Transcript Document

30
General, Organic, and
Biochemistry, 7e
Bettelheim,
Brown, and March
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30-1
30 Chapter 30
Immunochemistry
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30-2
30 The Immune System
• Figure 30.1 An overview of the immune system
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30 Innate Immunity
•
•
•
•
the first line of defense
has two forms: external and internal
is nonspecific and without memory
after a pathogen penetrates a tissue, innate immunity
creates physiological barriers, such as high O2
pressure
• when natural killer (NK) cells encounter cancerous
cells, viral infected cells, or other suspicious cells, they
attach themselves to these cells
• there is a proliferation of macrophages, which engulf
and digest bacteria and reduce inflammation
• the capillaries dilate to allow greater flow of blood to
the site of an injury
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30-4
30 Adaptive Immunity
• also called acquired immunity
• key features are specificity and memory
• uses antibodies specifically designed for each type of
invader
• the invader may be bacteria, viruses, molds, or pollen
grains
• in a second encounter with the same invader, the
response is more rapid, more vigorous, and more
prolonged
• the system is flexible; it is capable of making millions
of potential defenders
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30-5
30 Components
• antigen: a foreign substance that invades the body
• two types of white blood cells (lymphocytes) fight
against invaders: T cells and B cells
• T cells kill invaders by contact
• B cells synthesize antibodies, which are soluble
immunoglobins
• the basic molecules of the immune system belong to
the immunoglobin superfamily
• The immunoglobin superfamily
• all are glycoproteins
• the polypeptide chains of each have a constant region
and a variable region
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30 Immunoglobin Superfamily
• the constant region has the same amino acid sequence
in each of the same class of molecules
• the variable region is antigen specific
• The three representatives of the Ig superfamily:
• antibodies, which are soluble immunoglobins secreted
by the plasma cells
• T cell receptors (TcR), which recognize and bind
antigens presented to them
• major histocompability complex (MCH), which interacts
with an antigen and brings a characteristic portion of it
to the surface of the cell; such a surface presentation
them marks the diseased cell for destruction
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30 Speed of Immune Response
• the process of making the right immunoglobin is
relatively slow, often taking weeks and months
• the immune system is complex in that it involves
molecular signals and an interplay between various
cells
• its major elements are:
1. cells of the immune system
2. antigens and their perception by the immune system
3. antibodies designed to immobilize antigens
4. receptors on cells that recognize antigens
5. cytokines that control these interactions
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30 Organs and Cells
• exchange of compounds among three body fluids
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30 Lymphoid Organs
• Lymphoid organs
• the lymphatic capillary vessels drain the fluids that
bath the cells of the body
• the fluid in these vessels is called lymph
• lymphatic vessels circulate throughout the body and
enter lymphatic organs such as the thymus, spleen,
tonsils, and lymph nodes
• lymphocytes are found primarily in the lymphoid
organs; lymphocytes may be specific for a given
antigen or nonspecific
• T cells are lymphocytes that originate in bone marrow
but mature in the thymus gland
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30 Lymphoid Organs
• B cells are lymphocytes that originate and mature in
the bone marrow
• both T and B cells are found mostly in the lymph, but
small numbers are also found in the blood
• their entry into the blood is aided by signaling
molecules called cytokines
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30 The Immune System
Infection
Interferon
N O synthetas e
N onsp ecific
Macrop hages engulf
bacteria or virus an d digest them
Antigens (d iges ted ) are p res ented
on the su rface of macrophages
T cells
B cells
Sp ecific Killer T cells Memory cells
Plasma cells
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30 Internal Innate Immunity
• Cells of the internal innate immunity
• the two important cells are macrophages and natural
killer cells
• Macrophages
• they are nonspecific; they attack virtually anything that
is not recognized as part of the body
• they engulf nonself, destroy it, and display a small
portion of it on their surface
• Natural killer (NK) cells
• target abnormal cells
• once in contact, they release proteins called
performins that perforate target cell membranes
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creating pores
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30 Cells of Adaptive Immunity
• The two types of cells are T and B cells
• T cells interact with the antigen presented by the
macrophage and produce other T cells that are now
highly specific to the antigen
• when these T cells differentiate, they become killer T
cells
• killer T cells act through perforin
• other T cells become memory cells
• B cells are produced by plasma cells
• most plasma cells reside in lymph nodes
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30 Antigens and MHC
• Antigen: any molecule, usually foreign, capable
of eliciting synthesis of a specific antibody in
vertebrates
• they are also called immunogens
• three features characterize an antigen
1. foreignness
2. a molecular weight greater than 6000
3. sufficient complexity to elicit a response
• the smallest unit of an antigen capable of binding an
antibody is called the epitope
• to elicit a response, the antigen or epitope must be
brought to the surface of the infected cell
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30 MHC
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30 Immunoglobins
• Classes of immunoglobins
Class
Molecular
Weight
IgA
IgD
IgE
IgG
IgM
200,00 - 700,00
160,000
190,000
150,000
950,000
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Carbohydrate
Seru m
Con tent
Concen tration
(%)
(mg/100 mL)
7 - 12
<1
10 - 12
2-3
