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RBC
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Leukocyte
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Defence Against
Disease
Chapter 8
Pages 245-284
Chapter 8 - Defence Against
Disease
1
Immunity
Infection:
Defn: entry of a pathogen into the body of a organism
(host) that might cause disease.
Immunity
Defn: reactions that occur in a person in response to an
infection
The immune system
• The immune system is able to distinguish foreign
material from material that is made by the body.
• The immune system has two kinds of responses to
the entry of foreign material.
1.
Non- Specific Immunity: involves a natural immunity
that is non-specific.
2.
Specific Immunity (adaptive immunity): the action of
specific white blood cells (lymphocytes) to a specific
antigen (pathogen or part of) which acts to neutralize the
pathogen (also invokes production of memory cells)
2
How Does The Body Know What Cells To Attack
Self and Non-self
• All cells have marker proteins on their plasma membrane
• These proteins are the products of the MHC genes. Each
person has different MHC genes.
• Therefore marker proteins are specific to each
person/organism
• Cells with the body's own marker proteins are accepted as
“self”. These proteins are not antigenic to our own immune
system.
• Cells with foreign markers are recognised as “non-self”.
These marker proteins are antigenic for us.
How Does The Body Know What Cells To Attack
Antigens
•
The term “antigen” originates from “antibody generator”
•
Defined as a substance that, when it invades the body, will stimulate
the formation of a specific type of antibody
•
Usually protein or polysaccharide
•
May be free e.g. in the bloodstream, or attached to the cell surface of a
pathogen
•
Critical in differentiating “self” and “non-self”
•
Self antigens on the cell membranes are called “markers”.
•
Those markers critical to the success of transplantation form the
MHC (major histocompatability complex)
•
An antigen is typically a large complex molecule, not normally present
in the body, that is capable of producing an immune response
IMMUNE SYSTEM
Consists of Three Lines of Defence
Pathogen invades Tissue/ Cell
Non Specific Defence
Specific
Defence
acquired
resistance
Barriers
Physiological
Mechanisms
Chemical
Mechanisms
Phagocytes
and
NK Cells
Inflammatio
n
Basophils
Mast Cells and
platelets
Histamines &
phagocytosis
B Cells
T Cells
Memory Cells
Antibodies
Humoral Immunity
Cell Mediated
Immunity
1
2
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5
Non-Specific Immunity
reading: 246 – 250 Quick Check:1-7
Chapter 8 - Defence Against
Disease
Biozone: 147-148
7
Non-specific mechanisms
• Part of body’s natural
immunity
• Provide protection
• Are present at birth
• Either prevent entry of
pathogens or destroy
them
• Limit the onset and
development of
infection
• Directed against a wide
range of pathogens
Non-specific mechanisms:
Barriers: 1st line of defence
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1. The First Line of Defence
‘The Wall”
• The best action against micro-organisms is to
prevent their entry into the body altogether.
• The first line of defence against infection takes
place at the body surfaces.
Chapter 8 - Defence Against
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Skin
• An intact skin acts as a barrier against entry by microorganisms. A cut or abrasion will allow entry of bacteria
or viruses.
– Hardening of outer layers
• Provides a physical barrier
– Anti-bacterial and anti-fungal secretions
• Produced by sweat glands, sebaceous (oil)
glands, bacterial flora of the skin
– Lack of moisture
• Limits growth of microorganisms
The First Line of Defence continued….
Mucous Membranes
• secreted by the cells lining your respiratory tract
•
traps bacteria which are then swept upwards to the back
of the throat by the action of cilia.
• some of the mucus and bacteria is then swallowed,
coughed or sneezed out, or blown out through the nose.
• promote growth of natural flora whose secretions limit
pathogen growth
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The First Line of Defence continued….
Natural Secretions
• Many secretions of the body contain
bactericidal agents. Tears and saliva contain
lysozyme, an enzyme that cause bacteria to
lyse or burst. Acid in the stomach also kills
many bacteria.
