GENERAL PATHOLOGY OF

INFECTIOUS DISEASES
Al Munawir

Department of Pathology
Medical College
Jember University
2014

INFECTIOUS DISEASES

Are disorders in which tissue damage or

disfunction is produced by a
microorganism

Contagious (person to person)

Non contagious acquired from sources
such as animals, insects, soil, air or
originating from endogenous microbial
flora of the body

FACTORS THAT INFLUENCE THE

DEVELOPMENT OF DISEASE
VIRULENCE
HOST DEFENSE MECHANISMS
HOST FACTORS IN INFECTION

HERITABLE DIFFERENCES IN RESPONSE

TO INFECTING AGENTS
EFFECTS OF AGE ON RESPONSE TO
INFECTION
EFFECTS OF BEHAVIOR ON INFECTION
EFFECTS OF COMPROMISED HOST
DEFENSES ON INFECTION

VIRULENCE
IS THE CAPACITY OF AN ORGANISM
TO ACHIEVE INFECTION
THE ORGANISM MUST:

GAIN ACCESS TO THE BODY

AVOID MULTIPLE HOST DEFENSES
ACCOMODATE TO GROWTH IN THE
HUMAN ENVIRONMENT
PARASITIZE HUMAN RESOURCES

HOST DEFENSE MECHANISMS

SKIN
TEARS
NORMAL BACTERIAL FLORA
GASTRIC ACID
BILE
SALIVARY AND PANCREATIC SECRETIONS
FILTRATION SYSTEM OF NASOPHARYNX
MUCOCILIARY BLANKET
BRONCHIAL, CERVICAL, URETHRAL AND
PROSTATIC SECRETIONS
IMMUNE SYSTEM (neutrophils, monocytes,
complement, stationary mononuclear phagocyte system,
immunoglobulins, cell mediated immunity)

HOST FACTORS IN INFECTION

An infectious agent may
3.
4.

5.
6.

FAIL TO INFECT SOME PERSONS

PRODUCE ASYMPTOMATIC
INFECTIONS IN OTHERS
CAUSE MODEST SYMPTOMATIC
DISEASE IN SOME
PRODUCE LETHAL INFECTION

Heritable differences in response to infecting

agents

1.step in infection is often specific interaction of a binding

molecule on the infecting organism with a receptor
molecule on the host

IF THE HOST LACKS THE RECEPTOR MOLECULE,

THE ATTACHEMENT OF THE ORGANISM TO THE
TARGET CANNOT OCCUR

The containment or elimination of an infecting organism

also depends on specific molecular interactions between
the host and the organism

Effect of age on response to infection

The age of the host affects the outcome of exposure to

many infectious agents
Some organisms produce more severe disease in utero
than in children or adults (CMV, Rubella, human
parvovirus B19)
The course of common illnesses (viral or bacterial
diarrheas) in small children and infants - fluid loss
Tuberculosis in children < 3 y more severe,
disseminated (immaturity of cell mediated immune
system)
Older individuals symptomatic infection with EBV, or
varicella-zoster virus (viral pneumonia)
The elderly fare more poorly with almost all infections
(common respiratory illnesses are more often fatal in
persons ovver 65 y)

Effect of behavior on infection

STDs syphilis, gonorrhea, urogenital, chlamydial

infections, AIDS etc

Contact with farm animals (farmers, herders, meat

processors, drinking unpasteurized milk) brucellosis, Q
fever

Eating habits incompletely cooked meat

(toxoplasmosis)

Hygienic habits dirty hands diseases

Effect of compromised host defenses on infection

The state of host defense mechanisms affects the

susceptibility and response to infection
A disruption or absence of any of the complex host
defenses results in increased numbers and severity of
infections

Disruption of skin surface by trauma or burns

Injury to the mucociliary apparatus of the airways (smokers)

The use of cytotoxic and immunosupressive drugs

Congenital immunodeficiencies
AIDS epidemic
OPPORTUNISTIC PATHOGENS (most of them are part
of the normal endogenous human or environmental flora)

HOW INFECTIOUS AGENTS CAUSE

DISEASE

They can contact or enter host cells and directly

cause cell death
They can release

endotoxins or exotoxins that kill cells at a distance

enzymes that degrade tissue components or damage
blood vessels causing ischemic injury

They can induce host cell responses that may

causse additional tissue damage, usually by
immune mediated mechanisms

VIRUS INDUCED INJURY - viruses damage

host cells by entering them and replicating at
hosts expense

They have surface viral

proteins (ligands) that bind
to particular host proteins
(receptors)
The presence or absence
of host cell proteins that
allow the virus to attach is
one reason for VIRAL
TROPISM
The other reason is the
ability of the virus to
replicate inside some cells
but not in others

ONCE attached, the entire virion, or a portion

containing the genome and essential polymerases
penetrates the cell cytoplasm by

TRANSLOCATION OF
THE ENTIRE VIRUS
ACROSS THE PLASMA
MEMBRANE
FUSION OF THE VIRAL
ENVELOPE WITH THE
CELL MEMBRANE
RECEPTOR MEDIATED
ENDOCYTOSIS AND
FUSION WITH
ENDOSOMAL
MEMBRANES

WITHIN THE CELL

The virus uncoats,

separating its genome
from structural
components and
losing its infectivity
Viruses then replicate
using enzymes that
are distinct for each
virus family

VIRUSES KILL HOST CELLS AND CAUSE

TISSUE DAMAGE
By inhibiting host cell DNA, RNA or protein
synthesis - poliovirus
Viral proteins may insert into the hosts
plasma membrane and directly damage
its integrity or promote cell fusion HIV,
measels, herpesviruses
Viruses replicate efficiently and lyse host
cells (rhinovirus, influenzavirus
multiplication, yellow fever, polio or rabies)

