Download 07. Immunology

Slide 1
Lecture 7 — Immunology
Structure
Learning Outcomes
• Components
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Leukocytes
Lymphoid tissue
Recognition of self
• Innate Immunity
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Physical and chemical barriers
Phagocytosis
Inflammation
1.
List the principal lymphoid
tissues and outline their roles
2.
List the differences between
innate and adaptive immunity
3.
Outline some key processes
of innate immunity
4.
Explain some key features of
adaptive immunity
5.
Explain the pathophysiology
of some immune disorders.
• Adaptive immunity
– Humoral responses (B cells)
– Cell mediated responses (T
cells)
• Immune Disorders
– Autoimmune diseases
– AIDS
Dr Alan Tuffery — Physiology
Slide 2
Medical Science — 7
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Role of the Immune System (IS)
A network of cells and tissues that:
1. Defends the body against invading pathogens
2. Removes ‘worn-out’ cells
3. Destroys abnormal/mutant cells within the
body (e.g. control of cancer)
Immune System can also have harmful effects:
1. Allergies / autoimmune diseases
2. Tissue rejection.
Dr Alan Tuffery — Physiology
Medical Science — 7
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Slide 3
Infection-causing organisms (Pathogens)
FUNGUS
Epidermophyton
floccosum
(athlete’s foot)
BACTERIA
Staphylococcus
aureus
(causes sepsis)
VIRUS
PARASITE
Tapeworm
Dr Alan Tuffery — Physiology
Polio
Medical Science — 7
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Slide 4
Components — White Blood Cells
Lymphocyte
Monocyte/macrophage
– B cells - secrete
antibodies
– T cells - directly destroy
foreign cells
– Natural Killer cells - fight
– Phagocytosis
– Secrete cytokines
(signalling molecules
other than antibodies).
viruses
Dr Alan Tuffery — Physiology
Medical Science — 7
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Slide 5
Components —
Lymphoid Tissues
CENTRAL LYMPHATIC TISSUES
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Bone marrow - site of B cell development (and preT cell)
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Thymus – site of T cell development
PERIPHERAL LYMPHATIC TISSUES
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Spleen
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Lymph nodes
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Gut-associated lymphatic tissue (GALT)
[Peyer’s Patches]
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Adenoids
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Appendix
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Tonsils.
Dr Alan Tuffery — Physiology
Medical Science — 7
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Slide 6
Components — self-recognition
Major Histocompatibilty Complex
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MHC on every (nucleated) cell
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Also known as human
leukocyte associated antigens
(HLA)
Normally the body’s immune
system does not attack cells
that carry this ‘self’ marker
i.e. MHC
No two individuals, except
identical twins, will ever
share identical MHC.
Dr Alan Tuffery — Physiology
Transplant rejection
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Medical Science — 7
Organ transplants and skin grafts
may be rejected due to presence of
MHC
To minimise rejection, the MHC of
donor and recipient are matched as
closely as possible i.e. tissue typing
Siblings usually provide the closest
match
MHC do not play a role in transfusion
reactions because red blood cells do
not have MHC.
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Slide 7
Organisation of the Immune System
IMMUNE SYSTEM
ADAPTIVE IMMUNITY
(specific; acquired)
INNATE IMMUNITY
(non-specific; natural)
Skin & mucous membranes
Phagocytosis
Inflammation
Dr Alan Tuffery — Physiology
HUMORAL-MEDIATED CELL-MEDIATED
(antibody mediated)
T cells
B cells
Medical Science — 7
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Slide 8
Innate vs Adaptive Immunity
Adaptive
Innate
(Lymphocytes)
(Phagocytosis, Inflammation)
• Specific
• Nonspecific
– Responds to specific
– Defends against any
pathogens on 2nd or
pathogen upon first
exposure
later exposure
– Responds to infectious
agents, chemical irritants,
tissue injury, burns
Dr Alan Tuffery — Physiology
Medical Science — 7
– Comes into play after
nonspecific responses
have begun.
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Slide 9
Innate Immunity
• Initial & immediate response against invasion by a
variety of pathogens
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The response is rapid and non-specific
Main mechanisms
1. Interferon, NK cells and complement system
2. Phagocytosis (by neutrophils & macrophages)
3. Inflammation.
Dr Alan Tuffery — Physiology
Medical Science — 7
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Slide 10
Innate — 1. Interferon, Natural Killer Cells
Interferon
• Released by virusattacked cells
• Protects other cells
from any virus
• Anti-cancer effects
– Slows cell division
– Enhances action of
NK cells and
cytotoxic T cells (qv)
Dr Alan Tuffery — Physiology
Natural Killer cells
• Attack virusinfected cells…
• …Cause lysis
• NB Both IF and NK
cells are non-specific
— any virus.
Medical Science — 7
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Slide 11
Innate — 1. Complement System
Many very complex actions
• Innate response is recognition of microorganisms
• Lysis of invading micro-organisms
• Also reinforces other inflammatory
responses [hence name!].
