Download Evasion of Immunity I

Evasion of Immunity I
Vertebrate and invertebrate
immune systems.
Dr. Jo Hamilton
Parasitology BS
Introduction.
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Successful parasites have evolved strategies for
survival & development in both invertebrate and
vertebrate hosts.
The goal of a parasite is to propagate within the
host and be transmitted to the next host.
The goal of the parasitised host is to cure or limit
the infection.
During the next three lectures we will investigate
strategies used by parasites to evade the host
immune response.
In this session we will revisit the immune system
of both vertebrates and invertebrates.
Objectives and learning outcomes.
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By the end of this session students should be:
Familiar with fundamental biology of vertebrate
& invertebrate immune systems.
Familiar with the concept of innate and acquired
immunity in vertebrates.
Recognise that there is only innate immunity in
invertebrates.
Recognise the key players in both vertebrate and
invertebrate immune systems.
Immunity.
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Resistance to infection is called immunity.
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The term “immunity” is derived from the Greek
word “immunis” meaning exempt.
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There are two types of immunity in vertebrates.
– Innate immunity – present from birth.
– Acquired immunity – result of infection
or vaccination.
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Invertebrates only posses innate immunity.
Innate immunity in vertebrates (also
known as non-specific or natural immunity).
Characteristics:
 Present from birth.
 Non-specific - acts on many organisms and
does not show specificity.
 Does not become more efficient on
subsequent exposure to same organisms.
Innate immunity in vertebrates.
Non-specific Host Defences include:
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Mechanical / physical barriers – skin,
mucosal surfaces.
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Prevention of stasis – peristalsis, flow of
urine, upward movement of secretions in
bronchial tree, coughing, vomiting.
Innate immunity in vertebrates.
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Chemical defences - Low pH of stomach
contents, secretion of fatty acids in the skin.
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Biological defence – complement, lysozyme,
interferons, antimicrobial peptides, kinins,
adhesion molecules, hormones, lactoferrin.
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Cellular defence - e.g. phagocytes.
Innate immunity in vertebrates.
Some of the key players in innate immunity
to consider in more detail are:
 Complement.
 Opsonization.
 Phagocytosis & the oxidative burst.
 Inflammation.
Innate immunity in vertebrates –
complement.
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Complement. - complex of 17 proteins
present in normal serum.
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2 pathways – classical & alternative.
Innate immunity in vertebrates –
classical complement pathway.
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Antigen-antibody complex forms, constant
region of antibody changes shape.
Activates C1, acquires esterase activity.
Activated C1 activates C2 & C4 which
activates C3, etc.
Eventually, C8 & C9 activated forming
membrane attack complex (MAC) - pores in
target cell membrane - lysis.
Innate immunity in vertebrates alternative complement pathway.
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Alternative pathway - C3 can interact
directly with certain chemicals (teichoic acids,
LPS) found in bacterial cell walls and activate
the alternative pathway.
Innate immunity in vertebrates –
opsonization.
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Opsonization - process of coating microorganisms with plasma proteins to make them
more easily phagocytosable.
It is stimulated by complement bound to
antibody-antigen targets.
Opsonization promotes adhesion between
opsonized cell & macrophages. The opsonin
binds to receptors on phagocyte membrane.
Opsonization and phagocytosis are more
efficient in immune individuals.
Innate immunity in vertebrates–
cellular defence.
Cellular defence involves:
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Granulocytes (also known as the
polymorphonuclear leukocytes e.g. eosinophils,
basophils etc).
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The reticulo endothelial system (e.g.
macrophages, Kupffer cells of the liver and
natural killer (NK cells).
Innate immunity in vertebrates –
White blood cells.
Role of white blood cells in cellular defence.
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White blood cells (WBCs) are major
components of immune system.
Blood smear showing different blood cell types.
Innate immunity in vertebrates –
phagocytosis.
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Certain WBCs highly mobile & carry out
phagocytosis.
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WBCs chemotactically attracted to foci of
disease or tissue damage.
