Download Chapter 24 The Immune System

Chapter 24 The Immune System
Neisseria gonorrhoeae
Nertrophil
Neutrophil engulfing bacteria
Innate Immunity
先天性的免疫力
All animals have immune defenses
that are always at the ready.
Adaptive Immunity
適應性(後天)的免疫力
Vertebrates custom-tailor the
immune response to specific
pathogen.
Disorders of the
Immune System
Malfunctions of the immune response
can cause problems that range from
mild to severe.
All animals have innate immunity
病原
 Pathogens - agents that cause disease.
免疫系統
 Immune system - is the body’s system of defenses against agents
that cause disease.
先天性的免疫力
 Innate immunity is a series of defenses that
- act immediately upon infection.
- whether or not the pathogen has been encountered before.
Invertebrate Innate Immunity
Invertebrates rely solely on innate immunity, which may consist of
- an exoskeleton.
- low pH.
- the enzyme lysozyme.
- immune cells capable of phagocytosis, cellular ingestion
and digestion of foreign substances.
Vertebrates have innate and adaptive immunity.
Vertebrate Innate Immunity
Vertebrate innate immunity includes
- barriers such as skin and mucous membranes.
- nostril hairs, mucus, cilia in the respiratory tract.
嗜中性白血球
- neutrophils (phagocytic cells = phagocytes).
巨噬細胞
- macrophages (big eaters), large phagocytic cells that wander
through the interstitial fluid.
自然殺手細胞
- natural killer cells that attack cancer cells and virus-infected cells.
干擾素
- interferons, proteins produced by virus-infected cells, that help to
limit the cell-to-cell spread of viruses.
補體系統
- complement system, a group of about 30 kinds of proteins
that can act with other defense mechanisms.
The interferon mechanism against virus
Viral nucleic acid
Virus
Antiviral proteins block
viral reproduction
1
New
viruses
2 Interferon
genes
turn
on
DNA
mRNA
5
3
Interferon
molecules
Host cell 1
Makes interferon;
is killed by the virus
4
Interferon stimulates
cell to turn on genes
for antiviral proteins
Host cell 2
Is protected against the virus
by interferon from cell 1
An overview of animal immune systems
Innate immunity (24.1–3)
The response is the same whether
or not the pathogen has been
previously encountered
External
barriers (24.1)
• Skin/
exoskeleton
• Acidic
environment
• Secretions
• Mucous
membranes
• Hairs
• Cilia
Adaptive immunity
(24.4–15)
Found only in
vertebrates; previous
exposure to the
pathogen enhances the
immune response
Internal
defenses (24.1–2)
• Phagocytic cells
• NK cells
• Defensive
proteins
• Inflammatory
response (24.2)
• Antibodies (24.8–10)
• Lymphocytes
(24.11–13)
The lymphatic system (24.3)
Inflammation mobilizes the innate immune response
發炎反應
 Tissue damage triggers the inflammatory response,
a major component of our innate immunity, which can
- disinfect and clean infected tissue.
- limit the spread of infection to surrounding tissues.
 Bacterial infections can bring about an overwhelming systemic
inflammatory response leading to septic shock, characterized by
敗血性休克
- very high fever.
- low blood pressure.
The inflammatory responses
An innate body defense in vertebrates caused by a release of histamine and other
chemical alarm signals that trigger increased blood flow, a local increase in white blood cells,
and fluid leakage from the blood.
The resulting inflammatory response includes redness, heat, and swelling in the affected tissues.
Pin
Skin surface
Swelling
Bacteria
Histamine
Complement system
Blood clot
Phagocytes and
fluid move
into the area
Signaling
molecules
Phagocytes
White
blood cell
Blood vessel
1
Tissue injury; signaling
molecules, such as histamine,
are released.
2
Dilation and increased leakiness of
local blood vessels; phagocytes
migrate to the area.
3
Phagocytes (macrophages and
neutrophils) consume bacteria and
cellular debris; the tissue heals.
The lymphatic system becomes a crucial battleground
during infection
淋巴系統
Lymphatic system:
The vertebrate organ system through which
lymph circulates; includes lymph vessels,
lymph nodes, and the spleen.
The lymphatic system helps remove toxins and
pathogens from the blood and interstitial fluid and
returns fluid and solutes from the interstitial fluid
to the circulatory system.
The lymphatic system is involved in innate and adaptive immunity
and consists of a network of
- lymphatic vessels, lymph nodes and lymph.
Two main functions:
- return tissue fluid back to the circulatory system.
- fight infection.
 Lymphatic vessels 淋巴管
- collect fluid from body tissues.
- return it as lymph to the blood.
淋巴
 Lymph organs 淋巴器官
- include the spleen and lymph nodes.
