Download Immune System

Immunity: the body’s
defense system
An immune cell (macrophage)
engulfs a yeast cell (pathogen)
Bio 1b – Zoology
Hannah Nevins
Invaders :
pathogens
• The immune system recognizes foreign
bodies and responds with the production of
immune cells and proteins
• Two strategies have evolved: the innate and
the acquired immune systems
Innate Immunity of Invertebrates
• In insects, an exoskeleton made of
chitin forms the first barrier to
pathogens
• The digestive system is protected by low pH
and an enzyme that digests microbial cell walls
called lysosome
• Hemocytes circulate within hemolymph and
carry out phagocytosis, the ingestion and
digestion of foreign substances including
bacteria
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Innate Immunity of Vertebrates
The immune system of mammals is the best
understood of the vertebrates
• Innate defenses include:
– barrier defenses, phagocytosis,
antimicrobial peptides
• Additional defenses are unique to vertebrates:
the inflammatory response and natural killer
cells
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Human Lymphatic system
Interstitial fluid
Adenoid
Tonsil
Blood
capillary
Lymph
nodes
Spleen
Tissue
cells
Lymphatic
vessel
Peyer’s patches
(small intestine)
Appendix
Lymphatic
vessels
Lymph
node
Masses of
defensive cells
Fig. 43-7
Barrier Defenses
Barrier defenses include the skin and
mucous membranes of the
respiratory, urinary, and reproductive
tracts
• Mucus traps and allows for the removal of
microbes
• Many body fluids including saliva, mucus, and
tears are hostile to microbes
• The low pH of skin and the digestive system
prevents growth of microbes
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Cellular Innate Defenses
• White blood cells (leukocytes) engulf
pathogens in the body
• Groups of pathogens are recognized by Tolllike receptors (TLR)
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Phagocytosis:
Microbes
(=eating, =cells)
engulfing
pathogens PHAGOCYTIC CELL
Vacuole
Lysosome
containing
enzymes
Exocytosis – cellular
debris is released
Fig. 43-3
Phagocytosis
 A white blood cell engulfs a microbe, then
fuses with a lysosome to destroy the
microbe
 There are different types of phagocytic cells:
 Neutrophils engulf and destroy microbes
 Macrophages are part of the lymphatic system
and are found throughout the body
 Eosinophils discharge destructive enzymes
 Dendritic cells stimulate development of
acquired immunity
Cell Types: Red &
White
How your skin keeps out pathogens
 Ruptured mast cells (in
Pathogen
Splinter
Chemical
signals
Macrophage
Mast cell
Fig. 43-8-1
  increase blood flow
  increase phagocytic
cells
Capillary
Red blood cells
tissue) release histamines
 chemical signal to
other phagocytic cells
 Capillaries dilate,
 The clotting process also
starts
Phagocytic cell
 Platelets
 Clotting factors signal
 Fibrin produced
Fig. 43-8-2
Pathogen
Splinter
Chemical
signals
Macrophage
Fluid
Mast cell
Capillary
Red blood cells
Phagocytic cell
Fig. 43-8-3
Pathogen
Splinter
Chemical
signals
Macrophage
Fluid
Mast cell
Capillary
Red blood cells
Phagocytosis
Phagocytic cell
• More phagocytic cells are released
• Pathogenic bacteria are engulfed and destroyed
• Pus, a fluid rich in white blood cells, dead microbes, and cell
debris, accumulates at the site of inflammation
Thymus
Lymphocyte
maturation
 White blood cells called
Lymph
nodes
Spleen
Lymphatic
vessels
lymphocytes recognize
and respond to
antigens, foreign
molecules
 Lymphocytes that
mature in the thymus
above the heart are
called T cells, and those
that mature in bone
marrow are called B
cells
Fig. 43-7
Acquired Immunity results from B- and
T-cells
 T-cells
 B-cells
 Thymus
 Bone marrow & spleen
 Combats viruses
 Combats bacteria
(intracellular
pathogens)
(extracellular
pathogens)
Cell Types: Red &
White
Pathogens have antigens, B-cells have
antibodies
 Antigens:
 Each pathogen type has
unique surface
molecules
 Antibody binding:
 Causes antibodies to be
secreted from B-cell
 Antibodies:
 Surface proteins of B-
cell
 Match antigens
Both B- and T-cells have Antigen binding
sites
Antigenbinding
site
Antigenbinding site
Antigenbinding
site
Disulfide
bridge
C
C
Light
chain
Variable
regions
V
V
Constant
regions
C
C
Transmembrane
region
Plasma
