Download Adaptive (Specific) Immunity Mo O`Brien Lecturer

Adaptive (Specific) Immunity
Mo O’Brien
Lecturer (Adult Nursing Studies)
3.18b Ty Dewi Sant
02920 743415
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31/07/2017
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Overview
• The immune system includes all of the
structures and processes that provide a
defense against potential pathogens (disease
causing agents) .
• These defenses can be classified as INNATE
(NON-SPECIFIC / INBORN) immunity or
ADAPTIVE (SPECIFIC / ACQUIRED)
immunity.
• Although the two categories refer to different
defense mechanisms there are areas in
which they overlap.
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Innate (non specific) immunity
Includes both external and internal defenses
Defenses are always present in the body
Represent the first line of defense against
invasion by potential pathogens
Act fast but show low specificity in both
recognition and disposal of invading
organisms.
Do not show memory
If these defenses are not sufficient to destroy
the pathogens, lymphocytes may be
recruited and their specific actions used to
reinformce the non-specific immune
defenses.
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Innate (non specific) immunity
The innate immune system
distinguishes between the body’s own
tissue cells (‘self’) and
microorganisms.
Invading organisms are then ‘flagged’
for phagocytic attack
• See notes of previous lecture for more
on all of this
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Structures and defense mechanisms of non-specific (innate) immunity
External
Internal
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Structure
Mechanisms
Digestive tract
Physical barrier; Lysozyme (enzyme
that destroys bacteria)
Skin
High stomach acidity; normal
bacteria of colon offer protection
Respiratory
Tract
Secretion of mucus; cilia; alveolar
macrophages
Genitourinary
tract
Acidity of urine and vaginal lactic
acid
Phagocytic
cells
Ingest and destroy bacteria, cellular
debris, denatured proteins, toxins.
Interferons
Inhibit the replication of viruses
Compliment
proteins
Promote destruction of bacteria;
enhance inflmmatory response
Endogenous
pyrogen
Secreted by
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leucocytes and other
cells; produces fever
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Adaptive (Specific) Immunity
Is more complex than non-specfic
(innate) immune response
Is highly specific
It is induced and requires time to
develop
It shows memory (the secondary
response)
It is restricted to vertebrates.
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Adaptive (Specific) Immunity
o Cells are recognised by the body as
being either self or non-self, each
carrying ‘markers’ on their membranes
that similarly are referred to as selfantigens and non-self antigens.
o The body should not normally attack
self-antigens but will respond to the
presence of non-self antigens.
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Macrophages (‘the big eaters’), which are
mature monocytes found in tissues
throughout the body offer a ‘first up’ defense
while waiting for the body’s adaptive defense
mechanisms to fully engage.
The macrophages engulf the non-self antigen
by a process of phagocytosis i.e. the cells
ability to wrap around the antigen.
The fully active adaptive mechanism can
destroy the non-self antigen, the remnant
material being phagocytosed by
macrophages, assisted by neutrophils
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Adaptive (Specific)
Immunity
The adaptive defense
is the ability of the
body to recognise and
distinguish between
offending agents and
to develop specific
responses against
them.
The basis for these
defenses lies in the
blood
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Antigens
• Antigens are molecules that stimulate the
production of specific antibodies and
combine specifically with the antibodies
produced. (Antibodies are also referred to as
immunoglogulins)
• They invoke an immune response.
• Most antigens are large molecules (such as
proteins) and most are foreign to the blood and
other body fluids.
• They can enter the body from the
environment or can be generated within the
body.
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Environmental antigens…include
Inhaled macromolecules
(e.g. proteins on cat hairs
can trigger an asthma
attack in susceptible
people)
Ingested macromolecules
(e.g. shellfish proteins that
trigger an allergic response
in susceptible people)
Molecules that are
introduced beneath the
skin (e.g. on a splinter or in
an injected vaccine)
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Antigens generated within the cells of the body
…
include
Proteins encoded by
the genes of viruses
that have infected a
cell.
Abberrant proteins
that are encoded by
mutant genes e.g.
mutated genes in
cancer cells
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Antigens
The ability of a molecule to function as an antigen
depends not only upon it’s size but also upon the
complexity of it’s structure.
A large and complex molecule can have a number of
different antigenic determinant sites which are areas
of the molecule that stimulate production of, and
combine with different antibodies.
Most naturally occurring antigens have many
antigenic determinant sites and stimulate the
production of different antibodies with specificities
for these sites.
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Antigens – summary
An antigen (Ag) is any foreign substance that
enters the body and induces an immune
response
Antigens may be found on the surface of
pathogenic organisms, on the surface of red
blood cells and tissue cells, on pollens, in
toxins and in foods.
The critical feature of any substance called
an antigen is that it stimulates the activity of
certain lymphocytes classified as T or B
cells.
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A pathogen, such as a bacterium, has many different antigens on
its surface. Each of these antigens interacts with a specific B cell
receptor protein, thereby activating those B cells that can
produce antibodies against those specific antigens.
