General pathology of infectious

diseases
• Infectious diseases still important despite
vaccination/antibiotics
• In developing countries factors responsible for
high incidence
1. unsanitary living condition
2. malnutrition
- respiratory and diarrheal infections predominate
 Host-organism interaction
Commensals “microorganisms live on expense of host
without doing harm”
1. Bacteria living on skin
2. Vit. K producing intestinal bacteria flora

Pathogens “microorganisms that injure host”

- viruses - fungi
- bacteria - protozoa

Pathogenicity “capacity of particular microorganism to cause

disease”.

Virulence “degree of pathogenicity”

 Commonsals Pathogens
1. Immunosuppresion (opportunistic infections).
2. Site alterations
- E. coli in the urinary tract severe
urinary
infection.
- Streptococcus viridans in blood
(bacteremia)
diseased heart valves

bacterial endocarditis
Infection
- presence of microorganism in a part where it
is normally absent
- stimulates host response
- causes disease (infectious)

Outcome depends on balance between

microorganism aggressiveness Vs defense of host.
 Nonspecific defenses

I. Mechanical barriers
- Skin
- Mucous layer
II. Glandular and currents secretions
- Sweat
- Gastric juice
- Lysozyme enzyme
- Secretory IgA antibodies
- Tears
- Ciliated respiratory epithelial cells
- Diarrhea (in away a defensive mechanism)
- Urine
III. Phagocytosis
- Neutrophils
- Macrophages
 Opportunistic infections
• Seen in immunocompromised patients.

1. Rotavirus infantile diarrhea.

2. Hepatitis B, C and E virus viral hepatitis

3. Pneumocystis carinii respiratory infection

 Categories of infectious agents
• Infectious Organisms size
20nm 10 meters
• Prions
- modified host proteins
- cause spongiform encephalopathies: Kuru, CJD
cattle

Prion-associated bovine spongiform

encephalopathy (mad cow disease).

- not viruses (no RNA or DNA)

- protease-resistant
- combine with normal host proteins on surface of neurons

conformational change.
Prion-host protein complexes
internalized in neuron
cell damage

spongiform encephalopathy.

vacuolation of the neuron/glial tissue + amyloid

plaques.
Clinical features
- dementia
- disturbed gait
- abnormal movement
• rapidly fatal disease
• Infection through eating infected meat with prions.
Taxonomic class Sample species Related disease
1. Viruses Poliovirus Poliomyelitis
2. Chlamydiae Chlamydia trachomatis Trachoma

3. Rickettsiae Rickettsia prawazeki- Typhus fever

4. Mycoplasma Mycoplasma pneumoniae Atypical pneumonia

1.Bacteria, Staph. epidermidis Wound infection

Mycobacteria Vibrio cholerae Cholera
Strept.pneumoniae Pneumonia
Mycobacterium Tuberculosis
tuberculosis

6. Fungi Tricophyton spp. Tinea pedis

Candida albicans (Athlete’s foot)
Sporothrix schenkii Thrush
Histoplasma capsulatum Sporotrichosis
Histoplasmosis

7. Protozoa Giardia lamblia Giardiasis

Tryponosoma gambrense Sleeping sickness
Tryponosoma cruzi Chaga’s disease
Leishmania donovani Kala azar

8. Helminthes Enterobius vermicularis Enterobiasis

(pin worms)
 Routes of entry-dissemination-release
Spread of microbes
Rapid
- wet epithelial surfaces (mucosal surfaces)
Slow
- dry surface (skin)
Release of microbes from the body (transmission
of infections)
Many mechanisms including
- skin shedding - coughing/sneezing
- urination - defecation.
 Pathogenesis
How infectious agents cause disease ?

Infectious agents injure cells & cause tissue

damage by three general mechanisms:
1. Direct injury/damage/necrosis
2. Release of endotoxin/exotoxin/enzymes
3. Induction of host cell responses usually
immunological .
 Mechanism of virus-induced injury
Entry in to cell
Ligands (specific viral proteins) receptors (specific host
proteins)
HIV binds to CD4 (T-helper lymphocytes).

Viral tropism “tendency of virus to infect specific cells”

- Influenza virus infect respiratory epithelial cells.
Viruses damage host cells
Replication at host’s expense
- attachment
- penetration
- uncoating
- replication
- viral assembly (nuclear/cytoplasmic)
- release
 Viral induced cell damage
1. Inhibiting synthesis of DNA/RNA/protein (Poliovirus)
2. Virus protein insertion into the host cell’s plasma
membrane
- damage integrity
- promote cell fusion (HIV, measles, herpes virus).
3. Virus replication lysis host cells
(rhinovirus/influenza virus respiratory epithelial
cells)
(poliovirus lysis of neurons).
4. Immune mediated damage: immune system lymphocytes
recognize virus protein on surface of host cells
Attack virus-infected cells
(HBV causing acute liver failure).
5. Damaging defense mechanisms secondary infection
(damage to respiratory epithelium with subsequent bacteria
pneumonia).
(HIV depletes CD4+ lymphocytes leading to secondary
opportunistic infections: pneumocystis carinii pneumonia).

