Process

Disease Progression and Host-Pathogen Interactions

The process of infection involves a series of stages, from the initial colonization of the host by a pathogen to the development of disease and eventual recovery. Understanding these stages is crucial for identifying and controlling infectious diseases.

• Colonization: The pathogen enters and establishes itself in the host.

• Incubation Period: Time between pathogen entry and appearance of symptoms.

• Prodromal Stage: Early, mild symptoms appear.

• Illness Stage: Disease symptoms are most severe; pathogen is actively multiplying.

• Decline: Immune response or treatment reduces pathogen numbers; symptoms subside.

• Convalescence: Recovery and return to health.

Virulence factors are molecules produced by pathogens that enhance their ability to cause disease (e.g., toxins, adhesion molecules, enzymes).

Signs are objective evidence of disease (e.g., fever), while symptoms are subjective experiences reported by the patient (e.g., pain).

Disease Etiology and Koch’s Postulates

Determining the cause of a disease (etiology) is fundamental in microbiology. Koch’s Postulates are a set of criteria used to establish a causative relationship between a microbe and a disease:

1. The suspected pathogen must be present in all cases of the disease and absent from healthy individuals.

2. The pathogen must be isolated and grown in pure culture.

3. The cultured pathogen must cause the disease when introduced into a healthy host.

4. The same pathogen must be re-isolated from the experimentally infected host.

Modern molecular methods (e.g., PCR, sequencing) can help satisfy these postulates, especially for pathogens that cannot be cultured.

Routes of Infection, Transmission, and Epidemiology

Routes of Transmission

Pathogens can be transmitted through various routes, impacting the spread and control of infectious diseases:

• Contact Transmission: Direct (person-to-person) or indirect (via fomites).

• Vehicle-borne Transmission: Through contaminated water, food, or air.

• Vector-borne Transmission: Via insects or animals (e.g., mosquitoes, ticks).

Reservoirs are sources where pathogens persist (e.g., humans, animals, environment).

Examples of transmission routes:

• Respiratory route: Influenza, COVID-19, Whooping cough

• Oral-fecal route: Salmonella, Cholera, Listeria

Epidemiology and Disease Terminology

Epidemiology is the study of how diseases spread and affect populations. Key terms include:

• Endemic: Disease constantly present in a population.

• Epidemic: Sudden increase in disease cases above normal levels.

• Pandemic: Epidemic that spreads across countries or continents.

• Zoonotic: Disease transmitted from animals to humans.

• Sporadic: Occasional, irregular cases.

Epidemiological data can be visualized using heat maps, histograms, and demographic charts to track disease spread and impact.

Innate Immunity

Overview of Innate vs. Adaptive Immunity

The immune system has two main arms:

• Innate Immunity: Non-specific, immediate defense mechanisms present from birth.

• Adaptive Immunity: Specific, acquired responses that develop after exposure to pathogens.

Innate immunity includes physical, chemical, and cellular defenses, while adaptive immunity involves lymphocytes (T and B cells) and memory formation.

First Line Defenses: Barriers

First line defenses prevent pathogen entry:

• Physical Barriers: Skin, mucous membranes.

• Mechanical Barriers: Cilia movement, flushing by urine or tears.

• Chemical/Biochemical Barriers: Acidic pH, enzymes (lysozyme), antimicrobial peptides (defensins).

• Microbiome: Normal flora outcompete pathogens for resources.

Other innate responses include complement proteins, Toll-like receptors (TLRs), and interferons, which detect and respond to pathogens.

Second Line Defenses: Phagocytosis and Interferons

If pathogens breach first line defenses, second line defenses act rapidly and non-specifically:

• Phagocytic Cells: Neutrophils, macrophages, dendritic cells engulf and destroy pathogens.

• Phagocytosis Steps:

  1. Chemotaxis

  2. Adhesion

  3. Ingestion

  4. Maturation

  5. Killing

  6. Elimination

• Opsonization: Coating of pathogens to enhance phagocytosis.

• Interferons: Proteins produced in response to viral infection; inhibit viral replication.

• PAMPs and TLRs: Pathogen-associated molecular patterns recognized by Toll-like receptors to trigger immune responses.

Complement System and Inflammation

The complement system is a group of proteins that enhance immune responses via three pathways:

• Classical Pathway: Triggered by antibodies bound to pathogens.

• Alternative Pathway: Activated directly by pathogen surfaces.

• Lectin Pathway: Initiated by mannose-binding lectin binding to pathogen carbohydrates.

Functions of complement:

• Chemotaxis: Attracts phagocytes to infection site.

• Opsonization: Enhances phagocytosis.

• Membrane Attack Complex (MAC): Forms pores in Gram-negative bacteria, leading to lysis.

Inflammation is characterized by redness, heat, swelling, pain, and loss of function. It helps contain infections but can cause tissue damage if excessive.

Adaptive Immunity

Antibody-Mediated (Humoral) Responses

Adaptive immunity is specific and develops after exposure to antigens. B cells and plasma cells produce antibodies that neutralize pathogens.