Dr Alan Tuffery — Physiology
Slide 12
Medical Science — 7
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Innate — 2. Phagocytosis
SEM macrophage engulfing bacteria
Stages of Phagocytosis
1. Attachment
2. Internalisation (0.1 s)
3. Degradation
4. Exocytosis.
S&G. 23.3
Dr Alan Tuffery — Physiology
Medical Science — 7
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Slide 13
Innate — 3. Inflammatory Response
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Atopic_Dermatitis www.gcarlson.com
1. Bacteria enter tissue/damage
2. Release of histamine
Increased blood flow
Increased vascular
permeability
3. Increased leucocytes at site
Results
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Destroy or inactivate invaders
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Remove débris
Animation of allergic (atopic) response
Prepare for healing & repair.
Dr Alan Tuffery — Physiology
Medical Science — 7
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Slide 14
Adaptive Immunity
1.
Specificity
•
1.
Lymphocytes (B and T cells) bind and respond to foreign
molecules known as antigens via antigen receptors
Diversity
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The body possesses millions of lymphocytes that can recognise
and respond to millions of antigens (one each)
Memory
•
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1st exposure to an antigen generates lymphocytes & long-lived
memory cells – next exposure to the same antigen, memory cells
react more quickly & stronger response
Self-Tolerance
•
Lymphocytes can distinguish ‘self’ (our normal antigens) from
‘non-self’ (antigens from foreign material).
Dr Alan Tuffery — Physiology
Medical Science — 7
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Slide 15
Adaptive Immunity— humoral (antibody-mediated)
1. B Cells — Clonal Selection
• Antigen fits B cell’s receptors
• Proliferation and differentiation
into …
S&G 23.7 (see Sherwood 12-11)
1. Plasma cells
• Produce antibodies in blood
• (immunoglobulins I gG, IgM, IgE, IgA, I gD)
• Short-lived
2. Memory cells (clone)
• With same receptor
• Long-lived.
Dr Alan Tuffery — Physiology
Medical Science — 7
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Slide 16
Adaptive — Cell-mediated Immunity
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T cells must become
activated before they
can attack pathogens
The antigen is
‘presented’ to the T
cell by an ANTIGEN
PRESENTING CELL
(e.g. an infected
macrophage) via its
MHC
Dr Alan Tuffery — Physiology
Medical Science — 7
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Slide 17
Activated T cell enlarges & divides into:
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CYTOTOXIC T CELLS
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HELPER T CELLS (~70% of T cells)
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kill infected cells by lysis (direct action)
secrete cytokines that enhance the activity of cytotoxic T cells;
enhance phagocytosis
stimulate development of B cells into plasma cells (indirect action)
SUPPRESSOR T CELLS
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secrete cytokines that suppress the activity of B cells, helper
T cells and cytotoxic T cells; inhibit phagocytosis.
Dr Alan Tuffery — Physiology
Medical Science — 7
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Adaptive Immunity can be
NATURAL or ARTIFICIAL
Slide 18
Adaptive Immunity
Natural
Artificial
ACTIVE
ACTIVE
PASSIVE
Antibodies are
Antibodies or
lymphocytes are passed to foetus
via placenta
produced as a
or colostrum
result of infection
Dr Alan Tuffery — Physiology
PASSIVE
Antibodies are
Antibodies that
produced as a have been produced
result of
by another animal
immunisation
or given artificially.
with a vaccine
Medical Science — 7
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Slide 19
Immune Disorders – Autoimmune Diseases
If immune system does not recognise its ‘self’ (e.g.
MHC), it reacts against normal cells and tissues
DISEASE
SYMPTOMS
• Systemic lupus
erythematosus (SLE)
• fever, arthritis, mouth ulcers,
• Rheumatoid arthritis (RA)
• inflammation and damage to
the cartilage and bone of joints
• Multiple sclerosis (MS) (p116)
• T cells attack myelin:
Blurred vision,
Muscle weakness,
Ataxia
Dr Alan Tuffery — Physiology
Slide 20
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Medical Science — 7
Immune Disorders - AIDS
AIDS is caused by Human Immunodeficiency Virus (HIV)
HIV binds to the surface of helper T cells and its nucleic acids
(RNA and DNA) enter the T cell
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Inside the cell, HIV uses the cell to make copies of itself
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HIV slowly destroys helper T cells in the body
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(Helper T cells = 70% of all T cells)
When T cell function is impaired, immune responses weaken and
other diseases develop.
Dr Alan Tuffery — Physiology
Medical Science — 7
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Slide 21
Immune Disorders - AIDS
SYMPTOMS
HIV
Fatigue, fever, swollen glands, headache
AIDS
Swollen lymph nodes, decreased T cell count;
Susceptibility to pneumonia and Kaposi sarcoma;
AIDS dementia
TRANSMISSION
Through blood, semen, vaginal secretions and breast milk.
Dr Alan Tuffery — Physiology
Medical Science — 7
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Slide 22
Learning Outcomes
1.
List the principal lymphoid tissues and outline their roles
•
2.
List the differences between innate and adaptive immunity
•
3.
Thymus (T cell dev.); Gut —B cells)
Specificity, 1st exposure, cell-mediated, speed
Outline some key processes of innate immunity
•
phagocytosis, inflammation, immune memory, self recognition)
4.
Explain some key features of adaptive immunity
5.
Explain the pathophysiology of some immune disorders.
Dr Alan Tuffery — Physiology
Medical Science — 7
22
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