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T & B Lymphocyte Cells
 Come from hemapoietic
(blood forming) stem cells in
bone marrow (as do all
blood cells)
 T & B cells differ in their
development and method of
action
 To maximize the chances of
encountering antigens
lymphocytes continually
circulate between the blood
and certain lymphiod
tissues.
 A given lymphocyte spends
an average of 30 minutes
perday in the blood and
recirculates about 50 times a
day between blood and
lymphoid tissue
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B LYMPHOCYTE
T LYMPHOCYTE
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T Cells
Some immature stem cells migrate to the
thymus (hence ‘T’) and become T cells
making up about 80% of the lymphocytes in
the circulating blood.
Whlist in the thymus, these T lymphocytes
multiply and become capable of combining
with specific foreign (non-self) antigens.
They are then described as sensitised
Thymus derived cells produce an immunity
that is said to be cell mediated immunity
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Types of T cells and their functions
Cytotoxic (Tc) (or ‘killer’) T cells; destroy foreign
cells directly by speeding up the process of
apoptosis (programmed cell death) by forming a
pore that allows enzymes to enter the cell and bring
about destruction of it’s lysosomes. [These are not
to be confused with ‘natural killer cells’ – see innate
immunity.]
Helper T cells (Th); release substances known as
interleukins (IL) that stimulate other lymphocytes
and macropghages and thereby assist in the
destruction of foreign cells.
Regulatory T cells (Treg) suppress the immune
response in order to prevent overactivity. These may
inhibit or destroy active lymphocytes.
Memory T cells remember an antigen and start a
rapid response if that
antigen is contacted again. 21
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T Cells
The T cell portion of the immune
system is generally responsible for
defense against cancer cells, certain
viruses and other pathogens that
grow within cells (intracellular
parasites), as well as for the rejection
of tissue that has been transplanted
from another person
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The role of the Macrophages
Macrophages (“big eater”) are phagocytic
white blood cells derived from monocytes
that act as processing centres for non-self
antigens.
They ingest foreign proteins and break them
down within phagocytic vesicles and then
insert fragments of the foreign antigen into
their plasma membrane.
The T cell can then recognise the foreign
antigens that have been presented to it by
the macrophage.
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The role of the Macrophages
However the T cell will only recognise
these foreign antigens if there are also
antigens present on the macrophage that
the T cell can recognise as belonging to
‘self’.
‘Self’ antigens are know as MHC (major
histocompatibility complex) antigens
because of their importance in cross
matching for tissue transplantation
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A special receptor on the T cell must bind
with both the MHC protein and the foreign
antigen fragment. The activated T helper cell
then produces interleukins which stimulate
other leukocytes, such as B cells.
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B cells and antibodies
 An antibody (Ab), [also
known as an
immunoglobulin (Ig)] is
a substance produced
in response to an
antigen.
 Antibodies are
manufactured by B
lymphocytes
 These B cells must
mature in the foetal
liver or in lymphoid
tissue before becoming
active in the blood.
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B cell with specific
antigen receptor
B cell binds to antigen
Activated B cell multiplies
Plasma cells
B memory cells
Antibodies
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Activation
of B cells
The B cell combines
with a specific
antigen.
The cell divides to
form plasma cells
which then produce
antibodies.
Some of the cells
will develop into
memory cells which
protect against
infection.
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B cells and antibodies
• B cells have surface receptors that bind with
a specific type of antigen
• Exposure to that antigen stimulates the cells
to multiply rapidly and produce large
numbers (clones) of plasma cells.
• Plasma cells produce antibodies against the
original antigen and release these antibodies
into the blood, providing the type of
immunity known as humoral immunity
(humoral refers to body fluids as opposed to
cellular immunity which involves T cells i.e.
takes place directly
between the T cells and 30
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antigens).
B cells and antibodies
Humoral immunity generally protects against
circulating antigens and bacteria that grow outside
of cells (extracellular pathogens)
All antibodies are contained in a portion of the blood
plasma called the gamma globulin fraction
Some antibodies produced by B cells remain in the
blood to give long term immunity.
Some of the activated B cells do not become plasma
cells but like certain T cells they become memory
cells. On repeated contact with an antigen these
cells are ready to produce antibodies immediately.
Because the plasma contains other globulins as
well, antibodies have become known as
immunoglobulins.
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The Antigen – Antibody reaction
 The antibody that is produced in response
to a specific antigen, such as a bacterial
cell or a toxin has a shape that matches
some part of that antigen much in the
same way that the shape of a key matches
to the shape of its lock.
 The antibody can bind specifically to the
antigen that caused its production and
thereby destroy or inactivate it.
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B cells must be
activated by
helper T cells
before they
produce
antibodies.
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Complement
The destruction of foreign cells sometimes
requires the enzymatic activity of a group of
non-specific proteins in the blood, together
called COMPLIMENT.
Compliment proteins are always present in
the blood but they must be activated by
antigen-antibody complexes or by foreign
cell surfaces.
