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Infectious Diseases
Infection and Immunity

Definition of infection
①
Complex process of interaction between pathogen and human
body
Infection is composed of three factors: pathogen, host and
environment
There are commensalisms and opportunistic infection
②
③
• Infectious disease kill more people each year than do all
cancers and cardiovascular diseases.
• The impact of infectious diseases is greatest in lessdeveloped countries, where millions of people, mostly
children younger than 5 years of age, die of treatable or
preventable infectious diseases.
Classification of infections
1. Primary infection: Initial infection with
organism in host.
2. Reinfection: Subsequent infection by
same organism in a host (after recovery).
3. Superinfection: Infection by same
organism in a host before recovery.
4. Secondary infection: When in a host
whose resistance is lowered by
preexisting infectious disease, a new
organism may set up in infection.
Classification of infections
5. Focal infection: It is a condition where due
to infection at localized sites like appendix
and tonsil, general effects are produced.
6. Cross infection: When a patient suffering
from a disease and new infection it set up
from another host or external source.
7. Nosocomial infection: Cross infection
occurring in hospital.
8. Subclinical infection: It is one where
clinical affects are not apparent.
Infectivity and Virulence
• Infectious organisms cause diseases in which tissue dysfunction
results from an invading transmissible agent.
• Virulence refers to the complex of properties that allows that agent
to achieve infection and cause diseases of different degrees of
severity.
• The organism must (1) gain access to the body, (2) avoid multiple
host defenses, (3) accommodate to growth in the human, and (4)
parasitize human resources.
• Virulence reflects both the structures inherent to the offending
microbe and the interplay of those factors with host defense
mechanisms.
Sources of infection in Man
Man: Man is himself a common source of
infection from a patient or carrier.
Healthy carrier is a person harboring
pathogenic organism without causing
any disease to him. A convalescent
carrier is one who has recovered from
disease but continues to harbor the
pathogen in his body.
Sources of infection in Man
Animals: Infectious diseases transmitted from animals to
man are called zoonosis. Zoonosis may be bacterial,
(e.g. Plague from rat), rickettsial, (e.g. Murine typhus from
rodent), viral, (e.g. Rabies from dog), protozoal, (e.g.
Leishmaniasis from dogs), helminthic, (e.g. Hydatid cyst
from dogs) and fungal (zoophilic dermatophytes from cats
and dogs).
Sources of infection in Man
Insects: The diseases caused by insects
are called arthropod borne disease.
Insects like mosquitoes, fleas, lice that
transmit infection are called vector.
Transmission may be mechanical
(transmission of Dysentery or typhoid
bacilli by housefly) and these are
called mechanical vector. They are
called biological vector if pathogen
multiplies in the body of vector, e.g.
Anopheles mosquito in Malaria.
Sources of infection in Man
Some vectors may acts as reservoir
host, (e.g. ticks in Relapsing fever
and Spotted fever).
Soil: Spores of tetanus bacilli, Gasgangrene infection remain viable in
soil for a long time.
Clostridium tetani
Sources of infection in Man
Water: Vibrio cholerae, infective hepatitis virus (Hepatitis
A and Hepatitis E) may be found water.
Food: Contaminated food may be source of infection.
Presence of pathogens in food may be due to
external contamination, (e.g. food poisoning by
Staphylococcus).
Methods of transmission of
infection
• Contact
contact):
gonorrhea.
(sexual
syphilis,
• Inhalation:
influenza,
tuberculosis,
smallpox, measles,
mumps, etc.
Methods of transmission of infection
• Ingestion:
cholera
(water), food poisoning
(food) and dysentery
(hand borne).
• Inoculation:
tetanus
(infection), rabies (dog),
arbovirus (insect) and
serum hepatitis, i.e.
Hepatitis B (infection).
Human hand
contaminated with
colonies of
bacteria (blue/pink
patches)
Methods of transmission of infection
• Congenital:
syphilis,
rubella,
toxoplasmosis,
cytomegaloviruses
Eight week old fetus
attached to its placenta by
the umbilical cord
Methods of transmission of
infection
• Insects: they act as
mechanical
vector
(dysentery and typhoid
by
housefly)
or
biological
vector
(malaria) of infectious
disease
• Jatrogenic
and
laboratory
infections:
infection
may
be
transmitted
during
procedures
Infecting dose
• The minimum infection dose (MID) or
minimum lethal dose (MLD) is the
minimum number of organism required to
produce clinical evidence of infection or
dearth of susceptible animal.
• Route of infection
• Vibrio cholerae is effective orally. No effect
when it is introduced subcutaneously.
• Streptococci can initiate infection whatever
be the mode of entry.
Types of infectious diseases
• Infectious diseases may be localized or
generalized. Localized infections may be
superficial or deep-seated.
• Circulation of bacteria in the blood is
known as bacteremia (viruses – virusemia).
Types of infectious diseases
• Septicemia is the condition where
bacteria circulate and multiply in the
blood, form toxic products and cause
swinging type of fever.
• Pyemia is a condition where pyogenic
bacteria
produce
septicemia
with
multiple abscesses in the internal organs
