Far Eastern University – Nicanor Reyes Medical Foundation
Pathology A – Infectious Diseases
Pedrito Y. Tagayuna M.D.
 Humans and other animals harbor a complex ecosystem of
microbial flora (microbiome) that has important roles both in
health and diseases.
 Most infectious diseases are caused by pathogenic, non-
commensal organisms, which exhibit a wide range of virulence.
 Highly infectious microbes produce disease in a high fraction of
healthy individuals, sometimes at doses of only a few organisms.
Routes of Entry of Microbes
SKIN
 The intact keratinized epidermis protects against infection by
serving as a strong mechanical barrier
 It also produces antimicrobials such as fatty acids and defensins,
which are small peptides that are toxic to the bacteria.
 Most skin infections are initiated by mechanical injury of the
epidermis, which may range from minor trauma to large wounds
 In general, microorganisms cannot traverse the unbroken skin,
except from the larvae of Schistosoma, which releases enzymes
that dissolve adhesive proteins that hold keratinocytes together.
GASTROINTESTINAL TRACT
 Most GI pathogens are transmitted via food or water
contaminated with fecal material. When hygiene fails, diarrheal
disease becomes rampant.
 Acidic secretions of the stomach are highly effective in killing
certain organisms.
 Neutralizing acid secretions of the stomach reduces the
11
necessary infective dose (10 ) of Vibrio cholera by 10,000-
fold.
 Viscous mucus layer covers the entire gut protecting the surface
epithelium.
 Pancreatic enzymes and bile detergents can destroy organisms
with envelopes, such as certain viruses.
 Defensins are also produces by gut epithelial cells.
 IgA antibodies, produced in the mucosal lymphoid tissues (such
as Peyer’s patches) are secreted in the gut lumen and can
neutralize potential pathogens.
 Peristalsis can clear organisms and prevent local overgrowth.
 Clostridium difficile is a part of the normal flora of the gut that
creates a microenvironment that discourages colonization of
potential pathogens.
 GI infections may occur when:
 Local defenses are circumvented by the pathogen.
 The defenses are weakened that even normal flora can
produce disease.
 Norovirus is a non-enveloped virus which is resistant to
inactivation of acids, bile, and pancreatic enzymes can easily
spread.
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 Shigella is resistant to acid, hence it only needs a low
infective dose (100 bacteria)
 Intestinal protozoa, helminths, eggs, cysts also have acid-
resistant outer coats.
 Enteropathogenic pathogens can establish symptoms of GI
diseases via several distinct mechanisms:
 Adhesion and local proliferation, such as V. cholera,
enterotoxigenic E. coli (ETEC), which binds and proliferates to
the epithelium and elaborate exotoxins.
 Adhesion and mucosal invasion, such as Shigella, Salmonella
enterica, Campylobacter jejuni, and Entamoeba histolytica
which invades the mucosa and lamina propria, and cause
ulceration, inflammation, and hemorrhage, manifests
clinically as dysentery.
 Hijacking of the host pathways of antigen uptake, Peyer’s
patches are covered by M Cells which is responsible for the
uptake and delivery of antigens to the lymphoid tissues. Polio
virus is taken up via this pathway.
 Some infections do not need to establish infection with the host.
 Staphylococcus aureus contaminates food with a powerful
exotoxin that can cause acute food poisoning.
 Weakened local defenses, broad-spectrum antibiotic treatment,
ileus, or mechanical obstruction can exacerbate infections.
 Candida albicans only produce GI disease when the immune
system is weak.
RESPIRATORY TRACT
 Microorganisms are inhaled mainly in the dust or aerosols.
 The distance traveled by these organisms in the airways is
inversely proportional to their size.
 Large particles are trapped in the muco-ciliary blanket that lines
the nose and the upper respiratory tract.
 These particles are propelled back to the throat via the cilia
where they are either swallowed or expectorated.
 Smaller particles (less than 5 microns) are phagocytosed by
resident alveolar macrophages or by neutrophils.
 Different mechanisms of invasions:
 Pathogenic respiratory viruses attach and enter epithelial
cells in the lower respiratory tract and the pharynx, like that
of the Influenza virus which have envelope proteins called
hemagglutinins that binds to sialic acid on the surface of the
epithelial cells.
 The attachment induces endocytosis of the virus leading to
viral entry and replication. The resulting damage sets the
stage for superinfection by S. pneumoniae and S. aureus
leading to serious pneumonia.
 Certain toxins by Haemophilus influenza, Mycoplasma
pneumoniae, and Bordetella pertussis enhance their ability to
cause infection by impairing ciliary function.
 Primary resistance to killing following phagocytosis is another
important mechanism, like that of Mycobacterium tuberculosis
which survives within the phagolysosome of macrophages.
 Chronic impairment of muco-ciliary defense mechanism occurs
in smokers and patients with cystic fibrosis.
 Acute injury on the other hand occurs in patients undergoing  However, the most efficient mode of dissemination is via the
mechanical ventilation or those who aspirate gastric acid. blood stream. Blood-borne pathogens, viruses (Polio, HBV), most
 Infectious agents can cause respiratory infections in patients bacteria, fungi, some protozoa (African Trypanosomes) and
with systemic immunodeficiency: helminths are transported freely in the plasma.
 P. jiroveci in AIDS patients  Others are carried within the leukocytes like Herpes Simplex
 Aspergillus in patients with neutropenia Virus (HSV), HIV, Mycobacteria, certain fungi, and protozoa;
some are within the RBC like the malarial parasite.
UROGENITAL TRACT
 Urine is sterile, and the urinary tract (UT) is protected by regular
emptying during micturition.
 UT pathogens almost always gains access via the urethra and
must be able to adhere to the urothelium to avoid being washed
 Women have more than 10 times many UTI as men because the
distance between the bladder and the urethra is 5 cm in women
and 20 cm in men.
 Obstruction of the urine flow or reflux of the urine
compromises normal defenses and increases susceptibility to UTI
 The vagina is protected from pathogens by Lactobacilli during
puberty until menopause.
 Lactobacilli ferments glucose to lactic acid and produce a low
pH environment that suppresses growth of pathogens.
 Antibiotics (especially broad spectrum) can kill lactobacilli
and allow overgrowth of yeasts causing vaginal candidiasis.
 The uterine cervix covered by squamous mucosa is resistant to
infections; minor trauma to the cells may expose immature
proliferating epithelial cells to Human Papilloma Virus which can
cause cervical carcinoma.

