Download immunology

an organism that causes disease:
Bacteria, virus, protoctist, fungi
in tissues
recognisable symptoms
specific to pathogen
natural barriers to infection in humans
• Skin: a tough physical barrier
• Lysozyme: in tears, saliva & sweat,
Antibacterial hydrolyses bacterial cell walls
• HCl in stomach: kills most pathogens –
denatures enzymes
• Epithelial lining in respiratory tract
covered in mucus, traps pathogens &
prevents them reaching the cells beneath.
Cilia sweep mucus & pathogen to trachea.
PLASMA
Infection causes an inflammatory response
• pathogen enters the tissues and releases chemicals
• blood flow to the area increases
• & capillaries become more leaky and plasma moves
in to the surrounding tissue
• phagocytes are attracted to the site & leave the blood
by squeezing through the capillary walls:
polymorphs arrive first in greatest numbers, followed
by macrophages (made from monocytes) which are
larger and longer lived.
• phagocyte membrane invaginates and encloses
around the pathogen
• which is engulfed and forms a vesicle, called a
phagosome.
• lysosomes move to the phagosome and their
membranes fuse
• releasing hydrolytic enzymes which digest the
pathogen
• the soluble products are absorbed into the cytoplasm.
• phagocytes, dead pathogens and cell debris form
pus which results in swelling
• temperature increases at the site of infection helping
to denature pathogenic enzymes
pathogenic
vacuole
pathogen
This relies on the ability of lymphocytes to recognise
self and non-self tissue.
All cells have polysaccharides, glycoproteins and
glycolipids on their surface membrane that form
antigens. These antigens can trigger an immune
response.
Antigens present on the membrane our own cells are
called self antigens.
Antigens present on the membrane of cells from other
organisms, including other people, animals, bacteria,
fungi, plants and virus’ are called non-self antigens.
These non-self antigens may trigger an immune
response.
Different pathogens have different antigens; therefore,
the immune response needs to be specific to each.
Lymphocytes have receptors on their cell surface
membranes. These are complementary in shape to
antigens allowing antigens and receptors to fit together.
The lymphocytes with receptors to self antigens are
switched off in the developing foetus, leaving only those
that are not complementary to self cells.
There are many millions of different lymphocytes, but
only a few of each. Consequently this form of response
is slow.
B Lymphocyte
T Lymphocyte
Stem cells in the
bone marrow
Bone marrow
Stem cells in the
bone marrow
Thymus gland
Type of response
Antibody
mediated
Cell mediated
How they respond
Produces antibodies in
response to non-self
antigens, usually on
bacteria and virus’ in body
fluids such as blood and
tissue fluid
Produces a range of cells in
response to non-self
antigens, usually from viral
infections, attached to body
cells
Where formed
Mature
The non-self antigen attaches to the complementary
receptor on a specific B or T lymphocyte.
The lymphocyte is sensitised and becomes activated.
It divides by mitosis to produce clones.
B lymphocytes produce B clones that will form
antibodies.
T lymphocytes produce T clones, with different cells
carrying out different functions.
This is often called clonal expansion.
non-self antigen
receptor
Macrophage
or antigen
T or B
lymphocyte
Division +
differentiation
This response is triggered by the body’s own cells that have been
changed due to the presence of non-self material within them.
Non-self antigens are presented on the cell surface membrane,
marking them as different to the other body cells. Examples
include:
Macrophages – after engulfing and breaking down a pathogen
they cut out and present the pathogen non-self antigens on their
own surface membrane.
Body cells that have been invaded by a virus present non-self
viral antigens on the body cell membrane.
Cancer (tumour) cells present abnormal antigens on their cellsurface membrane.
• Clone cells differentiate (sub-divide) into:
• Killer T-cells (cytotoxic T-cells)
– destroy virus infected cells
– attach to the antigens on the cell-surface
membrane & produce chemicals
– e.g perforin (punches holes in cell-surface
membrane) & nitric acid
– Destroying the cell
• Helper T-cells
– stimulate B to divide to increase antibody
production
– promote and speed up the process of phagocytosis
– Attach opsonins to pathogens, marking them for
attention of phagocytes
– Secrete interferon that limits the ability of viruses to
replicate
• Memory T-cells
– Circulate in body fluids & respond to future infection
by the same pathogen.
– As they are already sensitised they rapidly produce
a large clone of T lymphocytes.
Virus /
abnormal self-antigens/
transplanted foreign
tissue
•T-helper
•T-killer
Division
+
T-lymphocyte
differentiation
•T-memory
are globular proteins which are
complementary to specific antigens and
which can react with the antigens
leading to their destruction
• B lymphocytes that have complementary receptors to
a pathogen’s antigens are sensitised.
• The specific B lymphocyte divides by mitosis and
clones
• to produce large numbers of plasma cells and a small
quantity of memory cells.
• Plasma cells are short lived (a few days) but each
produce millions of antibodies.
• Antibodies neutralise pathogens by carrying out
antigen-antibody reactions.
antibodies
differentiates
into either
Plasma cell
B-lymphocyte
memory cell
The antibodies produced by a specific antibody
mediated response will be complementary in shape
to the antigens on the invading bacterium.
