Host-Microbe Interactions, Epidemiology, and Immunology: Structured Study Notes

Host-Microbe Interactions

Symbiosis

Symbiosis describes the relationship between two organisms living together. These relationships can be classified based on the effects on each participant.

• Mutualism: Both organisms benefit. Example: Escherichia coli in the human intestine produce vitamin K for the host.

• Commensalism: One organism benefits, the other is unaffected. Example: Normal skin bacteria feed on dead skin cells.

• Parasitism: One organism benefits while the host is harmed. Example: Disease-causing bacteria infecting humans.

Key Vocabulary

• Colonization: Microorganisms grow on or in the body without causing disease.

• Infection: Invasion and multiplication of pathogens in the body.

• Pathogen: Microorganism capable of causing disease.

• Subclinical: Infection with no noticeable symptoms.

• Subacute: Disease develops more slowly than acute, faster than chronic.

• Symptoms: Changes noticed by the patient (pain, fatigue, nausea).

• Signs: Objective evidence observed by others (rash, fever, swelling).

• Primary infection: First infection that occurs.

• Secondary infection: Follows a primary infection due to weakened defenses.

• Opportunistic pathogen: Normally harmless microbes causing disease when immunity is weakened.

• Virulence: Degree of pathogenicity (severity of disease).

• Communicable: Can spread from person to person.

• Infectious dose (ID): Number of microbes required to establish infection.

Stages of Disease

• Incubation Period: Pathogen enters body, multiplies, no symptoms.

• Prodromal Stage: Mild symptoms begin (fatigue, malaise).

• Illness Stage: Symptoms are most severe, pathogen numbers highest.

• Decline Stage: Symptoms decrease, immune system or treatment reduces pathogen.

• Convalescence: Recovery, body returns to normal.

Distribution of Pathogens

• Localized Infection: Confined to one area (e.g., boil, abscess).

• Systemic Infection: Spreads throughout the body (e.g., sepsis).

• Sepsis: Life-threatening systemic inflammatory response caused by infection.

• "-emia": Presence of something in the blood (e.g., bacteremia, viremia, toxemia).

Etiology of Infectious Disease

Koch's Postulates are used to determine if a specific microorganism causes a specific disease.

1. Organism found in every diseased host.

2. Organism isolated and grown in pure culture.

3. Pure culture causes disease in healthy host.

4. Same organism recovered from newly infected host.

Exceptions: Viruses and some bacteria cannot be cultured; diseases may be caused by multiple pathogens; ethical issues prevent infecting humans; opportunistic pathogens may not always cause disease.

Mechanisms of Pathogenesis

• Ingested toxin: e.g., botulism.

• Colonize and produce toxins: e.g., food poisoning by Staphylococcus aureus.

• Invade tissue and damage cells: e.g., tuberculosis.

• Invade tissue and produce toxins: e.g., Streptococcus pyogenes.

How Bacteria Establish Infection

• Attach to host cells (adhesion)

• Colonize

• Avoid immune defenses

• Invade tissues

• Produce toxins

• Multiply

How Bacteria Breach the Body

• Breaks in skin, cuts, insect bites

• Mucous membranes (respiratory, digestive, urinary tracts)

How Bacteria Damage Cells

• Destroy cells directly

• Produce exotoxins

• Produce endotoxins

• Trigger inflammation

• Damage tissues during immune response

Exotoxins vs Endotoxins

Feature	Exotoxins	Endotoxins
Composition	Proteins	Lipopolysaccharide (LPS)
Source	Mostly Gram-positive, some Gram-negative	Gram-negative bacteria
Release	Secreted from living bacteria	Released when bacteria die
Potency	Extremely potent, specific targets	Less potent, general effects (fever, shock)

• Neurotoxins: Affect nervous system (e.g., botulinum, tetanus toxins).

• Enterotoxins: Affect intestines (e.g., cholera toxin).

• Cytotoxins: Damage or kill cells.

• Membrane-Damaging Toxins: Destroy cell membranes (e.g., hemolysins).

• Superantigens: Cause massive activation of T cells, cytokine storm (e.g., toxic shock syndrome).

Epidemiology

Basic Concepts

• Epidemiology: Study of how diseases occur, spread, and are controlled in populations.

• Etiology: Study of the cause of disease.

Incidence vs Prevalence

• Incidence: Number of new cases during a specific period.

• Prevalence: Total number of existing cases.

Disease Vocabulary

• Communicable: Spread person to person.