- are packed with white blood cells that fight infections.
The human lymphatic system
“swollen glands”
淋巴腺腫脹
Organs
Adenoid
Tonsils
Lymphatic ducts
that drain into veins
Lymph node
Masses of
lymphocytes (adaptive immunity).
and macrophages (innate immunity).
Lymph nodes
Thymus
Lymphatic
vessels
Valve
Lymphatic vessel
Spleen
Blood capillary
Tissue cells
Interstitial fluid
Appendix
Bone
marrow
Lymphatic
capillary
Cancer
The adaptive immune response counters specific invaders
 Adaptive immunity (acquired immunity) –
is a set of defenses, found only in vertebrates, that is activated
only after exposure to specific pathogens. Adaptive immunity
differs from individual to individual, depending on what
pathogens they have been previously exposed to.
 Our immune system responds to
foreign molecules called antigens, 抗原
which elicit the adaptive immune response.
 The adaptive immune system
- is found only in the vertebrates.
- reacts to specific pathogens.
- “remembers” an invader.
Memory of the adaptive immune response
感染
主動免疫
疫苗接種
 Infection or vaccination triggers active immunity.
疫苗接種
預防接種
 Vaccination, or immunization exposes the immune system to a vaccine,
疫苗
- a harmless variant.
- part of a disease-causing microbe.
(an inactivated bacterial toxin,
a dead or weakened microbe,
a piece of a microbe)
被動免疫
 We can temporarily acquire passive immunity
by receiving premade antibodies.
A soldier receiving a vaccination against the smallpox virus
Active immunity and Passive immunity
Lymphocytes mount a dual defense
Lymphocytes 淋巴細胞、淋巴球
- are white blood cells that spend most of their time in the tissues and
organs of the lymphatic system.
- are responsible for adaptive immunity.
- originate from stem cells in the bone marrow.
- B lymphocytes or B cells continue developing in bone marrow.
- T lymphocytes or T cells develop further in the thymus.
B cell (left) and T cell (right)
The development of B cells and T cells
Stem cell
Bone
marrow
Via
blood
Immature lymphocytes
Thymus
Antigen
receptors
B cell
Via
blood
T cell
Final maturation
of B and T cells in a
lymphatic organ
Lymph
nodes,
spleen, and
other
lymphatic
organs
Humoral
immune response
Cell-mediated
immune response
The function of B cells and T cells
 B cells
體液性免疫反應
participate in the humoral immune response
and secrete antibodies into the blood and lymph.
“humors”
 T cells
細胞性免疫反應
participate in the cell-mediated immune
response, attack cells infected with bacteria or
viruses.
promote phagocytosis by other white blood cells
and by stimulating B cells to produce antibodies.
each with different antigen receptors,
capable of binding one specific type of antigen.
Humoral immunity and Cellular immunity
The humoral immune response:
makes
which bind to
B cell
Antibodies
The cell-mediated immune response:
T cell
Infected
body cell
Self-nonself complex
Antigens in
body fluid
Antigens have specific regions
where antibodies bind to them
 Antigens
- are molecules that elicit the adaptive immune response.
- usually do not belong to the host animal.
- are proteins or large polysaccharides on the surfaces of
viruses or foreign cells.
protein-coat molecules of viruses.
part of the capsules and cell walls of bacteria.
macromolecules on the surface cells or other kinds of organisms (protozoans, parasitic worms).
blood cells or tissue cells from other individual (same or different species).
foreign molecules: bacterial toxin, bee venom.
抗原決定簇
 Antigenic determinants (epitope) are specific regions on an antigen
where antibodies bind.
- an antigen usually has several different determinants.
- the antigen-binding site of an antibody and an antigenic
determinant have complementary shapes.
The binding of antibodies to antigenic determinants
Antigen-binding site
Two different
antibody
molecules
Antigen
molecule
Antigenic
determinant
Clonal selection musters defensive force
against specific antigens
 When an antigen enters the body it activates only a small subset of
lymphocytes that have complementary receptors.
細胞株選擇
 In clonal selection, the selected lymphocyte cells
作用細胞
- multiply into clones of short-lived but fast-acting effector cells,
specialized for defending against the antigen that triggered the
response.
記憶細胞
- multiply into memory cells, which confer long-term immunity.
- Plasma cells are the effector cells produced during
漿細胞
clonal selection of B cells.
Clonal selection
The clonal selection of B cells occurs in two responses.
- In the primary immune response, clonal selection produces
effector cells and memory cells that may confer lifelong immunity.
- In the secondary immune response, memory cells are activated by
a second exposure to the same antigen.
原發免疫反應
繼發免疫反應
Primary vs. secondary immune responses
- The primary immune response
- occurs upon first exposure to an antigen.
