Session 22:

Infectious Pathology

1
 Learning tasks
At the end of this session, students are expected to be
able to:
• Explain pathogenesis of infectious agents.
• Categorize infectious agents.
• Explain viral infectious diseases.
• Explain bacterial infectious diseases.
• Explain fungal infectious diseases.
• Explain protozoans infectious diseases.
• Explain helminthes infectious diseases.

2
 Introduction
• Infectious diseases remain an important health
worldwide despite the availability and use of effective
vaccines and antibiotics.
• Infectious diseases are important causes of death to:
– Elderly.
– People with the acquired immunodeficiency syndrome
(AIDS).
– Persons with chronic diseases.
– Patients receiving immunosuppressive drugs.

3
 Introduction cont…
• In developing countries, unsanitary living conditions
and malnutrition contribute to a massive burden of
infectious diseases.
• The most common victims are children with
respiratory and diarrheal infections.
• A pathogen can establish infection if it possesses
virulence factors that overcome normal host defenses
or if the host defenses are compromised.

4
 Components of infectious diseases
transmission
1. An agent capable of infecting man.
2. A source (an infected host or reservoir).
3. A portal of exit from the source.
4. A suitable means of transmission.
5. A portal of entry into a new host.
6. A susceptible host.

5
Characteristics of infectious agents

1. Resistance
– Ability of an agent to survive under adverse condition.
2. Infectivity
– Capacity of a microorganism to enter a susceptible host.
3. Pathogenicity
– Capacity of an agent to cause an overt disease.
4. Antigenicity
– Ability of an agent to induce antibody production.

6
Characteristics of infectious agents
cont…
5. Toxigenicity
– Ability to produce a toxin that cause pathologic effects.
6. Virulence
– It is the degree of pathogenicity of an infectious agent.
– Refers to the severity of the disease.

7
 Host factors
• The host’s susceptibility to infection depends on :
1. Age.
2. Sex.
3. Nutritional status.
4. Co-morbid disease.
5. Body immunity.

8
 Host defenses against infection
• Skin
– Tough keratinized barrier, low pH, fatty acids.
• Respiratory system
– Alveolar macrophages and mucociliary clearance by
bronchial epithelium, IgA.
• Gastrointestinal system
– Acidic gastric pH, viscous mucus, pancreatic enzymes and
bile, defensins, IgA, and normal flora.
• Urogenital tract
– Repeated flushing and acidic environment created by
commensal vaginal flora
9
 Modes of transmission of infectious
agents
• Transmission of infections can occur by:
1. Contact (direct and indirect).
2. Respiratory droplets (Inhalation).
3. Fecal-oral route.
4. Blood borne contact.
5. Sexual transmission.
6. Vertical transmission from mother to fetus or newborn
(during pregnancy, giving birth and breastfeeding).
7. Insect/arthropod vectors.

10
Transmission of infectious agents to
the host
• The ability of a microbe to infect an individual as
well as the nature and extent of the disease also
depends on how it is transmitted to the host.
• This is determined by:
1. Virulence of infectious agent.
2. Portal of entry.
3. Vector medium (if any).
4. Predisposing or protective environmental factors.
• Infective dose is the minimum number of
microorganisms or infective agents required to cause
overt/clinical disease.
11
How microorganisms cause disease

• Infectious agents establish infection and damage

tissues by any of three (3) mechanisms:
1. They can contact or enter host cells and directly
cause cell death.
2. They may release toxins that kill cells at a distance,
release enzymes that degrade tissue components, or
damage blood vessels and cause ischemic necrosis.
3. They can induce host immune responses that,
although directed against the invader, cause
additional tissue damage.
12
 Categories of infectious agents
1. Prions.
2. Viruses.
3. Bacteria (including intracellular bacteria like
Chlamydia & Rickettsia).
4. Fungi.
5. Protozoans.
6. Helminthes.

13
 Prions
• Prions are composed of abnormal forms of a host
protein termed prion protein (PrP).
• Prions are not microorganisms.
• These agents cause transmissible spongiform
encephalopathies, including Kuru (associated with
human cannibalism), Creutzfeldt-Jakob Disease
(CJD).
• PrP is found normally in neurons.