• Noncommunicable: Cannot spread person to person.

• Endemic: Constantly present in a population (e.g., common cold).

• Epidemic: Large increase above expected levels.

• Pandemic: Worldwide epidemic.

• Sporadic: Occurs occasionally.

• Common Source Outbreak: Everyone exposed to same contaminated source (e.g., food).

• Fomite: Contaminated object spreading disease (e.g., door handles).

• Incidence (Attack Rate): Percentage of people who become ill.

• Case Fatality Rate: Percentage of infected people who die.

Predisposing Factors

• Age, poor nutrition, stress, diabetes, cancer, pregnancy, immunodeficiency, poor hygiene, smoking, alcohol use

Morbidity vs Mortality

• Morbidity: Rate of illness.

• Mortality: Rate of death.

Important Scientists

• John Snow: Father of epidemiology; traced cholera to water pump.

• Ignaz Semmelweis: Required hand washing; reduced puerperal fever.

• Florence Nightingale: Improved hospital sanitation; reduced infection rates.

Reservoirs of Infection

• Human Reservoir: Humans carrying pathogens; carriers may be asymptomatic.

• Animal Reservoir: Animals harbor pathogens (e.g., rabies).

• Zoonotic Disease: Disease transmitted from animals to humans.

• Zoonotic Vectored Disease: Requires insect vector (e.g., Lyme disease, West Nile virus).

• Environmental Reservoirs: Soil, water, food.

Modes of Transmission

• Contact: Direct (touching, kissing, sexual contact), congenital (mother to fetus), indirect (fomites), droplet (sneezing, coughing).

• Vehicle Transmission: Airborne, waterborne, foodborne.

• Vectors: Mechanical (pathogen carried externally, e.g., fly), biological (pathogen reproduces inside vector, e.g., mosquito).

Nosocomial Infection

• Definition: Hospital-acquired infection.

• Causes: Catheters, surgery, weakened immunity, poor hand hygiene.

• Common Pathogens: MRSA, Clostridioides difficile, Escherichia coli, Pseudomonas aeruginosa.

Precautions

• Universal Precautions: Treat all blood/body fluids as infectious.

• Standard Precautions: Universal plus hand hygiene, PPE, respiratory hygiene, safe sharps disposal.

• Transmission-Based Precautions: Extra precautions for airborne, droplet, or contact diseases.

Three Factors Influencing Disease

1. Host

2. Pathogen

3. Environment

Disease Control

• Isolation, quarantine, immunization, vector control

Organizations

• CDC: Centers for Disease Control and Prevention (U.S.)

• WHO: World Health Organization

• MMWR: Morbidity and Mortality Weekly Report (CDC publication)

Notifiable Diseases

• Examples: Measles, tuberculosis, COVID-19, rabies, salmonellosis

• Importance: Allows public health officials to detect outbreaks and monitor trends.

Emerging Diseases & Bioterrorism

• Emerging Diseases: New or rapidly increasing infectious diseases (e.g., COVID-19, Zika, Ebola).

• Bioterrorism: Intentional release of microorganisms or toxins to cause illness or fear.

Types of Epidemiology

• Descriptive: Studies who, where, and when disease occurs.

• Analytical: Studies why and how disease occurs by identifying risk factors.

• Experimental: Tests interventions (vaccines, treatments) through controlled studies.

Innate Host Defenses

Innate vs Adaptive Immunity

Feature	Innate Immunity	Adaptive Immunity
Timing	Present at birth, rapid response	Develops after exposure, slower first response
Specificity	Non-specific	Specific to pathogen
Memory	No memory	Has immunological memory

Types of Innate Defenses

• First Line of Defense: Skin, mucous membranes, secretions, normal microbiota

• Second Line of Defense: White blood cells, inflammation, fever, phagocytosis, complement, interferons

First Line of Defense

• Physical Barriers: Skin (keratin, shedding), mucous membranes (trap microbes), movement of fluids (tears, saliva, urine, cilia, peristalsis)

• Chemical Barriers: Sebum (lowers skin pH), lysozyme (breaks down peptidoglycan), gastric juice (acidic), microbiome (competes with pathogens, produces antimicrobials)

Second Line of Defense

• White Blood Cells: Granulocytes (neutrophils, eosinophils, basophils), agranulocytes (monocytes, lymphocytes)

• Inflammation: Protective response (PRISH: pain, redness, immobility, swelling, heat)

