المحاضرة الثالثة المناعة المكتسبة Adaptive immunity

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The adaptive immune
response
Dr.Wael Alturaiki
Lecture 3
16.09.2015
Adaptive immune system
• The adaptive immune response is different from
the innate immune response in that it has
specificity and memory.
– Specificity – ability to recognise and respond to
particular targets.
– Memory – second exposure to the same organism
produces a larger and more rapid response than
occurred at the primary exposure.
• The adaptive immune response is much
slower than the innate immune response.
Adaptive immune system
• Lymphocytes are the effector cells of the adaptive
immune system.
• They display highly diverse receptors for antigen.
• Each cell has multiple copies of a receptor for a single
antigen only, and thus responds only to one antigen.
• Antigens are molecules which are recognised by
receptors on lymphocytes, and elicit a specific immune
response to that antigen.
• Antigen presenting cells (APCs) collect antigens from
infected tissues, and carry to lymphoid tissues to display
and activate lymphoid cells.
• Cytokines act as messengers between cells of the
immune system.
Humoral and cell-mediated
immunity
• The adaptive or specific immune response involves two
main lines of defence: humoral immunity and cell
mediated immunity.
– Humoral immunity involves B lymphocytes (B cells)
– Cell-mediated immunity involves T lymphocytes (T cells)
• Both B cells and T cells are derived from stem cells in
the bone marrow, however they mature in different
parts of the body.
– B cells mature in the bone marrow then travel to lymphatic
tissues, especially the spleen and lymph nodes
– T cells mature in the thymus
Organs of the Immune Response
•
•
The organs of your immune system
are positioned throughout your body.
They are called lymphoid organs
because they are home to
lymphocytes--the white blood cells
that are key operatives of the
immune system. Within these
organs, the lymphocytes grow,
develop, and are deployed.
•
Key organs include the bone
marrow, the thymus and the
spleen.
•
In addition to these organs, clumps
of lymphoid tissue are found in
many parts of the body, especially
in the linings of the digestive tract
and the airways and lungs-gateways to the body. These
tissues include the tonsils, adenoids
and appendix.
Tonsils and
adenoids
Thymus
Lymph
nodes
Appendix
Bone
marrow
Lymph nodes
Lymphatic
vessels
Spleen
Peyer’s
patches
Lymph nodes
Lymphatic
vessels
Lymphatic system
•
•
•
•
•
The organs of your immune
system are connected with one
another and with other organs of
the body by a network of
lymphatic vessels.
Lymphocytes can travel
throughout the body using the
blood vessels.
The cells can also travel through
a system of lymphatic vessels
that closely parallels the body’s
veins and arteries.
Cells and fluids are exchanged
between blood and lymphatic
vessels, enabling the lymphatic
system to monitor the body for
invading microbes.
The lymphatic vessels carry
lymph, a clear fluid that bathes
the body’s tissues
Lymph node
Lymphatic
vessel
Lymph Nodes
Small, bean-shaped lymph nodes sit along the lymphatic vessels, with clusters in the neck,
armpits, abdomen, and groin.
Each lymph node contains specialized compartments where immune cells congregate
and encounter antigens.
Immune cells and foreign particles enter the lymph nodes via incoming lymphatic vessels or
the lymph nodes’ tiny blood vessels. All lymphocytes exit lymph nodes through outgoing
lymphatic vessels. Once in the bloodstream, they are transported to tissues throughout the
body. They patrol everywhere for foreign antigens, then gradually drift back into the lymphatic
system to begin the cycle all over again.
The spleen is another organ of the immune system that contains specialized compartments
where immune cells gather and confront antigens.
Incoming lymphatic vessel
Germinal
center
Follicle
Medulla
Vein
Artery
Paracortex
Cortex
Outgoing lymphatic vessel
B Cells
•
B cells work chiefly by secreting soluble substances known as
antibodies.
•
There are 1000s of different B cells, each recognises a different antigen on
the surface of a macrophage.
•
Each antigen stimulates production of a single specific antibody.
•
When a B cell meets and interacts with a specific antigen, the B cell
becomes metabolically active and begins to divide.
•
To respond to most antigens, B cells need the assistance of T helper
cells (TH cells).
•
When the B cell begins to divide, two types of daughter cells are produced:
– Plasma cells – specialized antibody factory. After 5 to 8 days it can
produce up to 30000 antibody molecules per second.
– Memory cells – long-lived B cells that remain in lymphoid tissues and
are responsible for the immunity that arises following infection or
vaccination. The response of memory B cells is faster and more
sensitive.
B cells
Antigen-specific
B cell receptor
Class II MHC and
processed antigen
are displayed
Antigen
Antibodies
B cell
Lymphokines
Antigen-presenting
bacteria
Plasma cell
Activated
helper T cell
What is an antibody?
Heavy chain
•
Each antibody is made up
of two identical heavy
chains and two identical
light chains, shaped to
form a Y.
Constant region
Light chain
Antigen-binding
region
Summary of immunoglobulin classes
•
IgG
–
–
–
IgG, IgD, IgE, and IgA
•
IgM
–
–
–
•
–
–
•
–
–
Located on the surface of antibody-producing
cells
Half-life of 3 days
Important in development of the immune
response
IgE
–
–
–
IgM
Found in external secretions, tears, saliva and
milk
Half-life of 6 days
Important in mucosal immunity
IgD
–
•
Produced early in infection response
Half-life of 10 days
Involved in agglutination and complement
activation
IgA
–
IgA
Most circulating antibodies (>80%) are IgG
Half-life of 21 days in serum
Involved in agglutination and complement
activation
Produced in allergic reactions
Half-life of 2 days
Attaches to mast cells
T cells
• T cells contribute to your immune defenses in two major
ways. Some help regulate the complex workings of
the overall immune response, while others are
cytotoxic and directly contact infected cells and
destroy them.