14
 Prions cont…
• Diseases occur when the PrP undergoes a
conformational change that confers resistance to
proteases.
– The protease-resistant PrP promotes conversion of the
normal protease-sensitive PrP to the abnormal form,
explaining the infectious nature of these diseases.
• Accumulation of abnormal PrP leads to neuronal
damage and distinctive spongiform pathologic
changes in the brain.

15
 Viruses
• Viruses are obligate intracellular parasites that depend
on the host cell’s metabolic machinery for their
replication.
• They consist of a nucleic acid genome surrounded by
a protein coat (called a capsid) that is sometimes
encased in a lipid membrane.
• Some viral components and particles aggregate within
infected cells and form characteristic inclusion bodies.
– For example: Cytomegalovirus (CMV), Herpesviruses,
smallpox virus, rabies virus.

16
 Viruses cont…
• Viruses are classified by:
i. Their nucleic acid genome (DNA or RNA but not
both).
ii. The shape of the capsid (icosahedral or helical).
iii. The presence or absence of lipid envelope.
iv. Their mode of replication.
v. The preferred cell type for replication (called
tropism).
vi. The type of pathology they cause.
17
 Viruses cont…
• Viruses can cause illnesses in several ways.
• Many viruses cause transient illnesses (e.g. colds,
influenza).
• Other viruses are not eliminated from the body and
persist within cells of the host for years:
– Continuing to multiply (e.g., chronic infection with
hepatitis B virus [HBV]).
– Surviving in some nonreplicating form (termed latent
infection) with the potential to be reactivated later (e.g.
herpes zoster virus, the cause of chickenpox establish
latency, later on reactivated and causing shingle).
18
 Viruses cont…
• Some viruses are involved in transformation of a host
cell into a benign or malignant tumor (e.g. Human
papillomavirus [HPV]-induced benign warts and
cervical carcinoma).
• Different species of viruses can produce the same
clinical picture (e.g. Upper respiratory infections).
• Conversely, a single virus can cause different clinical
manifestations depending on host age or immune
status (e.g. Cytomegalovirus).

19
 Mechanisms of viral injury
• Viruses can directly damage host cells by entering
them and replicating at the host’s expense.
• The manifestations of viral infection are largely
determined by the tropism of the virus for specific
tissues and cell types.
• A major determinant of tissue tropism is the presence
of viral receptors on host cells.

20
Mechanisms of viral injury cont…
• In some cases, host proteases are needed to enable
binding of virus to host cells.
• The ability of the virus to replicate inside some cells
but not in others depends on the presence of cell
type–specific transcription factors that recognize viral
enhancer and promoter elements.
• Physical circumstances, such as chemicals and
temperature, contribute to tissue tropism.

