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PATHOLOGICAL RESPONSE TO

INFECTIOUS AND PARASITIC


DISEASES
DR KASONDA
PEDIATRICIAN
LEARNING OBJECTIVES

a) Explain the overview of infectious diseases

b) Describe pathogenesis of infectious diseases

c) Describe categories of infectious diseases

d) Explain bacterial and chlamydia infectious diseases

e) Explain fungal infectious diseases

f) Explain viral infectious diseases

g) Explain protozoans and helminthes infectious diseases


Introduction to Infectious Diseases
Infectious diseases remain important causes of
death around the globe.
Infectious diseases are due to organisms ranging
in size from viruses to parasitic worms. It may be
contiguous in origin, results from nosocomial
organism or be due to endogenous microflora.
Infectious diseases are particularly important
causes of death among the elderly and
individuals with AIDS, as well as among those
with chronic diseases.
Medical advances like chemotherapy for tumours and
immuno- suppression for organ transplantation have
also created a whole new class of patients vulnerable
to usually innocuous but nevertheless opportunistic
organisms.
Infectious diseases can be transmitted through:
o Direct contact
o Respiratory droplets
o Faecal-oral routes
o Blood-borne contact
o Sexual transmission
o Vertical transmission
o Insect/arthropod vectors
Pathogenesis of Infectious Diseases
When microbes cause disease, the nature and extent
of the pathology depend on:
Agent factors
- The virulence of the microorganism (the ability to
cause disease).
High virulence suggests the capacity to cause disease in an
otherwise healthy persons
Low virulence implies that the agent causes disease only in
particularly susceptible persons.
Opportunistic infections are those which normally non-
pathogenic organisms produce disease in an immuno-
compromised host.
The pathogenicity:
o The mechanism(s) by which the infectious
agent causes disease.
Infectious agents can bind to or enter host cells and
directly cause cell death or dysfunction.
Pathogens can release endotoxins or exotoxins that kill
cells (or affect their function), release enzymes that
degrade tissue components, or damage blood vessels
and cause ischaemic injury.
Pathogens can induce host immune and inflammatory
responses that may cause additional tissue damage.
o Infective dose is the minimum number of
microorganisms or infective agents required to cause
overt/clinical disease.
Microorganisms may proliferate locally or spread
to other sites depending on microbial tissue
tropisms.
The route of secondary transmission of any given
infection is related to the target tissue and the
hardiness of the particular microbe.
After bypassing host tissue barriers, infectious
microorganisms must also evade host innate and
adaptive immunity to successfully proliferate and
be transmitted to the next host. Strategies include
Remaining inaccessible to host defences, either in areas
not reachable by antibodies or mononuclear cells such
as GI tract lumen or epidermis, inside cells, or
enshrouded within host proteins
Constantly changing antigenic repertoires
Inactivating antibodies or complement
Resisting phagocytosis
Growing within phagocytes after ingestion
Suppressing the host adaptive immune response, for
example by inhibiting MHC expression and antigen
presentation.
Host Factors
The hosts susceptibility to infection depends on
- Age
Sex
Nutritional status
Co-morbid disease
Body immunity
Hosts protective barriers include
-o Skin: Constantly sloughing keratin layer and normal
skin flora.
Respiratory system: Alveolar macrophages and mucociliary
clearance by bronchial epithelium.
GI system: Acidic gastric pH, viscous mucus secretions,
pancreatic enzymes and bile, normal gut flora.
Urogenital tract: Repeated flushing and commensal flora.
Transmission of Infectious Agents
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 and this is determined by:
Virulence
Portal of entry
Vector medium (if any)
Predisposing or protective environmental factors
The Categories of Infectious Diseases
Agents that cause infectious diseases range in size
from the 27-kD prion protein to the 20-nm
poliovirus to the 10-m tapeworm.
Prions are abnormal forms of a normal host prion
protein (PrP) found in high levels in neurons.
The function of PrP is unknown.
Prions (the name derives from proteinaceous
infectious particles) cause transmissible
spongiform encephalopathies.
Viruses
Viruses are obligate intracellular organisms that
commandeer the host cell's biosythetic and
replicative apparatus for their own proliferation.
They consist of a nucleic acid genome surrounded by a
protein coat (called a capsid) and, occasionally, a host-
derived lipid membrane.
Viruses may be classified by some combination of
their nucleic acid genome (DNA or ribonucleic acid
[RNA], but not both).
The shape of the capsid (icosahedral or helical), the
presence or absence of a lipid envelope, the mode of
replication, the preferred host cell type (called
tropism), or the type of pathology they cause.
Viruses are best visualized by electron microscopy.