The antibodies attach to the antigens and cause the
antigens to clump together (agglutinate), forming an
antigen-antibody complex.
This immobilises the pathogen and eventually the
complex will be engulfed by polymorphs and other
phagocytes.
B-memory
Macrophage
or pathogen
B-lymphocyte
mitosis
&
differentiation
B-plasma
antibodies
pathogen
agglutination
pathogen
polymorph/
macrophage/
phagocyte
Ingestion &
digestion
pathogen
The antibodies can also use other methods to
defend against infection:
B memory cells can live for many years in the body
fluids.
They remain inactive until stimulated by the same
antigen again.
They are able to divide rapidly, as they are already
sensitised and produce vast numbers of plasma
cells.
This is possible because there are more memory
cells than there were correct B cells initially.
The plasma cells produce the antibodies to destroy
the pathogen, the memory cells guarantee a long
term protection.
The initial response to the antigen when meeting it
for the first time is called the primary immune
response.
The production of plasma cells and antibodies from
memory cells on subsequent encounters with the
antigen is called the secondary immune response.
Primary response
• Production of antibodies by B-plasma
cells in response to pathogen entering
the body.
• Delay in their production allows the
pathogen to reproduce and damage the
body, producing the characteristic
symptoms associated with the pathogen
• As antibodies destroy the antigens,
fewer B-cells are made and their level
falls.
secondary response
• When a person encounters the pathogen
at a later date B-memory cells rapidly
divide to produce plasma cells.
• The response is rapid as the B memory
cells are already activated.
• Larger numbers of plasma cells are
produced, so larger numbers of
antibodies.
• There is not enough time for symptoms
of the disease to develop
SECONDARY
RESPONSE
•delayed start
•slow production
•low maximum
•lasts shorter time
time interval
weeks/years
PRIMARY RESPONSE
•immediate start
•faster production
•higher maximum
•lasts longer time
ACTIVE
PASSIVE
INVOLVES:
Individuals own immune system
producing specific antibodies
Donation of antibodies from another source
CELLS
INVOLVED:
B cells, T helper cells
None
Long term
(as memory cells produced)
Short term
(no memory cells, antibodies contain foreign
antigens that evoke immune response so are
destroyed)
RESPONSE
LENGTH:
NATURAL
HOW IT
WORKS:
contract
disease
e.g. chicken
pox
ARTIFICIAL
Injection of
dead/weakened
antigen, modified
toxins from
pathogen, isolated
antigens
(vaccination) e.g.
Measles
NATURAL
Placental transfer:
Antibodies formed by
mother cross placenta
Colostrol transfer:
Colostrum in breast milk
contains antibodies
ARTIFICIAL
Serum containing antibodies
made in individual or animal
recovering from disease
injected monoclonal
antibodies made by
removing sensitised & cloned
B cells from mouse injected
with specific antigen, B cells
hybridised with cancer cells &
resulting long lived
lymphocyte grown in
fermenter makes required
large numbers of antibody.
Adv: single type of antibody
produced, less allergies
Quick way treating already ill
people . e.g. tetanus
subsequent
encounters
short latent
period
body makes
long latent period
PRIMARY
RESPONSE
NATURAL
ACTIVE
1st antigen
encounter
T helper cells
B plasma cells
Antibodies
Memory cells
Long term
immunity
ACTIVE
vaccination
chickenpox
measles
e.g.
ARTIFICIAL
ACTIVE
e.g.
TB
meningitis
rubella
tetanus
SECONDARY
RESPONSE
rapid production
of plasma cells and
antibodies
placental
transfer
NATURAL
PASSIVE
antibodies
body receives
Body does not make antibodies
against non-self antigens
PASSIVE
Short term
immunity
colostrum
ARTIFICIAL
PASSIVE
e.g.
tetanus
•
•
•
•
•
Tissue transplants
The immune response usually occurs as a
result of infection.
Transplanted tissues and organs contain
non-self antigens, which also initiate an
immune response (unless from within same
person e.g. skin grafts or between
identical twins).
Transplant rejection is the main reason
for failing transplants.
T lymphocytes are sensitised by the nonself antigens in the transplanted tissue.
These clone producing Killer T-cells that
destroy the transplanted cells.
Non-self antigens on
transplanted tissue
complementary receptors
on specific T cells
attach to non-self antigens
on transplanted cells
T cell sensitised
& divides by mitosis
producing clones
clones differentiate
KILLER T CELLS
destroy targeted non-self cells
by producing perforins
non-self cells lyse
HELPER T CELLS
Play a smaller role
aiding B plasma cells to
produce antibodies
MEMORY T CELLS
Respond if non-self cells
transplanted on a second occasion
from same donor
Inject foreign antigens
into patients so that
their immune system is
too busy to recognise
the new organ
inject drugs to destroy
antibodies produced in
the immune response
inject drugs that
prevent cell division
use radiation to prevent
stem cells in the bone
marrow from
differentiating
Inject antibodies to
destroy recipients
B & T lymphocytes
Check donated tissue
for non-self antigens
• Successful transplants require:
– Tissue typing where markers on the donor and
recipient tissue are checked, and that with the
most matched markers will be used. Tissue
matching is most likely to occur between close
relatives.