such as the spleen, liver and kidney.
Stages of infectious disease
• Incubation period – no symptoms.
• Prodromal period – mild and
generalized
symptoms
(fever,
weakness, headache).
• Invasive stage – symptoms specific to
the disease.
• Decline stage – symptoms subside.
• Convalescence – no symptoms,
health returns to normal.
Host Defense Mechanisms
• The means by which the body prevents or contains infections.
• There are major anatomical barriers to infection mainly the skin
and the aerodynamic filtration system of the upper airway that
prevent most organisms from ever penetrating the body.
• The mucociliary blanket of the airways is also an essential defense,
providing a means of expelling organisms that gain access to the
respiratory system.
• The microbial flora normally resident in the gastrointestinal tract
and in various body orifices compete with outside organisms,
preventing them from gaining sufficient nutrients or binding sites in
the host.
Age Influences the Outcome of Infection
• The effect of age on the outcome of exposure to many
infectious agents is illustrated by fetal infections.
• Some organisms produce more severe disease in utero than
in children or adults.
• Infections of the fetus with cytomegalovirus (CMV),
rubellavirus, parvovirus B19, and Toxoplasma gondii interfere
with fetal development.
• Fetal protection is dependent on the presence of maternal
IgG antibodies, which cross the placenta. An acute infection
in a nonimmune pregnant woman may allow the organism to
infect the fetus.
• These infections are usually subclinical or produce minimal
disease in the mother but may lead to major congenital
abnormalities or death in the fetus
• Age also affects the course of common illnesses, such as the
diverse viral and bacterial diarrheas.
• Age also affects the course of common illnesses, such as the
diverse viral and bacterial diarrheas. In older children and
adults, these infections cause discomfort and inconvenience,
but rarely severe disease.
• The elderly fare more poorly with almost all infections than
younger persons.
• Common respiratory illnesses such as influenza and
pneumococcal pneumonia are more often fatal in those
older than 65 years of age.
People with Compromised Defenses are More Likely to
Contract Infections and to Have More Severe Infections
• Disruption or absence of any host defense mechanism
results in increased numbers and severity of infections.
• Disruption of epithelial surfaces by trauma or burns
frequently leads to invasive bacterial or fungal infections.
• Injury to the mucociliary apparatus of the airways, as in
smoking or influenza, impairs clearance of inhaled
microorganisms and leads to an increased incidence of
bacterial pneumonia.
• Congenital absence of complement components C5, C6, C7, and C8
prevents formation of a fully functional membrane attack complex
and permits disseminated, and often recurrent, Neisseria infections.
• Diseases such as diabetes mellitus and chemotherapeutic drugs that
interfere with the production or function of neutrophils increase the
likelihood of bacterial infections or invasive fungal infections.
• Organisms that cause disease mainly in hosts with impaired
immunity are termed opportunistic pathogens. These organisms,
many of which are part of the normal endogenous human or
environmental microbial flora, take advantage of a host's inadequate
defenses to stage a more violent and sustained attack.
Categories of infectious agents
1. Viral Infections
• Viruses range from 20 to 300 nm and consist of RNA or DNA
contained in a protein shell. Some are also enveloped in lipid
membranes.
• Viruses do not engage in metabolism or reproduction
independently, and thus are obligate intracellular parasites that
require living cells in order to replicate.
• After invading cells, they divert the cells' biosynthetic and
metabolic capacities toward the synthesis of virus-encoded
nucleic acids and proteins.
• Viruses often cause disease by killing infected cells, but many
do not.
• Viruses may also promote the release of chemical mediators
that elicit inflammatory or immunologic responses.
• The symptoms of the common cold are due to the release of
bradykinin from infected cells.
• viruses cause cells to proliferate and form tumors. Human
papillomaviruses (HPVs), for instance, cause squamous cell
proliferative lesions.
• Viruses can cause acute illness (common cold, influenza) or
chronic disease (HBV, HIV) and long term reactivation
(herpes virus).
• Some viruses infect and persist in cells without interfering
with cellular functions, a process known as latency.
• Latent viruses can emerge to produce disease years after the
primary infection.
• Opportunistic infections are frequently caused by viruses
that have established latent infections.
• CMV and herpes simplex viruses are among the most
frequent opportunistic pathogens because they are
commonly present as latent agents and emerge in persons
with impaired cell-mediated immunity
• Finally, some viruses may reside within cells, either by
integrating into their genomes or by remaining episomal,
and cause those cells to generate tumors. Examples of this
are Epstein-Barr virus (EBV), which causes endemic Burkitt
lymphoma in Africa, and other tumors in different settings,
and human T-cell leukemia virus-1 which causes a form of Tcell lymphoma.
Classification of viruses
1.
2.
DNA
RNA
Further classification:

