Lesson 14 - Pathogenesis of Infectious Diseases

Pathos (Greek)

• Disease

  • Emphasize the connection between the Greek root and its implications for the study of disease.

Pathogen

• A microbe capable of causing disease.

  • Briefly mention examples (bacteria, viruses, fungi, parasites).

Pathology

• The study of the structural and functional manifestations of disease.

  • Briefly mention key areas within pathology (e.g., anatomic pathology, clinical pathology).

Pathologist

• Physician specializing in pathology.

  • Highlight their role in diagnosing diseases through examining tissues, cells, and body fluids.

Pathogenicity

• The ability of a microbe to cause disease.

  • Briefly touch upon virulence factors (e.g., toxins, capsules) that contribute to pathogenicity.

Pathogenesis

• The steps involved in the development of a disease.

  • Briefly outline the stages: entry, adherence, invasion, damage, and host response.

Infectious Disease

• A disease caused by a microbe.

  • E.g., influenza, tuberculosis, HIV/AIDS

Infection

• Broad Definition

  • The presence of a pathogen within the body.

• Microbiological Definition

  • Colonization of the body by a pathogen, regardless of disease development.

• Example

  • Carriers of asymptomatic infections (e.g., individuals carrying Salmonella without experiencing illness).

Reasons Why Infection Does Not Always Occur | Unsuitable Environment

• Skin: Low pH, fatty acids, dryness create a barrier.

• Other examples: Stomach acidity, mucosal surfaces with protective secretions.

Reasons Why Infection Does Not Always Occur | Lack of Receptors

• Pathogens require specific receptors on host cells to attach and infect.

  • Briefly explain the concept of host-pathogen specificity.

Reasons Why Infection Does Not Always Occur | Antimicrobial Factors

• Lysozyme: Present in tears, saliva, and other secretions.

• Other examples: Antimicrobial peptides, complement system.

Reasons Why Infection Does Not Always Occur | Microbial Antagonism

• Normal microbiota compete for resources and space.

• Production of bacteriocins by normal microbiota.

Reasons Why Infection Does Not Always Occur | Host Factors

Nutrition, overall health, stress, age, and immune system status all play a significant role.

Stages of an Infectious Disease | Incubation Period

• Time between exposure and the appearance of the first symptoms.

• Length is influenced by factors like dose of pathogen, virulence, and host immunity.

Stages of an Infectious Disease | Prodromal Period

• Mild, nonspecific symptoms

• Time during which the patient feels “out of sorts” but does not yet experience actual symptoms of the disease

• E.g., fatigue, malaise, low-grade fever

• May last from several hours to a few days.

Stages of an Infectious Disease | Period of Illness

• Time of most severe symptoms

• Disease is most communicable during this phase

• Experiences the typical symptoms associated with that particular disease

Stages of an Infectious Disease | Convalescent Period

• Recovery phase.

• Symptoms gradually subside.

• Possible complications: Long-term damage, chronic infection.

Localized Infection

• Confined to a specific area.

  • E.g., Boils, abscesses, urinary tract infections (may initially be localized).

Systemic/Generalized Infection

• Spread throughout the body.

  • Mechanisms

    • Bloodstream, lymphatic system, nerves.

    • Examples: Septicemia, measles, disseminated tuberculosis.

Type of Disease Duration | Acute

• Rapid onset, short duration.

  • Examples: Influenza, measles, common cold.

Type of Disease Duration | Subacute

• Slower onset than acute, less sudden than chronic.

  • Examples: Subacute bacterial endocarditis (SBE)

Type of Disease Duration | Chronic

• Slow onset, long duration.

  • May persist for months or years or for a lifetime

  • Examples: Tuberculosis, hepatitis B, HIV/AIDS.

Symptom of Disease

• Subjective, experienced by the patient.

  • Examples: Pain, fever, headache, fatigue, nausea.

Signs of Disease

• Objective, observed by others or measured.

  • Laboratory test results are also considered _____

  • Examples: Rash, fever, swollen lymph nodes, abnormal heart sounds, elevated blood pressure.

Latent (Dormant) Infection

• May go from being symptomatic to asymptomatic and then, sometime later, go back to symptomatic

  • Greek, latens, means to lie hidden

  • Disease that is lying dormant, not currently manifesting itself

Latent Infection | Herpesvirus Infections - Cold sores (HSV-1)

Recurrent outbreaks triggered by stress, sunlight, fever.

Latent Infection | Herpesvirus Infections - Genital Herpes (HSV-2)

Similar pattern of recurrent outbreaks.

Latent Infection | Herpesvirus Infections - Shingles (Varicella-zoster virus)

• Reactivation of the chickenpox virus.

  • A painful infection of the nerves

Latent Infection | Syphilis

• A chronic disease caused by the spirochete Treponema pallidum.

  • Progresses through distinct stages.

