Transcript 26-17 Dendritic cells - McGraw Hill Higher Education

Chapter 26: Innate defences and the
immune system
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Evolution of immune responses
• All creatures are
subject to infection
and have
subsequently
developed means to
defend themselves
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Innate defence mechanisms
• First line of defence against infection
– external barriers
– phagocytic cells
– natural killer (NK) cells
• Non-specific immunity
– does not distinguish between pathogens
– activated rapidly when pathogens invade or after tissue
damage
– stops or retards growth of pathogen population
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External barriers
• Invading pathogens face defences when entering
body
• Enzymes
– e.g. lysozymes in tears and saliva
• Acid
– e.g. in stomach, sweat
• Bacterial flora
– e.g. in digestive tract, vagina
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Identifying an invader
• Pathogens distinguished from own (self) cells by
characteristic molecules on pathogen surface
– pathogen-associated molecular patterns (PAMP)
• Recognition of PAMPs results in release of
cytokines (glycoproteins)
– cytokines control actions of other cells
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Complement system
• System of about 20 proteins in body fluid
• If first protein is activated, the resulting
complement cascade results in
– local inflammation
– increased activity of phagocytic cells
– cell lysis and damage
• Actions of cytokines reinforce results of
complement
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Fig. 26.4: Complement cascade
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The inflammatory response
• Local changes in damaged area resulting in
redness, swelling and warmth
• Changes
– widening of capillaries and increased blood flow
– increased vascular permeability
 release of plasma into damaged tissue
 allows host defence cells and chemicals into area
– attraction of phagocytes and other defence cells to area
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Specific acquired immunity
• Specific immunity acts on specific pathogens (one
or a few similar pathogens)
– pathogens recognised by antigens on surface
• Exposure to novel pathogen results in primary
response
• Immunological memory produces secondary
response to subsequent exposure to pathogen
– secondary response is more efficient
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Cellular and humoral immunity
• Specific responses to invading pathogens are
cellular or humoral
• Cellular
– effective against viral infections and other intracellular
parasites
– mediated by T cells (T lymphocytes)
• Humoral
– effective against extracellular infections or phases of
infections
– mediated by B cells (B lymphocytes)
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Lymphocytes and specificity
• Each lymphocyte carries a different surface
receptor
• Variety of surface receptors generated by
rearrangements during rounds of cell division
• When a lymphocyte encounters its specific
antigen, it proliferates
• Cell population increases rapidly in process of
clonal selection
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Fig. 26.10: Immune repertoire
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Fig. 26.11: Clonal selection
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T lymphocytes
• Stem cells mature into T cells in thymus
• Possess T-cell receptor (TCR) proteins on surface
for recognising antigens
• T cells that recognise self cells are destroyed and
remaining cells are released
– helper (TH) cells produce cytokines
– cytotoxic (TC) cells lyse target cells
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B lymphocytes
• B cells mature in bone marrow
• Possess antibodies (immunoglobulins) on surface
for binding to antigens in presence of TH cells
• B cells die if they do not encounter their specific
antigen within a few days
• B cells that bind to antigens differentiate
– memory cells respond to same antigen in another
infection
– plasma cells produce antibody molecules
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Phagocytic cells
• White blood cells engulf and destroy invading
pathogens, including multicellular parasites
• Mononuclear phagocytes (rounded nucleus)
– macrophages and monocytes
• Polymorphonuclear granulocytes (multilobed
nucleus)
–
–
–
–
neutrophils
eosinophils
basophils
mast cells
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Dendritic cells
• Located in lymphatic tissue
– stimulate cell differentiation
– screen out self-reactive cells
• Also in blood, mucosal surfaces (gut, nasal
passage) and skin
• Dendritic cells
– break down antigen into fragments for subsequent
presentation to T cells
– concentrate antigen on surface to stimulate B cells
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NK cells
• Natural killer (NK) cells lyse cancerous or infected
cells
• Lack TCR so do not recognise antigens
• Respond to changes in carbohydrates on surface
of self cells once they become cancerous or
infected
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Antigens
• Surface molecule that can react with the variable
region of an antibody or TCR molecule
• Protein antigens
– sequences of ten amino acids or more
– sequences (epitopes) in long proteins may be antigenic
– dendritic cells break down long sequences for
presentation to T cells
– B cells recognise antigens as sequence of whole protein
• Carbohydrate antigens
– polysaccharides more likely to stimulate B cells than T
cells
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Antibodies (immunoglobulins)
• Antigen specificity of B cell depends on
configuration of antibody on surface or secreted in
solution