• Four main types of T cells:
– Helper T Cells
– Killer T cells
– Suppressor T cells
– Memory T cells
Helper T cells (CD4)
• Recognise antigens on the surface of white blood cells,
particularly macrophages.
• Enlarge and form a clone of T helper cells.
• Secrete interferon and cytokines which stimulate B cells
and killer T cells.
Killer T cells
• Also called cytotoxic T cells (CD8)
• Destroy abnormal body cells e.g. virus infected or cancer
cells.
• Stimulated by cytokines released by TH cells.
• Release perforin which forms pores in target cells – this
allows water and ions in and leads to lysis of the target
cell.
• Natural killer (NK) cells are another type of lymphocyte
that acts in a similar manner to cytotoxic T (TC)cells.
• Cytotoxic T cells need to recognize a specific antigen
bound to self-MHC markers, whereas natural killer (NK)
cells will recognize and attack cells lacking these. This
gives NK cells the potential to attack many types of
foreign cells.
Suppresor/Regulatory T cells
• Suppressor T cells or regulatory T cells control the
immune system when the antigen/pathogen has been
destroyed.
Memory T cells
• Can survive a long time and give lifelong immunity from
infection.
• Can stimulate memory B cells to produce antibodies.
• Can trigger production of killer T cells.
Role of antigen receptors in the immune
response
•
Both B cells and T cells carry customized receptor molecules that allow
them to recognize and respond to their specific targets.
•
The B cell’s antigen-specific receptor that sits on its outer surface is
also a sample of the antibody it is prepared to manufacture; this
antibody-receptor recognizes antigen in its natural state.
•
The T cell’s receptor systems are more complex. T cells can recognize an
antigen only after the antigen is processed and presented in
combination with a special type of major histocompatibility complex
(MHC) marker.
•
Killer T cells (CD8) only recognize antigens in the grasp of Class I MHC
markers, while helper T cells (CD4) only recognize antigens in the grasp of
Class II MHC markers. This complicated arrangement assures that T cells
act only on precise targets and at close range.
Antigen receptors
B cell
Killer cell
Antigenspecific
receptor
Antigen
Cell
membrane
MHC
Class I
Antigen-presenting cell
Helper T cell
T cell
receptor
CD8
protein
Cell
membrane
Infected cell
Antigenic
peptide
MHC
Class I
CD4
protein
Cell
membrane
T cell
receptor
Antigenic
peptide
MHC
Class II
Antigen-presenting cell
Role of cytokines in immune response
•
Cytokines are diverse and potent chemical messengers secreted by the
cells of your immune system. They are the chief communication signals of
your T cells. Cytokines include interleukins, growth factors, and interferons.
•
Lymphocytes, including both T cells and B cells, secrete cytokines called
lymphokines, while the cytokines of monocytes and macrophages are
dubbed monokines. Many of these cytokines are also known as
interleukins because they serve as a messenger between white cells, or
leukocytes.
•
Interferons are naturally occurring cytokines that may boost the immune
system’s ability to recognize cancer as a foreign invader.
•
Binding to specific receptors on target cells, cytokines recruit many other
cells and substances to the field of action. Cytokines encourage cell growth,
promote cell activation, direct cellular traffic, and destroy target cells-including cancer cells.
•
When cytokines attract specific cell types to an area, they are called
chemokines. These are released at the site of injury or infection and call
other immune cells to the region to help repair damage and defend against
infection.
Activation of B cells to make antibody
Circulating antibody
Antigen
Antigen-specific
B cell receptor
Antigen
Class II MHC
B cell
Antigenpresenting cell
Antigen is
processed
Class II MHC Antigen-presenting cell
and
processed
antigen are
displayed
Lymphokines
Activated
helper T cell
Antibodies
Plasma cell
Activation of T cells: Helper (CD4)
Antigen is
processed
Antigen
Processed antigen
and Class II MHC
are displayed
Macrophage
Class II MHC
Monokines
Helper T cell receptor
recognizes processed
antigen plus Class II
MHC
Antigen-presenting cell
Resting helper T cell
Lymphokines
MHC Class II
Activated helper T cell
Antigenic peptide
T cell receptor
CD4 protein
Helper T cell
Activation of T cells: Cytotoxic (CD8)
Antigen is
processed
Antigen
Processed antigen
and Class II MHC
are displayed
Macrophage
Resting helper T cell
receptor recognizes
processed antigen
plus Class II MHC
Class II MHC
Monokines
Resting helper T cell
Lymphokines
Activated helper T cell
Class I MHC
Processed antigen and Class I MHC
Infected cell
Antigen (virus)
Antigenic peptide
CD8 protein
Cytotoxic T cell
Infected cell
MHC Class I
Cytotoxic T cell
becomes activated
T cell receptor
Activated
cytotoxic T cell
Processed antigen
(viral protein)
Cell
dies
Cytotoxic T cell
Reference:
 Instant nots in Immunology,2009
 Website:
https://emmanuelbiology12.wikispaces.com/file/view/Adaptive+Immune+Res
ponse.ppt
Questions
Exercise
• Q1. Explain adaptive immune response! ( definition, types
and characterization)
• Q2. Describe the activation of B and T cells
.
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