Principles of Infectious Disease, Host-Microbe Interactions, and Immune System Disorders

Principles of Infectious Disease and Epidemiology

Types of Pathogens and Disease Occurrence

• Opportunistic pathogens cause disease only when the host is weakened, such as in individuals with compromised immune systems.

• Sporadic diseases are isolated infections within a population (e.g., Ebola).

• Endemic infections are routinely detected in a population or region (e.g., cold viruses).

• Epidemic refers to a widespread outbreak in a specific region and time frame.

• Pandemic occurs when an epidemic spreads across multiple countries.

• Emerging pathogens are newly identified agents or those with expanded distribution (e.g., SARS-CoV-2, Zika virus).

• Reemerging pathogens are infectious agents previously under control but now resurfacing (e.g., antibiotic-resistant bacteria).

• Zoonotic diseases are transmitted from animals to humans.

• Many zoonotic diseases are noncommunicable (do not spread person-to-person).

• Latent infections are typically asymptomatic, with no observable signs or symptoms.

Koch’s Postulates

• Set of criteria to establish a causative relationship between a microbe and a disease:

  1. The same organism must be present in every case of the disease.

  2. The organism must be isolated from the diseased host and grown in pure culture.

  3. The isolated organism should cause the disease when inoculated into a susceptible host.

  4. The organism must be re-isolated from the inoculated, diseased animal.

• Important for identifying causative pathogens of infectious diseases.

• Limitations:

  • Not applicable to noninfectious diseases.

  • Some infectious agents cannot be isolated or grown in the lab (e.g., obligate intracellular pathogens).

  • Some microbes lose virulence in pure culture or do not infect nonhuman hosts.

  • Not easily applied to latent diseases.

Sources and Transmission of Infectious Agents

• Reservoir: The natural habitat of a pathogen.

• Source: The immediate origin from which a pathogen is transmitted to a host.

• Endogenous source: Pathogen originates from the host's own body.

• Exogenous source: Pathogen comes from outside the host.

Pathogen Characteristics

• Infectivity: Ability of an agent to establish infection.

• Pathogenicity: General ability to cause disease.

• Virulence: Severity or degree of disease caused.

• Virulence factors help pathogens overcome host defenses (e.g., adherence, invasion, immune evasion).

• Prevention is especially important for vulnerable populations (babies, elderly, organ transplant recipients).

Host-Microbe Interactions and Pathogenesis

Normal Microbiota and Dysbiosis

• Normal microbiota colonize skin, digestive, genital, urinary, and respiratory tracts.

• Dysbiosis: Disruption of the normal microbiota, which can lead to disease.

Pathogen Adaptations and Virulence Factors

• Pathogens possess adaptations for interacting with host tissues and evading defenses.

• Virulence factors include mechanisms for adherence, invasion, immune evasion, and toxin production.

• Virulence factors can:

  • Directly damage host cells

  • Trigger harmful immune responses

Toxins

• Toxins: Molecules that cause tissue damage and immune suppression.

• Toxigenic: Microbes that produce toxins.

• Toxemia: Presence of toxins in the bloodstream.

• Two main classes:

  • Endotoxins: Part of Gram-negative bacterial cell walls; released upon cell death.

  • Exotoxins: Soluble proteins secreted by both Gram-positive and Gram-negative bacteria; highly toxic and target specific cells.

• Endotoxemia: Endotoxin in the bloodstream, can result from localized or systemic infections, or introduction of Gram-negative bacteria to sterile sites (e.g., during surgery).

• Types of exotoxins:

  • Neurotoxins: Affect the nervous system.

  • Enterotoxins: Target the gastrointestinal tract.

  • Hepatotoxins: Affect the liver.

  • Nephrotoxins: Damage the kidneys.

Steps for Pathogen to Establish Infection

1. Enter the host

2. Adhere to host tissues

3. Invade tissues and obtain nutrients

4. Replicate while evading immune defenses

5. Transmit to a new host

Cytopathic Effects

• Pathogens can cause cytopathic effects (CPE): observable changes in host cells due to infection.

• Cytocidal: Kill host cells.

• Noncytocidal: Damage but do not kill host cells.

• Bacteria induce CPE by invading cells, releasing toxins, or exploiting nutrients.

• Viruses induce CPE by disrupting cell function, causing cell lysis, or transforming cells (e.g., into cancer cells).

Innate and Adaptive Immunity

Lymphoid Tissues

• Primary lymphoid tissues: Sites of leukocyte production and maturation (thymus, bone marrow).

• Secondary lymphoid tissues: Filter lymph and sample antigens (lymph nodes, spleen, mucosa-associated lymphoid tissue [MALT]).

Cytokines and Immune Communication

• Cytokines: Signaling proteins for cell communication, initiating and coordinating immune responses.

• Most body cells can produce at least one cytokine.

• Cytokines are used as diagnostic and therapeutic markers.

• Cytokine storm: Excessive cytokine response, potentially harmful.

Inflammation and Fever

• Inflammation occurs in three phases:

  1. Vascular changes

  2. Leukocyte recruitment

  3. Resolution

• Fever benefits:

  • Enhances antiviral effects of interferons

  • Increases phagocyte efficiency

  • Boosts leukocyte production

  • Limits pathogen growth

  • Promotes tissue repair

Immune System Disorders

Immunodeficiencies

• Primary immunodeficiency: Congenital, inborn errors affecting immune factors, leading to deficient immunity.

• Treatments include bone marrow transplants, antibody administration, cytokine therapies, and experimental treatments (e.g., stem cell or thymus transplantation, gene therapy).

• Secondary immunodeficiency: Acquired, more common than primary; normal immune system declines due to age, infections, medical interventions, or systemic disorders (e.g., diabetes, malnutrition, alcoholism, hepatitis).

Allergy Testing and Management

• Identifying allergens is crucial for managing allergic diseases.

• Blood tests: Measure IgE titers against allergens.

• Skin tests: Quick and inexpensive, but may cause itchy lesions (wheal and flare).

• Patients should consult an allergist-immunologist for diagnosis and management.

Transplantation and Immune Rejection

• Transplanted tissue is rejected if cytotoxic T cells recognize it as foreign.

• Donor and recipient must have similar major histocompatibility complexes (MHCs) to reduce rejection risk.

Graft Type	Source	Rejection Risk	Example
Autograft	Self	None	Skin graft from own body
Isograft	Identical twin	Very low	Kidney transplant from twin
Allograft	Same species, not genetically identical	Moderate	Organ transplant from unrelated donor
Xenograft	Different species	High	Pig heart valve

• Immune-privileged sites (e.g., eye, brain, uterus, testicles) are less likely to reject grafts.

• Graft-versus-host disease (GVHD): Occurs when transplanted bone marrow's white blood cells attack the recipient's tissues.

Examples and Applications

• Example: SARS-CoV-2 is an emerging pathogen that caused a pandemic due to its rapid global spread.

• Example: Organ transplant recipients are at high risk for opportunistic infections due to immunosuppressive therapy.

• Example: Blood tests for IgE help diagnose allergies to specific substances such as pollen or food proteins.

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