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Infection and Immunity

What does a pathogen have to do?

 Infect (infest) a host

 Reproduce (replicate) itself
 Ensure that its progeny are transmitted to
another host
Viruses may be transmitted in the
following ways
 Direct transmission from person to person by
The major means of transmission may be
by droplet or aerosol infection (e.g., influenza,
measles, smallpox); by the fecal-oral route (e.g.,
enteroviruses, rotaviruses, infectious hepatitis
A); by sexual contact (e.g., hepatitis B, herpes
simplex virus type 2, human immunodeficiency
virus); by hand-mouth, hand-eye, or mouth-
mouth contact (e.g., herpes simplex, rhinovirus,
Epstein-Barr virus); or by exchange of
contaminated blood (e.g., hepatitis B, human
immunodeficiency virus).
Transmission from animal to animal,
with humans an accidental host.

Spread may be by bite (rabies) or by

droplet or aerosol infection from rodent-
contaminated quarters (e.g., arenaviruses,
Transmission by means of an
arthropod vector

e.g., arboviruses, now classified

primarily as togaviruses, flaviviruses, and
Entry into the Host
 Skin - dead cells, therefore cannot support virus replication.
Most viruses which infect via the skin require a breach in
the physical integrity of this effective barrier, e.g. cuts or
abrasions. Many viruses employ vectors, e.g. ticks,
mosquitos or vampire bats to breach the barrier.
 Respiratory tract - In contrast to skin, the respiratory tract
and all other mucosal surfaces possess sophisticated
immune defence mechanisms, as well as non-specific
inhibitory mechanisms (cilliated epithelium, mucus
secretion, lower temperature) which viruses must overcome.
Entry into the Host
 Gastrointestinal tract - a hostile environment; gastric
acid, bile salts, etc
 Genitourinary tract - relatively less hostile than the
above, but less frequently exposed to extraneous
viruses (?)
 Conjunctiva - an exposed site and relatively
Sites of virus entry
Transmission patterns
 Horizontal Transmission: Direct person-to-person
 Vertical Transmission: Relies on PERSISTENCE
of the agent to transfer infection from parents to
offspring. Several forms of vertical transmission can
be distinguished:
 1.Neonatal infection at birth, e.g. gonorrhorea, AIDS.
 2.Infection in utero e.g. syphilis, CMV, Rubella
 3. Germ line infection - via ovum or sperm.
Primary Replication
 Having gained entry to a potential host, the
virus must initiate an infection by entering a
susceptible cell. This frequently determines
whether the infection will remain localized at the
site of entry or spread to become a systemic
Localized Infections
 Viruses Primary Replication

 Rhinoviruses U.R.T.
 Rotaviruses Intestinal epithelium
 Papillomaviruses Epidermis
Systemic Infections
Virus Primary Replication Secondary Replication

Intestinal epithelium Lymphoid
tissues, C.N.S.
Oropharynx or Lymphoid cells,
G.U.tract C.N.S.
Spread Throughout the Host
 Apart from direct cell-cell contact, there are 2 main
mechanisms for spread throughout the host:
 via the bloodstream

 via the nervous system

via the bloodstream
 Virus may get into the bloodstream by direct
inoculation - e.g. Arthropod vectors, blood
transfusion or I.V. drug abuse. The virus may
travel free in the plasma (Togaviruses,
Enteroviruses), or in association with red cells
(Orbiviruses), platelets (HSV), lymphocytes
(EBV, CMV) or monocytes (Lentiviruses).
Primary viraemia usually proceeds and is
necessary for spread to the blood stream,
followed by more generalized, higher titre
secondary viraemia as the virus reaches other
target tissues or replicates directly in blood cells
via the nervous system
 spread to nervous system is preceded by
primary viraemia. In some cases, spread
occurs directly by contact with neurons at the
primary site of infection, in other cases via the
bloodstream. Once in peripheral nerves, the
virus can spread to the CNS by axonal
transport along neurons (classic - HSV).
Viruses can cross synaptic junctions since
these frequently contain virus receptors,
allowing the virus to jump from one cell to
Cell/Tissue Tropism
 Tropism - the ability of a virus to replicate in
particular cells or tissues - is controlled partly by
the route of infection but largely by the interaction
of a virus attachment protein (V.A.P.) with a
specific receptor molecule on the surface of a cell,
and has considerable effect on pathogenesis.
Many V.A.P.'s and virus receptors are now
Secondary Replication
 Occurs in systemic infections when a virus
reaches other tissues in which it is capable of
replication, e.g. Poliovirus (gut epithelium -
neurons in brain & spinal cord) or Lentiviruses
(macrophages - CNS + many other tissues). If a
virus can be prevented from reaching tissues
where secondary replication can occur,
generally no disease results.

