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Immunity
Learning outcomes
The Aim – You should be able to do the following;
(a) [PA] recognise phagocytes and lymphocytes under the light
microscope;
(b) state the origin and describe the mode of action of phagocytes;
(c) describe the modes of action of B-lymphocytes and T-lymphocytes;
(d) explain the meaning of the term immune response, making
reference to the terms antigen, self and non-self;
(e) explain the role of memory cells in long-term immunity;
(f) relate the molecular structure of antibodies to their functions;
(g) distinguish between active and passive, natural and artificial
immunity and explain how vaccination can control disease;
(h) discuss the reasons why vaccination has eradicated smallpox but
not measles, TB, malaria, sickle cell anaemia or cholera;
First Line of Defense
saliva
antibacterial
enzymes
skin
prevents
entry
stomach acid
low pH kills
harmful
microbes
tears
antibacterial
enzymes
mucus linings
traps dirt and
microbes
“good” gut
bacteria out
compete bad
Mechanical factors
•
•
•
•
Skin
Epidermis
Mucous membrane
Body hairs
Chemical factors
• Lysozyme in sweat, tears, saliva, and
tissue fluid
• Low pH in gastric juice
• Normal microorganism in the body
competes with pathogen for attachment
and nutrient
Second Line of Defense – Nonspecific Immune
Response
These are defenses the body uses no matter what the invader
may be. These defenses include:
– Phagocytosis – done by Macrophages and Neutrophils.
– Inflammation - caused by release of Histamine from leukocytes
– Fever – caused by histamines. The fever (high temp) kills invaders by
denaturing their proteins.
Composition of Human Blood
Composition of WBC
Neutrophils
70%
Eosinophils
1.5%
Basophils
0.5%
Monocytes
4
Lymphocytes
24
White blood cells are important in the body’s natural defenses against
pathogens. The following table identifies the major WBCs function and the
type of immune response:
Phagocytic cells of the immune
system
• The phagocytic cells of the immune
system originate from the bone marrow.
• Stem cells – Cells that differentiate into
other types of cells; they are self renewing
and continually perform cell division.
• All white blood cells (macrophages and
neutrophils) arise from a type of stem cell
called the haematopoietic stem cell (HSC)
Phagocytes
• Phagocytes are produced throughout life
by the bone marrow.
• They are stored in the bone marrow
before being distributed around the
body in the blood
• They are also known as scavengers,
removing dead cells and invasive
microorganisms.
Phagocytes
Squeezing through the
capillaries to patrol tissues
(liver, spleen, lymph nodes)
• There are two kinds
(a) Neutrophils
Form about 70% of the WBC in the
blood.
Travel throughout the body tissues.
They are released in large numbers
from the bone marrow during an
infection
They are short-lived
NEUTROPHILS (Granulocytes)
• The most common type of
Phagocyte it makes up 50 to
70% of the White Blood Cells in
the body. They then engulf and
destroy any pathogens they
encounter.
• They move form blood vessels to
injured tissues due to chemotaxis
– response to chemical signals
sent by damaged cells
Neutrophils self-destruct as they
phagocytose invaders – live only
for a few days
Macrophages/Monocytes
• Larger than neutrophils
• Tend to be found in
organs (lungs, liver,
spleen, kidney and lymph
nodes) rather than be
found in the blood.
• Leave the bone marrow
and travel in the blood
as monocytes
• Crucial role in initiating
immune responses.
MONOCYTES (Agranulocytes)
• Only constitute 5%
of the leukocytes,
but very effective
• Long-lived, excellent
phagocytes
• Some microbes can
evade them
• They circulate in the
blood for some time,
then they migrate
into body tissues and
become
macrophages
Monocytes or Macrophages also release
IL1 which induces fever and also stimulates
an immune response
MACROPHAGES (Agranulocytes)
• Phagocytes - they
consume and destroy any
pathogens they encounter.
They also rid the body of
worn out cells and cellular
debris
• They do not destroy the
pathogens completely, but
cut them up to display
antigens that can be
recognized by the
lymphocytes.
(i)
•
Phagocytes & phagocytosis
(Non specific immune response)
Phagocytes
- produced & stored in bone marrow before distributed in blood circulation
- ‘feed’ like Amoeba on bacteria, viruses and dead body cells.
Neutrophils
70% of WBC in blood
travel throughout the body (blood)
Macrophages
Larger than neutrophils
found mostly in lung, brain, liver,
kidney, spleen, & lymph nodes
leave the bone marrow & travel in
squeeze through the capillary wall
and into the infected tissue, engulf and blood as MONOCYTES ⇒ then
develop into MACROPHAGES once
digest offending bacteria
settle in organs
short-lived cells released in large
numbers during infection
long-lived cells which initiate
immune response by displaying
antigens to be recognised by
lymphocytes
Stages of Inflammation
1. Vasodilation: Increase in diameter and
permeability of blood vessels.
Triggered by chemicals released by damaged
cells: histamine, kinins, prostaglandins, and
leukotrienes.
