Infectious Diseases and Immune Defense Quiz

Micro-Infectious Diseases

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General Principles of Microbial Pathogenesis

• Infectious diseases remain a significant health concern worldwide, despite vaccines and antibiotics.
• Immunosuppressed individuals and those with chronic diseases are particularly vulnerable.
• Factors contributing to these issues include: inadequate access to healthcare, malnutrition
• Six of the top ten causes of death are infectious diseases
• Most deaths from infectious diseases occur in children
• Respiratory and diarrheal infections cause the greatest number of deaths

How Microorganisms Cause Disease

• Routes of entry:
  • Breaching epithelial surfaces
  • Inhalation
  • Ingestion
  • Sexual transmission
• Healthy individuals:
  • Entry through respiratory tract, gastrointestinal tract, or genitourinary tract by virulent microorganisms.
  • Skin (injured) is invaded by less virulent microorganisms.

General Principles of Microbial Pathogenesis (Skin)

• Protection via:
  • Intact keratinized epidermis - strong mechanical barrier
  • Antimicrobial fatty acids
  • Defensins - small peptides toxic to bacteria
• Intact skin can be traversed by:
  • Larvae of Schistosoma - release enzymes dissolving keratinocytes interconnections
  • Dermatophytes

General Principles of Microbial Pathogenesis (GIT)

• Transmission through contaminated food and drinks
• Local defenses:
  • Acidic gastric secretions - highly effective at killing organisms (Vibrio cholerae is reduced to 10,000 fold by stomach acid).
  • Viscous layer of mucus throughout the gut.
  • Pancreatic enzymes
  • Bile detergents
• IgA Abs - from lymphoid tissues (Peyer's patches)
• Peristalsis - prevents organism overgrowth.
• Normal gut flora - creates a microenvironment preventing colonization of potential pathogens (e.g., Clostridium difficile)

General Principles of Microbial Pathogenesis (Examples)

• Site | Major Local Defense(s) | Basis for Failure of Local Defense | Pathogens (examples)
• Skin | Epidermal barrier | Mechanical defects (punctures, burns, ulcers) | S. aureus, Candida albicans
• GI Tract | Epithelial barrier, acidic secretions, bile and pancreatic enzymes, normal protective flora | Attachment, local proliferation, local/external invasion, acid-resistant cysts and eggs | Vibrio cholerae, Giardia, Shigella
• Respiratory Tract | Mucociliary clearance | Ciliary paralysis by toxins, viral attacks | Influenza viruses, M. pneumoniae
• Urogenital Tract | Resident alveolar macrophages, urination, normal vaginal flora, intact epidermal/epithelial | Resistance to killing, microbial attachment | E. coli, C. albicans

Gastrointestinal Tract Infections

• Local defenses are circumvented by pathogens, or when weakened, normal flora can cause disease.
• Examples:
  • Norovirus - non-enveloped virus, resistant to acid, bile and pancreatic enzymes
  • Cystic protozoans
  • Eggs of Helminths - acid-resistant coat
  • Shigella

Enteropathogenic Pathogens and Gastrointestinal Disease

• Enteropathogenic pathogens establish symptomatic disease through several distinct mechanisms:
  • Adsorption and local proliferation (e.g., Vibrio cholerae, enterotoxigenic E. coli)
  • Adsorption and mucosal invasion (e.g., Shigella, Salmonella enterica, Campylobacter jejuni, Entamoeba histolytica)
  • "Hijacking" of host pathways of antigen uptake (e.g., Poliovirus)

Respiratory Tract

• Inhalation of dust/aerosols
• Particles inversely proportional to their size are trapped in the mucociliary blanket
• Particles < 5 microns are phagocytosized by resident alveolar macrophages or neutrophils recruited by cytokines