10 - 12
90 - 420
1 - 40
0.01 - 0.1
600 - 1800
50 - 90
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30 Immunoglobins
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30 Immunoglobins
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30 Immunoglobins
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30 B Cells and Antibodies
• antibody binding to the epitope of an antigen
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30 Divserification of Igs
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30 Monoclonal Antibodies
• when an antigen is injected into an organism, it may be
1 to 2 weeks before an antibody appears in the serum
• the antigen may have many epitopes, and the antisera
contains a mixture of immunoglobins with varying
epitope specificities
• even antibodies to a single epitope usually have a
variety of specificities
• monoclonal antibodies, in contrast, are the product of
cells cloned from a single B cell and have a single
specificity
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30 T Cells and Their Receptors
• T Cell Receptors
• each different T cell carries on its surface a unique T
cell receptor (TcR) that is specific for one antigen only
• a TcR is a glycoprotein made of two different subunits
cross-linked by disulfide bonds
• like immunoglobins, TcRs also have a constant (C) and
variable (V) regions
• TcRs can only interact when the epitope of an antigen
is presented by a MHC
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30 TcR Complex
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30 TcR Complex
• TcR alone, however, is not sufficient for antigen
binding
• also needed are proteins called cluster determinants
(CD) that act as coreceptors and/or signal transducers
• CD3 is a signal transducer
• upon antigen binding, CD3 becomes phosphorylated
which sets up a signaling cascade inside the cell
• CD4 and CD8 act as adhesion molecules as well as
signal transducers
• a unique feature of CD4 is that it binds strongly to a
glycoprotein on the surface of HIV
• through this binding to CD4, an HIV can enter and
infect T cells and cause AIDS
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30 Cytokines
• Cytokines: glycoproteins that are produced by
one cell and alters the function of another cell
• cytokines have no antigen specificity
• they are short lived and are not stored in cells
• they are released in bursts in response to all manner of
insult or injury
• they travel and bind to specific cytokine receptors on
the surface of macrophage and B and T cells, and
induce cell proliferation
• one set of cytokines are the interleukins (ILs)
• macrophages secrete IL-1 upon bacterial infection
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30 Classes of Cytokines
• Cytokines are classified by the secondary
structure of their polypeptide chains
1. four a-helical segments
• an example is IL-2, which activates other B and T cells
and macrophages
2. only b-pleated sheets in 2° structure
• an example is tumor necrosis factor (TNF)
3. both a-helical and b-pleated sheets segments
• an example is epidermal growth factor (EGF)
4. a subgroup called chemotactic cytokines (chemokines)
• they attract leukocytes to the site of infection or
inflammation
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30 Action of Cytokines
• when a tissue in injured, leukocytes are rushed to the
inflamed area
• cytokines help them migrate out of blood vessels to the
site of injury
• cytokines are also major players in
chronic inflammations
autoimmune diseases
asthma and other forms of allergic inflammation
transplant rejection
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30 How to Recognize Self
• One of the major problems facing body defenses
is how to recognize a foreign body as “not self”
and avoid attacking “self”
• Selection of T and B cells
• T cells mature in the thymus gland
• during maturation, those T cells that fail to interact with
MHC and thus cannot respond to foreign antigen are
eliminated through a selection process
• T cells that express receptors TcR that are prone to
interact with normal self antigens are also eliminated
through a selection process
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30 How to Recognize Self
• Selection of T and B cells (cont’d)
• the maturation of B cells in the bone marrow depends
on their engagement with their receptors, BcR, with
antigen
• those B cells that are prone to interact with self
antigens are eliminated before they leave the bone
marrow
• many signaling pathways control the proliferation of B
cells
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30 How to Recognize Self
• Discrimination of the cells of the innate system
• natural killer cells and macrophages have no specific
targets and no memory of what epitopes signal danger
• still, they must discriminate between normal and
abnormal cells
• innate immunity cells have activating receptors and
inhibitory receptors on their surfaces
• an inhibitory receptor recognizes the epitome of a
normal cell, binds to it, and prevents activation of killer
cells or macrophages
• when a macrophage encounters a foreign antigen, the
antigen binds to the activating receptor; this binding
prompts the macrophage to destroy the antigen
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30 How to Recognize Self
• Autoimmune diseases
• in spite of the safe guards to prevent acting against
“self”, some parts of the immune system may go awry
• autoimmune diseases include
the skin diseases psoriasis and eczema
myasthenia gravis
rheumatoid arthritis
multiple sclerosis
insulin-dependent diabetes
allergies
Crohn’s disease
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30 How to Recognize Self
• Autoimmune diseases (cont’d)
• the major drugs for treating autoimmune diseases are
the glucocorticiods, the most important of which is
cortisol
• the glucocorticoids regulate the synthesis of cytokines
either by interacting directly with their genes or
indirectly through transcription factors
• macrolid drugs, such as cyclosporine A and
rapamycin, bind to receptors in the cytosol and,
through secondary messengers, inhibit the entrance of
nuclear factors into the nucleus
• the absence of nuclear factors prevents transcription
of cytokines
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30 Immunochemistry
End
Chapter 30
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