Transcript Immunology - University of Montana

Immunology
Chapter 43
Immune System
• A wide variety of pathogens (including parasites)
think that animal hosts are excellent habitats and
very tasty
• To stop from becoming a bacterial hotel, animals
have ways to fight back
• Most critical component – know self from nonself cells and tissues
• Next, know how to kill the invaders without
harming yourself
Two main components of vertebrate immune response:
Why is the innate immune response critical ?
Time!
Innate Immunity - External
• Skin
– Barrier, oil glands and sweat modify pH, salt level
• Mucous Membranes
– Barrier, mucous traps and cilia removes particles
• Secretions
– Stomach acid, lysozyme
Innate Immunity – Internal
• Phagocytic cells
– Recognize non-self
– Phagocytosis – engulf invader
– Digest and display
Figure 43.4 Phagocytosis
1 Pseudopodia
surround
microbes.
Microbes
2 Microbes
are engulfed
into cell.
MACROPHAGE
3 Vacuole
containing
microbes
forms.
Vacuole
Lysosome
containing
enzymes
4 Vacuole
and lysosome
fuse.
5 Toxic
compounds
and lysosomal
enzymes
destroy microbes.
6 Microbial
debris is
released by
exocytosis.
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Innate Immunity – Internal
• Phagocytic cells
– Recognize non-self
– Phagocytosis – engulf invader
– Digest and display
• Antimicrobial proteins
– Defensins, etc. - lysis of bacterial walls
– Complement – lysis by cascade
The Defensins and
cathelicidins
home
Jan, 2001. The Defensins and cathelicidins [online]. Seacroft and St James's
University Hospitals, UK. Available from http://www.cysticfibrosismedicine.com
Anti microbial peptides called defensins and cathelicidins are innate immune
factors present in airway surface liquid and make up part of the lung's natural
defences (Bals et al, 1998; Bals et al, 1998; Singh et al, 1998). These peptides are
produced by several different cell types including airway epithelial cells,
macrophages and neutrophils. The defensins appear to be present in equivalent or
higher concentrations in cystic fibrosis lungs as compared to controls. In cystic
fibrosis their ability to kill bacteria may be impaired by the presence of abnormally
high sodium concentrations within airway surface fluids (Bals et al, 1998; Bals et al,
1998, Goldman et al, 1998). Cathelicidin peptides also appear to have a wide range
of antimicrobial activity although they may be under expressed in cystic fibrosis
airways. The development of topically administered antimicrobial peptides may
have a future role in the treatment of cystic fibrosis.
Innate Immunity – Internal
• Phagocytic cells
– Recognize non-self
– Phagocytosis – engulf invader
– Digest and display
• Antimicrobial proteins
– Defensins, etc. lysis of bacterial walls
– Complement – lysis by cascade
• Inflammatory response
– Injury causes release of signals (eg. Histamines) which increase
blood flow to site
– Causes heat and swelling
Chemical
signals released
by mac’s and
mast cells
Capillaries get
leaky, agents
move from blood
to site
Chemokines
released, attract
more cells
Neutrophils and
Mac’s eat em’ up
Innate Immunity – Internal
• Natural killer cells
– Recognize and attack infected cells or cancer cells
– Surface receptors recognize foreign antigens on self
cell
– NK attach and kill target cell (apoptosis)
• Invertebrate Immunity
– Only innate but still complex
– Has recognition factors and antibacterials
Two main components of vertebrate immune response:
Acquired Immunity
• Lymphocyte
– White blood cell that recognizes specific component
(usually protein) of an invader
• Antigen
– Any foreign component that can elicit an immune
response
• T cells
– Develop in thymus, recognize antigens by specific
receptor (T cell receptor)
• B cells
– Develop in bone marrow, recognize antigen by
specific receptor (B cell receptor)
Figure 43.7 Epitopes (antigenic determinants)
Antigenbinding
sites
Antibody A
Antigen
Antibody B
Antibody C
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Epitopes
(antigenic
determinants)
Figure 43.5 The human lymphatic system
1 Interstitial fluid bathing the
tissues, along with the white
blood cells in it, continually
enters lymphatic capillaries.
Interstitial
fluid
Lymphatic
capillary
2 Fluid inside the
lymphatic capillaries,
called lymph, flows
through lymphatic
vessels throughout
the body.
Adenoid
Tonsil
4 Lymphatic vessels
return lymph to the
blood via two large
ducts that drain into
veins near the
shoulders.
Lymph
nodes
Blood
capillary
Spleen
Peyer’s patches
(small intestine)
Tissue
cells
Lymphatic
vessel
Appendix
Lymphatic
vessels
Lymph
node
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Masses of
lymphocytes and
macrophages
3 Within lymph nodes,
microbes and foreign
particles present in
the circulating lymph
encounter macrophages, dendritic cells,
and lymphocytes,
which carry out
various defensive
actions.
Specificity –
what does he mean by that?
• Do T cells and B cells have specific
receptors?
