GENERAL PATHOLOGY OF INFECTIOUS Marian Michelle M.

Marquez, MD, PTRP

College of Dentistry

DISEASES National University - MOA

OUTLINE
• Human Pathogens
• The Microbiome
• Techniques for Identifying Infectious Agents
• Entry, Spread and Transmission of Microbes
• How Microbes Cause Disease?
• How Microbes Evade the Immune System
MATCH THE DISEASE WITH THE
CORRESPONDING INFECTIOUS AGENT
The following diseases are caused by which
infectious agent?
1. COVID-19 A. Virus
2. Tuberculosis B. Bacteria
3. Candidiasis C. Parasite
4. Elephantiasis D. Fungi
5. Hepatitis A E. Prions
CATEGORIES OF INFECTIOUS AGENTS
PRIONS
• Proteinaceous infectious particle
• Infectious protein: prion protein (PrP) – found in neurons
• Causes spongiform encephalopathies:
Ø Kuru (associated with human cannibalism)
Ø Hereditary or sporadic Creutzfeldt-Jakob disease (CJD)
Ø Bovine spongiform encephalopathy (BSE) (mad cow disease)
Ø Variant Creutzfeldt-Jakob disease (vCJD) (probably transmitted to humans through consumption of
meat from BSE-infected cattle)
VIRUS
Characteristics:
1. Viruses do not have a cellular organization
2. Contains ONLY one type of nucleic acid, DNA or
RNA, never both
3. Obligate intracellular parasites
4. They lack the enzymes necessary for protein and
nucleic acid synthesis and are dependent for
replication on the synthetic machinery of host cells.
5. They multiply by a complex process and NOT by
binary fission.
6. They are unaffected by antibacterial antibiotics.
 SELECTED HUMAN VIRAL DISEASES AND THEIR
PATHOGENS
Organ Pathogen Disease Organ Pathogen Disease
System System
Respiratory Adenovirus Upper and lower respiratory Systemic Measles Measles (Rubeola)
infection Rubella German measles
Rhinovirus Upper respiratory infection Varicella-zoster Chickenpox/ Shingles
Influenza A/B Influenza HIV AIDS
Digestive Mumps virus Mumps Herpes-simplex 1 “Cold sore”
Rotavirus Childhood gastroenteritis CNS Poliovirus Poliomyelitis
Norovirus Gastroenteritis
Hepatitis A Acute viral hepatitis Skin/ Human Papiloma- Warts
Hepatitis B Acute or chronic hepatitis
genital virus (HPV) Cervical carcinoma
 BACTERIA
REVIEW: GRAM-POSITIVE? GRAM-NEGATIVE?
A B
BACTERIA
• Prokaryotes: lack true nucleus and some organelles
• Classified by:
o Gram staining (positive or negative)
o Shape (spherical, called cocci, or rod-shaped, called bacilli)
o Requirement for oxygen (aerobic or anaerobic)
o Special structures (capsule, flagella, pili, spore)
• Bacteria synthesize their own DNA, RNA, and proteins, but they depend on the host
for favorable growth conditions.
SELECTED HUMAN BACTERIAL DISEASES AND
PATHOGENS
Category Pathogen
Pyogenic cocci Neisseria meningitidis
infections Neisseria gonorrhea
Streptococcus pneumoniae
Streptococcus pyogenes
Staphylococcus aureus
Gram-negative Escherichia coli, Klebsiella
infections pneumoniae, Proteus mirabilis,
Pseudomonas aeruginosa
Clostridial Clostridium tetani
infections Clostridium botulinum
Treponemal Treponema pallidum
infections
Disease
Meningitis
Gonorrhea
Pneumonia
Strep pharyngitis, scarlet fever
Cellulitis, pneumonia
Urinary tract infection, wound infection, abscess,
pneumonia, sepsis, shock
Tetanus (lockjaw)
Botulism (paralytic food poisoning)
Syphilis
SELECTED HUMAN BACTERIAL DISEASES AND
PATHOGENS
Category Pathogen Disease
Enteric infections Enteropathogenic E. coli, Shigella Invasive or noninvasive gastroenterocolitis
spp.,Vibrio cholerae, Salmonella spp.