VERTICAL TRANSMISSION  The consequence of blood-borne spread of pathogen vary widely

 It is a common mode of transmission which occurs from mother
to fetus or newborn child and may occur via several routes:
 Placental-fetal transmission - most likely occurs in mothers
infected with the pathogen during pregnancy, the infections
may result to interference of the fetal development
depending on its age and time of infection. (Ex: Rubella
st
infection during the 1 trimester may lead to heart
malformations, mental retardation, cataracts, deafness,
rd
while during the 3 trimester, it has little effects).
 Transmission during birth – caused by contact with the
infectious agent during passage through the birth canal (Ex:
Chlamydial and Gonococcal conjunctivitis).
 Postnatal transmission via maternal milk – agents passed
via this fashion include Cytomegalovirus (CMV), Human
Immunodeficiency Virus (HIV), and Hepatitis B virus (HBV).
Spread and Dissemination within the body
 Some pathogens remain localized to the initial site of infections;
others have the capacity to invade other tissues via the
lymphatics, the blood, or the nerves.
 S. aureus secretes hyaluronidase which degrades the ECM
allowing the microbes to follow tissues planes of least resistance.
 Rabies virus and Varicella may spread to the CNS by infecting
peripheral nerves then traveling intracellularly along axons.
depending on the:
 Virulence of the organism
 Magnitude of infection
 Pattern of Seeding
 Host Factors (e.g. Immune Status)
 Sporadic blood stream invasion by low-virulence or nonvirulent
organisms (e.g. brushing the teeth) is common but quickly
controlled by the normal host defenses.
 Disseminated bacteremia, viremia, fungemia, or parasetemia by
virulent pathogens often produces severe illness.
 Such infections can produce SIRS that manifests as fever, low
BP, and coagulopathies that may progress to organ failure.
 In other instances, the major sign of the spread is related to
tissue seeding, which may take different forms:
 Single large infectious nidus (Abscess, Tuberculoma)
 Multiple small sites (Miliary tuberculosis, Microabscess)
 Infection of the heart and vessels (Infectious endocarditis,
myocotic aneurysm)
 Others cause patterns of disease because of tropism to specific
tissues:
 Neurotropic viruses – Rabies, Polio, Varicella
 Schistosoma mansoni localizes to the vessels of the portal
system, and mesentery.
 Schistosoma haematobium travels to vessels in the urinary
bladder and causes cystitis.

