Transcript T Cells

PowerPoint® Lecture Slides
prepared by
Janice Meeking,
Mount Royal College
CHAPTER
21
The Immune
System: Innate
and Adaptive
Body Defenses:
Part B
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Properties of specific immunity
• Specificity – activated by and responds to a specific
antigen
• Versatility – is ready to confront any antigen at any time
• Memory – “remembers” any antigen it has encountered
• Tolerance – responds to foreign substances but ignores
normal tissues
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Complete Antigens
• Substances that can mobilize the immune system and
provoke an immune response
• mostly large, complex molecules not normally found in
the body (nonself)
• Important properties of antigene:
• Immunogenicity – ability to stimulate proliferation
of specific lymphocytes and antibody production
• Reactivity – ability to react with products of
activated lymphocytes and the antibodies released in
response to them
• Complete antigens include foreign protein, nucleic acid,
some lipids, and large polysaccharides
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Haptens (Incomplete Antigens)
• Small molecules, such as peptides, nucleotides, and
many hormones, that are not immunogenic but are
reactive when attached to protein carriers
• If they link up with the body’s proteins, the adaptive
immune system may recognize them as foreign and
mount a harmful attack (allergy)
• Haptens are found in poison ivy, dander, some
detergents, and cosmetics
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Cells of the Adaptive Immune System
• Two types of lymphocytes
• B lymphocytes – oversee humoral immunity
• T lymphocytes – non-antibody-producing cells that
constitute the cell-mediated arm of immunity
• Antigen-presenting cells (APCs):
• Do not respond to specific antigens
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Lymphocytes
• Immature lymphocytes released from bone marrow are
identical
• During their development the lymphocyte:
• Must become able to recognize its one specific
antigen – become immunocompetent
• Must be relatively unresponsive to self so it will not
attack the body’s own cells – self tolerance
• Location of becoming immunocompetent is the key for a
lymphocyte to become B cell or a T cell
• B cells mature in the bone marrow
• T cells mature in the thymus
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Immunocompetent B or T cells
• It is genes, not antigens, that determine which foreign
substances our immune system will recognize and resist
• Become immunocompetent before they encounter
antigens they may later attack
• Immunocompetence - displaying a unique type of
receptor that responds to a specific antigen
• Each cell develops numerous plasma membrane proteins
that serve as antigen receptors and become
immunocompetent.
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Immunocompetent B or T cells
• An immunocompetent cell divides rapidly to form a
clone of cells with identical receptors. All clones yet to
encounter an antigen are called the virgin/naive
lymphocyte pool.
• Are exported to secondary lymphoid tissue where
encounters with antigens occur
• Mature into fully functional antigen-activated cells upon
binding with their recognized antigen
• Clonal selection of B or T cells occurs when antigens
bind to their receptors, causing them to proliferate.
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T Cells
• T cells mature in the thymus under negative and
positive selection pressures
• Positive selection
• Selects T cells capable of binding to self-MHC
proteins (MHC restriction)
• Negative selection
• Prompts apoptosis of T cells that bind to selfantigens displayed by self-MHC
• Ensures self-tolerance
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B Cells
• B cells mature in red bone marrow
• Self-reactive B cells
• Are eliminated by apoptosis (clonal deletion) or
• Undergo receptor editing – rearrangement of their
receptors
• Are inactivated (anergy) if they escape from the
bone marrow
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Antigen-Presenting Cells (APCs)
• Major rolls in immunity are:
• To engulf foreign particles
• To present fragments of antigens on their own surfaces, to be
recognized by T cells
• Major APCs are
• Dendritic cells (DCs),
• Dendritic cells (DC) are bone marrow-derived cells that are
specialized to take up, process and present antigen
• Dendritic cells are present in small quantities in tissues that
are in contact with the external environment, mainly the skin
(where they are often called Langerhans cells) and the inner
lining of the nose, lungs, stomach and the intestines.
