Download Antibodies

Animations…
• http://highered.mheducation.com/sites/007
2507470/student_view0/chapter22/animatio
n__the_immune_response.html
•
• http://www.sbs.utexas.edu/psaxena/Microbi
ologyAnimations/Animations/HumoralImmu
nity/micro_humoral.swf
What is a
cytotoxic T cell?
Differences between humoral and cell mediated immunity
Humoral Immunity
Main blood cells
involved
Where are the cells
produced and
mature?
Production of
antibodies?
How are pathogens
identified?
How are pathogens
killed?
How do cells divide
once they are
stimulated?
Cell mediated immunity
Differences between humoral and cell mediated
immunity
Humoral Immunity
Cell mediated immunity
Main blood cells
involved
B lymphocytes
T lymphocytes
Where are cells
produced and
mature?
Produced and mature in the Produced in the bone marrow,
bone marrow
mature in the thymus gland
Production of
antibodies?
Involves production of
antibodies
Does not involve production of
antibodies
How are pathogens
identified?
Via antigens in the blood/
tissue fluid
Via antigens on the surface of
infected cells.
How are pathogens
killed?
By antibodies
By specialised ‘cytotoxic T cells’
How do cells divide
once they are
stimulated?
cells divide into either
plasma cells or memory
cells
cells divide into different types
of specialist T cells
Antibodies
Learning Objective:
In order to be successful in this lesson you must be able to:
The formation of antigen-antibody complexes and the subsequent
destruction of pathogens.
The definition
of an antibody.
The structure of
an antibody.
PROGRESS
The formation of
antigen-antibody
complexes and the
subsequent
destruction of
pathogens.
Today we are covering from the
specification:
Pages 109 - 111 of your text book
Why?
Antibodies
• Antibodies are proteins synthesised by B
cells that recognise and bind to specific
antigens
• Antigens are foreign substances that
stimulate the production of antibodies
• Many of the molecules on the surface of
viruses and bacteria are antigens
Antibody Structure
The specificity of the
antibody depends on its
variable regions
Antigen
Variable
regions (red)
The constant
regions are the
same for all
antibodies
Light chain
Hinge region
Disulphide bridges
Heavy chain
Constant regions
(blue)
Each antibody has a different shaped variable region (Due to different amino acid
sequences) that is complementary to one specific antigen
Agglutination
 Antibodies can cause
microbes to stick
together
 This makes it
easier for
phagocytes
to engulf
them
How do
antibodies
function?
Neutralisation
 Some pathogens make us ill by producing toxins
 Some antibodies work by
neutralising these
toxins
Opsinisation or the Complement Cascade
 The binding of an antibody to the surface of a pathogen can
set of a chain reaction with blood proteins, which...
 ... causes the pathogen to swell up an burst.
 Viruses have proteins on their surface which recognise
and bind to receptors on the surface of the host cell
 This is how many viruses enter their host cell
 Antibodies can bind to viruses
and stop them attaching to
their host cells
Antibodies
• The remarkable specificity of antibodies makes
them promising agents for human therapy. But
there are problems…
• What is needed is a way to make "monoclonal
antibodies"
– The response of the immune system
to any antigen, even the simplest, is
polyclonal. That is, the system
manufactures antibodies of a great
range of structures.
– Even if one were to isolate a single
antibody-secreting cell, and place it
in culture, it would die out after a
few generations because of the
limited growth potential of all
normal somatic cells.
What is needed is a way
to make "monoclonal
antibodies"
Monoclonal antibodies
• This problem was solved for mice in 1975 with a
technique devised by Köhler and Milstein (for which
they were awarded a Nobel Prize).
• An antibody-secreting B cell, like any other cell, can
become cancerous. The unchecked proliferation of
such a cell is called a myeloma.
• Köhler and Milstein found a way to combine
– the unlimited growth potential of myeloma cells with
– the predetermined antibody specificity of normal immune
spleen cells.