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Release from the Body and transmission of microbes Host Pathogen Interactions
 Depending on the location of the infection, exit may be via:
 Skin Shedding HOST DEFENSE AGAINST INFECTIONS
 Coughing  Outcome of an infection is determined by the virulence factor of
 Sneezing the pathogen and the nature of the host immune response.
 Voiding of urine and feces  Darwinian forces also drive the continuing evolution of a
 Sexual contact remarkable array of highly diverse microbes, which are
 Insect Vectors constantly threatening to get a step ahead of host defenses.
 Some pathogens are released for only brief periods of time or
periodically during disease flares. IMMUNE EVASION BY MICROBES
 S. typhi can be shed for long periods by asymptomatic hosts
 Pathogens exhibit wide variations in hardiness.
 Some survive for extended periods in dust, food or waters
such as bacterial spores, protozoan cysts, and helminth eggs
 Fragile pathogens persist outside the body only for a short
time and must be immediately transmitted often by direct
contact.
 Most pathogens are transmitted from person to person via
respiratory, fecal-oral, or sexual routes.
 Respiratory viruses and bacteria are infectious only when
lesions are open to the airways.
 Pathogens aerosolized in droplets are released in the air via
coughing.
 Influenza viruses are spread via large droplets that can travel
no more than 3 feet from the source.
 M. tuberculosis and Varicella-Zoster virus can spread in
small droplets or within dust particles that can travel longer.
 Antigenic Variation
 Enteric pathogens are spread via the fecal-oral route, which is
 Antibodies against microbes act as opsonins to facilitate
by ingestion of stool-contaminated water or food.
phagocytosis and fix the complement, and cytotoxic T cells
 Water-borne viruses include Hepatitis A and E viruses,
recognize antigens presented by infected host cells.
poliovirus, and rotavirus.
 Microbes have many strategies to change their coats to
 Other pathogens include V. cholerae, Shigella,
evade this kind of immune defense.
Campylobacter jejuni, and Salmonella.
 Borellia and trypanosomes have sophisticated genetic
 Some parasitic helminths shed eggs in stool and hatch as
mechanisms that allow them to switch their major surface
larvae capable of penetrating skin of the host.
proteins.
 Sexual transmission often entails prolonged intimate or mucosal
 Influenza viruses have complex RNA genome that allows
contact includes the spread of the following:
frequent recombination events, permitting antigenic drifts
 HIV, Herpes Simplex Virus, HPV
and shifts.
 Treponema pallidum, Neisseria gonorrhea
 Other microbes generate numerous genetic variants through
 Candida mutations like the 90 serotypes of S. pneumoniae, each with
 Even arthropods: Phthiris pubis (Crab lice) different capsular polysaccharide.
 Saliva is responsible for transmission of viruses that replicate in
the salivary glands or oropharynx including EBV and Rabies.
 Protozoa and helminths have evolved complex life cycles that
involve intermediate hosts bearing successive developmental
stages of the pathogen.
 Few pathogens can be transmitted via zoonotic infections or the
transmission from animals to humans either by direct contact or
ingestion of animal product or invertebrate vector.