Single or double
strand

Envelope on no
envelope
RNA Viruses
• A number of important pathogenic RNA viruses (e.g., human
immunodeficiency virus [HIV]-1, hepatitis C virus) differ from
many DNA viruses in that the RNA viral polymerases do not
proofread the RNA strand being synthesized.
• This has two important consequences. First, the mutation
rate and therefore the plasticity of these viruses in
circumventing therapies is very high. Second, a greater
percentage of daughter virions are inactive.
• The common cold is an acute, self-limited upper respiratory tract
disorder caused by infection with a variety of RNA viruses, including
more than 100 distinct rhinoviruses and several coronaviruses.
• Infection is more likely during the winter months in temperate areas
and during the rainy seasons in the tropics, when spread is
facilitated by indoor crowding.
• The viruses infect the nasal respiratory epithelial cells, causing
increased mucus production and edema, viruse have a tropism for
respiratory epithelium and optimally reproduce at temperatures
well below 37° C.
• The resulting stasis of secretions may predispose to secondary
bacterial infection and lead to bacterial sinusitis and otitis media.
DNA Viruses
• The virus family Herpesviridae includes a large number of
enveloped, DNA viruses, many of which infect humans. Almost all
herpes viruses express some common antigenic determinants, and
many produce type A nuclear inclusions (acidophilic bodies
surrounded by a halo).
• The most important human pathogens among the herpes viruses
are varicella-zoster, herpes simplex, EBV, human herpesvirus 6
(HHV6, the cause of roseola), and CMV. Recently, HHV8 was
implicated in the pathogenesis of KS in HIV-infected patients. These
viruses are also distinguished by their capacity to remain latent for
long periods of time
This is cytomegalovirus (CMV) infection in the lung. Note the very large
cells that have large violet intranuclear inclusions with a small clear halo.
Basophilic stippling can be seen in the cytoplasm.
This is a microscopic section from the edge of one of a group of small round
clear vesicles on the skin, just above the lip. Notice the mauve to pink
homogenous intranuclear inclusions in the epithelial cells of the epidermis.
This is typical for Herpes simplex virus (HSV) infection. The most common
sites for Herpes simplex virus infections (either primary or reactivation) are
skin and mucus membranes. HSV type I is seen most often in oral cavity,
while HSV type II is more commonly
a sexually
transmitted disease.
Herpes
simplex
By electron microscopy, viral particles of any herpesvirus appear as arrays
and scattered single particles as shown here in a nucleus of a neuron from
the cerebrum from a patient with herpes simplex encephalitis. Herpesviruses
are large encapsulated viruses that contain double-stranded DNA in the
nucleocapsid surrounded by the viral envelope.
2. Bacteria
• Lack nuclei but have rigid cell wall containing two
phospholipid bilayer (gram negative species) or single
bilayer( gram positive species).
• Are major cause of sever infectious disease.
• Grow extracellularly (e.g.: pneumococcus) or intracellularly
(mycobacterium tuberculosis).
14
12
• Normal person carry 10 bacteria on the skin and 10
bacteria in GIT, 99.9 of them are anaerobic
Exotoxins
• proteins
• usually enzymes
• destroy cellular structures
• destroy extracellular matrix
•Can be produced by either Gram (+) or Gram
(-) organisms
Endotoxin
• Lipopolysaccharide - endotoxin
• peptidoglycan -endotoxin-like action
• cell envelope components
• not proteins/enzymes
• Gram negative LPS cell wall components (Lipid A and Core
Sugars)
3. chlamydiae, Rickettsia and mycoplasma.
• Similar to bacteria but lack certain structures ( a cell wall in
mycoplasma)or metabolic capabilities (ATP synthesis in
chlamydia).
• Chlamydia cause genitourinary infection, conjunctivitis and
RT infection in newborn.
• Rickettsia transmitted by insect vectors and cause
hemorrhagic vasculitis, Q-fever, or encephalitis.
• Mycoplasma bind to surface epithelial cells and cause
