Transcript respiratory syncytial virus (RSV) infection

Immunopatholgy
RSV
blood flukes
• The diseases in which pathology is largely caused by
the immune response, is known as immunopathology
• This is true to some degree in most infections; for
example, the fever that accompanies a bacterial
infection is caused by the release of cytokines by
macrophages
• Most important examples are
– Leprosy √
– respiratory syncytial virus (RSV) infection
– Blood flukes
• In adults, it may only produce symptoms of a
common cold, such as a stuffy or runny nose, sore
throat, mild headache, cough, fever, and a general
feeling of being ill
• But in premature babies and kids with diseases that
affect the lungs, heart, or immune system, RSV
infections can lead to other more serious illnesses
respiratory syncytial virus (RSV) infection
• Bronchiolitis caused by RSV is the major cause of admission of young
children to hospital
• 4500 deaths out of 90,000 cases each year in the US alone
• The first indication that the immune response to the virus might have
a role in the pathogenesis of this disease came from the observation
that infants vaccinated with an alumprecipitated killed virus
preparation had a more severe illness than children who did not
receive the vaccine
• This occurred because the vaccine failed to induce neutralizing
antibodies but succeeded in producing effector TH2 cells
• When the vaccinated children encountered the virus, the TH2 cells
released interleukins IL-3, IL-4, and IL-5, which induced
bronchospasm, increased the secretion of mucus, and increased
tissue eosinophilia
• Another example of a pathogenic
immune response is the response to
the eggs of schistosomes (blood flukes)
• These helminth parasites lay their eggs
in the hepatic portal vein
• Some reach the intestine and are shed
in the feces, spreading the infection
TH2
• other eggs lodge in the portal
circulation of the liver, where they elicit
a potent immune response leading to
chronic inflammation, hepatic fibrosis,
and eventually liver failure
• This process reflects the excessive
activation of TH1 cells and can be
modulated by TH2 cells, IL-4, or CD8 T
cells, which can also produce IL-4
TH1
Allergy/ Hypersensitive
Reactions
• Adaptive immune responses
elicited by potentially harmless
antigens i.e. not associated with
infectious agents leading to
harmful (immune mediated)
hypersensitivity reactions known
generally as allergic reactions
• e.g. response to inherently
harmless 'environmental‘ antigens
such as pollen, food, and drugs
• The ability of the immune system to respond
inappropriately to antigenic challenge was recognized
early in this century
• Two French scientists, Paul Portier and Charles Richet,
investigated the problem of bathers in the
Mediterranean reacting violently to the stings of
Portuguese Man of War jellyfish
• They knew that the localized reaction of the bathers was
the result of toxins
• Their first attempt met with disastrous results.
• Portier and Richet injected dogs with the purified toxins,
followed later by a booster of toxins
• Instead of producing antibodies against the toxins, the
dogs immediately reacted with vomiting, diarrhea,
asphyxia, and, in some instances, death
• Clearly this was an instance where the animals
“overreacted” to the antigen
• Portier and Richet coined the term anaphylaxis, loosely
translated from Greek to mean the opposite of
prophylaxis, to describe this overreaction
• Richet - awarded the Nobel Prize in Physiology or
Medicine in 1913
• Phylaxis- Protection against infection
AnaphylaxisHistory
Classification of types of hypersensitivity
reactions by Coombs and Gell
• Hypersensitivity reactions due to immunological responses
were classified into four broad types by Coombs and Gell
• Hypersensitivity reactions due to immunological responses
were classified into four broad types according to
– Type of immune response I.e. humoral or cell mediated
– antigens
• Types I-III are antibody-mediated and are distinguished by
the different types of antigen recognized and the different
classes of antibody involved
– Type I is IgE
– while types II and Ill are mediated by lgG
• Type IV is cell- mediated responses
Type I hypersensitivity
• Type I hypersensitivity reactions
in this classification are immediate-type allergic
reactions mediated by IgE antibodies
• but many of the allergic diseases that are
initiated by IgE antibodies, such as allergic
asthma, have chronic features characteristic of
other types of immune response, particularly of
TH2 cell-mediated type IV hypersensitivity
• Classical allergic reactions are dependent upon
previous exposure and sensitization to specific
allergens that result in the development of
antigen specific IgE antibodies
• Classical allergic reactions occur when allergens
bind and crosslink allergen specific IgE
antibodies present on the cell membranes of
mast cell and basophils, triggering the release of
numerous me
Allergic
symptoms – due
to inflammatory
mediators
• In hay fever (allergic rhinoconjunctivitis), for example, symptoms occur
when allergenic proteins leached out of grass pollen grains come into
contact with the mucous membrane of the nose and eyes
• A predisposition to become IgE -sensitized to environmental allergens is
called atopy both genetic and environmental- that may contribute to
predisposition
Fig. lgE-mediated
reactions to
extrinsic antigens.
All lgE-mediated
responses involve
mast-cell
degranulation,
but the symptoms
experienced by the
patient can be very
different depending,
for example,
on
whether the allergen
is injected directly
into the bloodstream,
is eaten, or comes
into contact with the
mucosa of the
respiratory tract
• IgE may protect external mucosal surfaces by promoting
inflammation, enabling IgG, complement proteins, and
leucocytes to enter the tissues
• The main biological role of IgE is thought to be in adaptive
immunity to infection with parasitic worms (helminths)
and arthropods
• The Fc portion of IgE made against parasitic worms and
arthropods can bind to eosinophils enabling
opsonization
• It is often made in response to allergens
• IgE makes up about 0.002% of the serum antibodies with
a half-life of 2 days
• Most IgE is tightly bound to basophils and mast cells via
its Fc region
• IgE is a monomer and has 2 epitope-binding sites
IgE
T he first signal (indicated as 1 in the figure)
required for B-cell activation is delivered
through its antigen receptor (top panel).
For thymus-dependent antigens- the second
signal (indicated as 2) is delivered by a helper T
cell that recognizes degraded fragments of the
antigen as peptides bound to MHC class
II molecules on the B-cell surface (center
panel); the interaction between CD40
ligand (CD40L, also called CD154) on the
T cell and CD40 on the B cell contributes
an essential part of this second signal.
For thymus-independent antigens, a
second signal can be delivered along
with the antigen itself, through Toll like
receptors that recognize antigen associated
TLR ligands, such as bacterial
lipopolysaccharide (LPS) or bacterial DNA
(bottom panel)
Fig. Helper T cells stimulate the proliferation and then the differentiation of antigen-binding
B cells.
The specific interaction of an antigen-binding B cell with a helper T cell leads to the expression
of the B -cell stimulatory molecule CD40 ligand on the helper T-cell surface and to the secretion
by the T cell of the B cell stimulatory cytokines IL-4, IL-5, and IL-6, which drive the proliferation
and differentiation of the B cell into

antibody-secreting plasma cells

memory cell