Certain viruses have the propensity to aggregate
within the cells they infect and form characteristic
inclusion bodies. These may be visualized by light
microscopy and may be diagnostically helpful.
Example CMV-infected cells are markedly enlarged and have
characteristic inclusion bodies-both eosinophilic nuclear
inclusions and smaller basophilic cytoplasmic inclusions.
In comparison, herpes viruses can form a large nuclear
inclusion surrounded by a clear halo and in chronic hepatitis
B virus (HBV) infections, accumulated hepatitis B surface
antigen (HBsAg) forms so-called ground-glass hepatocytes.
Most viruses do not give rise to readily demonstrable
inclusions.
Viruses account for a large share of human infections.
Different species of viruses can produce the same clinical
picture (e.g. upper respiratory infection).
Conversely, a single virus can cause different clinical
manifestations depending on host age or immune status
(e.g. CMV).
While many viruses cause transient illnesses (e.g. the
common cold and influenza), others can persist within cells
of the host for years, either continuing to multiply (e.g.
chronic HBV) or surviving in some non-replicating
form with potential for reactivation (latent
infection).
The herpes varicella-zoster (chickenpox) virus, establishes
latency in the dorsal root ganglia. Later reactivation results in
shingles, an extremely painful cutaneous lesion.
Some viruses also have the nasty capacity to
transform host cells into neoplastic cells.
Mechanism of Infection in Viral
Diseases
Viruses can directly damage host cells by entering them and
replicating at the host's expense.
The predilection to infect certain cells and not others is called tissue
tropism and is determined by several factors.
Host-cell receptors for a particular virus, cell type-specific
transcription factors that recognize viral enhancer and promoter
sequences and physical barriers.
Many viruses use normal cellular receptors of the host to enter cells.
Once viruses are inside host cells, they can injure or kill in several
ways :
o Lysis of host cells
Viral replication interferes with normal cellular functions and may lead to cell
death.
For example, 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.
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.
Although this is a normal response to eliminate virally
infected cells, it can clearly lead to significant host injury.
Liver cell injury during HBV infection is largely driven by
cytotoxic T lymphocytemediated destruction of infected
hepatocytes.
Alteration of apoptosis pathways
Some virus-encoded proteins induce apoptosis.
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.
Induction of cell proliferation and
transformation, resulting in cancer.
Examples include EBV, HBV, HCV, HPV, and human T-cell
leukemia/lymphotropic virus-1.
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.
Damage to cells involved in antimicrobial defense,
leading to secondary infections. For example, viral
damage to respiratory epithelium predisposes to
subsequent bacterial pneumonia, and HIV
depletion of CD4+ helper T lymphocytes leads to
opportunistic infections.
Bacterial and Chlamydia
Pathogenesis of Bacterial Injury
The ability of bacteria to cause disease (virulence)
depends on their ability to o Adhere to host cells
Adhesins are bacterial surface molecules that bind to host
cells; they typically have rather limited structural diversity
but have broad host cell specificity.
Fibrillae cover the surface of gram-positive bacteria.
Although some pili allow exchange of genes
between bacteria, most are involved in
adherence.
Invade cells and tissues
Facultative intracellular bacteria infect epithelial cells
(Shigella and enteroinvasive E.
coli), macrophages (M. tuberculosis,
Mycobacterium leprae), or both (S. typhi).
Intracellular growth is a strategy that not only allows escape
from certain immune effector mechanisms (e.g. antibodies)
but can also facilitate bacterial spread within the body.
Macrophage migration carries M. tuberculosis from the lung
to other sites.
Deliver toxins that damage cells and tissues
Bacterial endotoxin is a lipopolysaccharide (LPS) that is a
major component of the outer cell wall of gram-negative
bacteria.
Exotoxins are secreted proteins that directly cause cellular
injury and frequently underlie disease manifestations.
Mechanisms of Host-Mediated Immune
Injury
Host immune responses to microbes can
themselves be the cause of tissue injury.
Although the granulomatous inflammatory
reaction to M. tuberculosis sequesters the
bacilli and prevents spread, it also produces
tissue damage and fibrosis.
Similarly, the liver damage occurring after HBV
infection of hepatocytes is due to the immune
response against infected liver cells and not to
cytopathic effects of the virus.
Bacteriophages, Plasmids and
Transposons
These are mobile genetic elements that infect
bacteria and can indirectly promulgate human
disease by encoding bacterial virulence factors
(e.g. adhesins, toxins, or enzymes).
Exchange of these elements between bacteria