Salmonella enterica serotype Typhi Typhoid fever

Mycobacterial Mycobacterium tuberculosis Tuberculosis
infections Mycobacterium leprae Leprosy

Childhood Haemophilus influenzae Meningitis, upper/lower respiratory infection

bacterial infections Bordetella pertussis Pertussis (whooping cough)
Corynebacterium diphtheriae Diphteria
FUNGI
• Eukaryotes with thick cell walls composed of complex
carbohydrates such as beta-glucans, chitin, and mannosylated
glycoproteins.
• Can grow: as rounded yeast cells, or as slender, filamentous
hyphae
• Some of the most important pathogenic fungi exhibit thermal
dimorphism: they grow as hyphal forms at room temperature, but as
yeast forms at body temperature.
• Produces sexual spores or, more commonly, asexual spores called
conidia.
SELECTED FUNGAL DISEASES AND PATHOGENS
Category Pathogen Disease
Superficial Malassezia furfur Pityriasis versicolor
mycoses
Cutaneous mycoses Tinea pedis Athlete’s foot
Tinea cruris Jock itch
Tinea capitis Scalp ringworm
Opportunistic fungi Candida albicans Candidiasis
Pneumocystis jiroveci Pneumonia in AIDS patients
 Entamoeba histolytica

PROTOZOA
• single-celled eukaryotes that are major causes of disease
and death in developing countries.
• can replicate intracellularly within a variety of cells or
extracellularly in the urogenital system, intestine, or blood.
Ø Sexually-transmitted: Trichomonas vaginalis Trichomonas vaginalis
Ø Most prevalent intestinal protozoans: Giardia lamblia, Entamoeba
histolytica
Ø Bloodborne protozoa: Trypanosoma, Plasmodium, Leishmania
Ø Though contact or eating undercooked meat: Toxoplasma gondii
HELMINTHS
• Parasitic worms, with highly differentiated multicellular organisms.
• Reproduction: sexual reproduction in the definitive host and asexual
multiplication in an intermediate host or vector.
• 3 groups:
1. Roundworms (Nematodes): circular in cross-section and nonsegmented
- Intestinal nematodes: Ascaris lumbricoides, Strongyloides stercoralis, and hookworms.
- Nematodes that invade tissues: Wuchereria bancrofti and Trichinella spiralis
2. Tapeworms (Cestodes): have a head (scolex) and a ribbon of multiple flat
segments (proglottids)
- Fish, beef, and pork tapeworms that make their home in the human intestines,
potentially producing cysts in many organs.
3. Flukes (Trematodes): leaf-shaped flatworms with prominent suckers
- Liver and lung flukes and schistosomes
ECTOPARASITES
• Insects (e.g., lice, bedbugs, fleas) or arachnids (e.g., mites,
ticks, spiders) that cause disease by biting or by attaching to
and living on or in the skin.
• Infestation of the skin by arthropods: characterized by itching
and excoriations, such as pediculosis caused by lice attached
to hairs, or scabies caused by mites burrowing into the stratum
corneum.
• At the site of bites, mouth parts may be found associated with
a mixed infiltrate of lymphocytes, macrophages, and
eosinophils.
THE MICROBIOME
THE MICROBIOME
• Diverse microbial population of bacteria, fungi, and viruses
found in or on the human body.
• The diversity of bacteria is greatest in the oral cavity and the
stool, intermediate on the skin, and least in the vagina.
• Important roles:
Ø e.g. normal flora of the intestinal tract:
- responsible for absorption of digested foods
- for maintaining the integrity of the epithelium and the normal
functioning of the intestinal immune system
- competitively inhibiting invasion and colonization by potentially
pathogenic microbes
THE MICROBIOME
• In a healthy person, a part of the bacterial population at
various body sites is relatively stable over time, but may be
altered by diet and environment.

• Dysbiosis: changes in composition of the microbiome that are

associated with disease.
Ø Use of some antibiotics kill or inhibit normal commensal bacteria,
allowing overgrowth of the toxin-producing Clostridium difficile
Ø The microbiome in the stool of obese individuals is less diverse than
that of lean individuals
Ø The intestinal bacterial populations in individuals with inflammatory
bowel disease are altered
TECHNIQUES FOR IDENTIFYING
INFECTIOUS AGENTS
IDENTIFYING MICROBES IN TISSUE AND FLUIDS
1. Culture: useful for detecting bacteria and fungi
2. Histology: use of classic and specialized stains
Ø Organisms are usually best visualized at the advancing edge of a lesion rather than at its center,
particularly if there is necrosis.