2. Phagocyte Migration and Margination:
Margination is the process in which phagocytes
stick to lining of blood vessels.
Extravasation (Emigration): Phagocytes
squeeze between endothelial cells of blood
vessels and enter surrounding tissue.
Stages of Inflammation (Continued)
Phagocytes are attracted to site of infection
through chemotaxis.
Phagocytes destroy microbes, as well as dead
and damaged host cells.
3. Tissue Repair: Dead and damaged cells
are replaced.
Second Line of Defense in Action/ Inflammatory Response
The Inflammatory Response IS A NONSPECIFIC
DEFENSE REACTION OF THE BODY TO TISSUE
DAMAGE.
1. Despite the initial defenses of the skin and mucous
membranes, pathogens sometimes enter the body.
2. When pathogens enter the body, the immune system has a
second line of defense. The body's second line of defense acts
when tissues are injured.
3. The mast cells found in connective tissues and basophils
release a chemical called HISTAMINE, when injured - which
starts a series of changes called the inflammatory response.
4. Histamine increases blood flow to the injured area and
increases the permeability of the surrounding capillaries, as a
result, fluid and neutrophils leak from blood vessels into nearby
tissue to destroy pathogens by phagocytosis.
The Second Line of Defense in Action –
cont’d.
5. Pathogens are attacked by phagocytic white blood
cells (leukocytes) such as Neutrophils and
Monocytes in response to chemokines – chemical
signals
6. Certain toxins released by pathogens may raise
body temperature, but leukocytes can do the
same by releasing molecules called pyrogens –
fevers inhibit microbial growth, speed up chemical
reactions and tissue repair
7. Antimicrobial agents collectively called the
complement system lyses invading cells
8. Interferons are proteins secreted by virusinfected cells that limit cell-to-cell spread of the
virus
(c) describe the modes of action of Blymphocytes and T-lymphocytes;
(d) explain the meaning of the term immune
response, making reference to the terms
antigen, self and non-self;
The Immune Response
Immunity: “Free from burden”. Ability of an
organism to recognize and defend itself
against specific pathogens or antigens.
Immune Response: Third line of defense.
Involves production of antibodies and
generation of specialized lymphocytes
against specific antigens.
Antigen: Molecules from a pathogen or
foreign organism that provoke a specific
immune response.
ANTIGENS ☺
• All cells possess antigens
in their cell surface
membranes which acts as
markers, enabling cells to
recognize each other.
• The body can distinguish
between its own antigens
(“self”) and a foreign
antigen (“non-self”) and
usually make antibodies
against non-self antigens.
• Microorganisms carry
antigens on their surface.
Antigens
• An antigen is a molecule which can cause
antibody formation
• Each antigen is recognized by a specific
antibody
• All cells possess antigens in their cell
surface membranes
• Usually proteins or glycoproteins
B cells and T cells
Similarities
•
Both B & T cells are produced before birth in bone
marrow.
•
Only mature lymphocytes can execute immune
response.
•
When mature, all B & T cells circulate between blood
& lymph
Differences
B cells
T cells
remain in bone marrow until they
are mature
T cells mature once migrated from
the bone marrow to the thymus
gland.
then spread throughout the body
concentrating in lymph nodes &
spleen
Membrane bound antibody
Concentrating in the blood
T cell receptors
• When the pathogen first enter the body, macrophages
engulf and digest microbes (including their antigens)
through a process of called phagocytosis.
• Some of the digested antigens are then displayed on the
surfaces of the macrophages. This is called antigen
presentation
• Any B cells whose cell surface receptors fit the antigens
respond by dividing repeatedly by mitosis & after
several generations will differentiate into PLASMA
CELLS
MHC class 2 (antigen presenting cell) ; MHC class 1 (all nucleated cells)
Clonal selection
(f) relate the molecular structure of
antibodies to their functions;
• 1 type of antibody molecule which responds to 1 antigen
• Each cell then divides to a small group of identical cells able to
produce the same type of antibody. This is known as a clone
• WHAT ARE ANTIBODIES?
Immunoglobulin
Y-shaped globular glycoproteins that identify and neutralize
foreign particles
- consist of 4 polypeptide chains: 2 heavy & 2 light chains
hold by disulphide bridges
- the variable region which is different in each type of antibody
is dictated by the amino acid sequences
-
The hinge region gives the flexibility for
antibody to bind to antigen
• Combine with viruses/toxins to prevent
them from invading cells
• Antibodies with multiple antigen binding sites
cause agglutination of bacteria reducing the
chances of spread throughout the body
• Bursting bacteria cell walls – together with
other molecules some Ab ‘punch’ holes in the
cell walls of the bacteria causing them to burst
• Attach to bacteria making it easier for
phagocytes to ingest them.
• Combine with toxins, neutralizing them and
making the, harmless, these antibodies are
called antitoxins
The cells involved are lymphocytes, called T cells
• Unlike B cells, which can recognize antigen alone on its
membrane bound antibody, T cell receptors can only recognize
antigen that is bound to cell membrane protein MHC.