Peristalsis
 Diarrhoea eliminates pathogens by movement
towards the anus for elimination
 Vomiting also results in removal of pathogens
from body
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The First Line of Defence continued….
Enzymes
– Lysozyme in tears, saliva, sweat, nasal
secretions and tissue fluids breaks up (lyses)
the cell wall of certain bacteria
Natural Flora
• Many different bacteria are normally found on
the skin, gut and in the vagina. These bacteria
are harmless to the body and occur naturally.
• The presence of these bacteria can inhibit the
growth of pathogenic bacteria as they compete
for nutrients and space.
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The First Line of Defence continued….
Gastro-intestinal secretions
– HCl in stomach, alkaline fluids e.g. bile in
duodenum
• Are of a pH which is outside the range
of tolerance for many microorganisms
Hairs and cilia
– Filter inhaled air
– Remove micro-organisms and other
antigenic material (e.g. pollen)
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Non-specific mechanisms:
2nd Line of defence
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The Second Line of Defence
“The Dumb Soldiers”
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The Second Line of Defence continued …
PHAGOCYTES
Phagocytes (group of cells)
• (particular) white blood cells
• formed in the bone marrow
• very motile and can move between cells
• engulf and destroy micro-organisms and
foreign materials through phagocytosis
• include the following groups:
1. Neutrophils
2. Monocytes/ Macrophages
3. Eosinophils
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(a) SEM (4300x) : macrophage pulling rod-shaped E.coli towards it with long
cytoplasmic extensions. Several bacteria on the macrophage’s surface are
being engulfed
(b) Events of phagocytosis
The Second Line of Defence continued …
Monocytes
• Largest of the white blood cells
Macrophage destroying bacterial cells
• become macrophages when they leave the bloodstream
Macrophages
• gather in various tissues such as the lungs, liver, kidneys
and brain.
• are particularly active against micro-organisms that can
live inside the cells of the person they infect.
• engulf bacterium
Neutrophils
•
•
•
•
•
•
The most numerous of the phagocytotic cells
Granulated nucleus
Attacks bacteria
Die after engulfing bacterial pathogen
Their dead cells become the bulk of
‘pus’ at wounds
The Second Line of Defence continued …
Eosinophils
• can be phagocytotic.
• secrete enzymes to kill parasitic worms among other
pathogins
Non-phagocytic leucocytes Basophil
- contain granules of toxic chemicals that can
digest foreign microorganisms. These are
cells involved in an allergic response
Basophils are a type of white
blood cell (leukocyte). These
cells help you fight infections
by releasing histamine and
other chemicals like heparin
(antocoagulant)
Mast Cells
- similar to basophils, mast cells contain a
variety of inflammatory chemicals including
histamine and seratonin. Cause blood
vessels near wound to dilate! and increase
permeability of the capillaries
a large connective tissue cell that
contains histamine and heparin and
serotonin which are released in allergic
reactions or in response to injury ...
LEUKOCYTES
LEUKOCYTES
All produced in the Bone Marrow from Stem Cells
Granular Leukocytes
Agranular Leukocytes
Have large, lobbed nuclei and distinctive granules
in their cytoplasm
Cytoplasm usually lacks granules
and the nucleus is more
rounded
Neutrophils
Eosinophils
Basophils
Lymphocytes
•Most
numerous
WBC
•Main phagocytotic
cell
•Ingest bacteria and
phagocytize dead
cells
•Produce
enzymes which
detoxify foreign
proteins
and
fight
parasatistic
infection
•Produce and
release heparin
and histamine
in response to
injury
or
infection
(T and B)
•Some produce
antibodies (B
Cells) and
others attack
invading cells
directly (T
Cells)
Monocytes/
Macrophages
•Largest WBC
• monocytes
grow into
macrophages
•Phagocytotic
cells that don’t
usually die after
consuming
pathogen
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The Second Line of Defence continued …
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The Second Line of Defence continued …
Complement Proteins
Phagocytes are able to recognise foreign bodies
with the aid of complement proteins.