atypical pneumonia or nongonococcal urethritis.
4. Fungi
• Have thick, chitin containing cell wall and grow in humans as
budding yeast cell and slender tube (hyphae).
• In healthy person fungi produce; superficial infection
(athletes foot caused by tinea), abscess (sporotrichosis) and
granuloma (Histoplasma).
• In immunocompromised hosts, opportunistic fungi (candidia
and aspergillus) cause systemic infection characterized by
tissue necrosis, hemorrhage and vascular occlusion.
With a PAS stain, the budding cells and pseudohyphae (short filaments that are
not true hyphae) of Candida stain bright red.
2nd Year Pathology 2010
5. protozoa.
• Single cell with nucleus, a pliable plasma membrane and
complex cytoplasmic organelles.
• Trichomonas vaginalis is transmitted sexually.
• Intestinal protozoa (Entameba histolytica and giardia) are
infective when swallowed.
• Blood born protozoa (leishmanial species) are transmitted by
blood-sucking insects.
Protozoal Infections
• Protozoa cause human disease by diverse mechanisms. Some, such as
Entamoeba histolytica, are extracellular parasites capable of digesting
and invading human tissues.
• Others, such as plasmodia, are obligate intracellular parasites that
replicate in, and kill, human cells. Still others, such as trypanosomes,
damage human tissue largely by eliciting inflammatory and
immunologic responses. Some protozoa (e.g., Toxoplasma gondii) can
establish latent infections and cause reactivation disease in
immunocompromised hosts.
6. Prions
• Composed of modified host protein.
• They are not virus because they lack RNA or DNA.
• Cause spongiform encephalopathies.
• Associated with neurodegenerative disease, including fatal familial
insomnia.
How microorganism cause disease ?
• Infectious agents damage tissue by entering cells, releasing
toxins or damaging blood vessels.
• Microbes induce host cellular responses that cause
additional tissue damage including suppuration, scarring,
hypersensitivity reaction.
Viruses injury to host tissue
A. Viruses enter host cell by.
1. Binding to host cell surface protein (e.g. HIV to CD4 cells).
2. Translocation into cytosol from plasma membrane or
endosomal membrane.
3. Replication via virus specific enzyme.
B. Viral infection can be abortive, latent ( e.g-varicella zoster
virus) and or persistent (HBV).
C. Virus kill host cells by
1. Inhibiting host cell DNA, RNA or protein synthesis(polio
virus).
2. Damaging the plasma membrane.
3. Lysing cells ( influenza virus).
Inducing a host immune response to virus infected cells (HBV).
Bacterial injury to host cells
A. Bacterial injury depend on ability to deliver toxins ( vibrio cholera )or
to adhere to host cells and enter them (listeria monocytogens).
B. Bacterial adhesins include filamentous pilli (Escherichia coli and
Neisseria gonorrhea) that determine to which host cells the microbe
will attaches (bacterial tropism).
C. Bacterial endotoxins is a lipopolysaccharide that induce fever via host
lymphokines, including TNF and IL-1.
D. Bacterial exotoxins are composed of binding part and a catalytic
part, and inactivate host protein or degrades it (botulim toxins).
E. Bacteria may reproduce within the phagolysosome (Mycobacterrium)
or cytosol (Shigella)
Immune evasion (avoid)by Microbes
1. Remaining inaccessible within the lumen of small intestine
(toxin –producing Clostridium difficile) or rapidly entering
host cells(malaria in to liver).
2. Producing a capsule that cover the antigens and preventing
phagocytosis (streptococcus pneumoniae).
3. Changing their surface antigens(rhino virus).
4. Infecting lymphocytes(HIV and EBV) and damaging host
immune system.
Spectrum of inflammatory response to
infection.
1. Suppurative inflammation-mostly extracellular gram positive cocci and gram
negative rods-haemophilus influenza.
2. Mononuclear inflammation.
3. Cytopathic-Cytoproliferative inflammation: virus mediated damage to
individual host cells in the absence of host inflammatory response-it may
show inclusion bodies (CMV), polykaryones (measles), Blisters (herpes),