- is slower than the secondary immune response.
- The secondary immune response
- occurs upon second exposure to an antigen.
- is faster and stronger than the primary immune response.
Clonal selection of B cells in the primary and secondary
immune response
Primary immune response
2
1 B cells with
different
antigen
receptors
Secondary immune response
Antigen
molecules
Antigen
receptor
on the cell
surface
Antibody
molecules
3 First exposure
to the antigen
Cell activation:
growth, division,
and differentiation
Antigen
molecules
Antibody
molecules
4
6 Second exposure
5
to the same antigen
First clone
Endoplasmic
reticulum
Plasma (effector) cells secreting antibodies
Second clone
Clone of plasma (effector) cells
secreting antibodies
Memory cells
Clone of memory cells
The two phases of adaptive immune response
Antibody concentration
Second exposure
to antigen X,
first exposure
to antigen Y
Secondary immune
response to
antigen X
First exposure
to antigen X
Primary immune
response to
antigen X
Primary immune
response to
antigen Y
Antibodies
to Y
Antibodies
to X
0
7
14
21
35
28
Time (days)
42
49
56
Antibodies are the weapons of the
humoral immune response
Antibodies are secreted
- by plasma (effector) B cells.
- into the blood and lymph.
An antibody molecule
- is Y-shaped. 抗原結合位
- has two antigen-binding sites specific to the
antigenic determinants that elicited its secretion.
Antigen
Antigen-binding
sites
Light
chain
Light chain
C
C
Heavy
chain
Heavy chain
Antibody structure and the binding of an
antigen-binding site to its complementary antigen
A computer graphic of an antibody molecule
C: constant region
V: variable region
Five major classes of antibodies
All are mark invaders for elimination
免疫球蛋白
Ig: immunoglobulin
Antibodies mark antigens for elimination
Antibodies promote antigen elimination through several mechanisms:
1. neutralization, binding to surface proteins on a virus or bacterium
and blocking its ability to infect a host.
2. agglutination, using both binding sites of an antibody to join
invading cells together into a clump.
3. precipitation, similar to agglutination, except that the antibody
molecules link dissolved antigen molecules together.
4. activation of the complement system by antigen-antibody complexe
Effector mechanisms of the humoral immune response
Binding of antibodies to antigens
inactivates antigens by
Specific recognition-and-attack phase
Neutralization
(blocks viral binding sites;
coats bacteria)
Agglutination
of microbes
Activation of the
complement system
Complement
molecule
Bacteria
Virus
Antigen
molecules
Bacterium
Non-specific destruction phase
Precipitation of
dissolved antigens
Foreign cell
Enhances
Leads to
Phagocytosis
Cell lysis
Macrophage
Hole
Monoclonal antibodies are powerful tools
in the lab and clinic
單株抗體
 Monoclonal antibodies (mAb) are
- identical antibodies.
- produced by cells that are all descendants of a single, hybrid cell.
- form cell culture.
多株抗體
 Polyclonal antibodies are a mixture of different antibodies produced
by different clones of cells from live animals.
 To make the hybrid cell with desirable properties, two cells are fused.
1. A cancerous tumor cell, able to multiply indefinitely.
2. A normal antibody-producing B cell, which is producing the
desired antibody.
How to make a monoclonal antibodies
Applications of monoclonal antibodies
Immunofluorescence staining and western blotting (laboratory research)
Blood types (diagnosis)
Herceptin:
Anti-HER2/neu receptor antibody.
Target therapy for cancers (clinical treatment)
Monoclonal antibodies used in a home pregnancy test
Early pregnancy
(hCG in the blood and urine)
Urine is applied
to the strip
hCG
hCG/mAb
complex
hCG
Control
mAb
Helper T cells stimulate the humoral and
cell-mediated immune responses
In the cell-mediated immune response, an antigen-presenting cell
抗原呈現細胞 APC
displays
- a foreign antigen (a nonself molecule).
- one of the body’s own self proteins (MHC) to a helper T cell.
輔助性T 細胞
主要組織相容性複合體
The helper T cell’s receptors
- recognize the self-nonself complexes.
- the interaction activates the helper T cells.
The helper T cell can then activate
- cytotoxic T cells, which attack body
cells that are infected with pathogens.
- macrophages.
細胞毒性T細胞, 殺手T細胞
- B cells.