Complement proteins help phagocytes by:
1.
Sticking to invading microorganisms to
become more readily identifiable by
phagocytes.
2.
Some stimulate phagocytes to become more
active.
3.
Some attract phagocytes to the site of
infection.
4.
Some complement proteins destroy the
membranes of
invading micro-organisms.
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Compliment Proteins continued …
Consequences of complement
fixation
 Membrane attack complex
results in lesions/holes in
foreign cell. These result
in death
 Amplifies inflammatory
response because fixation
causes the release of
vasodilators and
chemotaxis chemicals
 Foreign cell is made sticky
and easier to phagocytise
OPSONIZATION
Complement:
at least 20 different types of plasma proteins
Usually in inactive form
Bind to sugars or protein on foreign cell “complement
fixation”
The Second Line of Defence continued …
Natural killer cells (NK cells)
• are a type of lymphocyte (like macrophages)
• police the body in blood and lymph
• lyse and kill cancer cells and virus-infected cells
• act against any such target (i.e. non-specific)
• recognise certain sugars on invader’s surface
• are not phagocytic: attack membrane of target cell and
cause it, and its nucleus, to disintegrate
The Second Line of Defence continued …
Interferons.
• are a group of antiviral chemicals
• are secreted by some cells when they are
infected by virus particles.
• act on uninfected cells making them more
resistant to the virus.
• interfer with virus replication
• stimulate macrophages to destroy virus infected
cells
• are produced very early during viral infection.
• if a person develops a cold or flu, then the
interferons have failed.
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The Second Line of Defence continued …
Fever
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The Cause of Fever
Biozone– Fever p152
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The Second Line of Defence continued …
Inflammatory response
Four signs of Inflammation
1. Redness
1.
Increased blood flow to area brings chemical
and cellular agents to the site of injury and
potential infection
2. Heat
1.
Results from increased blood flow
3. Swelling
1.
2.
Because blood vessels become more
permeable and “leak” more fluid into
surrounding tissues
This encourages lymphatic return past
stationary lymphocytes in lymph nodes
4. Pain
• Adaptive because we protect area and prevent
further damage
Inflammatory response continued …
Prevents spread of damaging agents to nearby
tissues
Disposes of cell debris and pathogens
Sets the stage for repair
The Second Line of Defence continued …
Inflammation
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Inflammation
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Key Elements of the 2nd Line of Defence
FEATURE
PRODUCED/
FOUND
FUNCTION
KEY
FEATURES
Leokocyte
Monocytes
Macrophages
Neutrophils
Basophils
Eosinophils
Nk Cells
Mast Cells
Stem Cells
Interferons
Compliment
Proteins
Vasodilation
Inflammation
Fever
Interleukin-1
Prostaglandins
Pyrexia
-
Cytokines
Histamines
Seratonin
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Specific Immunity
3nd Line of defence
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The Lymphatic System
Function:
• 1. take up excess tissue fluid and return it to
the bloodstream
• 2. absorb fats at the intestinal villi and
transport to the circulatory system
• 3. defend against disease
Chapter 8 - Defence Against
Disease
The Lymphatic System
Components include:
– Bone Marrow (stem cells differentiate into lymphocytes
– Lymphocytes: T and B (plasma & memory) Cells,
Macrophages & NK cells
– Lymph vessels
– Lymph organs: Thymus, spleen,
– Lymph nodes: tonsils, adenoids, armpits, groin etc
– Lymph: fluid of the vessels containing cells of the lymph
and foreign material (antigens) that have drained into it!
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Chapter 8 - Defence Against
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Lymph Nodes
• Biozone– The Lymphatic System p153
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Specific Immunity
The Third Line of Defence
Once a pathogen or other foreign material has
entered the body, it is not only bombarded
with your non-specific defences but is subject
to attack by cells of immune system, the T
and B Lymphocytes.
