HOST DEFENSE &
VIRAL VACCINE
HOST DEFENSES
Immunity: mechanisms used by the body
as protection against microbes and other
foreign agents.
Nonspecific immunity (innate, natural )
Specific immunity
NON SPECIFIC DEFENSES
Interferons
Natural killer cell
Phagocytosis
Fever
Mucociliary clearance
Age
INTERFERONS
The IFNs are host-coded proteins that are
members of the large cytokine family and that
inhibit viral replication.
They are produced very quickly (within hours) in
response to viral infection and are one of the
body’s first responders in the defense against
viral infection.
IFN was the first cytokine to be recognized.
INTERFERON
Heterogenous group of glycoproteins produced
after viral infection.
Inhibit the growth of viruses by blocking the
translation of viral protein.
On the basis of the cell of origin divided into
group
Leucocyte -------------- alpha interferon
Fibroblast -------------- beta interferon
Lymphocyte ----------- gamma interferon
Alpha and Beta interferon are induced by
viruses whereas gamma interferon is induced
ALPHA & BETA INTERFERONS
Induced by viruses.
Inhibit the intracellular replication of both RNA
and DNA viruses.
Act by inducing the synthesis of three cell
coated proteins that inhibit the translation of
viral mRNA.
These three proteins are
2,5 – oligonucleotide synthetaze
ribonuclease
protein kinase
Phagocytosis
Figure 16.8a
COMPLEMENT SYSTEM
The complement systems
Consists of ~30 proteins that complement the
action of the immune system
Functions:
Inflammation
Stimulate leukocytes
Increase phagocytosis by opsonization
ALPHA DEFENSINS
α-Defensins are a family of positively
charged peptides with antiviral activity.
They interfere with human immunodeficiency
virus (HIV) binding to the CXCR4 receptor and
block entry of the virus into the cell.
APOLIPOPROTEIN B RNA-EDITING
ENZYME (APOBEC3G)
APOBEC3G is an important member of the innate
host defenses against retroviral infection,
especially against HIV.
APOBEC3G is an enzyme that causes
hypermutation in retroviral DNA by deaminating
cytosines in both mRNA and retroviral DNA,
thereby inactivating these molecules and reducing
infectivity
Fever
Pyrogens are substances that stimulate fever
External, e.g. bacterial endotoxin
Internal (endogenous), e.g. interleukins (IL-1)
Body temperature increases in response to
pyrogens to:
Stimulate WBC to destroy microbes
increase in immunological response(e.g.
proliferation and activation of lymphocytes)
Slow down growth of or kill pathogens
PHYSICAL & CHEMICAL BARRIERS
Respiratory tract
Nose - nasal hair, mucus
secretions (phagocytes
and antibacterial
enzymes), irregular
chambers
ciliated epithelium (nasal
cavity, sinuses, bronchi
and trachea)
Cough reflexes
Alveolar macrophages
SPECIFIC DEFENSES
Most important specific defense is Acquired
Immunity either
Actively acquired by exposure to virus (Active
immunity).
Passively acquired by the transfer of immune
serum ( Passive immunity).
ACTIVE IMMUNITY
NEUTRALIZATION:
Neutralization of the infectivity of virus by
antibody binding to proteins on the outer
surface of virus.
This binding prevent the interaction of the virus
with cell recepters.
It cross link the viral protein and stabilizes the
virus so uncoating does not occur.
Antibody coated virus is rapidly phagocytosed.
COMPLIMENT MEDIATED LYSIS
Lysis of virus infected cell in presence of
antibody and compliment.
Antibody bind to virus specific antigen on cell
surface and then bind compliment, which
enzymatically degrade the cell membrane.
CYTOTOXIC T CELL MEDIATED LYSIS
CD-8 positive T cells recognize viral antigen when
presented in association with class I MHC protein.
They kill virus infected cells by three methods:
Releasing Perforins which make holes in cell
membrane of infected cell.
Releasing proteolytic enzyme ( granzymes)
which degrade cell content.
Activating FAS protein which causes
programmed cell death (apoptosis).
PASSIVE IMMUNITY
The term passive refers to the administration of
preformed antibodies.
Two types of immune gobulin preparations:
High titer of antibody against specific virus.
Heterogeneous mixture of antibodies with
low titer.
High titer preparations are used after exposure
to hepatitis B, Rabies and Varicella zoster virus.
Low titer immune globulin is used mainly to
prevent hepatitis A.
VIRAL VACCINES
The purpose of viral vaccines is to use the
immune response of the host to prevent viral
disease.
Vaccination is the most cost effective method
of prevention of serious viral infections.
Immunity to viral infection is based on the
development of an immune response to
specific antigens located on the surface of
virus particles or virus-infected cells.
There are two types of vaccine that induce active
immunity.
Contain live virus ( live attenuated vaccine)
Contain killed virus ( killed virus vaccine)
Live vaccines are preferred to killed virus vaccine
because their protection is greater and longer
lasting.
PASSIVE IMMUNIZATION
Provided by the administration of preformed
antibody called immune globulins.
Rabies immune globulin (RIG)
Hepatitis B immune globulin (HBIG)
Varicella-zoster immune globulin (VZIG)
Immune globulin in prevention of Hepatitis A or
measles.
HERD IMMUNITY (COMMUNITY IMMUNITY)
The risk of infection among susceptible
individuals in a population is reduced by the
presence of adequate numbers of immune
individuals.
This effect is reflected in dramatic decreases in
the incidence of disease, even when all
susceptible individuals have not been
vaccinated.
Individuals protected by herd immunity remain
susceptible to infection upon exposure.