often endows the recipient with a survival
advantage (e.g. antibiotic resistance), and/or
converts otherwise nonpathogenic bacteria
into virulent ones.
Bacteria
Bacterial infections are common causes of disease.
Bacterial cells are prokaryotes, they have a cell
membrane but lack membrane-bound nuclei and other
membrane-enclosed organelles.
They are also bound by a cell wall usually consisting of
peptidoglycan, a polymer made up of a mixture of
sugars and amino acids, many antibiotics function by
inhibiting cell wall synthesis (e.g. penicillin).
Bacterial cell walls generally occur in one of two
varieties o A thick wall surrounding the cell membrane
that retains crystal violet stain (Grampositive).
A thin cell wall sandwiched between two phospholipid
bilayer membranes (these do not retain crystal violet stain
and are thus gram-negative).
Bacteria are classified by:
o Gram staining (positive or negative)
o Shape (e.g. spherical ones are cocci, rod-shaped ones
are bacilli)
o Form of respiration (aerobic or anaerobic)
Many bacteria have flagella that permit movement.
Others bacteria possess pili that allow attachment to
host cells.
Most bacteria synthesize their own DNA, RNA, and
proteins, but look to the host for their nutrition.
Most bacteria remain extracellular, while some can
grow only within host cells (obligate intracellular
bacteria), still others can survive and replicate either
outside or inside of host cells (facultative intracellular
bacteria).
Normal healthy people are colonized by o As
many as 1010 bacteria in the mouth o 1012
bacteria on the skin
1014 bacteria in the gastrointestinal (GI) tract
Aerobic and anaerobic bacteria in the mouth,
particularly Streptococcus mutans, contribute to
dental plaque, a major cause of tooth decay.
Bacteria colonizing the skin include
Staphylococcus epidermidis and
Propionibacterium acnes, the cause of acne. In
the colon, 99.9% of bacteria are anaerobic.
Chlamydiae, Rickettsias, and Mycoplasmas
Like bacteria, these organisms divide by binary fission
and are sensitive to antibiotics.
However, they are considered separately here because
they lack certain structures (e.g. mycoplasma lack a cell
wall) or metabolic capabilities.
Chlamydia cannot synthesize adenosine triphosphate
[ATP]) that distinguish them from bacteria.
Chlamydia and rickettsia species are obligate
intracellular organisms that replicate in membrane-
bound vacuoles in epithelial cells and the cytoplasm of
endothelial cells, respectively.
Rickettsiae are notable for their transmission by
arthropod vectors, including lice, ticks, and mites
Chlamydia trachomatis is the most frequent
infectious cause of female sterility (by scarring
fallopian tubes) and blindness (causing
conjunctival inflammation that eventually
scars and opacifies the cornea).
By injuring endothelial cells, rickettsiae cause
hemorrhagic vasculitis (often presenting as a
rash), but they can also cause pneumonia or
hepatitis or injure the central nervous system
and cause death.
Fungal, Protozoans and Helminthes
Fungi are eukaryotes possessing thick chitin-containing cell walls
and ergosterol-containing cell membranes; these unique wall and
membrane constituents are the targets of most antifungal agents.
Fungi can grow either as budding yeast forms or as slender
filamentous hyphae.
Hyphae may be septate (cell walls separate individual cells) or
aseptate, a distinction important in clinical diagnosis.
Many pathogenic fungi show thermal dimorphism, that is, they
grow as hyphae at room temperature but as yeast at body
temperature.
Fungi may produce spores sexually or, more commonly, asexual
spores (conidia), the latter are produced on specialized structures
or fruiting bodies arising along hyphal filaments.
Fungi may cause superficial or deep infections.
Superficial infections typically involve the skin,
hair, or nails. Dermatophytes (skin lovers) are
fungal species confined to superficial skin layers,
these infections are commonly referred to by the
term tinea and vascular occlusion.
AIDS patients in particular are frequent victims of
the opportunistic fungus Pneumocystis jiroveci
(formerly called P. carinii).
Protozoa
Protozoa, single-celled eukaryotes, are among the major
causes of morbidity and mortality in developing countries.
Parasitic protozoa can replicate o Intracellular in many cell
types (e.g. malaria in erythrocytes, Leishmania in
macrophages).
Extracellular in the urogenital system, intestine, or blood.
Trichomonas vaginalis is a sexually transmitted protozoan
that can colonize the vagina and male urethra.
The most prevalent intestinal protozoans, Entamoeba
histolytica and Giardia lamblia, have two forms, which are
Non-motile cysts that are resistant to stomach acids and are
infectious when ingested, o Motile trophozoites that multiply in
the intestinal lumen
Blood-borne protozoa (e.g. Plasmodium,
Trypanosoma, and Leishmania) replicate
within insect vectors before transmission to
new human hosts.
Toxoplasma gondii is acquired either by
contact with oocysts-shedding kittens or by
consumption of cyst-ridden undercooked
meat.