This system is slower to take action but is more
specific in its attack.
T and B Cells are the bodies special forces
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Specific Immunity
The Third Line of Defence
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The Second Line of Defence continued …
• This line of defence requires a specific response
to a particular infection by the immune system
and results in adapted or acquired immunity.
• The specific immunity acquired is generally
long lasting, often for life.
• This third line of defence involves special white
blood cells known as lymphocytes.
• Lymphocytes attack the particular invader, but
also remember the attack (memory cells) so
that a latter infection may be stopped more
rapidly.
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The Second Line of Defence continued …
Two main groups of lymphocytes are involved
in specific immunity:
B Cells
T Cells
• B Cells mature in the bone marrow to produce
• T Cells leave the bone marrow and mature in
the thymus gland, where they turn into Tlymphocytes or T-cells.
• B and T Cells work together and help each
other!!
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B Cells & the
Humoral (Antibody Mediated)
Immunity
Ballistics
Chapter 8 - Defence Against
Disease
B Cells & the
Humoral (Antibody Mediated)
Immunity
• B Cells provide - Humoral (Antibody Mediated)
Immunity
• they can produce large quantities of antibodies in
response to a foreign antigen
• Must recognise ‘non-self’ antigen by binding to it to its
receptor site
• Requires a helper T- Cell to activate the B Cell
• Once activated by a Helper T Cell, it divides madly
producing two types of daughter cells including:
• Plasma B cells
• Memory B Cells
• These cells are clones of the original activated cell and
thuis produce the same antibody. This is known as the
Clonal Selection Theory (see page 255)
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B-Cells
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B-Cells in Action
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B-memory Cells
• When the plasma cells produce new antibodies
and B-cells, some produced differentiate into
other cells called B-memory cells.
• B-memory cells have the same antigenantibody specificity as the original parent B-cell.
• Memory cells can survive for many years or
even life.
• If a second infection ever occurs, the Bmemory cells react faster and more vigorously
than the initial infection.
• Remain in circulation, producing small
quantities of antibody
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B-Plasma Cells
• Produce and secrete huge quantities of
antibody molecules
• These antibodies bind with antigens forming an
antibody-Antigen complex
• Plasma cells are relatively short living &
broken down following infection
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Antibodies“immunoglobulins”
• B-cells have immunoglobulins on their surfaces.
• Immunoglobulins are proteins that identify
antigens.
• Immunoglobulins are also called antibodies.
• The immunoglobulins of each B-cell have a specific
structure and recognise only one kind of antigen.
• There are millions of antigens that the body must
be able to respond. In response to this millions of
different B-cells are produced with different
immunoglobulins on their surfaces.
• Self – tolerance is the ability of the immune system
to recognise and ignore its own tissues early in
development
• Auto-immune disorder is the condition occuring
when the body attacks
own
tissues
Chapter 8 - its
Defence
Against
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The Structure of Antibodies
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Action of Antibodies
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Action of Antibodies
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“immunoglobulins”
more facts!
•
immunoglobulins – ig for short
•
Whenon the surface of a Lymphocyte – they are receptor sites.
Off, they are antibodies!
•
both t and b cells have immunoglobulins on their surface
•
secreted immunoglobulins are called antibodies
•
it is the binding of antigen to receptor which triggers the
specific immune response
•
during maturation, the genes that determine ig structure are
continually being rearranged. this leads to new combinations of
shape and charge in the antigen binding site
•
antibodies can combine with two antigens at once. this can
cause clumping, or agglutination
•
the antigen – antibdy complex promotes phagocytosis
•
activates complement proteins
•
Chapter 8 - Defence Against
neutralizes the binding
site of
an antigen
Disease
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Clonal selection Theory
When an antigen enters the body it probably passes many B
cells before it meets one with the immunoglobulan with
which it can combine. In effect the antigen ‘selects’ the
B cell that will lead to its death
•
Antigen ‘selects’ B Cell and its immunoglobulan
•
B cell rapidly reproduces (mitosis) to produce identical daughter cells
•
Each of these reproduces rapidly to produce a large clone of cells
•
Cell cloned in this way will have exactly the same DNA and antibodies
•
Most will differentiate into in plasma B cells, others into memory cells
Chapter 8 - Defence Against
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T-Cells
• When T-cells mature in the thymus, many
different types of T-cells are produced which
recognise many different antigens.