6. Indirect damage
(Poliovirus kills neurons leading to muscular atrophy)

7. Causing cancer through cell proliferation & transformation

(HBV may lead to liver cancer).
 Mechanisms of bacterial induced injury
• Bacterial damage to host tissue depends on their
ability to
1. Adhere/enter host cells
2. Deliver toxins

• Steps are
1. Adherence is through adhesins
2. Inhibition of protein synthesis
3. Multiplication of bacteria with lysis of host cells.
 Bacterial toxins
1. Endotoxins
2. Exotoxins
Endotoxins
- lipopolysaccharides
- structural components of outer cell wall of gram
negative bacteria.
- E. coli
- Salmonella typhi
Biological activities of endotoxins include
1. Induction of fever
2. Septic shock
3. Acute respiratory distress syndrome
 Exotoxins
• secreted proteins
• directly cause cellular injury
• determine disease manifestations.
Examples include
1. Diphtheria toxin
- secreted by Corynebacterium diphtheria
- causes neural & myocardial dysfunction.
2. Tetanospasmin
- secreted by Clostridium tetani
- causes violent muscular contraction (tetanus)
 Immune evasion by microbes
• A mechanism on the part of infectious agents to
escape humoral & cellular immune responses by
1. Remaining inaccessible
2. Cleaving antibody
3. Resisting complement-mediated lysis
4. surviving in phagocytic cells
3. Varying or shedding antigens
4. Causing immunosuppression
 Special techniques in diagnosing
infectious agents
• Some microorganism can be seen in H&E-stained
sections such as
- bacterial clumps,
- inclusion bodies caused by herpes virus,
- candida
- most protozoa e.g. Entameba & all helminthes.

• Many microorganisms can only be seen after the

application of special techniques or stains.
Technique Agent(s) detected

1. Gram stain Most bacteria

2. Acid fast stain Mycobacteria

3. Sliver stain Fungi, legionella, pneumocystis

4. Periodic acid-schiff (PAS) Fungi, amebae

5. Mucicarmine stain Cryptococci

6. Giemsa stain Campylobacter, malaria

7. Antibody probes Viruses, rickettsiae

8. Culture All classes

9. DNA probes Viruses, bacteria, protozoa

Selected Human Infectious
diseases
 Rhinoviruses and influenza viruses
• The most important & best studied.
• Rhinoviruses
- responsible for common cold
- are RNA viruses
- attach to respiratory epithelial cells
- induce acute inflammation with excessive mucus secretion
- has >100 serotypes
- escape antibody.

Influenza virus
- RNA virus
- three types A, B & C. It
- caused pandemic of 1918: all people susceptible to the new
influenza virus (contigenic shift).
 Morphological features and complications
• In essence an upper respiratory tract infection
- mucosal hyperemia + swelling (rhinitis)
- may be complicated by
-sinusitis
- otitismedia
- pharyngitis
- tonsillitis
- laryngo-tracheo-bronchitis
- bronchiolitis and
- streptococcal pneumonia.
 Bacterial Respiratory Infections
Bacterial pneumonia

- the most important infectious disease

- immediate cause of death in hospitalized patient
 Hemophilus influenzae infection
Hemophilus influenzae
- gram negative organism
- it is the major cause of
- acute lower respiratory tract infections
- suppurative meningitis in children up to 5 years of age.
Spectrum of diseases
Upper RTI
- pharyngitis
- otitis media
- sinusitis
- laryngitis: vocal cords swell rapidly leading to suffocation

H. Influenzae pneumonia
- following viral RTI
- has a high mortality rate
Laryngeo-tracheo-bronchitis
- leads to airway obstruction (plugging by dense, fibrin-rich exudate)
 Tuberculosis
• Caused by mycobacterium tuberculosis and Mycobacterium
bovis
• infection affects about 1/3 of the world population
• kills about 3 million patients each year.
• transmitted by inhalation
• M. bovis transmitted through milk of diseased cows.
• M. avium and M. intracellulare cause infection in AIDS
patients
• M. leprae cause Leprosy
• Mycobacteria
- aerobic bacilli
- have waxy coat: retain red dye when treated with acid
(AFB)
- grow very slowly in culture (4-6 weeks).
 Pathogenesis