Helminthes
Parasitic worms are highly differentiated
multicellular organisms with complex life cycles.
Most alternate between sexual reproduction in
the definitive host and asexual multiplication in
an intermediary host or vector.
Depending on the species, humans may harbor
adult worms (e.g. Ascaris lumbricoides),
immature forms (e.g. Toxocara canis), or asexual
larval forms (e.g. Echinococcus species).
Once adult worms take up residence in humans,
they generate eggs or larvae destined for the next
phase of the cycle.
This is significant in that helminthic disease is
usually proportionate to the number of infecting
organisms.
Moreover, pathology related to helminth
infections is usually due to inflammatory
responses to the eggs or larvae rather than to the
adult forms (e.g. the robust granulomatous
inflammation in schistosomiasis).
Strongyloides stercoralis is an exception in that
larvae can become infectious in the gut and cause
overwhelming autoinfection in
immunocompromised hosts.
Key Points
Diseases caused by microbes involve interplay of
microbial virulence and host responses.
Infectious diseases are due to organisms ranging in size
from viruses to parasitic worms. It may be contiguous
in origin, results from nosocomial organism or be due
to endogenous microflora.
Infectious agents can directly cause cell death or
dysfunction by binding to or by entering host cells.
Infectious diseases can be transmitted through o Direct
contact o Respiratory droplets o Faecal-oral routes o
Blood-borne contact o Sexual transmission o Vertical
transmission o Insect/arthropod vectors
Injury may be due to local or systemic release of
bacterial products, including endotoxins,
exotoxins, or superantigens.
Pathogens can induce immune responses that
cause tissue damage.
Absence of an immune response may reduce the
damage induced by some infections, conversely,
immunocompromise can allow uncontrolled
expansion of opportunistic agents or of
microorganisms that can directly cause injury.

Evaluation
What are the causes of infectious disease?
What are the factors making one susceptible
to infections?
What is pathogenicity?

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