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 Resistance to antimicrobial peptides
 Epithelial cells and leukocytes produce defensins and
cathelicidins (cationic antimicrobial peptides) that forms
pores in the microbial membranes.
 This can augment anti-microbial immunity by inducing the
production of pro-inflammatory chemokines and cytokines.
 Resistance is a factor of virulence in Shigella, S. aureus, and
Candida.
 Microbial strategies include change in net surface charge
and membrane hydrophobicity that prevents antimicrobial
insertion; they also secrete proteins that inactivate the
peptides, and pumps that export the peptides.
 Resistance to killing by phagocytes
 The carbohydrate capsule on the surface of many bacteria
that causes pneumonia or meningitis (Streptococcus
pneumoniae, Neisseria meningitidis, Haemophilus influenzae)
prevents phagocytosis.
 E. coli that causes meningitis in newborns synthesizes
capsules containing sialic acid that will not bind C3b.
 S. aureus exhibit Protein A which binds to Fc portions of
antibodies to inhibit phagocytosis.
 Pathogens resistant to intracellular killings: Listeria
monocytogenes, Cryptococcus neoformans, and some
protozoans (Leishmania, Trypanosomes, Toxoplasmas)
 Evasion of apoptosis and manipulation of host cell metabolism
 Some viruses produce proteins that interfere with apoptosis,
which may buy them time to replicate, enter latency, or even
transform host cells.
 Microbes that replicate intracellularly also express factors
that modulate autophagy.
 Resistance to cytokine-, chemokine-, and complement-
mediated host defense
 Many viruses express factors that interfere with the actions
of these proteins.
 Some produce soluble homologues of IFN-α/β or IGN-γ
receptors that function as decoys.
 Viruses also produce proteins that inhibits JAK/STAT pathway
 Others produce proteins that inactivate or inhibit double-
stranded RNA-dependent protein kinase (PKR), which is an
important mediator of anti-viral effects of IFN.
 Evasion of recognition by CD4 and CD8 T cells
 DNA viruses bind to or alter localization of MHC I proteins.
 Herpes simplex virus (HSV) exhibit MHC I homologues that
can inhibit NK cells by engaging NK cell inhibitory receptors.
 HSV can also target MHC II for degradation
 Immunoregulatory mechanisms to downregulate anti-microbial
T-cell response
 In Chronic viral infections, T cells acquire effector functions
but gradually lose their potency as infection progresses.
 Upregulation of immunoinhibitory T cell pathway (PD-1
pathway) maintains T-cell tolerance to self-antigens, is an
important mediator of T-cell exhaustion in chronic viral
infections.
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Infections in People with Immunodeficiency
 Antibody Deficiencies
 Patients with X-linked agammaglobulinemia lead to
increased susceptibility to infections by extracellular
bacteria including S. pneumoniae, H. influenzae, and S.
aureus, as well as few viruses (rotavirus & enterovirus).
 Complement Deficiencies
 Early component deficiency of the complement may lead to
susceptibility to infections by encapsulated bacteria such as
S. pneumoniae.
 Late component deficiency (Membrane attack complex: C5-
C9) can lead to Neisseria infections.
 Defects in neutrophil function
 Increased susceptibility to infections with S. aureus, some
gram-negative bacteria, and fungi.
 TLR deficiency
 Mutations in MyD88 or IRAK4 predispose to pyogenic
bacterial infections, particularly invasive infections with
Streptococcus pneumoniae.
 Impaired TLR3 are associated with childhood herpes simplex
virus encephalitis.
 T cell defects
 Susceptibility to intracellular pathogens, particularly viruses,
and some parasites.
 Inherited mutations that impair the generation of TH1 cells
are associated with atypical mycobacterial infection.
 Defects that impair the generation of TH17 cells are
associated with chronic mucocutaneous candidiasis.
Host Damage
 Infectious agents can establish infection and damage tissues by
three mechanisms:
 Contact or enter cell host and cause cell death directly, or
cause changes in cellular metabolism and proliferation that
can eventually lead to transformation.
 Release toxins that kill at a distance, release enzymes that
degrade tissue components, or damage blood vessels and
cause ischemic injury.
 Induce host immune response that can cause additional
tissue damage.
MECHANISM OF VIRAL INJURY
 Viruses can directly damage host cells by entering them and
replicating at the host’s expense.
 Major determinant of tissue tropism is the presence of viral
receptors on the host cells.