membrane
Heavy chains
chain
chain
Disulfide bridge
B cell
(a) B cell receptor
Cytoplasm of B cell
Cytoplasm of T cell
T cell
(b) T cell receptor
Fig. 43-9
Antigenbinding
sites
Epitopes
(antigenic
determinants)
Antigen-binding sites
Antibody A
C
Antigen
Antibody C
C
Antibody B
Fig. 43-10
Lymphocyte Development
 The acquired immune system has three
important properties:
 Receptor diversity
 A lack of reactivity against host cells
 Immunological memory
A Pathogen is tagged for Attack; a B-cell
is “selected for cloning
 Antibodies cause:
 Neutralization
 Selection causes rapid
clonal replication
 Agglutination
 Precipitation
 rupture
Selection
Replication
Fig. 43-14
Antigen molecules
B cells that
differ in
antigen
specificity
Antigen
receptor
Antibody
molecules
Clone of memory cells
Clone of plasma cells
The B-cells form Two cell Types:
 Memory Cells
 Plasma Cells
 Long-lived
 Secrete many
antibodies to mark and
block more bacteria
 Await future encounters
with specific antigen
Selection
Replication
Secondary Immune Response
 Get a disease, you get
 Immunization: injecting
natural immunization
chemical or heat
inactivated antigens
 e.g. chicken pox
 a.k.a vaccination
Antibody concentration
Primary immune response
Secondary immune response
104
103
Antibodies
Antibodies
to A
to B
102
101
1000
7
Exposure
to antigen A
14 21 28 35 42 49 56
Exposure to
antigens A and B
Time (days)
Fig. 43-15
Antibody concentration
(arbitrary units)
Primary immune response
to antigen A produces
antibodies to A.
Secondary immune response to
antigen A produces antibodies to A;
primary immune response to antigen
B produces antibodies to B.
104
103
Antibodies
to A
102
Antibodies
to B
101
100
0
7
Exposure
to antigen A
14
21
28
35
Exposure to
antigens A and B
Time (days)
42
49
56
Pathogens can evolve to avoid detection
 Some pathogens change surface proteins
 Memory cells can not recognize
 Pathogens have shorter generation time relative to host,
:. they can evolve faster
 What does this mean for the efficacy of any given
human-made antibiotic?
 Some pathogens like AIDS hide inside your body’s cells
 Intracellular invaders are dealt with by T-cells
Like B-cells, T-cells have…
 Diverse antigen receptors
 Two types: Cytotoxic T-cell, Helper T-cell
Infected cell
Antigen
fragment
Class I MHC
molecule
T cell
receptor
(a)
Microbe
Antigenpresenting
cell
1 Antigen
associates
with MHC
molecule
1
1
2
2
Cytotoxic T cell
2 T cell
recognizes
combination
(b)
Antigen
fragment
Class II MHC
molecule
T cell
receptor
Helper T cell
Cytotoxic T-cells
Cytotoxic T cell
Perforin
Granzymes
CD8
TCR
Once bound to CD8 receptor, T-cell
becomes an “active killer”
Class I MHC
molecule
Target
cell
Peptide
antigen
Fig. 43-18-1
Cytotoxic T-cells
Cytotoxic T cell
Perforin
Granzymes
CD8
TCR
Class I MHC
molecule
Target
cell
Pore
Peptide
antigen
Perforins – create pores in surface of target cell
Granzymes – enter cell initiate apoptosis (cell death)
Fig. 43-18-2
Cytotoxic T-cells
Released cytotoxic T cell
Cytotoxic T cell
Perforin
Granzymes
CD8
TCR
Dying target cell
Class I MHC
molecule
Target
cell
Pore
Peptide
antigen
Perforins – create pores in surface of target cell
Granzymes – initiate apoptosis (cell death)
Fig. 43-18-3
Fig. 43-17
Antigenpresenting
cell
Peptide antigen
Bacterium
Class II MHC molecule
CD4
TCR (T cell receptor)
Helper T cell
Humoral
immunity
(secretion of
antibodies by
plasma cells)
+
Cytokines
+
B cell
+
+
Cytotoxic T cell
Cell-mediated
immunity
(attack on
infected cells)
Cytotoxic T-cells attack diseased of
cancerous cells labeled with MHCs
 Normal cells make MHC (Major Histocompatibility
Complex) molecules
 Abnormal cells –like those with viruses – make MHCs
which bind to viral proteins
 Those antigens are presented on the surface of the
infected cell
 Then detected by cytotoxic T-cells
… and the infected cell is destroyed
Major Histocompatibility Complex Genes
have ~100 Alternative Alleles
 Each MHC type presents a different type of antigen for
T-cells to recognize as alien
 Gene polymorphism increases chances of matching
antigens
 Thus increased MHC diversity = increased disease
resistance
 One study looked at male selection using old t-shirts and
MHC analysis: females favor males with MHCs which
differ from their own --- why is this adaptive?