• Phagocytosis: Engulfing and destroying microbes (neutrophils, macrophages, dendritic cells)

• Complement System: Plasma proteins enhance immune defenses (opsonization, inflammation, lysis)

• Fever: Slows microbial growth, enhances immune function

• Interferons: Released by virus-infected cells, inhibit viral replication, activate NK cells

Phagocytosis Steps

1. Chemotaxis: Movement toward chemicals released by pathogens/damaged tissue.

2. Adherence: Phagocyte attaches to pathogen (recognizes PAMPs via TLRs).

3. Ingestion: Phagocyte surrounds pathogen, forms phagosome.

4. Digestion: Phagosome fuses with lysosome, forms phagolysosome, enzymes destroy pathogen.

Inflammation

• Purpose: Eliminate pathogens, remove damaged tissue, begin healing.

• Acute: Rapid onset, short duration, beneficial.

• Chronic: Long-lasting, can damage healthy tissue.

• Histamine: Released by basophils/mast cells, dilates blood vessels, increases permeability.

Cell Communication

• Cytokines: Chemical messenger proteins.

• Chemokines: Attract immune cells to infection sites.

• Colony-Stimulating Factors (CSFs): Stimulate bone marrow to produce more WBCs.

• Interferons (IFNs): Warn nearby cells, slow viral replication, activate NK cells.

• Interleukins (IL): Stimulate growth and activation of immune cells.

• Tumor Necrosis Factor (TNF): Promotes inflammation, causes fever, destroys infected cells.

• Cytokine Storm: Excessive immune response, severe inflammation, organ damage, shock, death.

Complement System

• Opsonization: Complement proteins coat pathogens, enhancing phagocytosis.

• Inflammation: Attracts WBCs, increases inflammation.

• Cell Lysis: Membrane Attack Complex (MAC) forms holes in microbial membranes.

Pathway	Trigger
Classical	Antigen-antibody complexes
Alternative	Microbial cell surfaces
Lectin	Mannose-binding lectin binds carbohydrates on microbes

Adaptive Immunity

Overview

Adaptive immunity is the third line of defense, specific to antigens, slower on first exposure, and has immunological memory.

Humoral vs Cell-Mediated Immunity

Feature	Humoral Immunity	Cell-Mediated Immunity
Main Cells	B cells	T cells
Maturation	B cells mature in bone marrow	T cells mature in thymus
Function	Produce antibodies	Kill infected cells, activate other immune cells
Targets	Extracellular pathogens	Intracellular pathogens, viruses, cancer cells

Antigen and Hapten

• Antigen: Substance recognized as foreign, triggers immune response (e.g., bacteria, viruses, toxins, pollen).

• Hapten: Small molecule, antigenic only when attached to larger protein (e.g., penicillin allergy).

Key Cytokines

• Interleukin (IL): Stimulates B and T cell growth, coordinates immune responses, promotes inflammation.

• Chemokine: Attracts immune cells to infection site.

• Interferons: Inhibit viral replication, protect nearby cells, activate NK cells.

• TNF-α: Promotes inflammation, causes fever, activates immune cells, destroys tumor cells.

Antibody Structure and Types

• Antibody (Immunoglobulin, Ig): Y-shaped protein made by plasma cells, binds specific antigen.

• Structure: 2 heavy chains, 2 light chains, variable region (binds antigen), constant region (determines class).

Type	Features
IgG	Most abundant, secondary response, crosses placenta, long-term immunity
IgM	First produced, largest (pentamer), activates complement
IgA	Secretions (saliva, tears, breast milk, mucus), protects mucosal surfaces
IgD	On immature B cells, B-cell receptor
IgE	Allergies, asthma, parasitic worms, stimulates histamine release

Clonal Selection and Expansion

• Clonal Selection: Antigen binds to matching B or T cell, activating it.

• Clonal Expansion: Activated cell divides, producing effector and memory cells.

Antigen-Presenting Cells (APCs) and MHC

• APCs: Dendritic cells, macrophages, B cells; process and display antigens to T cells using MHC II.

• MHC Class I: All nucleated cells, presents to CD8 T cells, displays intracellular antigens.

• MHC Class II: Only on APCs, presents to CD4 T cells, displays extracellular antigens.

B Cell Activation

• T-Dependent: APC presents antigen to helper T cell, cytokines activate B cells, strong response, long-lasting memory.

• T-Independent: Some antigens activate B cells without helper T cells, mostly IgM produced, weak memory.