•The pathogenesis of destruction & caseous necrosis

Mycobacterium tuberculosis
- no known exotoxin, endotoxin or histolytic enzymes
- escapes killing by being inside macrophages
- induce delayed hypersensitivity
- stimulates macrophages to secrete TNF-ά
- causes fever & tissue damage.
•Hypersensitivity reaction type IV (cell mediated) explains tissue
destruction in tissue .
On initial exposure to the microorganisms
- nonspecific inflammatory response
- 2-3 weeks later reaction becomes granulomatous
- Center of granuloma becomes caseous (typical
tubercle)

Pattern of host response depends on whether

infection represents 1st (primary) or 2nd exposure or
(secondary in already sensitized host
 Primary tuberculosis
• Begins with inhalation of mycobecteria to periphery of the lung
• Followed by phagocytosis by alveolar macrophages
• Bacilli multiply and lyse host cells
• Bacilli infect other macrophages that transport bacilli to hilar
lymph nodes.
• T- cell mediated immunity develops
• CD4 + (helper) secrete interferon gamma, which activate
macrophages to kill the bacilli + granuloma formation.
• CD8+ (suppressor) T cells kill infected macrophages resulting in
caseation
• Control of 95% of the infection
• Calcified scar in lung parenchyma and hilar lymph nodes (Ghon
complex)
 Secondary & disseminated TB
• Occurs when
- reinfection
- reactivation of primary infection
• Progression occurs from lesion into disseminated disease because of
- high virulence of bacilli
- patient is particularly susceptible
• Granulomas in secondary T.B. occur at apex of lung
• Disseminated granulomas occur in
- lungs - bone marrow
- kidneys - other organs
-meninges
• Caseous necrosis may be followed by cavitation with rupture into
blood vessels spreading of Mycobacteria throughout the body
and into airways.
Miliary tuberculosis: hematogenous dissemination of
tuberculous lesion through out body .

Diagnosis: examination of the sputum for AFB or culture

Treatment: combination therapy

 Leprosy (Hansen’s disease)
• Caused by Mycobacterium leprae.
• Affects skin & peripheral nerves
• Transmission by aerosols from lesions in the upper respiratory tract.

taken up by alveolar macrophages

blood

cool skin & tissues.

• organism
- secretes no toxin
- acid fast-bacillus.

• Cell mediated immunity recognizes protein specific to M. leprae

• Immunization by BCG confers 50% protection

 Host response
T-cell immunity Tuberculoid
leprosy

Anergy (lacking T-cell immunity) Lepromatous

leprosy

Intermediate state i.e. between 1 & 2.

 Morphology
Tuberculoid leprosy
Localized skin lesions: flat/ red lesions enlarge become
irregular in shape
- Indurated, elevated hyperpigmented margins
- Depressed pale centers
Nerves are enclosed within granulomatous reactions
- small nerves destroyed skin anesthesia atrophy.
traumas
ulcerations-contracture-autoamputation of fingers/toes.
facial nerve leads to
paralysis of lids-keratitis-corneal-ulceration.
Tuberculoid leprosy
Tuberculoid leprosy
Nerve thickening
 Microscopy

Granulomatous lesions

- epithelioid macrophages,

- giant cells and

- few surviving bacilli

- T lymphocytes of CD4 & CD8 types. []

Tuberculoid leprosy
 Lepromatous leprosy
• This involves
- skin, - upper airway passages
- peripheral nerves - testes
- anterior eye - hands & feet

• Vital organs & CNS rarely affected

• Skin lesions
- macular/papular/nodular
- seen on face/ear, wrist/elbow & knees.
- hypo-esthetic or anesthetic
• Progression & coalescence of facial lesions leonine facies
• Peripheral nerves
- symmetrically involved loss of sensation &
trophic changes in hands/feet.
Lepromatous leprosy face
Leprosy loss of sensation
 Microscopic features of lepromatous
leprosy
• Large number of macrophages laden with AFB
(Lepra cells). [] []

• Similar lesions are also found in lymph nodes & in

advanced cases liver & spleen.

• Testes involved with destruction of seminiferous

tubules sterility
Lepromatous leprosy mic
Lepra bacilli modified ZN stain
Lepromin test
“delayed type hypersensitivity reactions to dermal
injection of bacterial extract called lepromin”

Erythema nodosum leprosum

- life threatening vasculitis & glomeruloniphritis
- resulting from antigen/antibody complexes
- Antibody is not protective
- seen in lepromatous leprosy
Erythema nodosum