Figure 43.8 Antigen receptors on lymphocytes
V
V
C
C
Light
chain
V
Disulfide
bridge
Antigenbinding site
V
Antigenbinding
site
Antigenbinding
site
C C
Variable
regions
Constant
regions
Transmembrane
region
V V
C C
Plasma
 chain
Heavy chains
membrane  chain
Disulfide bridge
T cell
B cell
Cytoplasm of B cell
Cytoplasm of T cell
(a) A B cell receptor consists of two identical heavy
(b) A T cell receptor consists of one
chains and two identical light chains linked by
 chain and one  chain linked by
several disulfide bridges.
a disulfide bridge.
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Specificity –
what does he mean by that?
• Do T cells and B cells have specific
receptors?
– They have different types of receptors
– Each cell’s receptors recognize only one
antigen
– Your lymphocytes can recognize thousands of
antigens, only one antigen/clone
• There are many of each clone in your bloodstream
or lymph nodes
Humoral Immunity
• Antigen presenting cell contacts and activates
helper T cells
• Cytokines (protein signals) released
– Eg. interleukins
• B and T cells activated
Figure 43.15 The central role of helper T cells in
humoral and cell-mediated immune responses
1 After a dendritic cell engulfs and degrades a bacterium, it displays
bacterial antigen fragments (peptides) complexed with a class II
MHC molecule on the cell surface. A specific helper T cell binds
to the displayed complex via its TCR with the aid of CD4. This
interaction promotes secretion of cytokines by the dendritic cell.
Cytotoxic T cell
Dendritic
cell
Bacterium
Peptide antigen
Class II MHC
molecule
Helper T cell
Cell-mediated
immunity
(attack on
infected cells)
TCR
2
3
1 CD4
Dendritic
cell
Cytokines
2 Proliferation of the T cell, stimulated
by cytokines from both the dendritic
cell and the T cell itself, gives rise to
a clone of activated helper T cells
(not shown), all with receptors for the
same MHC–antigen complex.
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
B cell
3 The cells in this clone
secrete other cytokines
that help activate B cells
and cytotoxic T cells.
Humoral
immunity
(secretion of
antibodies by
plasma cells)
Humoral Immunity
• Antigen presenting cells contacts and activates
helper T cells
• Cytokines (protein signals) released
• B and T cells activated
– Cell binding produces greater response
Humoral Immunity
• Antigen presenting cells contacts and activates
helper T cells
• Cytokines (protein signals) released
• B and T cells activated
– Cell binding produces greater response
• B cells divide (clones)
• B-cells release antibody (Plasma cells)
• Memory cells saved for later
Bacterium
Macrophage
Peptide
antigen
Class II
MHC
molecule
B cell
2
1
TCR
3
Clone of plasma cells
Endoplasmic
reticulum of
plasma cell
CD4
Cytokines
Helper T cell
Secreted antibody
molecules
Activated
helper T cell
Clone of memory
B cells
Figure 43.13 The specificity of immunological memory
1 Day 1: First
exposure to
antigen A
2 Primary
response to
antigen A
produces antibodies to A
3 Day 28:
Second exposure
to antigen A; first
exposure to
antigen B
4 Secondary response to antigen A produces antibodies
to A; primary response to antigen B produces antibodies to B
Antibody concentration
(arbitrary units)
104
103
Antibodies
to A
102
Antibodies
to B
101
100
0
7
14
21
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28
35
Time (days)
42
49
56
Cell-mediated Immunity
• Cytotoxic T cells recognize infected self
cells
• Bind to cell and initiate apoptosis (process
of cell self-destruction)
1 A specific cytotoxic T cell binds to a 2
class I MHC–antigen complex on a
target cell via its TCR with the aid of
CD8. This interaction, along with
cytokines from helper T cells, leads to
the activation of the cytotoxic cell.
The activated T cell releases perforin
molecules, which form pores in the
target cell membrane, and proteolytic
enzymes (granzymes), which enter the
target cell by endocytosis.
Cytotoxic T cell
3 The granzymes initiate apoptosis within the
target cells, leading to fragmentation of the
nucleus, release of small apoptotic bodies,
and eventual cell death. The released
cytotoxic T cell can attack other target cells.
Released
cytotoxic
T cell
Perforin
Cancer
cell
Granzymes
1 TCR
Class I MHC
molecule
Target
cell
3
CD8
2
Peptide
antigen
Apoptotic
target cell
Pore
Cytotoxic
T cell
Antibodies
• Soluble proteins that recognize antigens
on invaders
• Found in blood, mucus, and mother’s milk
• Antibody binding neutralizes invaders or
activates immune response
Immunity
• Active Immunity
– Produced by contact with an infectious agent
– Can be natural (poked with a stick) or artificial
(stuck with a needle - vaccination)
– See Jenner, milkmaids, and cowpox
• Passive Immunity
– Transfer of serum from survivor to you
– Eg. Mother’s milk, snake anti-venom
Acquired Immunodeficiency Syndrome
(AIDS)
• Human immunodeficiency virus (HIV)
infects and kills helper T cells
Acquired Immunodeficiency Syndrome
(AIDS)
• Human immunodeficiency virus (HIV)
infects and kills helper T cells
• HIV is an RNA virus, it mutates rapidly
• Once in your cells it incorporates into your
DNA
• Transmission requires someone’s body
fluid getting into you
Herpes virus – fast growth, bursts cell quickly
AIDS Virus –
Slow growth, maximum
virus production