Compliment is so called as it assists with
immune reactions.
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Some of the actions of
Complement are
It coats foreign cells to help
phagocytes recognize and engulf them
It destroys cells by forming complexes
that punch holes in plasma membranes
It promotes inflammation by increasing
capillary permeability
It attracts phagocytes to an area of
inflammation
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The compliment system is directed to defend against
bacterial invasion.
The system consists of inactive precursors that are
activated by proteolytic enzymes in a cascade,
which like other cascade systems, multiplies the
number of molecules involved at each step.
The system can be activated by the specific immune
system (the classical pathway) or the non-specific
immune system (the alternative pathway).
Both pathways end in the production of chemicals
known as complement fragments and these promote
phagocytosis and a structure known as a membrane
attack complex (This is a ring of compliment
fragments that inserts itself into the membrane of
invading cells, forming a large pore that causes the
cell to lyse [i.e. cell death])
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Compliment Cascade
Activation of the cascade
can be by the classical
specific immune system
or by the non-specific
production of a C3stabilizing combination of
a non-antigenic but nonself molecule and factors
B and D.
Like all cascade systems,
there is a multiplication of
active molecules at each
step, and these molecules
cause inflammation,
phagocytosis, chemotaxis
and cell lysis.
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The Immunoglobulins
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 Main form of antibodies in
circulation (75%) and is
termed the ‘work horse’
antibody.
lgG
 It is important for
opsonization because
phagocytes have receptors
which bind to the region of
IgG molecules.
 Production increased after
immunization;
 secreted during secondary
response
 Found in blood, lymph and
intestines
 Enhances phagocytosis,
neutralizes toxins and
activates compliment
 Crosses the placenta and
confers passive immunity
from mother to foetus.
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lgA
Main antibody type in external secretions, such as
saliva & mother’s milk. Also found in tears, sweat,
mucus and digestive juices.
Comprises 15% of the immunoglobulins. May appear
early in the course of infection and its detection has
a role in the diagnosis of acute infection
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lgM
 Forms the bodies natural
antibodies e.g. ABO blood
groups.
 Function as antigen
receptors on lymphocyte
surface prior to
immunization
 secreted during primary
response – the first antibody
to be secreted after
infection.
 Stimulates agglutination and
activates compliment
 Comprises 10% of the
immunoglobulins
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lgD
• Function as antigen
receptors on
lymphocyte surface
prior to immunization
• Comprise < 1% (approx
0.2%) of the
immunoglobulins
• Needed for B cell
maturation and is
located on the surface
of B cells
• other functions
unknown but may be
related to the inhibition
of autoimmune disease.
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lgE
• Located on basophils,
binds to mast cells and
eosinophils and is
therefore responsible
for allergic symptoms
in immediate hypersensitivity reactions
(e.g. asthma, eczema,
hay fever, anaphylaxis)
and is also activated
when parasitic infection
present.
• < 0.1% (approx 0.004%)
of the immunoglobulins
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Naturally Acquired Immunity
Immunity may be acquired naturally through
contact with a specific disease organism, in
which case, antibodies manufactured by the
infected persons cells act against the
infecting agent or it’s toxins.
The infection that triggers the immunity may
be so mild so as to cause no symptoms
(subclinical)
Nonetheless it will stimulate the host’s cells
to produce an active immunity.
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Naturally Acquired Immunity
Each time a person is invaded by disease
organisms cells manufacture antibodies
that provide immunity against infection.
Such immunity may last for years and in
some cases for life.
Because the host is actively involved in
the production of antibodies, this type of
immunity is called active immunity.
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Naturally Acquired Immunity
Immunity also may be acquired naturally by
the passage of antibodies from a mother to
her foetus through the placenta.
Because these antibodies come from an
outside source, this type of immunity is
called passive immunity.
The antibodies obtained in this way do not
last as long as actively produced antibodies,
but they do help the infant for about 6
months, at which time the child’s own
immune system begins to function.
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Artificially Acquired Immunity
A person who has not been exposed to
repeated small doses of a particular
organism has no antibodies against that
organism and may be defenseless against
infection
Therefore artificial measures may be used to
cause the person’s immune system to
produce antibodies.
To administer virulent pathogens would be
very dangerous so virulence is reduced in
the laboratory setting before it is
administered.
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Artificially Acquired Immunity
 In this way the immune system is made to produce
antibodies without causing serious ill health – this
protective process being referred to as vaccination
or immunisation, whilst the substance administered
is referred to as the vaccine.
 A vaccine is generally administered as a
preventative measure designed to provide protection
in anticipation of invasion by a particular disease
causing organism.
 All vaccines carry a risk of adverse side effects and
may be contraindicated in some cases e.g. vaccines
that contain live virus should not be administered to
individuals who are immunosuppressed (i.e. with a
CD4 count of less than 200 / ml of blood) or to
pregnant women as there is a risk that they may
cross the placenta and harm the foetus.
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