Types of T - Cells
Helper T - Cells
Cytotoxic (Killer)
T Cells
Memory T Cells
Helper T-cells (Th)
• Release chemicals which attract phagocytes
• Stimulate cell division in B-Cells
• Produce chemicals that stimulate other T Cells
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T-Cells
Cytotoxic T-Cells (Tc)
• Another type of T-cell, cytotoxic T-cells (Tc), kills
body cells that have been infected with a virus.
• Tc cells kill the infected cell by secreting proteins that
punch holes in the membrane of the cell and the
contents ooze out.
• Tc cells can only kill a virus when it is inside a cell.
• Some Tc cells also destroy cancer cells.
Suppressor T Cells (Tsc)
• regulates immune response by turning it off
when the infection passes
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T-Cells
Cytotoxic T-Cells (Tc)
• Another type of T-cell, cytotoxic T-cells (Tc), kills
body cells that have been infected with a virus.
• Tc cells kill the infected cell by secreting proteins that
punch holes in the membrane of the cell and the
contents ooze out.
• Tc cells can only kill a virus when it is inside a cell.
• Some Tc cells also destroy cancer cells.
Memory T Cells (Tm)
• Remain in circulation (spleen) for many years after
infection
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Allergies and Hypersensitivity
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Allergies and Hypersensitivity
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Allergies and Hypersensitivity
IgE binds
with mast
cells which
are now
sensitised to
the allergenproducing
histamines –
inflammator
y response –
increase
blood
volume;
permeability
of vessels,
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Blood Groups – Blood Antigens
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Rhesus Incompatibility
• A red blood cell antigen, the rhesus factor is present on
the red blood cells of a majority of people. Such people
are rhesus positive (RH+). If the antigen is absent a
person is rhesus negative (Rh-). If a person who is Rhand comes into contact with RH+ blood will respond by
producing antibodies against the antigen. This can
become critical in pregnancy
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Rhesus Incompatibility
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Acquiring Specific Immunity
• Acquired Immunity is the term used to describe
when antibodies are required to form immunity from
a specific antigen.
• Passive Immunity is when antibodies are received
by an outside source (vaccination).
• Passive naturally occuring
Passive induced
• Active Immunity is when antibodies are produced
within a person (B-cells and T-cells).
Chapter 8 - Defence Against
Disease
• Active naturally occuring
Active induced
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Acquiring Specific
Immunity
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Acquiring Specific Immunity
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Acquiring Specific Immunity
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Classification of Bacteria
Gram Stains pages 214-215
• 1984, bacteriologist, Joachim Gram developed the gram stain
• Gram stain distinguishes between two main groups of bacteria
• Important stain to help identify which drugs are useful
• Gram Positive bacteria take up the violet colour of the stain
– Gram + have a cell wall layer of teichoic acid
– Are particularly susceptible to penicillin and sulphonamide
drugs
• Gram Negative bacteria fail to take up the stain and by default
stain pink
– Gram – have no teichoic acid in their walls and smaller
amounts of disaccharides and amino acids
– Outer layer of lipid compounds enables these bacteria to
resist penicillin and other drugs
– Also makes phagocytosis of the bacteria very difficult
– Effective drugs include streptomycin, tetracycline
– S. empidermis: gram negative (susceptible to penicillin)
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– S. ecoli: gram negative (resistant to penicillin)