– X-rays to irradiate bone marrow and lymph
tissue to inhibit lymphocyte production and slow
down rejection. Unfortunately this increases the
chances of infection during treatment and has
unpleasant side effects.
– Immunosuppresion, using drugs to inhibit DNA
replication, & therefore cell division and cloning
of lymphocytes to delay rejection. Need to be
taken for the life of the transplant. It
compromises the immune system & infections are
more likely as the whole immune response is
depressed. Other strategies such as monoclonal
antibodies, anti-viral drugs & anti-bacterial
mouthwashes help fight any infections.
There needs to be a delicate balance between
reducing the risk of rejection and restricting
side-effects from the immunosuppressant.
LOW
LOW
HIGH
HIGH
•Increased infection risk
•Increased side effects
of toxic drugs e.g. hair
loss
BLOOD TRANSFUSIONS
• Erythrocytes (RBCs) have antigens on
their cell-surface membrane.
• The blood of any one person will not have
the antibodies that correspond to the
antigens on their RBCs, as this would trigger
an immune response.
• This is because the B lymphocytes that
would produce the antibodies that
correspond to these self-antigens are
switched off during foetal development.
• There is a variety of different antigens on the
erythrocytes of different people.
• In the ABO system there are 2 different
antigens, but 4 different possible blood groups
(known as polymorphism).
• Donated blood must be compatible with the
recipient to avoid an immune response.
• This happens because the person getting the
blood transfusion (recipient) has antibodies that
will react with antigens on the red blood cells
that they receive.
• Recipients red blood cells are not damaged by
the donors antibodies because there are not
enough to cause a response.
• If antigen and antibody are mixed they will form
antigen-antibody complexes causing the RBCs
to agglutinate or clump.
• This agglutination could block capillary
networks (particularly in the kidney) leading to
organ failure and death.
antigen
a
a antibody
ANTIGENS & ANTIBODIES PRESENT IN THE ABO BLOOD GROUP SYSTEM
RED
BLOOD
CELL
BLOOD
GROUP
ANTIGEN
ANTIBODIES
IN
PLASMA
A
B
A
B
AB
O
A & B NONE
b
b
b
b
anti-b
a
b
a
anti-a
NONE
a
anti-a & anti-b
INTERACTIONS BETWEEN ABO BLOOD GROUPS
RECIPIENT BLOOD
A
antigen A
B
DONOR
BLOOD
ANTIGEN
A
B
AB
O
anti-b
anti-a
NONE
anti-a + anti-b
















antigen B
AB
antigens A+B
O
NONE
ANTIBODY
examples
• A donor with blood group A can give blood
to a recipient with blood group A because
the recipient has no anti-a antibodies that
correspond to the A antigens on the
donor’s RBCs.
• A donor with blood group A cannot give
blood to a recipient with blood group B
because the recipient has anti-A
antibodies which will react with the A
antigens on the donor’s RBCs, causing
agglutination.
Universal Donor
Universal Recipient
Has no antigens to be
agglutinated
Has no antibodies to
agglutinate donated
antigens
A
B
O
AB
The Rhesus System
• The rhesus antigen (or antigen D) is
either present or absent on the cellsurface membrane of erythrocytes.
• Approx. 85% of individuals possess the
antigen and are described as rhesus
positive (Rh+)
• Rhesus negative individuals (Rh-) do not
possess the rhesus antigen.
• Antibodies for the rhesus antigen are
not naturally produced by the body,
therefore are absent form the plasma.
• HOWEVER, they may be produced as a
result of
–Rhesus positive blood being donated
to a rhesus negative recipient (rare due
to blood matching techniques)
–A rhesus negative mother carrying a
rhesus positive baby.
•
•
•
•
1st pregnancy
Mother rhesus negative
Baby rhesus positive
Baby’s Rh+ RBC enter mother’s bloodstream
Mother makes anti-D antibodies to destroy Rh+
antigen, a slow process, so baby born before
significant numbers are produced
2nd pregnancy
• If baby is Rh+ & foetal RBCs enter maternal
circulation, relevant B lymphocytes are already
sensitised and large numbers of anti-D antibodies
are produced immediately.
• Anti-D antibodies cross the placenta & enter baby’s
bloodstream
• causing agglutination of foetal RBCs
-
+
+
-
+
-
-
Rhesus negative RBC
+
Rhesus positive RBC
Rhesus antibody
•
•
•
•
•
2nd pregnancy
This is known as haemolytic disease of the
newborn
Few cases occur as mothers identified as rhesus
negative are given an injection of anti-D antibodies
during pregnancy.
These attach to any foetal RBCs that may have
entered the maternal circulation before the mother’s
B lymphocytes are stimulated to produce ant-D
antibodies.
Following birth the mother is given another injection
of anti-D antibodies, if the baby is rhesus positive.
If the mother is not identified as rhesus negative
the baby can be treated with a blood transfusion.