• Macrophages that are found all over the body
• Activated B cells
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Importance of Cellular and humoral Responses
• Importance of Humoral Response (Soluble antibodies)
• The simplest ammunition of the immune response
• Interact in extracellular environments such as body secretions,
tissue fluid, blood, and lymph
• Importance of Cellular Response (T-cells)
• T cells recognize and respond only to processed fragments of
antigen displayed on the surface of body cells
• T cells are best suited for cell-to-cell interactions, and target:
• Cells infected with viruses, bacteria, or intracellular
parasites
• Abnormal or cancerous cells
• Cells of infused or transplanted foreign tissue
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Humoral Immunity Response
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Humoral Immunity Response
• Antigen challenge – first encounter between an antigen and a
naive immunocompetent cell
• Takes place usually in the spleen or lymph node
• If the lymphocyte is a B cell:
• The challenging antigen provokes a humoral immune
response
• Antibodies are produced against the challenger
• Clonal Selection - A naive, immunocompetent B cell is
activated when antigens bind to its surface receptors
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Fate of the Clones
• Most clone cells become antibody-secreting plasma cells
• Plasma cells secrete specific antibody at the rate of 2000
molecules per second
• Secreted antibodies:
• Bind to free antigens
• Mark the antigens for destruction by specific or
nonspecific mechanisms
• Clones that do not become plasma cells become memory
cells that can mount an immediate response to
subsequent exposures of the same antigen
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Antibodies
• Also called immunoglobulins
• Plasma cells make over a billion types of antibodies
• makes the gamma globulin portion of blood proteins
• Are soluble proteins secreted by activated B cells and
plasma cells in response to an antigen
• Are capable of binding specifically with that antigen
• There are five classes of antibodies: IgD, IgM, IgG, IgA,
and IgE
• Antibodies themselves do not destroy antigen; they
inactivate and tag it for destruction
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Basic Antibody Structure
• Consists of four polypeptide chains linked together with
disulfide bonds
• Two identical heavy (H) chains and two identical light
(L) chains
• The four chains bound together form an antibody monomer
• Each chain has a variable (V) region at one end and a
constant (C) region at the other
• Variable regions of the heavy and light chains combine
to form the antigen-binding site
• Constant region Determine the class of the antibody
(one of the 5 groups)
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Classes of Antibodies
• IgD – monomer attached to the surface of B cells,
important in B cell activation
• IgM – pentamer released by plasma cells during the
primary immune response
• IgG – monomer that is the most abundant and diverse
antibody in primary and secondary response; crosses the
placenta and confers passive immunity
• IgA – dimer that helps prevent attachment of pathogens to
epithelial cell surfaces
• IgE – monomer that binds to mast cells and basophils,
causing histamine release when activated
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Antibodies functions
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http://www.as.wvu.edu/~rbrundage/chapter12b/sld012.htm
Neutralization – by binding to specific sites on the antigen,
the antibody prevents its binding to cells
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Actions of antibodies – agglutination and precipitation
• Ab molecules have at least 2 binding sites
• Ag have many antigenic determinant sites
• When Ag are far apart Ab will bind with 2 binding sites to the same
antigen
• If Ag are close, Ab can bind to antigenic determinant sites of
different Ag.
• As a consequence, the Ab “tie” Ag molecules together. Such a
complex is called immune complex
• When the complexes are too big to be soluble they “sink” in a
process called precipitation
• When the target Ag are on the surface of the cell or virus the
formation of the large complex is called agglutination (example:
clumping of RBCs in incompatible blood transfusion)
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Complement Fixation and Activation
• Complement fixation:
• Main mechanism used against cellular antigens
• Antibodies bound to cells change shape and expose
complement binding sites
• This triggers complement fixation and cell lysis
• Complement activation:
• Enhances the inflammatory response
• Uses a positive feedback cycle to promote
phagocytosis
• Enlists more and more defensive elements
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Activation of complement (nonspecific reaction) – when
antibody bind to antigen, the Ab shape changes and that allows
the binding of the complement proteins (which pathway?)