Antibody Functions

1. Neutralization: Block toxins/viruses from attaching to cells.

2. Agglutination: Clump bacteria for easier removal.

3. Opsonization: Coat pathogens for easier phagocytosis.

4. Complement Activation: Activate classical pathway.

5. ADCC: NK cells destroy antibody-coated cells.

Immunological Memory and Tolerance

• Memory B and T cells: Faster, stronger response to future infections.

• Immunological Tolerance: Immune system does not attack self-antigens; failure leads to autoimmune disease.

Primary vs Secondary Immune Response

Feature	Primary	Secondary
Exposure	First	Subsequent
Speed	Slow (days)	Fast
Antibody Type	Mostly IgM	Mostly IgG
Antibody Levels	Lower	Higher
Duration	Shorter	Longer

CD4 vs CD8 T Cells

• CD4 (Helper T Cells): Coordinate immune responses, activate B cells/macrophages, release cytokines.

• CD8 (Cytotoxic T Cells): Kill virus-infected/cancer cells, release perforin and granzymes.

Natural Killer (NK) Cells

• Kill virus-infected and tumor cells without prior exposure or antigen presentation.

Types of Adaptive Immunity

Type	How Acquired
Naturally Acquired Active	Infection stimulates antibody/memory cell production
Naturally Acquired Passive	Maternal antibodies via placenta/breast milk
Artificially Acquired Active	Vaccination stimulates antibody/memory cell production
Artificially Acquired Passive	Injection of preformed antibodies

Practical Applications of Immunology

Vaccines

• Variolation: Exposing healthy person to smallpox material for immunity; pre-modern vaccine.

• Vaccination: Term from Latin "vacca" (cow); Edward Jenner used cowpox to protect against smallpox.

• Vaccine: Preparation containing weakened, killed, or pieces of pathogen (or genetic material) to stimulate immune response without causing disease.

• Herd Immunity: Enough people immune reduces disease transmission, protects vulnerable individuals.

Types of Vaccines

Type	Description	Advantages	Disadvantages
Attenuated (Live)	Weakened live pathogen	Strong, long-lasting immunity	Not safe for immunocompromised; rare reversion
Inactivated (Killed)	Killed pathogen	Cannot cause disease	Weaker immunity; boosters needed
Subunit	Pieces of pathogen (proteins, sugars)	Very safe; fewer side effects	Often requires boosters/adjuvants
Toxoid	Inactivated bacterial toxin	Protects against toxin effects	Booster doses often required
Recombinant	Genetic engineering to make antigen proteins	Safe and targeted	May require multiple doses
DNA Vaccine	DNA encoding pathogen protein	Stable; stimulates B and T cells	New technology; few human examples
mRNA Vaccine	mRNA instructs cells to make antigen protein	Fast to develop; strong response	Requires cold storage; may need boosters

Monoclonal Antibodies

• Laboratory-produced, identical antibodies recognizing one antigen.

• Production: Immunize mouse, remove B cells, fuse with myeloma cells, form hybridomas, produce antibodies.

• Uses: Cancer treatment, autoimmune diseases, COVID-19, diagnostic tests, pregnancy tests.

ELISA (Enzyme-Linked Immunosorbent Assay)

• Laboratory test to detect antibodies or antigens.

• Direct ELISA: Detects antigen (e.g., viral proteins).

• Indirect ELISA: Detects antibodies (e.g., HIV, COVID-19).

• Interpretation: Positive = color change; negative = no color change.

Quick Review / High-Yield Facts

• Symbiosis: Mutualism (both benefit), commensalism (one benefits, other unaffected), parasitism (one benefits, host harmed).

• PRISH (Inflammation): Pain, redness, immobility, swelling, heat.

• White Blood Cells: Neutrophils (bacteria), eosinophils (parasites/allergies), basophils (histamine), monocytes (macrophages), lymphocytes (B, T, NK cells).

• Complement = OIL: Opsonization, inflammation, lysis (MAC).

• Antibodies: IgG (most common, crosses placenta), IgM (first made), IgA (secretions), IgD (B-cell receptor), IgE (allergies/parasites).

• MHC: MHC I → CD8 (killer T cells), MHC II → CD4 (helper T cells).

• Four Types of Immunity: Natural active (infection), natural passive (mom), artificial active (vaccine), artificial passive (antibody injection).

• Vaccine Types: Live attenuated, inactivated, subunit, toxoid, recombinant, DNA, mRNA.

• ELISA: Direct = antigen, indirect = antibody.