Localized Infections:
Virus: Primary Replication:
Rhinoviruses U.R.T.
Rotaviruses Intestinal epithelium
Systemic Infections:
Virus: Primary Replication:
Lymphoid tissues,
Enteroviruses Intestinal epithelium
Oropharynx or
Herpesviruses Lymphoid cells, C.N.S.
Incubation periods of viral infections
Influenza 1-2d Chickenpox 13-17d

Common cold 1-3d Mumps 16-20d

Bronchiolitis,croup 3-5d Rubella 17-20d

Acute respiratory 5-7d Mononucleosis 30-50d

Dengue 5-8d Hepatitis A 15-40d

Herpes simplex 5-8d Hepatitis B 50-150d

Enteroviruses 6-12d Rabies 30-100d

poliomyelitis 5-20d Papilloma 50-150d

Measles 9-12d HIV 1-10y

Types of Infection

 Inapparent infection( Subclinical

infection) .
 Apparent infection:
 Acute infection
 Persistent Infection
Chronic infections
Latent Infection
Slow virus infections
Inapparent or subclinical infections
occur when too few cells are infected to
cause clinical symptoms. But, infections
are major source of contagion and can
result in sufficient antibody stimulation to
cause immunity from further infections.
Acute infections occur when clinical
manifestations of disease are observed for a short
time (days to weeks) after a short incubation period.
Infections have recoveries associated with elimination
of the virus from the body.
The infection is classified as localized or
disseminated, depending on whether the virus has
traveled from its site of implantation to its target organ.
。 Acute infections may lead to persistent or latent
Viral Persistence

Viral infections are usually self-limiting.

Sometimes, however, the virus persists
for long periods of time in the host. Long-
term virus-host interaction may take
several forms.
Chronic Infection
 Viruscan be continuously detected ;
mild or no clinical symptoms may be
Chronic infections occur with a number of
animal viruses, and the persistence in certain
instances depends upon the age of the host
when infected. Infants infected with hepatitis
B virus frequently become persistently
infected (chronic carriers); most carriers are
asymptomatic. Animal studies have shown
that in chronic infections the viral population
often undergoes many genetic and antigenic
Latent infection
The Virus persists in an occult, or cryptic,
from most of the time. There will be
intermittent flare-ups of clinical disease ,
Infectious virus can be recovered during
flare-ups . Latent virus infections typically
persist for the entire life of the host
Herpesviruses typically produce latent infections. Herpes
simplex viruses enter the sensory ganglia and persist in a
noninfectious state that is not understood at the molecular
level. There may be periodic reactivations during which
lesions containing infectious virus appear at peripheral sites
(e.g., fever blisters). Chickenpox virus (varicella-zoster) also
becomes latent in sensory ganglia. Recurrences are rare and
occur years later, usually following the distribution of a
peripheral nerve. Other members of the herpesvirus family
also establish latent infections, including cytomegalovirus and
Epstein-Bart virus. All may be reactivated by
immunosuppression. Consequently, reactivated herpesvirus
infections may be a serious complication for persons
receiving immunosuppressant therapy.
Slow virus infection
A prolonged incubation period, lasting months or
years, daring which virus continues to multiply.
Clinical symptoms are usually not evident during
the long incubation period .
Spongiform encephalopathies are a
group of chronic, progressive, fatal
infections of the central nervous system
caused by unconventional, transmissible
agents called prion. The best example of
this type of "slow virus" infection is Kuru
and Bovine spongiform encephalopathy
occurs in humans.
Overall fate of the cell
 The cell dies in cytocidal infections
this may be acute (when infection is brief and self-
limiting) or chronic (drawn out, only a few cells
infected while the rest proliferate)-Cytocidal
 The cell lives in persistent infections
this may be productive or nonproductive (refers
to whether or not virions are produced) or it may
alternate between the two by way of latency and
reactivation - Steady state infection
Special cases

 Transformation-Integrated infection
(Viruses and Tumor)
 Apoptosis
Types of Viral infections at the cellular level
Type Virus production Fate of cell
Abortive - No effect
Cytolytic + Death
Productive + Senescence
Latent - No effect
DNA viruses - Immortalization
RNA viruses + Immortalization
Mechanisms of viral cytopathogenesis
Inhibition of cellular protein Polioviruses, HSV,
synthesis poxviruses, togaviruses

Inhibition and degradation of herpesviruses

cellular DNA
Alteration of cell membrane
structure All enveloped viruses
Glycoprotein insertion HSV, VZ virus, HIV
Syncytia formation HSV, naked viruses
Disruption of cytoskeleton Togaviruses,
permeability herpesviruses
Inclusion bodies Rabies

Toxicity of Virion components Adenovirus fibers