Urogenital Tract

• Protection from infection through regular emptying during micturition.
• Factors:
  • Anatomy - Females have shorter urethras, resulting in more UTIs
  • Obstruction of urinary flow
  • Reflux of urine
  • Antibiotic use - killing lactobacilli
  • Trauma to cervical epithelium

Vertical Transmission

• Transmission from mother to fetus/newborn:
  • Placental-fetal transmission (e.g., Rubella infections)
  • Transmission during birth (e.g., gonococcal and chlamydial conjunctivitis)
  • Postnatal transmission through maternal milk (e.g., cytomegalovirus, HIV, hepatitis B virus)

Spread and Dissemination of Microbes Within the Body

• Disease-causing organisms can remain localized or invade tissues.

• Spread via lymphatics, blood, or nerves

  • Example: S. aureus spreads through tissues, lymphatic vessels, and regional lymph nodes to blood (bacteremia), then to distant organs such as the heart and bone

• Exit from the body: skin shedding, coughing, sneezing, urination, defecation, sexual contact, insect vectors

Host-Pathogen Interactions

• Factors influencing the outcome of infection:
  • Virulence of the microbe
  • Nature of the host immune response (eliminate, exacerbate, principal cause of tissue damage)
• Immune evasion:
  • Antigenic variation
  • Resistance to antimicrobial peptides
  • Resistance to killing by phagocytes
  • Evasion of apoptosis and host cell metabolism manipulation
  • Resistance to cytokine-, chemokine- and/or complement-mediated host defense
  • Evasion of recognition by CD4+ helper T cells and CD8+ cytotoxic T cells
  • Immunoregulatory mechanisms to downregulate anti-microbial T-cell responses
  • "Lie low" by establishing a latent infection
• Genetic reassortment, high mutation rate, and diverse serotypes can contribute to the development of infectious diseases and cause varying degrees of infection.
• Mechanisms of Host Immunity Damage:
  • Inflammation (granulomas- TB)
  • Inflammation Due To Immune Complexes (examples: rheumatic fever, glomerulonephritis)
  • Chronic Inflammation
  • Cancer
• Defects in neutrophil function
• Defects in Toll-like receptor (TLR) signaling pathways (Mutations in MyD88 or IRAK4 predispose to pyogenic bacterial infections and impair TLR3 responses)
• T-cell defects (Inherited mutations can impair the generation of TH1 and TH17 cells resulting in atypical mycobacterial infections or chronic mucocutaneous candidiasis respectively).

Mechanisms of Viral Injury

• Enter cells > replication > direct damage to the host cells

• Tropism - preference for specific cells by viruses

  • Factors include the presence of viral receptors on host cells and physical barriers
  • Example: -Enteroviruses can resist degradation in the intestine by acids, bile and digestive enzymes. -Rhinoviruses only reproduce in the upper respiratory tract due to their optimal temperature requirements.

• Mechanisms include direct cytopathic effects, anti-viral immune responses, and transformation of infected cells into malignancies

• Viral receptors that bind to particular proteins on the surface of host cells include HIV glycoprotein gp120 interacting with CD4 on T cells, chemokine receptors CXCR4 (T cells) and CCR5 (macrophages), and EBV binding to complement receptor 2.

Mechanisms of Bacterial Injury

• Bacterial virulence depends on the microbe's ability to adhere to host cells, invade cells and tissues, and/or deliver toxins.
• Bacterial adhesins bind to host cells or the ECM
• Pili are filaments on the surface of bacteria which allow bacteria to adhere to host cells
• Mobile genetic elements (plasmids, bacteriophages) move genes between microbes that influence pathogenicity and drug resistance
• Virulence of intracellular bacteria including ways bacteria can inhibit host protein synthesis, replicate rapidly, lyse host cells within hours
• Bacteria evade the immune responses by producing toxins- bacterial proteins that cause cellular injury and disease including endotoxins and exotoxins such as proteases, hyaluronidases, coagulases, or fibrinolysins)
• Bacterial toxins that alter intracellular signaling or regulatory pathways, such as neurotoxins (e.g., Clostridium botulinum and Clostridium tetani), disrupt neurotransmitter release causing paralysis
• Superantigens, bacterial toxins that stimulate large numbers of T cells, generating a massive immune response

