Immune To Viruses

Viruses
Immune response to virus

Introduction
Virus
• Submicroscopic pathogens whose size is measured in
nanometers
• Their basic structure consists of a core of DNA or RNA
packaged into a protein coat or capsid
• In some viruses, the capsid is surrounded by an outer
envelope of glycolipids and proteins derived from the
host cell membrane
• Capable of causing severe, and sometimes lethal, disease
in humans, ranging from childhood infections to
inflammatory diseases with a predilection for a specific
organ, disseminated disease in immunocompromised
patients, cancer, and congenital abnormalities
Basic structure of virus
• Viruses are obligate intracellular pathogens that rely on
the host cell for their replication and survival.
• They infect their host cells by
• Attaching to specific receptors on the cell surface;
• Penetrating the host cell membrane; and releasing
their nucleic acid
• which then directs the host cell’s machinery to
produce more viral nucleic acid and proteins.
• These components assemble to form intact viruses
that are released by lysis of the cell or by budding
off the cell’s surface
Basic step of a virus life cycle
Immune defense against viral infection
• Two important nonspecific defenses against viruses involve

type I interferons and natural killer (NK) cells
• Virus-infected cells are stimulated to produce IFN-α and
IFN-β following recognition of viral RNA by toll-like
receptors (TLR)
• Interferons inhibit viral replication by inducing the
transcription of several genes that code for proteins with
antiviral activity
• IFN-α and IFN-β also enhance the activity of NK cells,
which bind to virus-infected cells and release cytotoxic
proteins such as perforin and granzymes, causing the cells
to die and release the viruses
• When innate defenses are insufficient in preventing viral infection,
specific humoral and cell-mediated defenses are activated.
• Virus-specific antibodies are produced by B cells and plasma
cells and can attack free virus particles in several ways.
• Antibodies play a key role in preventing the spread of a viral
infection through neutralization
• Secretory IgA antibodies play an especially important role in
this process because they neutralize viruses in the mucosal
surfaces
• IgM and IgG antibodies can bind to viruses in the
bloodstream and inhibit dissemination of the infection.
• IgG antibodies promote phagocytosis of viruses through their
opsonizing activity and promote destruction of viruses through
antibody-dependent cell-mediated cytotoxicity (ADCC)
• IgM antibodies may also inactivate viral particles by
agglutinating them
• Elimination of intracellular viruses requires the action of
cell-mediated immunity.
• Type 1 helper (Th1) cells and cytotoxic T lymphocytes
(CTL) play a key role in this mechanism of defense.
• Th1 cells produce interferon-γ, which induces an antiviral
state within the virus-infected cells, and IL-2, which assists
in the development of effector CTLs
• To recognize the virus infected host cell, the T-cell receptor
(TCR) on the CTL must bind to a viral antigen complexed
with class I major histocompatibility complex (MHC) on the
surface of the infected cell
• CD8 is a co-receptor in this interaction. Interaction of
costimulatory molecules, such as B7 and CD28, provides
secondary signals necessary for the CTL response.
• These molecular interactions stimulate the granules in the CTL
to release a pore-forming protein called perforin, which
produces pores in the membrane of the infected host cell, and
proteases called granzymes, which enter the pores.
• These enzymes activate apoptosis in the host cell, interrupting

the viral-replication cycle and resulting in release of assembled
infectious virions. The free virions can then be bound by
antibodies.
• The CTL response is powerful and involves a series of cell

divisions that can produce up to 50,000 times the original
number of cells in a period of 1 to 3 weeks
Viral immune escape mechanism
• Viruses are rapidly dividing agents that undergo frequent

genetic mutations
• These mutations result in the production of new viral
antigens, which are not recognized by the initial immune
response to the virus
• For example, continual antigenic variation in the influenza
virus results in the emergence of novel infectious strains
that require development of new vaccines every year to
protect the population.
• Antigenic variation is also seen in other viruses, including
rhinoviruses, which cause the common cold, and HIV,
which causes AIDS
Viral immune escape mechanism
• Some viruses can escape the action of components of

the innate immune system such as interferons,
complement proteins, or the lysosomal enzymes in
phagocytic cells.
• For example, the hepatitis C virus can block

interferon-mediated degradation of viral RNA and
herpes simplex viruses (HSV) produce a protein that
binds to the complement component, C3b,resulting in
inhibition of the complement pathways
• Viruses can evade the host’s defense by suppressing the adaptive
immune system.
• Some viruses, such as the cytomegalovirus (CMV) and HIV, do
this by reducing the expression of class I MHC molecules on the
surface of virus-infected cells, making them less likely to be
recognized by CTLs.
• Other viruses, such as rubeola, can cause decreased expression of
class II MHC molecules, resulting in reduced Th cell activity.
• Some viruses can alter the function of certain cells of the immune
system after directly infecting them.
• For example, the Epstein-Barr virus (EBV) causes polyclonal
activation in B lymphocytes, whereas HIV suppresses the function
of CD4 Th cells.
• EBV can also inhibit immune responses by producing a protein
that can suppress Th1 cells because of its similarity to interleukin-
10 (IL-10)
• Some viruses, such as CMV, varicella-zoster virus (VZV), and
HIV, can remain in a latent state by integrating their nucleic
acid into the genome of the infected host cells.
• In this situation, the virus is only stimulated to replicate again

if the host is exposed to other infectious agents or if the host’s
immune defenses decline.
• Latent viruses can remain silent within host cells for years
because they are hidden from the immune system, although
reactivation can occur later in life
End

Immune To Viruses

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Viruses

Immune response to virus

• Two important nonspecific defenses against viruses involve

• These enzymes activate apoptosis in the host cell, interrupting

• The CTL response is powerful and involves a series of cell

• Viruses are rapidly dividing agents that undergo frequent

• Some viruses can escape the action of components of

• For example, the hepatitis C virus can block

• In this situation, the virus is only stimulated to replicate again

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