 Many of the host cell proteins normally function as receptors for
host factors:
 Gp120 of HIV binds to CD4 on T cells and to the chemokine
receptors CXCR4 on T cells, and CCR5 on macrophages.
 EBV binds to complement 2 receptors (CD21/CR2) on B cells.
 Other tropisms are explained by the different kinds of cell-
lineage specific factors:
 JCV (John Cunningham Virus) can only replicate in
oligodendroglia cells because its viral genes needed for
productive infection requires host transcription factors only
found in the glial cells.
 Physical barriers also can contribute to tissue tropism.
 Enteroviruses can replicate in the GIT because they can resist
inactivation by acids, bile, and digestive enzymes.
 Rhinoviruses infect host cells within the URT because they
replicate optimally at the lower temperatures found in sites
exposed to the ambient atmosphere
 Viruses can damage the host cells via these mechanisms:
 Direct cytopathic effect
 Some viruses prevent synthesis of critical host
macromolecules or by producing degradative enzymes and
toxic proteins.
 Poliovirus inactivates cap-binding protein, which is
essential for translation of host cell mRNA.
 HSV produces proteins that inhibit synthesis of cellular
DNA and mRNA.
 Viruses can induce cell death by activation of death
receptors, and by triggering intracellular apoptotic
machineries.
 Large amounts of viral proteins are synthesized including
unfolded or misfolded ones that trigger ER stress response
which activates pro-apoptotic proteins.
 Some viruses encode proteins that are pro-apoptotic like
HIV vpr protein.
 Anti-viral immune response
 CTLs (Cytotoxic T lymphocytes) can be responsible for the
tissue injury.
 Transformation of the infected cell
 Expression of virus-encoded oncogenes, viral proteins that
inactivate key tumor suppressors, and insertional
mutagenesis, in which expression of host gene is altered
by insertion of viral genome, can cause viral
transformation by oncogenic viruses.
Page 5 of 10
MECHANISMS OF BACTERIAL INJURY
 Bacterial Virulence
 Damage to host tissue depends on the ability of the bacteria
to adhere to host cells, to invade cells and tissues, or to
deliver toxins.
 Virulence genes in pathogenic bacteria encode proteins that
confer the said properties.
 Various strains of Salmonella that infect humans are closely
related enough to form a single species, meaning they share
many ‘housekeeping’ genes.
 Differences in a relatively small number of pathogenicity
genes determine whether the strain causes life threatening
typhoid fever or self-limited enteritis.
 Virulence genes are frequently grouped together in clusters
called pathogenicity islands.
 Mobile Genetic Elements
 Plasmids and bacteriophages can transmit functionally
important genes to bacteria, including genes that influence
pathogenicity and drug resistance.
 Genes for toxins are sometimes found in the plasmids but
more often found in the genomes of bacteriophages
including the genes encoding for pathogenesis of cholera,
diphtheria, and botulism.
 Genes for acquired antibiotic resistance are more frequently
found on plasmids.
 Quorum Sensing is a process wherein bacteria coordinately
regulate gene expression within a large population.
 A bacterium can induce expression of virulence factors as
they grow to high concentrations in tissues.
 S. aureus can regulate virulence factors by secreting
autoinducer peptides, as the population increases, these
peptides increase, stimulating toxin production.
 Biofilms can also be formed by a community of bacteria in
which the organisms live within a viscous layer of
extracellular polysaccharides that adhere to host tissues.
 Biofilms protect the microbes from immune effector
mechanisms and increase their resistance to drugs.
 Bacterial Adherence to host cells
 Adhesins are bacterial surface proteins that bind bacteria to
host cells or ECM. These are limited to structural type but
have a broad range of host cell specificity
 Streptococcus pyogenes adheres to host tissues using the
adhesins: Protein F and Teichoic acid, which project from
the bacterial cell wall and bind to fibronectin.
 Pili are filamentous proteins on the surface of bacteria that
act as adhesins.
 The stalk is composed of conserved repeating subunits;
the variable subunits at the tip determine the tissue-
binding specificity.
 E. coli that cause UTI specifically express a pilus which
binds to Gal (α1-4) Gal moiety expressed in uroepithelial
cells.
 N. gonorrhea have variations in their pili to escape from
the host immune system.
 Virulence of Intracellular Bacteria
 Some bacteria use the host immune response to gain entry
into macrophages.