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Phagocytosis begins with engulfment of
particulate matter (e.g. bacteria, clumps of
virions, cell debris, etc.) into a phagosome.
Innate immunity in vertebrates –
phagocytosis cont’d.
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The phagosome fuses with lysosomes to form
the phagolysosome.
Lysosomes contain number of enzymes
including acid hydrolases, lysozyme, neutral
proteases, myeloperoxidase, lactoferrin, &
phospholipase A.
These enzymes can degrade biomolecules.
Innate immunity in vertebrates –
oxidative burst.
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Once engulfed, the white cell must kill the
organisms by some means such as the
“respiratory (or oxidative) burst".
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Many pathogens and parasites succeed because
they are able to avoid phagocytosis.
Innate immunity in vertebrates –
inflammation .
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Inflammation - (or inflammatory response)
mechanism by which phagocytes and
complement are recruited to site of tissue
invasion.
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Non-specific reaction to tissue damage. Cell
damage initiates a complex series of steps
leading to inflammation.
Innate immunity in vertebrates –
inflammation. Inflammation involves:
• Vasodilation - swelling.
• adhesion of leukocytes to endothelial cells
of post-capillary venule, & emigration of
phagocytes into tissues.
• redness (blood flow).
• pain (prostaglandins bind to nerve
receptors).
• heat (pyrogens).
• Inflammation localised to area of infection /
injury by release of substances from microorganisms or chemical mediators released
from cells in tissues, e.g. histamine from
mast cells.
• Once organisms are destroyed inflammation
settles down (resolves).
Acquired immunity (only in
vertebrates).
Also known as adaptive immunity / specific immunity.
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Develops as response to an infection.
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Called adaptive as immune system adapts itself to
previously unseen molecules.
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The induction of immunity by infection, or with a
vaccine, is called active immunity.
Acquired immunity.
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Induction of immunity by infection, or with
vaccine, called active immunity.
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Non-immune individual can be made immune by
transferring serum or lymphocytes from immune
individual. This is know as passive immunity
and demonstrates that serum constituents
(antibodies) and lymphocytes are involved in
immunity.
Acquired immunity.
Characteristics of acquired immunity:
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Immunological recognition.
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Discrimination between self and non-self.
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Immunological specificity.
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Immunological memory.
Acquired immunity.
Immunity mediated by immune system, responds to
infection by mounting immune response. An
immune response must:
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Recognise a micro-organism or parasite as
foreign (non-self) as distinct from self.
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Respond to the presence of a foreign organism
by production of specific antibodies and specific
lymphocytes.
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Mediate the elimination of such organisms.
Acquired immunity.
There are two types of acquired immunity.
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Cell-mediated immunity - this is immunity
mediated by T-cells. T cells secrete lymphokines
(e.g. interleukin-2) which interact with other cell
types, and either activate or repress an immune
response.
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Humoral immunity - this is blood-specific
immunity mediated by antibodies (Abs).
Acquired immunity – cell mediated
immunity.
Acquired immunity – cell mediated
immunity.
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Key cells involved in acquired immunity
response are lymphocytes.
Two types lymphocyte develop in bone marrow
from common precursor.
Each different response mediated by different
sets of lymphocytes.
Following invasion by a foreign organism,
lymphocytes proliferate (i.e. divide) and
differentiate (i.e. specialize).
Acquired immunity – cell mediated
immunity, B lymphocytes.
B lymphocytes (B cells):
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Found fixed in the lymph nodes, liver and
spleen.
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They are bone marrow-derived lymphocytes,
mature in Peyers’ Patches of the pancreas.
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During maturation, antigen-specified antibody
is displayed on the cell surface.
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If the cell is activated by an antigen, the B cells
excrete antibody.
Acquired immunity – cell mediated
immunity, T lymphocytes.
T lymphocytes (T-cells):
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Found in lymph nodes, liver, spleen, also freely
circulating in the blood.
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Matures in thymus. They have cell surface
receptor of a pre-determined specificity.
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These cells regulate cellular immunity.