• T cells develop surface receptors called T-cell receptors where
they become ‘programmed’ for the antigen of their specific enemy
• If an antigen is presented to a T cell with a complementary
shaped receptor, the T cell is stimulated, increases in size and
starts to divide
• T cells reproduce rapidly, however they do not produce antibodies
like B cells
Activated T helper cells
T Helper
Killer T
recognise the non-self antigen
(from the foreign cells) that the
macrophages display on their outer
surface.
Cytotoxic (kill cell)
attack & kills body cells that have
been infected by virus, bacteria or
fungus.
release a powerful group of
chemicals called cytokines to
stimulate B cells to proliferate
Kill the infected cells by secreting
proteins (perforin) that punch holes
in the membrane of the cell, and the
stimulate macrophages to carry out contents ooze out.
phagocytosis more vigorously.
In addition to helper & killer cells, memory T cells are produced which
remain in the body & become active quickly during secondary response
(e) explain the role of memory cells in long-term
immunity;
Memory cells
• Remain circulating in the
body for a long time for
rapid response
• If the same antigen is
reintroduced a few weeks
or months after the first
infection, memory cells will
divide rapidly and develop
into plasma cells and more
memory cells.
• This allows rapid response
to future infection.
Primary response is
slow because at
this stage there are
very few B cells
that are specific to
the antigen
Secondary response
is faster because
there are many
memory cells which
quickly divide and
differentiate into
plasma cells
• Many more antibodies
are produced in the
secondary response
• Memory cells are the
basis of
immunological
memory
• The ability of the
immune system to
• Each time a pathogen
respond quickly to
with different antigens
antigens that it
infects us, the primary
recognizes as having
response must occur
entered the body
before we become
before
immune and during that
time we often feel ill.
(g) distinguish between active and passive,
natural and artificial immunity and
explain how vaccination can control
disease;
• Natural active immunity
(immunity gained following infection)
⇒ body manufactures antibodies when
exposed to an infectious agent.
• Artificial Active Immunity
(immunity gained by antibodies made other than in
the host)
⇒ vaccination
or immunisation
• small dose of antigen is usually safe because the pathogen
is either killed or attenuated
• individual does not contract the disease itself, but is
stimulated to manufacture antibodies against the antigen.
• second, booster, injection is given and this stimulates a
much quicker production of antibody
• Natural passive immunity
(immunity gained by antibodies made other than in the host)
⇒Antibodies made in one individual are passed
into another individual of the same species.
• Artificial passive immunity
⇒Antibodies which have been made in one
individual are extracted and then injected into the
blood of another individual which may, or may not,
be of the same species.
(h) discuss the reasons why vaccination has
eradicated smallpox but not measles, TB,
malaria or cholera;
Eradication of smallpox
• Smallpox was caused by variola virus & transmitted
by directed contact
It is distinguished by red spots containing transparent
fluid appearing over the body & swollen eyelids
• 12-30 % of sufferers died while many who recovered
were often blinded.
• Reasons for the success of the vaccine included:
- The variola virus did not mutate and change its antigens.
- It was made from a live harmless strain of a similar virus
- Infected people were easy to identify.
- Smallpox does not infect animals.
- It could be freeze-dried & kept for 6 months aiding distribution
Measles
• Measles is caused by a virus by airborne droplets. It causes
rash & fever & fatal complications e.g. blindness & brain damage
• However, measles is still a major disease in overcrowded cities, insanitary
conditions & places with high birth rate
• This disease easily transmitted among malnourished
infants suffering Vit. A deficiency, thus have low resistance
• This disease offers the promise of eradication if
worldwide surveillance was followed-up by vaccination.
• However, so far it has failed because:
- poor response to the vaccine been shown by some children, who need nutrition.
- High birth rates and shifting populations make following-up cases difficult.
- Migrants and refugees may spread the disease.
- Measles is highly infectious & 95% immunity of a population is required to
prevent transmission.
- The vaccine only has a 95% success rate.
Poor response
- Some people do not respond at all, or not very well, to
vaccination
- This could be due to defective immune system & thus,
do not develop B & T cells OR suffer from malnutrition
& do not have protein to make antibodies
Antigenic variation
- Although each time you get a cold you have a similar
set of symptoms, each new cold is in fact caused by a
slightly different virus with slightly different antigens.
The virus that causes colds has > 113 different strains
due to high mutation rate
- No effective vaccines against malaria & sleeping sickness
- This is because the pathogens (e.g. Plasmodium & Trypanosoma) can have
numerous antigens on their surfaces at different stages in its life cycle.
- This makes it impossible for immune system to respond effectively
Antigenic concealment
- Some pathogens escape from attack by immune system by living inside
cells e.g. Plasmodium enters liver cells or RBC & protected from
antibodies
- Some pathogens remain invisible to immune system by covering their
bodies in host proteins
- It is difficult to develop effective vaccines because there is a short period
of time for an immune response to occur before the pathogen “hide”