 M. tuberculosis activate the alternative complement
pathway resulting to opsonization with C3b. Once coated
with C3b, M. tuberculosis binds to CR3 complement
receptor and, enters & replicates within the phagosome.
 Gram-negative bacteria use a complex secretion system to
enter epithelial cells.
 Type III secretions consists of needle-like structures
projecting from the bacterial surface that bind to host
cells.
 These then form pores in the host cell membrane and
inject bacterial proteins that mediate the rearrangement
of host cell cytoskeleton to facilitate bacterial entry.
 Listeria monocytogenes, once inside, modify actin and
promote the direct spreading of the organism to the cells.
 Shigella and E. coli inhibit host protein synthesis, replicate
rapidly, and lyse the host cell within hours.
 M. tuberculosis blocks fusion of the lysosome with the
phagosome allowing it to proliferate unchecked.
 L. cytogenes produce pore-forming protein Literiolysin O,
and two phospholipases that degrade the phagosome
membrane, allowing it to escape to the cytoplasm.
 Facultative intracellular bacteria:
 Infect epithelial cells (Shigella, Enteroinvasive E. coli [EIEC])
 Infect Macrophages (M. tuberculosis, M. leprae)
 Infect both (Salmonella Typhi)
 M. tuberculosis can migrate to distant sites via the draining
lymph nodes carried by macrophages infected with the bacilli
 Bacterial Toxins
 Toxins are classified as endotoxin (component of the
bacterial cell wall) or exotoxin (secreted by the bacteria).
 Bacterial Endotoxin
 This is a Lipopolysaccharide (LPS) in the outer membrane of
Gram negative bacteria that both stimulates the host’s
immune response and injures the host.
 Lipid A, anchors LPS in the host cell membrane via long-chain
fatty acids, has the endotoxic activity.
 Lipid A is connected to a conserved core carbohydrate chain,
attached to a variable carbohydrate chain called the O
antigen.
Page 6 of 10
 Response to Lipid A is beneficial; it activates the protective
immunity, stimulating production of cytokines and
chemokines.
 High levels of endotoxin play a pathogenic role in septic
shock, DIC, and adult respiratory distress syndrome via
induction of excessive levels of cytokines such as TNF, IL-1,
IL-12.
 Bacterial Exotoxins
 Secreted bacterial proteins that cause cellular injury and
disease.
 Enzymes
 Proteinases, Hyaluronidases, Coagulases, Fibrinolysins
 Acts on their respective substrates in vitro
 S. aureus causes staphylococcal scalded skin syndrome by
degrading proteins that hold keratinocytes together,
causing epidermis to detach from the deeper skin.
 Toxins that alter intracellular signals or regulatory pathways
 Most toxins have an (A) active subunit with the enzymatic
activity and a (B) binding subunit that binds to receptors of
the cell surface.
 The effects depend on the binding specificity of the B
domain and the cellular pathway affected by the A domain
 Bacillus anthracis, Vibrio cholera, some strains of E. coli
 Neurotoxins
 Produced by Clostridium botulinum and Clostridium tetani
which inhibits release of neurotransmitters.
 These toxins do not kill neurons, instead, the A domains
interact specifically with proteins involved in secretion of
NTA at the synaptic junction.
 Both tetanus and botulism can result to death due to
respiratory failure because of paralysis of the chest and
diaphragm muscles.
 Superantigens.
 Bacterial toxins that stimulate large number of T
lymphocytes by binding to conserved portions of the T-
cell receptor, leading to massive T cell proliferation and
cytokine release.
 These high levels of cytokines can cause capillary leak and
shock.
 Superantigens made by S. aureus and S. pyogenes cause
toxic shock syndrome (TSS).
SEXUALLY TRANSMITTED INFECTIONS
 Increased risk due to unsafe sex and limited access to health care
 Presence of STI in children, unless acquired during birth, is
strongly suggestive of sexual abuse.
 C. trachomatis and N. gonorrhea is almost always transmitted via
sexual intercourse, but some pathogens like Shigella spp. and E.
histolytica are typically spread by other means but can be
occasionally transmitted via sexual contact.
 STIs may become established and spread from urethra, vagina,
cervix, rectum, or oral pharynx.
 Infection with one STI-associated organism increases the risk for
additional STIs.
 The microbes that cause STIs can be spread from a pregnant
woman to the fetus and cause severe damage.
 C. trachomatis acquired perinatally causes conjunctivitis
 HSV infection causes visceral and CNS diseases.
 Syphilis (T. pallidum) frequently causes miscarriage
 HIV may be fatal to children infected prenatally or perinatally