3. Serology: essential in detecting pathogen-specific antibodies

Ø Antibody titers, Assay for serum antibodies (Hepatitis)

4. Molecular diagnostics
Ø Nucleic acid amplification techniques: Polymerase chain reactions (PCR)

5. Proteomics
Ø Mass spectrometry
ENTRY, SPREAD AND TRANSMISSION
OF MICROBES
ROUTES OF ENTRY OF MICROBES
Site Major Local Defense(s)
• Microbes can enter the host
Skin • Epidermal barrier
through:
ü breaches in the skin Gastrointestinal • Epithelial barrier
tract • Acidic secretions
ü by inhalation or ingestion
• Bile and pancreatic enzymes
ü by sexual transmission • Normal flora
• First-line defenses against Respiratory • Mucociliary clearance
infection: tract • Resident alveolar macrophages
ü intact skin and mucosal surfaces Urogenital tract • Urination
• Normal vaginal flora
• Intact epidermal/epithelial
barrier
ROUTES OF ENTRY OF MICROBES
• Skin
ü Breaks in the skin: via wound or surgical
incision, burns, diabetic and pressure-related
foot sores
ü Intravenous catheter, needle-stick injury
ü Animal bites, insect bites
• Gastrointestinal tract (GI tract)
ü Bacteria, virus: ingestion, release of toxins
in the GI tract
ü Fungi: infection in immunocompromised
ü Parasites: ingestion of cysts/eggs/larvae in
meat
• Respiratory tract
ü inhalation of dust and aerosol particles
ü particles smaller than <5um travel directly
to the alveoli
ü failure of mucociliary defenses
• Urogenital tract
ü almost always invaded from the exterior by
way of the urethra
ü obstruction of urinary flow
ü UTI: women > men (5cm vs 20cm urethra)
SPREAD AND DISSEMINATION
OF MICROBES
• Some microorganisms proliferate locally, at the site
of initial infection, whereas others spread to distant
sites.
Ø Lysis and invasion
Ø Through blood and lymph
Ø Cell-to-cell transmission
• The major manifestations of infectious disease may
appear at sites distant from the point of microbe
entry
• The consequences of the spread of pathogens
depends on the virulence of the organism
TRANSMISSION OF MICROBES
1. Contact (direct and indirect) Disease:
2. Respiratory droplets • Malaria –
3. Fecal-oral route • Gonorrhea –
4. Sexual transmission • Hepatitis A –
5. Vertical transmission (mother to fetus) • HIV/AIDS –
6. Insect/arthropod vectors • Covid-19 –
HOW MICROBES CAUSE DISEASE?
VIRAL INJURY
Mechanisms:
Ø Host receptors for viruses
Ø Specificity of transcription factors
Ø Physical characteristics of tissues
Once inside the host, they cause damage by:
v Direct cytopathic effects
v Anti-viral immune responses
v Transformation of infected cells
BACTERIAL INJURY
Mechanisms:
Ø Bacterial virulence Ø Bacterial toxins
• Quorum sensing: virulence genes, are • Endotoxins: in lipopolysaccharide of Gram
expressed after bacteria reach high ______ bacteria
concentrations • Exotoxins: secreted proteins that cause
• Biofilm formation cellular injury and disease
ü A-B toxins: B. anthracis, V. cholerae
Ø Bacterial adherence: ü Superantigens: S. aureus, S. pyogenes
• Adhesins: bacterial surface molecules that ü Neurotoxins: C. botulinum, C. tetani
bind to host cells or extracellular matrix ü Enterotoxins: S. aureus, V. cholerae
• Pili (N. gonorrhea) ü Enzymes: Proteases by S. aureus
HOW MICROBES EVADE THE IMMUNE
SYSTEM?
IMMUNE EVASION BY MICROBES
• Antigenic variation
• Modification of surface proteins
• Overcoming antibodies and complement
• Resisting phagocytosis and bacterial
killing by phagosomes
• Escaping inflammasome
• Disruption of interferon pathways
• Decreased T-cell recognition
THANK YOU Questions?