Stages of Syphilis | Primary Syphilis

• Appearance of a painless chancre at the site of infection.

  • Highly infectious.

Stages of Syphilis | Secondary Syphilis

• Rash, fever, swollen lymph nodes, mucous membrane lesions.

  • Systemic spread of the infection.

  • Spirochete enters the bloodstream, the chancre disappears

Stages of Syphilis | Latent Syphilis

• No or few symptoms.

  • May last for years or even decades or for a lifetime

  • Bacteria remain dormant in the body.

Stages of Syphilis | Tertiary Syphilis

• Severe complications affecting the heart, brain, and other organs.

  • Cause destruction of the organs in which they have been hiding, sometimes leading to death

  • Can occur years after the initial infection.

Chancre

refers to an open lesion

Primary Infection

• The initial infection.

  • Often weakens the host's defenses.

Secondary Infection

• Caused by a different pathogen.

  • Occurs as a consequence of the primary infection.

Steps in Pathogenesis of Infectious Diseases | Entry

• Pathogens enter through various portals

  • E.g., skin, respiratory tract, gastrointestinal tract, urogenital tract

Steps in Pathogenesis of Infectious Diseases | Attachment

Pathogens adhere to host cells using specific receptors and adhesins.

Steps in Pathogenesis of Infectious Diseases | Multiplication

• Pathogens replicate within the host.

  • May multiply in one location of the body (localized infection) or it may multiple throughout the body (systemic infection)

Steps in Pathogenesis of Infectious Diseases | Invasion

Spread of the pathogen to other tissues.

Steps in Pathogenesis of Infectious Diseases | Evasion of Host Defenses

• Mechanisms to avoid immune system recognition and destruction

  • E.g., capsules, toxins

Steps in Pathogenesis of Infectious Diseases | Damage to Host Tissues

• Can occur through various mechanisms

  • May cause patient’s death

  • E.g., toxin production, inflammation, immune response

Virulence Factors

• Traits that enable a pathogen to cause disease by escaping various host defense mechanisms

  • Phenotypic characteristics that enable microbes to be virulent, which is dictated by organism’s genotype

  • Examples: Toxins, capsules, adhesins, pili, enzymes, evasion mechanisms

Virulence

The degree of pathogenicity.

Virulence Factor | Attachment

• Receptors and Adhesins

  • Pathogens bind to specific receptors on host cells.

    • Adhesins (e.g., pili, fimbriae) on pathogen surface mediate attachment.

• Importance

  • Essential for colonization and subsequent infection.

Exoenzyme

Enable pathogens to evade host defense mechanisms, invade, or cause damage to body tissues

Enzyme | Necrotizing Enzymes

these enzymes destroy host tissues (e.g., proteases in Clostridium perfringens).

Enzyme | Coagulase

• enzyme that is produced by Staphylococcus aureus to form a fibrin clot around the bacteria.

  • Virulence factor that causes clotting

Enzyme | Kinases

• Dissolve fibrin clots, allowing for bacterial spread (e.g., streptokinase).

  • Exoenzymes that dissolve clots

  • Enables pathogens that produce them to escape from clots

Enzyme | Hyaluronidase

• Breaks down connective tissue, facilitating tissue invasion.

  • Enables pathogens to spread through connective tissue by breaking down hyaluronic acid

  • “spreading factor”

Enzyme | Collagenase

• Degrades collagen, aiding in tissue invasion.

• Breaks down collagen; enables pathogens to invade tissues

Enzyme | Hemolysins

• Damage red blood cells, releasing iron for bacterial growth.

• Enzymes that cause damage to the host’s RBC

Enzyme | Lecithinase

Causes destruction of host cell membranes

Toxins (Virulence Factor)

Ability of pathogens to damage host tissues and cause disease may depend on the production and release of various types of poisonous substances

Toxins | Endotoxins

• Components of Gram-negative bacterial cell walls (LPS).

  • Integral parts of the walls of Gram-negative bacteria

  • Can cause a number of adverse physiologic effects

  • Cause fever, shock, and other systemic effects.

Toxins | Exotoxins

• Proteins secreted by bacteria (various pathogens)

  • Often named for the target organs they affect

  • Toxins that are produced within the cells and then released from the cells

  • Include neurotoxins, enterotoxins, cytotoxins, and others.

Toxin Examples | Neurotoxins

• Tetanus toxin, botulinum toxin.

• Targets neurons

Toxin Examples | Enterotoxins

• Toxins that affect gastrointestinal tract, often causing diarrhea and sometimes vomiting

  • Produced by E. coli, Salmonella, C. difficile.

Attachment | Receptors (Integrin)

• Molecules on host cells that particular pathogens recognize and bind (attach) to.

  • A particular pathogen can only attach to cells bearing the appropriate receptor

  • Examples: Glycoproteins, glycolipids.