21
 Mechanisms on how viruses
damage/kill host cells cont…
• Once viruses are inside host cells, they can damage or kill
the cells by a number of mechanisms:
1. Lysis of host cells (Direct cytopathic effects).
2. Immune cell-mediated killing.
3. Alteration of apoptosis pathways.
4. Induction of cell proliferation and transformation,
resulting in cancer.
5. Inhibition of host cell DNA, RNA or protein synthesis.
6. Damage to plasma membranes.
7. Damage to cells involved in antimicrobial defense,
leading to secondary infections.
22
 Mechanisms on how viruses
damage/kill host cells cont…
1. Lysis of host cells (Direct cytopathic effects).
a) Viral replication interferes with normal cellular
functions and may lead to cell death.
• For examples:
Viral replication and release is the mechanism by which
influenza virus kills respiratory epithelial cells, yellow
fever virus kills hepatocytes and poliovirus and rabies
destroy neurons.
 Mechanisms on how viruses
damage/kill host cells cont…
1. Lysis of host cells cont...
b) Viruses can kill cells by:
Preventing synthesis of critical host macromolecules,
Producing degradative enzymes and toxic proteins.
Inducing apoptosis.
• For examples:
Poliovirus blocks synthesis of host proteins.
Herpes simplex virus produces proteins that inhibit
synthesis of cellular DNA and mRNA and other proteins
that degrade host DNA.
Most of viruses trigger apoptosis of host cells by cell-
intrinsic mechanisms that activate proteases that mediate
apoptosis (caspases).
 Mechanisms on how viruses
damage/kill host cells cont…
2. Immune cell-mediated killing.
• Viral proteins expressed on host cell surfaces are
recognized as foreign by the immune system and
induce attack by cytotoxic T lymphocytes.
• Normal antiviral immune responses:
Viral proteins on the surface of host cells may be
recognized by the immune system and lymphocytes may
attack virus-infected cells.
 Mechanisms on how viruses
damage/kill host cells cont…
2. Immune cell-mediated killing cont...
Cytotoxic T lymphocytes (CTLs) are important for
defense against viral infections, but CTLs also can be
responsible for tissue injury.
Acute liver failure during hepatitis B infection may be
accelerated by CTL-mediated destruction of infected
hepatocytes (a normal response to clear the infection).
 Mechanisms on how viruses
damage/kill host cells cont…
2. Immune cell-mediated killing cont...
• Although this is a normal response to eliminate
virally infected cells, it can clearly lead to
significant host injury.
• Thus, liver cell injury during HBV infection is
largely driven by cytotoxic T lymphocyte-mediated
destruction of infected hepatocytes.
 Mechanisms on how viruses
damage/kill host cells cont…
3. Alteration of apoptosis pathways.
• Some virus-encoded proteins (including TAT and
gp120 of HIV and adenovirus E1A) induce
apoptosis.
Indeed, this may be a protective host response to
eliminate virus-infected cells.
• In contrast, some viruses encode genes that inhibit
apoptosis.
Such strategies may enhance viral replication and
promote persistent viral infections, but they may also
promote virus-induced cancers.
 Mechanisms on how viruses
damage/kill host cells cont…
3. Alteration of apoptosis pathways cont...
• Thus, some viruses can stimulate apoptosis by
production of proteins that are proapoptotic (e.g.
HIV vpr protein).
 Mechanisms on how viruses
damage/kill host cells cont…
4. Induction of cell proliferation and
transformation, resulting in cancer.
• Examples of oncogenic viruses include
EBV.
HBV.
HCV.
HPV.
Human T-cell leukemia/lymphotropic virus-1.
• Transformation of infected cells into benign or
malignant tumor cells.
 Mechanisms on how viruses
damage/kill host cells cont…
4. Induction of cell proliferation and
transformation, resulting in cancer cont…
• Different oncogenic viruses can stimulate cell
growth and survival by a variety of mechanisms,
including:
Expression of virus-encoded oncogenes, antiapoptotic
strategies.
Insertional mutagenesis (in which the insertion of viral
DNA into the host genome alters the expression of
nearby host genes).
 Mechanisms on how viruses
damage/kill host cells cont…
5. Inhibition of host cell DNA, RNA or protein
synthesis.
• These effects may eventually cause cell death, or
they may lead to more subtle cellular dysfunction.
• For example:
Poliovirus inactivates a cap-binding protein essential for
translation of host cell messenger RNA (mRNA).
o However, translation of poliovirus mRNA remains
unaffected.
 Mechanisms on how viruses
damage/kill host cells cont…
6. Damage to plasma membranes.
• Viral proteins can insert into host plasma
membranes and thereby:
Alter their integrity.
Promote cell fusion
• Example of viruses:
HIV.
Measles virus.
Herpesviruses.
 Mechanisms on how viruses
damage/kill host cells cont…
7. Damage to cells involved in antimicrobial
defense, leading to secondary infections.
For example:
• Viral damage to respiratory epithelium predisposes
to subsequent bacterial pneumonia.
• HIV depletion of CD4+ helper T lymphocytes leads
to opportunistic infections.
 Bacteria
• Bacterial infections are common causes of disease.
• Bacteria are prokaryotes, meaning that they have a
cell membrane but lack membrane-bound nuclei and
other membrane-enclosed organelles.
• Most bacteria are bound by a cell wall consisting of
peptidoglycan.
– A polymer of long sugar chains linked by peptide bridges
surrounding the cell membrane.