warty changes (HPV).
4. Necrotizing inflammation-caused by uncontrolled viral infection-sever
tissue necrosis in absence of inflammatory infiltrate as in bacterial toxins
(Clostridium difficile)
Actinomycosis
• Actinomycosis is a slowly progressive, suppurative, fibrosing
infection involving the jaw, thorax, or abdomen.
• The disease is caused by a number of anaerobic and
microaerophilic bacteria termed Actinomyces, and the most
common is Actinomyces israelii.
• These organisms are branching, filamentous, gram-positive
rods that normally reside in the oropharynx, gastrointestinal
tract, and vagina without producing disease.
• Pathogenesis and Pathology: Actino-myces can cause disease only if
inoculated into anaerobic deep tissues. Trauma can produce tissue
necrosis, providing an excellent anaerobic medium for growth of
Actinomyces and can inoculate the organism into normally sterile tissue.
• Actinomycosis occurs at four distinct sites:
1. Cervicofacial actinomycosis results from jaw injury, dental extraction,
or dental manipulation.
2. Thoracic actinomycosis: aspiration of organisms contaminating dental
debris.
3. Abdominal actinomycosis traumatic or surgical disruption of the bowel,
especially the appendix.
4. Pelvic actinomycosis is associated with the prolonged use of
intrauterine devices
• Actinomycosis begins as a nidus of proliferating organisms that
attract an acute inflammatory infiltrate.
• The small abscess grows slowly, becoming a series of abscesses
connected by sinus tracts that burrow across normal tissue
boundaries and into adjacent organs.
• Eventually, a tract may penetrate onto an external surface or
mucosal membrane, producing a draining sinus.
• Within the abscesses and sinuses are pus and colonies of
organisms that appear as hard, yellow grains, known as sulfur
granules, because of their resemblance to elemental sulfur.
• Histologically, the colonies appear as rounded, basophilic grains
with scalloped eosinophilic borders.
Syphilis
• Syphilis is a chronic systemic infection that is transmitted almost exclusively
by sexual contact or from an infected mother to her fetus (congenital
syphilis).
• Infection is caused by Treponema pallidum, a thin, long spirochete.
• Pathogenesis and Pathology: Person-to-person transmission requires direct
contact between a rich source of spirochetes (e.g., an open lesion) and
mucous membranes or abraded skin of the genital organs, rectum, mouth,
fingers, or nipples.
• The organisms reproduce at the site of inoculation, pass to regional lymph
nodes, gain access to systemic circulation, and disseminate throughout the
body.
• Although T. pallidum induces an inflammatory response and is taken up
by phagocytic cells, it persists and proliferates.
• Chronic infection and inflammation cause tissue destruction, sometimes
for decades.
• The course of syphilis is classically divided into three stages.
1. Primary Syphilis is Characterized by the Chancre: ulcer at the site of T.
pallidum entry. It appears 1 week to 3 months after exposure and
tends to be solitary.
• Spirochetes tend to concentrate in vessel walls and in the epidermis
around the ulcer. The vessels display a characteristic vasculitis, in which
endothelial cells proliferate and swell, and vessel walls become
thickened by lymphocytes and fibrous tissue.
• Chancres are painless and heal without scarring.
2. Secondary Syphilis Features the Systemic Spread of the Organism
• In secondary syphilis, T. pallidum spreads systemically and proliferates
to cause lesions in the skin, mucous membranes, lymph nodes,
meninges, stomach, and liver.
• Lesions show perivascular lymphocytic infiltration and endarteritis
obliterans. The most common presentation of secondary syphilis is an
erythematous and maculopapular rash, involving the trunk and
extremities and often includes the palms and soles.
• The rash appears 2 weeks to 3 months after the chancre heals.
Lesions on mucosal surfaces of the mouth and genital organs, called
mucous patches, teem with organisms and are highly infectious.
3. The Gumma is the Hallmark Lesion of Tertiary Syphilis