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The prevention of bacterial and viral adhesion
• Covered by Ab, pathogens have reduced ability to attach to
body surfaces and penetrate.
Fig. 1: Bacterial
Adherence Via Pili
Fig. 1A: Blocking Bacterial
Adherence with Antibody
Molecules
http://www.cat.cc.md.us/courses/bio141/lecguide/unit3/humoral/abydefense/opsonization/opsonization.html
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http://www.as.wvu.edu/~rbrundage/chapter12b/sld012.htm
Phagocytes membrane carry receptors that can bind to the complex of the
complement proteins and antibodies. The binding results in much more
efficient phagocytosis. The antibodies in such a complex are called
opsonins and the effect is called opsonization (enhanced attachment )
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Other actions of antibodies
• Attraction of phagocytes – the antigen-antibody
complex attracts phgocytes that destroy pathogens
• Antibodies may promote inflammation through the
stimulation of basophils and mast cells
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Immunological Memory
• Primary response – the initial response to an antigen
• Cellular differentiation and proliferation, which occurs on the first
exposure to a specific antigen
• Lag period: 3 to 6 days after antigen challenge
• Peak levels of plasma antibody are achieved in 10 days
• Antibody levels then decline
• If the antigen is not present anymore, the antibody production
decrease. This reduction happens because:
• Plasma cells have short life span (few days)
• Suppressor T cells suppress plasma cells production
• IgM molecules are the first to appear during primary response. IgM
provide the immediate defense. This defense is limited because no
memory cells are being produced
• IgG – rise slow. Memory cells are formed
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Secondary antibody response
• Secondary immune response – re-exposure to the same antigen
• Sensitized memory cells respond within hours
• Antibody levels peak in 2 to 3 days at much higher levels than in
the primary response
• Antibodies bind with greater affinity, and their levels in the blood
can remain high for weeks to months
• Memory B cells can leave for 20 years or longer
• When a second exposure to antigen occur, memory B cells
differentiate into plasma cells
• This response is immediate because memory B cells are activated by
relatively low levels of antigen
• The antibody titer rises rapidly and to higher levels than during
primary response
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The Primary and Secondary Immune Responses
Figure 22.22
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Cellular response
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Antigen Recognition and MHC Restriction
• Immunocompetent T cells are activated when the V
regions of their surface receptors bind to a recognized
antigen
• T cells must recognize:
• Nonself (the antigen)
• Self (a MHC protein of a body cell)
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Self-Antigens: MHC Proteins
• Major histocompatibility complex - MHC proteins, mark a
cell as self
• The two classes of MHC proteins are:
• Class I MHC proteins – found on virtually all body
cells
• Class II MHC proteins – found on certain cells in the
immune response
• Each MHC molecule has a deep groove that displays a
peptide, which is a normal cellular product of protein
recycling
• In infected cells, MHC proteins bind to fragments of
foreign antigens, which play a crucial role in mobilizing
the immune system
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MHC classes – class I
• Class I – found on all nucleated cells (“hey, I’m an abnormal
cell – please kill me”)
• “Sign” infected, sick or abnormal cells that need to be
destroyed by the T-cells
• When type I are forming they “pick up” peptides from the
cytoplasm and carry them to the cell surface
• If the peptides are normal (healthy cell) the T-cells will
ignore them
• If the cytoplasm contain abnormal peptides or viral
proteins, T-cells will be activated. This activation will
lead to the cell destruction
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MHC classes – class I
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MHC classes – class II
• Class II MHC proteins are found only on mature B cells,
some T cells, and antigen-presenting cells (“Hey, this
antigen is dangerous – get rid of it”)
• Class II are found on cells that the body does not need to
destroy – it is only a mean to present non-self material
• Phagocytes cells engulf and break down pathogens