• Each antibody is made up of
– variable region
 differs between antibodies and binds to antigen
– constant region
 does not differ between antibodies
 e.g. region that binds to receptors on phagocytes
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T-cell receptors (TCRs)
• TCRs are antigen-binding receptors on surface of
T cells
• Can only recognise antigens that are bound to
major histocompatibility complex (MHC)
• Once an antigen is recognised, the T cell
proliferates and differentiates
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Major histocompatibility complex
(MHC)
• MHC presents antigen to T cells
• Present on all cells, but most abundant on
professional antigen-presenting cells
– dendritic cells, macrophages, B cells
• T cells recognise combination of antigen and
associated MHC molecule
– increases specificity of T cell as T-cell clones will only
recognise antigen + that type of MHC molecule
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Fig. 26.18: MHC complex interaction
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Question 1:
Phagocytosis:
a) is carried out by cells of the adaptive immune
system
b) is restricted to macrophages
c) is important in bacterial infections
d) is a process that does not involve energy
e) results in division of the cell
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Tolerance and autoimmunity
• Random generation of antigen receptors means
that self-reactive receptors are produced
• Generally, self-reactive cells are discovered and
destroyed in the thymus (T cells) and bone marrow
(B cells)
• When this does not happen, autoimmune diseases
develop
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Lymphatic network
• Lymphocytes circulate though the body in blood
and lymphatic vessels
• Lymphatic vessels are part of lymphatic network
• Primary lymphoid organs
– thymus and bone marrow
– produce lymphocytes
• Secondary lymphoid organs
– lymph nodes, spleen, tonsils
– act as filters and site of coordinated immune response
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Fig. 26.20: Lymphocyte recirculation
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Humoral responses
• Foreign antigen is carried by dendritic cells from
site of invasion to lymph node
• TH cells differentiate into daughter cells producing
one of two sets of cytokines
– one set promotes cellular immunity
– one set promotes antibody production
• If B cells receive a signal from TH cells to produce
antibody, they differentiate into plasma cells and
manufacture IgM and other antibodies
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Cellular responses
• Controlled by cytokines from TH cells
– promote accumulation of phagocytic cells at infection
sites
– activate macrophages
• May also involve TC cells
– viral antigens from virus-infected cells appear on
specialist MHC molecules and stimulate TC cells
– TC cells then lyse infected cells, disrupting infection cycle
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Fig. 26.24: Phagocytosis and killing
of bacteria
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Question 2:
Which of the following is a correct statement about
natural killer cells?
a) They proliferate in response to antigen
b) They kill target cells by phagocytosis and
intracellular digestion
c) They are a subset of polymorphonuclear cells
d) They kill target cells in an extracellular fashion
e) They are particularly effective against certain
bacteria
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Immunity to infection
• Pathogens may possess many antigens on their
surface
• The success of the immune response depends on
which antigens elicit a response and the nature of
that response
– neutralising and disrupting antibodies
– phagocytosis
– macrophage activation
• Depends on the cytokines produced in the initial
stages of the infection
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Defence against tumours
• Most proliferating cancer cells are self cells and so
are not normally destroyed by the immune system
• It is possible that some cancers may be
recognised as non-self
– virus-induced cancers may express viral antigens on
surface
– fetal antigens may be expressed in adult tumours
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Allergy and hypersensitivity
• Reaction to non-threatening antigens can produce
unnecessary immune system responses
– allergic reactions
• Production of IgE antibody in response to allergen
antigen
• Binds to surface of mast cells, promoting
inflammatory response when antigen appears
• Allergens in blood stream may cause severe
reactions
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Fig. 26.26: Allergy
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Immunity in animals
• Invertebrate immune systems are not as specific
as those of vertebrates
• Phagocytic cells destroy pathogens and damaged
tissue
• Some organisms have antisomes that mark
material for destruction
– can by induced (produced when needed) in some
invertebrates and chordates
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Immunity in plants
• Plant cell walls provide a physical barrier to
invasion by pathogens
• Plants produce antibiotics and enzymes to destroy
pathogens (humoral mechanism)
• Plants undergo self-destruction of damaged cells
(cellular mechanism)
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Summary
• Non-specific or innate defences are the first line of
defence
• Specific immune responses are carried out by cells
called lymphocytes and assisted by other cells
such as phagocytes, dendritic cells and NK cells
• Lymphocytes continually circulate around the body
monitoring a wide range of sites
• Self-recognition is central to the immune response
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