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Two main T cell types: helper T cells (Th cells
have the CD4+ receptor) & suppressor /
cytotoxic T cells (Tc cells display the CD8+
receptor).
Acquired immunity – cell mediated
immunity, macrophages.
A third important cell type are
macrophages.
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These cells play essential role in processing &
presenting immunogens to lymphocytes.
Also important effector cells (i.e. they carry out
destruction of foreign material e.g.
phagocytosis).
Carry receptors for antibody molecules which
allows them to attach to antibody-antigen
complexes before phagocytosing them.
Acquired immunity – generation of
immune response.
In order for an immune response to be activated, an
object must first be recognised as foreign.
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An immunogen is any molecule that stimulates
an immune response. In general, proteins are the
best immunogens, followed by carbohydrates
and then nucleic acids. Lipids are very poor.
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An antigen is any molecule that is capable of
generating an antibody response (antigen =
antibody generating).
Acquired immunity – generation of
immune response.
Upon an initial infection, it takes about 4-7 days to
generate an immune response.
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After seven days get primary immune
response. Initially, IgM produced but B cells
differentiate further into IgG producing cells.
After about three weeks primary immune
response turned off.
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During this initial period Ab producing cells and
memory B cells are formed.
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When same agent encountered by host again,
body recognises it, stimulates the memory cells
to secrete Abs. This is called the secondary
immune response.
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Memory can last for few weeks or can last for
years.
Acquired immunity – generation of
immune response.
There are three types of effector immune response.
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Humoral (blood) - antibody response mediated
by B cells & regulated by T cells.
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Cell-mediated (cellular) - delayed-type
hypersensitivity and cytotoxicity mediated by
CD4+ and CD8+ T cells.
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Tolerance - non-specific response mediated by T
cells. Healthy individuals tolerant to own tissues,
sometimes immune response fails to recognise
self giving rise to autoimmune diseases or
transplant rejection in transplantation surgery.
Humoral immunity – antibodies.
Large glycoproteins released by B cells. Antibodies
(Abs) specifically interact with antigens. Body
can produce millions of antibody specificities
genetically as the B cells mature. There are five
classes of Ab:
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IgM – largest & first Ab to be made antibody
response. IgM can mediate neutralisation, fix
complement, agglutinate and immobilise
antigens.
IgG - this is the main serum Ab. This is
synthesized during the secondary immune
response. Able to do all Ab mediated functions.
Humoral immunity – antibodies
cont’d.
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IgA - is mucosal antibody. Sometimes called
secretory Ab as mucosal cells secrete them when
mucosal pathogens begin to establish colonies.
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IgD - is receptor antibody found on the surface
of immunocompetent cells. This functions in the
afferent response.
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IgE - binds to the surface of mast cells causing
degranulation of the cell and release of histamine
into circulation. This ab is involved with
allergies.
Humoral immunity – antibodies
cont’d.
Abs are important for us in five ways.
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neutralisation - an Ab molecule covers up sites
on toxic molecule or virus.
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opsonization - this is Ab-mediated phagocytosis.
Macrophages have antibody receptor sites on
surface, able to bind to antigen-antibody
complexes before phagocytosing them.
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complement fixation - a complicated system that
reacts to antigen/antibody complexes (see also
complement notes in innate immunity).
Humoral immunity – antibodies
cont’d.
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agglutination/precipitation - Abs cross-link
antigens into large complexes making them
easier to phagocytose & destroy.
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immobilization - Abs bind to flagella etc. &
prevent organisms from escaping macrophage
death.
Cellular immunity – Th and Tc
cells.
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Often directed against intracellular parasites &
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cancer. Infected cells killed by macrophages
under directions of CD4+ Th cells. Cytotoxic T
cells (CD8+ directed) also participate by
releasing toxic components which kill the cell.
Cells involved in cellular immunity must be able
to recognise self, especially as many of their
targets are cells infected by agents that are within
them. This means killing ones own cells in an
effort to rid the infection. Self recognition is
mediated by the Major Histocompatibility
Complex antigens (MHC antigens). All our cells
display these MHC antigens in specific patterns
on the cell surface.