Sexually Transmitted Diseases

• STIs can be transmitted from the urethra, vagina, cervix, rectum, or oral pharynx.
• Infection with one STI increases the risk of additional STIs (examples N. gonorrhoeae, C. trachomatis).
• A pregnant woman can pass STIs to the fetus or child (e.g. C. trachomatis, HSV, HIV), causing serious damage.

Spectrum of Inflammatory Responses to Infection

• Suppurative (Purulent) Inflammation: Increased vascular permeability, leukocytic infiltration, and mainly neutrophils are indicative of inflammation; neutrophilic massing and tissue necrosis form pus (e.g., pneumococcal pneumonia).
• Mononuclear and Granulomatous Inflammation: Accumulation of activated macrophages ("epithelioid" cells), possible fusion to form giant cells. An area of caseous necrosis can also form (e.g., secondary syphilis).
• Cytopathic-Cytoproliferative Reaction: Characterized by cell necrosis, or cellular proliferation, usually with sparse inflammatory cells (e.g., Herpesvirus).

Tissue Necrosis

• Clostridium perfringens and other organisms cause rapid necrosis (gangrenous necrosis) from powerful toxins.
• Lesions resemble infarcts without inflammatory cells.

Chronic Inflammation and Scarring

• Many infections induce chronic inflammation that can lead to complete healing or extensive scarring (e.g., chronic HBV infection causing cirrhosis).
• Scarring involves dense fibrous septae surrounding newly generated hepatocytes.

Special Techniques for Diagnosing Infections

• Gold standards for diagnosis:

  • Culture
  • Biochemical or serologic identification
  • Molecular diagnosis

• Specific techniques and corresponding infectious agents:

  • Gram Stain: Most bacteria
  • Acid-fast Stain: Mycobacteria, Nocardia
  • Silver Stain: Fungi, Legionella, Pneumocystis
  • Periodic Acid-Schiff (PAS): Fungi, Amebae
  • Mucicarmine: Cryptococci, Fungi
  • Giemsa: Campylobacter, Leishmania, Malaria (parasites)
  • Antibody stains: All classes
  • DNA probes: All Classes
  • Culture: All classes

Viral Infections

• Common viral diseases and their associated organ systems are presented.

Acute (Transient) Infections

• Measles: Leading cause of vaccine-preventable death, single-stranded RNA virus. Cells are invaded, causing respiratory droplets.
• Mumps: Pain and swelling of salivary glands.
• Poliovirus: Acute systemic viral infection causing paralysis of limb and respiratory muscles. Fecal-oral route of transmission.
• Viral Hemorrhagic Fevers: Systemically caused by enveloped RNA viruses from several families (Arenaviruses, Filoviruses, Bunyaviruses, and Flaviviruses). Spread person to person.

Chronic Latent Infections (Herpesviruses)

• Latency is the persistence of viral genomes in cells.
• Herpesviruses are prevalent in humans.
• Herpes simplex viruses (HSV 1 and 2), varicella-zoster virus (VZV), and cytomegalovirus (CMV).

Chronic Productive Infections

• Hepatitis B Virus: Part of the hepadnavirus DNA virus family that can be transmitted percutaneously, perinatal, and sexually.
• Cellular injury from the host immune response to infected hepatocytes leads to the disease.

Transforming Infections

• Epstein-Barr virus (EBV): Can lead to infectious mononucleosis and malignancies such as lymphomas and nasopharyngeal carcinoma.

Explore the essential concepts related to infectious diseases and the immune system in this quiz. The questions cover aspects such as barriers to infection, local defense mechanisms, and the impact of malnutrition on disease incidence. Perfect for students studying microbiology or immunology.