Viral proteins on the surface of the host cells

may be recognized by the immune system and
host lymphocytes may attack the infected cells
HBV, respiratory syncytial virus
Viruses may damage cells involved in host
antimicrobial defense, leading to SECONDARY
INFECTION pneumonia, opportunistic
infections
Viral killing of one type of cells may cause
damage to other cells that depend upon their
integrity (polio-denervation of motor neuronsatrophy or necrosis of distal skeletal muscle
cells)

Slow viral infections (subacute sclerosing

panencephalitis caused by measles virus)
culminate in severe progressive disease
after a long latency period)
Some of them (EBV,HPV, HBV, HTLV-1)
can cause cell proliferation and neoplastic
transformation

BACTERIA INDUCED INJURY

Damage

to host cells depends on the

ability of bacteria to adhere to and
enter host cells or to deliver toxins

BACTERIAL ADHESINS molecules that

bind bacteria to host cells limited in type
but with a broad range of host cell specificity

BACTERIAL ENDOTOXIN
A lypopolysacharide - a structural
component of the outer cell wall of gram
negative bacteria
LPS - a long chain fatty acid anchor lipid
A, connected to a core sugar chain THE
SAME IN ALL GRAM NEGATIVE
BACTERIA
Attached to the core sugar is a variable
carbohydrate chain (O antigen) which is
ussed as a serotype and distinguishes
different bacteria

BACTERIAL ENDOTOXIN

Biologic activities COME FROM LIPID A

AND CORE SUGARS
Induction of fever
Septic shock
Disseminated intravascular coagulation (DIC)
Acute respiratory distress syndrome (ARDS)
Effects on the cells of the immune system

They are mediated by

Direct effect of endotoxin
Induc
ction of host cytokines (IL-1, TNF etc.)

BACTERIAL EXOTOXINS

Are secreted proteins that directly cause

cell injury and determine disease
manifestations
Bacillus anthracis
Diphteria toxin
Vibrio cholerae
E. coli
Clostridium perfringens
Clos
stridium tetani
Clos
stridium botulinum

INFLAMMATORY RESPONSE TO
INFECTIOUS AGENTS
The morphological patterns of
inflammatory response to infectious
agents are limited
At the microscopic level, many pathogens
evoke identical reaction patterns
Few of the features are unique or
pathognomonic of each agent

THERE ARE 5 MAIN HISTOLOGIC

PATTERNS OF TISSUE REACTION
1. SUPPURATIVE
POLYMORPHONUCLEAR
INFLAMMATION
2. MONONUCLEAR INFLAMMATION
3. CYTOPATHIC-CYTOPROLIFERATIVE
INFLAMMATION
4. NECROTIZING INFLAMMATION
5. CHRONIC INFLAMMATION AND
SCARRING

SUPPURATIVE POLYMORPHONUCLEAR
INFLAMMATION

SUPPURATIVE POLYMORPHONUCLEAR
INFLAMMATION

MONONUCLEAR INFLAMMATION

MONONUCLEAR INFLAMMATION

CYTOPATHIC-CYTOPROLIFERATIVE
INFLAMMATION

CYTOPATHIC-CYTOPROLIFERATIVE
INFLAMMATION

NECROTIZING INFLAMMATION

CHRONIC INFLAMMATION AND

SCARRING

IMMUNE EVASION BY
MICROBES
By remaining inaccessible
By cleaving antibody, resisting
complement mediated lysis or surviving in
phagocytic cells
By varying or shedding antigens
By causing specific or nonspecific
immunosupression

By remaining inaccessible

Microbes that propagate in the lumen of the intestine

(Clostridium difficile) or gallbladder (S. typhi)
Viruses shed from the luminal surface of the cells (CMV
in urine or milk, poliovirus in stool)
Viruses that infect keratinized epithelium (poxviruses
molluscum contagiosum)
Because of rapid invasion of host cells before humoral
response becomes effective (malaria sporozoites
entering liver cells; Trichinella entering muscles)
Some larger parasites form cysts with thick fibrous
capsule

By cleaving antibody, resisting complement

mediated lysis or surviving in phagocytic
cells

Carbohydrate capsule on the surface covers bacterial

antigens and prevents phagocytosis by neutrophils

Seccretion of leukotoxins that kill neutrophils

Streptococcus pneumoniae
Neisseria meningitidis
Haemophilus
Klebsiella
E. coli

Pseudomonas

Seccrtetion of proteases that degrade antibodies

Neisseria
Haemophilus
Streptocccocus spp.

By cleaving antibody, resisting complement

mediated lysis or surviving in phagocytic
cells

Some bacteria have antigens that prevent

activation of complement by the alternative
pathway and lysis

Other have very long antigens that bind host

antibody and activate complement at such a
distance that lysis is not possible

K antigen of some E.coli bacteria

Some gram-negative bacteria

Some are covered by antigen that binds Fc

portion of the antibody and inhibit phagocytosis

Staphyloccoci

By varying or shedding antigens

Normally, viral infection evokes

neutralizing antibodies which prevent viral
attachment, penetration or uncoating

This mechanism cannot protect agains

viruses with many antigenic variants
Rhinoviruses
Influenzaviruses

By varying or shedding antigens

Pneumococci are capable of more than 80

permutations of their capsular
polysaccharides in repeated infections
the host will not racognize the new
serotype

Shistossoma mansoni sheds and loses

parasite antigens before they are
recognized by the host immune system

By causing specific or nonspecific

immunosupression

Viruses that infect lymphocytes directly

damage the host immune system
HIV
EBV

Opportunistic infections develop