• They did this by literally fusing myeloma cells with
antibody-secreting cells from an immunized mouse.
The technique is called somatic cell hybridization. The
result is a hybridoma.
What are the monoclonal antibodies
used for?
•
•
•
•
Separation of a chemical from a mixture
Immunoassay
Cancer treatment
Transplant surgery
http://www.biotopics.co.uk/microbes/a
ntbod.html
Ethical production and use of
monoclonal antibodies
• The development of monoclonal antibodies
has provided society with the power to treat
diseases in a whole new way.
• However with this power and opportunity
comes great responsibility.
• The use of monoclonal antibodies raises some
ethical issues
Ethical issues
Concerns for animal welfare:
• Production involves the use of mice (to produce antibodies
and cancer cells).
Religious beliefs and Natural Law (based on the principle that
God designed the world):
• To eliminate the need for humanisation of the antibody,
transgenic mice can be used (genetic engineering).
Dangers to Humans:
• There have been some deaths associated with the use of
monoclonal antibodies for the treatment of multiple
sclerosis.
• Testing for the safety of new drugs presents dangers e.g.
monoclonal antibody (TGN1412) induced multiple organ
failure in 6 healthy volunteers in London in March 2006.
Ethical issues
We must balance the advantages that a new
medicine provides with the dangers that its
production might bring. Then we can make
decisions at an individual, local, national and
global level about the ethical use of drugs such
as monoclonal anitibodies.
Learning outcomes
Student should be able to understand the following:
• Antibody structure and the formation of an antigenantibody complex
• The use of monoclonal antibodies in enabling the
targeting of specific substances and cells.
Candidates should be able to
– evaluate methodology, evidence and data relating to the
use of monoclonal antibodies
– discuss ethical issues associated with the use of
monoclonal antibodies
– explain the role of the scientific community in validating
new knowledge about monoclonal antibodies, thus
ensuring integrity
– discuss the ways in which society uses scientific knowledge
relating to monoclonal antibodies to inform decisionmaking.
Plenary: True or False?
1) Antibodies have a variable region specific to a
pathogens antigens.
2) Antibodies contain a sulphide bridge.
3) A antigen-antibody complex is formed when an
antibody binds to a pathogen’s antigens.
4) Agglutination makes it easier for phagocytes to
engulf pathogens.
5) Neutralisation only occurs with viruses.
6) Opsonisation causes phagocytes to swell and burst.
7) Antibodies can stop viruses entering host cells.
8) The primary immune response produces memory cells.
9) The secondary immune response is caused by
vaccination.
10) The secondary immune response is quicker.
Primary – establishes immunological
memory
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Primary and secondary responses
Annotate your graph of the primary and secondary responses
by adding the following labels:
- First dose of antigen
- Second dose of antigen
- Time between 1st and second exposure
- Primary response
- Secondary response
Questions:
1) Compare the primary and secondary responses in terms of
time taken, decline of antibodies and antibodies produced.
2) Memory cells are produced in the primary response, how
else could these be produced without the person being
infected?
Extra challenge: What causes the secondary response to occur
more rapidly?
LO:
Antibody Concentration – Primary and Secondary Response
Primary Response
1. Infection (Ag)
2. Lag phase
3
Antibodies produced
4
Antibody level rises
to combat infection
5
Ag dealt with
6
Ab level declines – short lived
Secondary Response
After the primary response, Antibodies do not stay in blood – the level declines
If the body is infected by the same Antigen a second time Antibodies must be made again
Re-infection causes much more rapid and a stronger immune response – concentration of Antibodies
rises sooner- reaches a higher concentration – more plasma cells than in primary response – more
cells to respond to Antigen; less time to produce same number of plasma cells –hence, a greater
[Antibody] compared to primary response; increased affinity of Antibody for Antigen.
This is due to the presence of memory cells (made during the primary response) – no need for antigen
presentation and clonal selection
Long-lived; basis of vaccination
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