• Antibody Classes:

  • IgG: Most abundant, crosses placenta, long-term immunity.

  • IgM: First produced, effective in agglutination.

  • IgA: Found in mucosal areas, protects body surfaces.

  • IgE: Involved in allergic responses and defense against parasites.

  • IgD: Functions mainly as a B cell receptor.

• Antigen Processing and Presentation: Phagocytes present antigens to T cells to initiate adaptive responses.

• Primary vs. Secondary Response: Secondary exposure leads to faster, stronger antibody production (basis for immunization).

Antibody titers and response patterns help diagnose acute vs. chronic infections.

Cell-Mediated Responses

T cells mediate cellular immunity, crucial for eliminating intracellular pathogens.

• Helper T cells (Th): Recognize antigens on MHC II, release cytokines to activate B and cytotoxic T cells.

• Cytotoxic T cells (Tc): Recognize antigens on MHC I, kill infected cells via perforin-granzyme or CD95 pathways.

• Memory T cells: Provide long-term immunity.

• Regulatory T cells (Treg): Suppress immune responses to prevent autoimmunity.

Antigen presentation differs for endogenous (MHC I) and exogenous (MHC II) antigens, influencing the type of immune response.

Antigen Presentation, Allergic Reactions, and Autoimmunity

Antigen processing and presentation are central to immune recognition:

• Exogenous Antigens: Presented by MHC II on antigen-presenting cells (APCs).

• Endogenous Antigens: Presented by MHC I on all nucleated cells.

• Self Antigens: Normally ignored; recognition can lead to autoimmunity.

Allergies are hypersensitivity reactions (Types I-IV) to antigens, leading to excessive inflammation. Cytokine storms can cause severe systemic inflammation (e.g., sepsis).

Autoimmunity occurs when the immune system attacks self tissues, often influenced by genetics and environment.

Evading the Immune Response

Bacterial Pathogen Evasion Mechanisms

Bacteria have evolved strategies to avoid immune detection and destruction:

• Resisting Defensins and Complement: Mutations prevent binding or degrade immune components.

• Resisting Phagocytosis: Alter surface molecules to avoid recognition.

• Intracellular Survival: Some bacteria (e.g., Listeria, Salmonella) hide inside host cells, avoiding immune attack.

• Examples:

  • Staphylococcus: Binds antibodies in reverse to block recognition.

  • Listeria: Moves cell-to-cell using actin, grows at low temperatures.

  • Salmonella: Survives in macrophage vacuoles, disseminates systemically.

• Vaccine Challenges: Some pathogens (e.g., Neisseria gonorrhoeae) evade immunity, making vaccine development difficult.

Viral Pathogen Evasion Mechanisms

Viruses employ multiple strategies to evade both innate and adaptive immunity:

• Envelope Mimicry: Use host-derived membranes to avoid detection (e.g., HIV, SARS-CoV-2).

• Antigenic Variation: Rapid mutation or modification of surface antigens (e.g., HIV, norovirus).

• Latency: Enter dormant states to hide from immune surveillance (e.g., HIV).

• Reduction of Surface Antigens: Decrease antibody binding (e.g., HIV).

• Immune Modulation: Encode proteins that block or mimic host immune responses.

Pathogen Evolution and Immune Countermeasures

Microbial evolution impacts disease control and immune evasion:

• Selection Pressure: Drives adaptation and increased virulence.

• Patho-adaptation: Rapid acquisition of new virulence factors.

• Viral Evolution: High mutation rates, gene swapping (antigenic drift and shift) lead to immune escape and outbreaks.

• Immune System Adaptation: VDJ recombination in lymphocytes generates diverse antigen receptors, enhancing pathogen recognition.

Antigenic drift involves small genetic changes, while antigenic shift involves major changes, often leading to pandemics.

Summary Table: Key Immune Components and Their Functions

Component	Type	Main Function	Example
Skin	Physical Barrier	Prevents pathogen entry	Blocks bacteria, viruses
Phagocytes	Cellular Defense	Engulf and destroy pathogens	Macrophages, neutrophils
Complement	Protein System	Opsonization, lysis, chemotaxis	MAC formation
Antibodies	Adaptive Immunity	Neutralize pathogens, opsonization	IgG, IgM, IgA
T cells	Adaptive Immunity	Kill infected cells, regulate immunity	Helper, cytotoxic, regulatory
Interferons	Cytokine	Inhibit viral replication	Type I IFN

Key Equations and Concepts

• Antibody Titer: Measurement of antibody concentration in serum.

• Basic Reproductive Number (R0): Average number of secondary cases produced by one infected individual in a susceptible population. Equation: $R_0 = \beta \times D$ where $\beta$ = transmission rate, $D$ = duration of infectiousness.

• Antigenic Drift vs. Shift:

  • Drift: Small, gradual genetic changes.

  • Shift: Abrupt, major genetic changes (e.g., reassortment in influenza).

Additional info: Where original notes were brief, academic context and definitions have been added for clarity and completeness.