Spectrum of Inflammatory Responses to Infection

1.) SUPPURATIVE OR PURULENT INFLAMMATION

 Characterized by increased vascular permeability and leukocytic

infiltration, predominantly neutrophils.
 These neutrophils are attracted to the site by chemoattractants
from pyogenic (Pus-forming) bacteria that evoke this reponse.
 Mostly extracellular gram positive cocci, and gram negative rods.
 Masses of dying and dead neutrophils and liquefactive necrosis
of the tissue forms pus.
 How destructive the lesions are depends on the location and the
organism involved.
 Pneumococci usually spare alveolar walls and cause lobar
pneumonia that resolves completely
 Staphylococci and Klebsiella destroy the alveolar walls and
form abscesses that heal with scar formation.

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2.) MONONUCLEAR AND GRANULOMATOUS INFLAMMATION
 Diffuse, predominantly mononuclear, interstitial inflammation
are common features of all chronic inflammatory processes
 When they develop acutely, they often are a response to viruses,
intracellular bacteria, or intracellular parasites.
 Which mononuclear cell predeominates within the lesion
depends on the host immune response to organisms
 Plasma cells are abundant in primary and secondary syphilis
 Lymphocytes predominate in HBV infections or viral
infections of the brain.
 Presence of lymphocytes indicate cell-mediated response.
 Granulomatous inflammation is a distinctive form of
mononuclear inflammation usually evoked by infection that
resist eradication and are capable of stimulating strong T-cell
mediated immunity.
 M. tuberculosis, Histoplasma capsulatum, Schistosoma eggs
 Granulomatous inflammation is characterized by accumulation
and aggregation of epitheloid cells which may fuse to form giant
cells.
3.) CYTOPATHIC-CYTOPROLIFERATIVE REACTION
 Usually produced by viruses
 Characterized by cell necrosis or cellular proliferation usually
with sparse inflammatory cells.
 Some have visible viral aggregates visible as inclusion bodies.
 Some induce cells to fuse and form multinucleated cells called
polykaryons.
 Focal cell damage in the skin may cause epithelial cells to
become detached, forming blisters.
 Some can cause epithelial cells to proliferate.
 Venereal Warts caused by HPV
 Umbilicated papules of molluscum contagiosum caused by
poxviruses
 Viruses can contribute to the development of malignancies.
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4.) TISSUE NECROSIS
 Organisms that secrete powerful toxins that cause such rapid
and severe necrosis (gangrenous necrosis) that tissue damage is
the dominant feature.
 C. perfringens, C. diphteriae
 E. histolytica can cause colonic ulcers and liver abscesses
characterized by extensive tissue destruction with
liquefactive necrosis.
 Some viruses can cause widespread and severe necrosis of the
body tissues associated with inflammation.
 Total destruction of temporal lobes by Herpesvirus
 Total destruction of the liver by Hepatitis B virus
5.) CHRONIC INFLAMMATION AND SCARRING
 Chronic inflammation may lead to complete healing or to
extensive scarring.
 HBV infection may cause cirrhosis, in which dense fibrous
setae surround nodules of regenerating hepatocytes with
complete loss of normal liver architecture and changes in
blood supply.
 Exuberant scarring response is the major cause of destruction.
 Pipestem fibrosis of the liver, fibrosis of the bladder wall
caused by schistosomal eggs.
 Constrictive Fibrous pericarditis in tuberculosis.
Special Techniques for Diagnosing Infectious Agents Emerging Infections
 The gold standards for diagnosis of infections are:
 Culture
 Biochemical or Serologic Identification
 Molecular Diagnosis
 Some infectious agents are directly observed by Hematoxylin
and Eosin (H&E) staining.
 Inclusion bodies formed by CMV and HSV
 Bacterial Clumps
 Candida and Mucor
 Protozoans and Helminths
 Many infectious agents are best visualized by special stains on
the basis of particular characteristics of their cell wall or coat
 Gram
 Acid-fast
 Silver
 Mucicarmine
 Giemsa
 Acute infections can be diagnosed serologically by detecting
pathogen-specific antibodies in the serum
 Presence of IgM shortly after the onset of symptoms is
often diagnostic.
 Specific antibody titers can be measured early in the
Bioterrorism
infection and again 4-6 weeks later during convalescent
 Can be classified into 3 categories:
period. A four-fold rise in titer is usually considered
diagnostic.
CATEGORY A
 Nucleic acid amplification tests (PCR, transcription-mediated
 Pose the highest risk
amplification) are increasingly being used to rapidly identify
 Readily disseminated or transmitted from person to person
microbes.
 High mortality
 Potential for major public health impact
 Might cause public panic and social disruption
 Might require special action for public health preparedness
 Ex.: Smallpox

CATEGORY B
 Relatively easy to disseminate
 Produce moderate morbidity but low mortality
 Require specific diagnostic and disease surveillance
 Many are foodborne or waterborne
 Ex.: Brucella sp., Vibrio cholera, and Ricin toxin from castor
beans

CATEGORY C
 Include emerging pathogens
 Can be engineered for mass dissemination
 Available, ease of production and dissemination
 Potential for high morbidity and mortality
 Great impact on health
 Ex.: Hantavirus and Niphavirus

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 “Mittys iksā. Āeksia tolī kostōbi issi.”
(You’re a fool. The masters are too strong.)

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