35
 Bacteria cont…
• There are two common forms of cell wall structure:
– Thick wall that retains crystal-violet stain (Gram-positive
bacteria).
– Thin cell wall surrounded by an outer membrane (Gram-
negative bacteria).
• Bacteria are classified by:
– Gram staining (positive or negative).
– Shapes (spherical ones are cocci; rod-shaped ones are
bacilli).
– Need for oxygen (aerobic or anaerobic).

36
 Bacteria cont…
• Motile bacteria have flagella that rotate and move the
bacteria.
• Some bacteria possess pili that can attach bacteria to host
cells or extracellular matrix.
• Bacteria synthesize their own DNA, RNA and proteins,
– But they depend on the host for favorable growth conditions.
• Most bacteria remain extracellular.
• Some can grow only within host cells (obligate intracellular
bacteria e.g. Chlamydia, Rickettsia).
• Others can survive and replicate either outside or inside of
host cells (facultative intracellular bacteria).
37
 Bacteria cont…
• Normal healthy people can be colonized by as many
as 1012 bacteria on the skin, 1010 bacteria in the
mouth, and 1014 bacteria in the gastrointestinal tract.
• Bacteria colonizing the skin include Staphylococcus
epidermidis and Propionibacterium acnes, the cause
of acne.
• Aerobic and anaerobic bacteria in the mouth,
particularly Streptococcus mutans, contribute to
dental plaque, a major cause of tooth decay.
• Most of normal intestinal flora of an individual
human are anaerobes. 38
 Chlamydia
• Chlamydia is an obligate intracellular bacteria
which replicate inside membrane-bound vacuoles in
epithelial cells.
• Chlamydia gets most or all of their energy source
(ATP) from the host cell.
• Chlamydia trachomatis is the most frequent
infectious cause of:
– Female sterility (by scarring and narrowing of the
fallopian tubes).
– Blindness (by chronic inflammation of the conjunctiva
that eventually causes scarring and opacification of the
cornea). 39
 Rickettsia
• Rickettsiae is an obligate intracellular bacteria
which replicate inside membrane-bound vacuoles in
endothelial cells.
• Rickettsia gets most or all of their energy source
(ATP) from the host cell.
• Causes hemorrhagic vasculitis, injure CNS (as in
Rocky Mountain spotted fever and epidemic
typhus).
• Transmitted by arthropod vectors, including:
– Lice (in Epidemic typhus).
– Ticks (in Rocky mountain spotted fever and ehrlichiosis).
– Mites (in Scrub typhus). 40
 Mechanisms of bacterial injury
• Bacterial damage to host tissues depends on the
ability of the bacteria to:
1. Adhere to host cells.
2. Invade cells and tissues.
3. Deliver toxins.

41
 Fungi
• Eukaryotes that possess thick, chitin-containing cell
walls and ergosterol-containing cell membranes.
• Fungi can grow either as rounded yeast cells,
slender, filamentous hyphae or dimorphic.
• Hyphae may be septate or aseptate.
• Some of pathogenic fungi exhibit thermal
dimorphism.
– Grow as hyphal forms at room temperature but as yeast
forms at body temperature.
• Fungi may produce sexual spores or, more
commonly, asexual spores called conidia. 42
 Fungi cont…
• Fungi may cause superficial or deep infections.
• Superficial infections involve the skin, hair, and nails.
– Fungal species that cause superficial infections are called
dermatophytes (‘skin lovers’) or Tinea infections.
• Certain fungi invade the subcutaneous tissue, causing
abscesses or granulomas sometimes called
mycetomas.
• Deep fungal infections can spread systemically and
invade tissues, destroying vital organs in
immunocompromised hosts.
– Usually resolve or remain latent in otherwise normal hosts.
43
 Fungi cont…
• Fungi are also divided into endemic and opportunistic
species.
• Endemic fungi are invasive species that are limited to
particular geographic regions.
• Opportunistic fungi (e.g., Candida, Aspergillus,
Mucor, Cryptococcus) in immunodeficient
individuals, give rise to life-threatening invasive
infections with little or no inflammatory response.