• A phagosome containing pathogens (with exogenous
antigens) merges with a lysosome
• This antigen processing creates fragments that are bound
to type II MHC and inserted into the cell membrane
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MHC classes – class II
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Cell-Mediated Immune Response
• Two major populations of T cells mediate cellular immunity:
• CD4 cells (T4 cells) are primarily helper T cells (TH)
• CD8 cells (T8 cells) are cytotoxic T cells (TC) that
destroy cells with foreign antigens
• MHC restriction – TH and TC bind to different classes of
MHC proteins
• TH / CD4 cells bind to antigen linked to class II MHC
proteins
• TC / CD8 cells are activated by antigen fragments presented
by class I MHC proteins
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Major Types of T Cells
Adaptive defenses
Cellular immunity
Immature
lymphocyte
Red bone marrow
T cell
receptor
Class II MHC
protein
T cell
receptor
Maturation
CD4
cell
Thymus
Activation
APC
(dendritic cell)
Activation
Memory
cells
CD4
Class I MHC
protein
CD8
cell
APC
(dendritic cell)
CD8
Lymphoid
tissues and
organs
Helper T cells
(or regulatory T cells)
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Effector
cells
Blood plasma
Cytotoxic T cells
Figure 21.16
Specific T-cells roles: Helper T Cells (TH)
• Regulatory cells that play a central role in the immune response
• Once primed by APC presentation of antigen, they:
• Chemically or directly stimulate proliferation of other T cells
• Stimulate B cells that have already become bound to antigen
• Without TH, there is no immune response
• TH cells interact directly with B cells that have antigen fragments
on their surfaces bound to MHC II receptors
• TH cells stimulate B cells to divide more rapidly and begin
antibody formation
• Most antigens require TH co-stimulation to activate B cells
• Cytokines released by TH amplify nonspecific defenses
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Specific T-cells roles: Cytotoxic T Cell (Tc)
• TC cells, or killer T cells, are the only T cells that can
directly attack and kill other cells
• They circulate throughout the body in search of body cells
that display the antigen to which they have been sensitized
• Their targets include:
• Virus-infected cells
• Cells with intracellular bacteria or parasites
• Cancer cells
• Foreign cells from blood transfusions or transplants
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Mechanisms of Tc Action
• Bind to the target cell and release perforin into its
membrane
• In the presence of Ca2+ perforin causes cell lysis
by creating transmembrane pores
• Secreting lymphotoxin, which fragments the target cell’s
DNA
• Secreting
gamma
interferon,
phagocytosis by macrophages
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which
stimulates
Antigen Recognition and the Activation of Cytotoxic T Cells
Figure 22.17
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Other T Cells
• Suppressor T cells (TS) – regulatory cells that release
cytokines, which suppress the activity of both T cells and
B cells
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T Cell Activation
•
APCs migrate to lymph nodes and other lymphoid
tissues to present their antigens to T cells
•
T cell activation is a two-step process
•
Antigen binding
•
Co-stimulation
•
It means that the T cell has to “check twice” to
make sure that it is APC presenting foreign antigen
•
The co-stimulation helps to ensure that the immune
system does not attack self
•
Co-stimulation will trigger clonal selection
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T Cell Activation: Co-Stimulation
• Without co-stimulation, anergy occurs
• T cells
• Become tolerant to that antigen
• Are unable to divide
• Do not secrete cytokines
• T cells that are activated
• Enlarge, proliferate, and form clones
• Differentiate and perform functions according to
their T cell class
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T Cell Activation
• Primary T cell response peaks within a week after signal
exposure
• T cells then undergo apoptosis between days 7 and 30
• Effector activity decreases as the amount of antigen declines
• The disposal of activated effector cells is a protective
mechanism for the body
• activated T-cell can be dangerous because they produce
cytokins that can promote unnecessary inflammation.
• Memory T cells remain and mediate secondary responses to
the same antigen
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A Summary of the Pathways of T Cell Activation
Figure 22.19
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