MHC: major histocompatibility complex
The activation of a helper T cell and its roles in immunity
Phagocytic cell
(yellow) engulfing
a foreign cell
Self-nonself
complex
Macrophage
Microbe
B cell
T cell
receptor
Interleukin-2
stimulates
cell division
5
3
1
2
Helper
T cell
4
6
7
Interleukin-2
activates B cells
and other T cells
Self protein
Antigen from the microbe
(nonself molecule)
Antigen-presenting
cell
Binding
site for the
self protein
Interleukin-1
stimulates the
helper T cell Binding
site for the
antigen
Humoral
immune
response
(secretion of
antibodies by
plasma cells)
Cytotoxic
T cell
Cell-mediated
immune
response
(attack on
infected cells)
Cytotoxic T cells destroy infected body cells
 Cytotoxic T cells
- are the only T cells that kill infected cells.
- bind to infected body cells.
- destroy them.
 Cytotoxic T cells also play a role in protecting the body against the
spread of some cancers (about 20% of human cancers are caused by
viruses).
How a cytotoxic T cell kills an infected cells
1
A cytotoxic T cell binds
to an infected cell.
2
Perforin makes holes in the
infected cell’s membrane,
and an enzyme that
promotes apoptosis enters.
Self-nonself
complex
Infected cell
Perforin
molecule
A hole
forming
Foreign
antigen
Cytotoxic
T cell
Enzymes that
promote
apoptosis
3
The infected cell
is destroyed.
Activation of helper T cells and cytotoxic T cells
HIV destroys helper T cells,
compromising the body’s defenses
後天免疫缺乏症候群
 AIDS (acquired immunodeficiency syndrome), results from
人類免疫缺陷病毒
infection by HIV, the human immunodeficiency virus.
The AIDS virus usually attacks helper T cells,
impairing the
- cell-mediated immune response.
- humoral immune response.
- opening the way for
opportunistic infections.
伺機性感染
A human helper T cell (red) under
attack by HIV (blue dots)
 AIDS patients typically die from
- opportunistic infections.
- cancers.
The best way to stop AIDS is to educate people about
how the virus is transmitted
The rapid evolution of HIV complicates AIDS treatment
 HIV mutates very quickly.
Natural
 New strains are resistant to AIDS drugs.
 Drug-resistant strains now infect new patients.
Dr. David Da-I Ho
selection!
A “cocktail” of three separate drugs, the current treatment for people living with HIV
The immune system depends on
our molecular fingerprints
自體移植 autograft
同系移植 isograft
系體移植 allograft
異種移植 xenograft
 The immune system normally reacts
- only against nonself substances.
- not against self.
 Transplanted organs may be rejected because the transplanted cells
lack the unique “fingerprint” of the patient’s self proteins,
called major histocompatibility complex (MHC) molecules.
主要組織相容性複合體
 Donors are used that most closely match the patient’s tissues.
 Transplants between identical twins do not typically have this problem.
Malfunction or failure of the immune system
causes disease
自體免疫性疾病
 Autoimmune diseases occur when the immune system turns
against the body’s own molecules.
 Examples of autoimmune diseases include
- lupus. 紅斑狼瘡
- rheumatoid arthritis. 類風濕性關節炎
- insulin-dependent diabetes mellitus. 胰島素依賴性糖尿病
- multiple sclerosis. 多發性硬化症
 Factors for autoimmune diseases
- Gender.
- Genetics.
- Environment.
B cell
B cell
Lupus
Rheumatoid arthritis
Tc cell
Tc cell
Multiple sclerosis
Insulin-dependent diabetes mellitus
Immunuodeficiency disease
免疫缺陷病
 Immunodeficiency diseases occur when an immune response is
- defective.
- absent.
 SCID: severe combined immunodeficiency.
嚴重複合型免疫缺乏症 “Bubble boy”
 Immunodeficiency acquired in life.
- AIDS.
- Hodgkin’s disease.
 The immune system may be weakened by
- physical stress.
- emotional stress.
(Students are more likely to be sick during a week of exams)
Allergies are overreactions to
certain environmental antigens
過敏
Allergies are hypersensitive (exaggerated) responses to otherwise
harmless antigens in our surroundings.
過敏原
Antigens that cause allergies are called allergens.
 Allergic reactions typically occur
- very rapidly.
- in response to tiny amounts of an allergen.
 Allergic reactions can occur in many parts of the body, including
- nasal passages.
- bronchi.
- skin.
 Symptoms of allergic reactions
- sneezing.
- runny nose.
- coughing.
- wheezing.
- itching.
The two stages of an allergic reaction
致敏化
Sensitization: Initial exposure to an allergen
Later exposure to the same allergen
B cell
(plasma cell)
Mast
cell
Antigenic determinant
1 An allergen (pollen
grain) enters the
bloodstream.
Histamine
2 B cells make
antibodies.
3 Antibodies
attach to a
mast cell.
4 The allergen binds
to antibodies on
a mast cell.
5 Histamine is
released, causing
allergy symptoms.
Anaphylactic shock
過敏性休克
An “epi pen” for counteraction of anaphylactic shock