44
 Fungi cont…
• Patients with HIV/AIDS often are infected by the
opportunistic fungi:
– Candida albicans causing oral, esophageal candidiasis.
– Cryptococcus neoformans causing meningitis.
– Pneumocystis jiroveci (previously called Pneumocystis
carinii) causing Pneumonia.

45
 Protozoa
• Protozoa are single-celled eukaryotes.
• Protozoa can replicate:
– Intracellularly within a variety of cells (e.g., Plasmodium in
red cells, Leishmania in macrophages)
– Extracellularly in the urogenital system, intestine or blood.
• Trichomonas vaginalis is sexually transmitted
flagellated protozoal parasite that often colonize the
vagina and male urethra.

46
 Protozoa cont…
• The most prevalent intestinal protozoans are
Entamoeba histolytica and Giardia lamblia.
– Ingested as nonmotile cysts in contaminated food or water
and become motile trophozoites that attach to intestinal
epithelial cells.
• Blood borne protozoa (e.g. Plasmodium,
Trypanosoma, Leishmania) are transmitted by
insect vectors, in which they replicate before being
passed to new human hosts.
• Toxoplasma gondii is acquired either through contact
with oocyst-shedding kittens or by eating cyst-
ridden, undercooked meat.
47
 Helminthes
• They are highly differentiated multicellular
organisms.
• They have complex life cycles.
– Most alternate between sexual reproduction in the
definitive host and asexual multiplication in an
intermediate host or vector in their life cycles
• Humans may harbor adult worms (e.g., Ascaris
lumbricoides), immature stages (e.g., Toxocara
canis), or asexual larval forms (e.g., Echinococcus
spp.).

48
 Groups of Helminthes
1. Roundworms (Nematodes)
• Circular in cross-section and nonsegmented.
– E.g. Ascaris lumbricoides and hookworms.
2. Tapeworms (Cestodes)
• Have head (scolex) and a ribbon of multiple flat
segments (proglottids).
– E.g. Fish, beef, and pork tapeworms.
3. Flukes (Trematodes)
• Leaf-shaped flatworms with prominent suckers that
are used to attach to the host.
– E.g. Blood, liver and lung flukes. 49
 Strategies (mechanisms) in which
microbes evade immune system
1. Remaining inaccessible to host defences.
2. Constantly changing antigenic repertoires.
3. Inactivating antibodies or complement.
4. Resisting phagocytosis.
5. Growing within phagocytes after ingestion.
6. Suppressing the host adaptive immune response.

50
 Key points
• Infectious diseases are due to organisms ranging in
size from viruses to parasitic worms.
• Pathogenicity is the capacity of a particular microbe
to cause disease.
• Spread of microbes to other sites depend on microbial
tissue tropisms.
• Prions are not microorganism; they are abnormal host
proteins commonly seen in neurons.
• Most of intestinal bacteria are anaerobes.
• Tinea infections are caused by superficial fungi.
• Any stage of helminthes can cause inflammation.
51
 Review questions
1. Explain pathogenesis of infectious agents.
2. Explain five (5) mode of transmission of infectious
diseases.
3. Explain five (5) mechanisms on how viruses
damage or kill the cells once they are inside host
cells.
4. Explain three (3) mechanisms on how bacteria cause
diseases.
5. List five (5) strategies used by microbes to evade
immune system.
52
 References
• Kumar V. ; Abbas A. K. ; Aster J. C.;(2013): Robbins
and Contran Pathologic Basis of Disease (9th Ed.)
Elsevier Saunders, USA. Pg. 309-322.
• Xiu P.;(2012): Crash Course Pathology (4th Ed.)
Elsevier Saunders, USA. Pg. 25-35.

53