Attachment | Adherin (Ligands)

• Molecules on the pathogen surface that bind to host receptors.

  • Molecules on the surface of a pathogen that recognize and attach to receptors on the surface of a host cell

  • Examples: Pili, fimbriae, viral envelope proteins.

Bacterial Fimbriae (Pili)

• Thin, hairlike, flexible projections composed primarily of an array of proteins called pilin

  • Structure

    • Hair-like protein appendages on the bacterial surface.

  • Function

    • Enable bacteria to adhere to host cells and surfaces.

Bacterial Fimbriae (Pili) Example | N. gonorrhoeae

adherence to urethral epithelium, which causes urethritis.

Bacterial Fimbriae (Pili) Example | E. coli

adherence to bladder cells which causes cystitis

Bacterial Fimbriae (Pili) Example | S. pyogenes

adherence to pharyngeal cells.

M-protein

• A type of pilus in S. pyogenes that mediates adherence and inhibits phagocytosis.

  • Serves as a virulence factor in 2 ways:

    • Enables bacteria to adhere to pharyngeal cells

    • Protects the cells from being phagocytized by WBC

Obligate Intracellular Pathogens

• Cannot survive or multiply outside of host cells.

  • Rely on host cell machinery for essential functions.

  • Examples:

    • Bacteria: Rickettsia, Chlamydia, Ehrlichia, Anaplasma;

    • Protozoa: Plasmodium (malaria), Babesia.

Rickettsia

• Invade endothelial and vascular smooth muscle cells.

  • "Leaky membranes" – require host cell environment for essential functions.

    • Can produce their own ATP but leaky membranes require them a host cell to multiply

Chlamydia

• Invade various cell types (e.g., epithelial cells and cells of the respiratory and genital tracts)

  • "Energy parasites" – utilize host cell ATP.

Intraleukocytic Pathogens | Erlichia spp.

• Infect monocytes.

  • Causes a disease known as human monocytic ehrlichiosis

Intraleukocytic Pathogens | Anaplasma phagocytophilum

• Infect granulocytes.

  • Causing human anaplasmosis

Intraerythrocytic Pathogens | Plasmodium spp.

• Infect red blood cells.

  • Causes malaria

Intraerythrocytic Pathogens | Babesia spp.

• Infect red blood cells.

  • Causes babesiosis

Facultative Intracellular Pathogens

• Can survive and multiply both inside and outside of host cells.

  • “Facultative Intracellular Parasites”

  • Examples: Mycobacterium tuberculosis, Salmonella, Listeria monocytogenes.

  • Often reside within phagocytes (macrophages, neutrophils).

  • Can be grown in the lab on artificial media are also able to survive within pathogens

Intracellular Survival Mechanisms | Resisting Digestion

Mycobacterium tuberculosis: Waxy cell wall resists digestion.

Intracellular Survival Mechanisms | Preventing Phagolysosome Fusion

Toxoplasma gondii inhibits fusion of phagosome with lysosome.

Intracellular Survival Mechanisms | Escaping the Phagosome

Listeria monocytogenes escapes the phagosome and replicates in the host cell cytoplasm.

Macrophages and Neutrophils

• Two most important categories of phagocytes in the human body

  • “Professional phagocytes”

Evasion of Host Defenses | Antigenic Variation

• Pathogens change their surface antigens to evade immune recognition.

  • Examples: Influenza virus, Trypanosoma brucei.

Evasion of Host Defenses | Camouflage and Molecular Mimicry

Pathogens mimic host molecules to avoid detection.

Evasion of Host Defenses | Destruction of Antibodies

Some bacteria produce IgA proteases to degrade antibodies.

Pyrogens

Substances that cause fever

Septic Shock

type of shock that results from Gram-negative sepsis

Shock

A life-threatening condition resulting from very low blood pressure and an inadequate blood supply to body tissues and organs, especially kidneys and brain

Flagella

Virulence factor; they enable flagellated bacteria to invade aqueous areas of the body

Capsules

Virulence factor; they protect encapsulated bacteria from being phagocytized by phagocytic WBC

Toxins | Tetanospamin

Affects control of nerve transmission, leading to a spastic, rigid type of paralysis in which the patient’s muscles are contracted

Toxins | Botulinum Toxin

Blocks nerve impulses but by a different mechanism, leading to a generalized, flaccid type of paralysis in which the patient’s muscles are relaxed

Toxins | Exfoliative Toxin

Causes the epidermal layers of skin to slough away, leading to a disease known as scalded skin syndrome

Toxins | Erythrogenic Toxin

Produced by some strains of S. pyogenes which causes scarlet fever

Toxins | Leukocidins

Toxins that destroy WBC

Toxins | Diphtheria Toxin

Produced by toxigenic strains of C. diphtheriae which inhibits protein synthesis