Cellular immunity – Major
Histocompatibility Complex.
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Macrophages must process the antigen & then
display pieces of the antigen on its cell surface.
They then present this antigen to T cells, which
recognize the antigen as being foreign as well as
recognising the MHC antigens. If the T cell
“sees” both antigen and MHC it becomes
activated: if it “sees” only the MHC antigen
nothing happens.
When macrophages display antigen plus Class I
MHC they stimulate CD8+ cells (i.e. they make
cytotoxic T cells) when they displayed antigen
plus Class II MHC they stimulate CD4+ cells (i.e.
helper T cells).
Invertebrate immune system.
Comparison of vertebrate & invertebrate immunity.
Vertebrates
Innate Immunity
(e.g. antimicrobial peptides)
Invertebrates
Innate Immunity
(e.g. antimicrobial
peptides)
Acquired immunity
--------------------Phagocytic cells
Phagocytic cells
(Macrophages neutrophils etc)
(Haemaocytes)
----------------------------------Melanization
----------------------------------Phenoloxidase cascades
Cytokines
Macrokines
Immune competent tissues
Immune competent tissues
N.B. Invertebrate immune system comprises only innate system; it is
non-specific and has no memory component. Vertebrate immune
system both innate and acquired components.
Invertebrate immunity.
The invertebrate immune system is comprised of two
branches:
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The humoral response (N.B. this is not
antibody mediated) is concerned with soluble
components such as antimicrobial peptides
(AMPs), agglutinins (lectins) and macrokines
(these are similar to cytokines).
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The cellular response includes phagocytosis
(haemocytes), encapsulation and nodulation.
Invertebrate immunity – humoral
response.
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Antimicrobial peptides. Wide range including
defensins, cecropins, andropins, ceratotoxins,
drosomycin & penaeidins etc. Their action leads
to lysis of invading organism e.g. bacteria &
protozoa.
Macrokines. There is growing evidence of
these cytokine-like molecules. Haemolymph
preparations have been shown to stimulate
vertebrate immune effector cells (e.g.
macrophages).
Agglutinins (lectins). Agglutinate invading
organisms making them easier to phagocytose.
Invertebrate immunity – cellular
response.
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Phagocytosis - Haemocytes (amoebocytes)
front line of invertebrate cellular. Foreign
(non-self) invaders are taken into a
phagocytotic vacuole where proteolytic
enzymes & free oxygen radicals destroy the
pathogen (in a similar way to vertebrate
macrophages). Bacteria and yeast
(<10microns) can be phagocytosed.
Invertebrate immunity – cellular
response cont’d.
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Encapsulation - If invader too large for
phagocytosis (e.g. the egg of a parasitic wasp),
encapsulation might ensue. Invader is
compacted under layer of haemocytes. This is
accompanied by melanization. The melanized
capsule adheres to host tissues but is walled
off from the host. Phenoloxidases mediate
melanization reaction but also have other
tasks including wound healing, cuticle
pigmentation & sclerotisation.
Invertebrate immunity – cellular
response cont’d.
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Nodulation - Microaggregates of haemocytes
& bacteria encased in haemocytes are
melanised & removed from circulation.
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Phagocytosis, encapsulation and nodulation
mediated by eicosanoids (prostaglandins,
leukotrienes).
Invertebrate immunity –
mechanical / physical barriers.
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In addition to the cellular & humoral
defences, invertebrates also have mechanical
or physical defences.
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These include the cuticle, epithelia and in the
case of insects the peritrophic membrane.
Summary.
By the end of this session you should be:
 Familiar with fundamental biology of vertebrate
& invertebrate immune systems.
 Familiar with the concept of innate and acquired
immunity in vertebrates.
 Recoginise that invertebrates have only innate
immune system.
 Recognise the key players in both vertebrate and
invertebrate immune systems.
Next session.
We will:
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Describe immunity to particular parasites.
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Explore the strategies that parasites use to
evade the hosts’ immune system.