Pathology of Infectious

7/23/2019 Pathology of Infectious

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GENERAL PATHOLOGY OF

INFECTIOUS

DISEASES Al Munawir

Department of PathologyMedical CollegeJember University

2014



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

TEARSNORMAL BACTERIAL FLORA

GASTRIC ACID

BILE

SALIVARY

AND

PANCREATIC

SECRETIONS

FILTRATION SYSTEM OF NASOPHARYNX

MUCOCILIARY

BLANKET

BRONCHIAL,

CERVICAL,

URETHRAL

AND

PROSTATIC

SECRETIONSIMMUNE

SYSTEM

(neutrophils,

monocytes,

complement, stationary mononuclear phagocyte system, immunoglobulins, cell mediated immunity)



HOST

FACTORS

IN

INFECTION

An

infectious

agent

may

3. FAIL TO INFECT SOME PERSONS

4. PRODUCE

ASYMPTOMATIC

INFECTIONS IN OTHERS

5. CAUSE MODEST SYMPTOMATIC

DISEASE

IN

SOME6. 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

agentsSome 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

ccaausse

additional

tissue

damage,

usually

by

immune mediated mechanisms



VIRUS INDUCED INJURY - viruses damage

host cells by entering them and replicating at

host’s 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 host’s

plasma

membrane

and

directly

damage

it’s 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

neurons-

atrophy or necrosis of distal skeletal muscle

cceells)



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 sserotype 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

Induccttion 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.

ccooli Clostridium

perfringens

Clossttridium

tetani

Clossttridium

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

INFLAMMATION3. CYTOPATHIC-CYTOPROLIFERATIVE

INFLAMMATION

4. NECROTIZING

INFLAMMATION5. CHRONIC INFLAMMATION AND

SCARRING



SUPPURATIVE POLYMORPHONUCLEAR

INFLAMMATION



MONONUCLEAR 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

B l i tib d i ti l t



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

Streptococcus

pneumoniae

Neisseria

meningitidis

Haemophilus

KlebsiellaE. coli

Seccr r etion of leukotoxins that kill neutrophils Pseudomonas

Seccr r tetion of proteases that degrade antibodies

Neisseria

Haemophilus

Streptoccccocus

spp.

B l i tib d i ti l t



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

K

antigen

of

some

E.coli

bacteria Other

have

very

long

antigens

that

bind

host

antibody

and

activate

complement

at

such

a

distance

that

lysis

is

not

possible

Some

gram-negative

bacteria Some

are

covered

by

antigen

that

binds

Fc

portion

of

the

antibody

and

inhibit

phagocytosis Staphyloccoci




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




Pneumococci

are

capable

of

more

than

80

permutations of their capsular

polysaccharides – in repeated infections

the

host

will

not

racognize

the

new

serotype

Shistossooma

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

Pathology of Infectious

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