• Following secondary syphilis, an asymptomatic period lasts for years.
However, spirochetes continue to multiply, and the deep-seated lesions of
tertiary syphilis gradually develop in one third of untreated patients.
• The appearance of a gumma in any organ or tissue is the hallmark of tertiary
syphilis.
• Gummas are most commonly found in the skin, bone, and joints, although
they can occur anywhere.
• These granulomatous lesions are composed of a central area of coagulative
necrosis, epithelioid macrophages, occasional giant cells, and peripheral
fibrous tissue.
• Gummas are usually localized lesions and generally do not contribute to the
disease process.
• Rather, the underlying mechanism for much of the damage associated
with tertiary syphilis is focal ischemic necrosis secondary to obliterative
endarteritis.
• T. pallidum induces a mononuclear inflammatory infiltrate composed
predominantly of lymphocytes and plasma cells. These cells infiltrate
small arteries and arterioles, producing a characteristic obstructive
vascular lesion (endarteritis obliterans).
Tuberculosis
• Tuberculosis is a chronic, communicable disease in which the
lungs are the prime target, although any organ may be
infected.
• The disease is mainly caused by M. tuberculosis hominis
(Koch bacillus) but also occasionally by M. tuberculosis bovis.
• The characteristic lesion is a spherical granuloma with
central caseous necrosis. M. tuberculosis is an obligate
aerobe, a slender, beaded, nonmotile, acid-fast bacillus.
• Tuberculosis is one of the most important human bacterial
diseases.
• M. tuberculosis is transmitted from person to person by aerosolized
droplets.
• Coughing, sneezing, and talking all create aerosolized respiratory
droplets; usually, droplets evaporate, leaving an organism (droplet
nucleus) that is readily carried in the air.
• Pathogenesis:
• The course of tuberculosis depends on age and immune competence,
as well as the total burden of organisms. Some patients have only an
indolent, asymptomatic infection, whereas in others, tuberculosis is a
destructive, disseminated disease.
• Many more persons are infected with M. tuberculosis than develop
clinical symptoms. Thus, one must distinguish between infection and
active tuberculosis.
• Tuberculous infection refers to growth of the organism in a person,
whether there is symptomatic disease or not.
• Active tuberculosis denotes the subset of tuberculous infections
manifested by destructive and symptomatic disease.
• Primary tuberculosis occurs on first exposure to the organism and can
pursue either an indolent or aggressive course .
• Secondary tuberculosis develops long after a primary infection,
mostly as a result of reactivation of a primary infection. Secondary
tuberculosis can also be produced by exposure to exogenous
organisms and is always an active disease.
This is an acid fast stain of Mycobacterium tuberculosis (MTB). Note the
red rods--hence the terminology for MTB in histologic sections or smears:
acid fast bacilli.
Giardia lamblia





Most prevalent pathogenic intestinal protozoan worldwide.
Infection may be subclinical or may cause acute or chronic
diarrhoea.
Not killed by chlorine.
Reside in duodenum.
Adhere to but do not invade intestinal epithelial cells.
Diagnosis of infectious diseases


Epidemiological dates
Clinical features
Symptoms and signs

Laboratory findings
Routine examination of blood, urine, feces
Bio-chemical examinations
Etiological examinations
Direct exam
Isolation of pathogen
Molecular biological examinations
Immunological examinations
Endoscope examinations
Image examinations
Treatment of infectious disease

General and supporting therapy
Isolation of patients, rest, diet, nursing



Pathogen or specific therapy
Symptomatic therapy
Rehabilitation
Physiotherapy acupuncture

Chinese herbs or tradition medicine
Prevention of infectious disease


Management of source of infection
Cut off of route
Personal hygiene, public hygiene, insecticide, disinfection

Protect susceptible population
Active immunization
Passive immunization