1. Fig. 43-1
Chapter 43
The Immune System
1.5 µm

2. Pathogens (microorganisms and viruses)
Fig. 43-2
Pathogens
(microorganisms
and viruses)
INNATE IMMUNITY
Barrier defenses:
Skin
Mucous membranes
Secretions •
Recognition of traits
shared by broad ranges
of pathogens, using a
small set of receptors
Internal defenses:
Phagocytic cells
Antimicrobial proteins
Inflammatory response
Natural killer cells •
Rapid response
ACQUIRED IMMUNITY
Humoral response:
Antibodies defend against
infection in body fluids. •
Recognition of traits
specific to particular
pathogens, using a vast
array of receptors
Cell-mediated response:
Cytotoxic lymphocytes defend
against infection in body cells. •
Slower response

3. Fig. 43-3
Microbes
PHAGOCYTIC CELL
Vacuole
Lysosome
containing
enzymes

4. Activates antimicrobial peptide by infecting with bacteria
Fig. 43-4
Activates antimicrobial peptide by infecting with bacteria
Engineered to express the GFP gene upon activation of the innate immune response

5. Can a single antimicrobial peptide protect fruit flies against infection?
In 2002, Bruno Lematire et al.,
To test the function of a single antimicrobial peptide.
Drosomycin or defensin
A single antimicrobial peptide in the fly’s body can provide an effective and specific immune defense against a particular pathogen.

6. Fruit fly survival after infection by N. crassa fungi
Fig. 43-5
RESULTS
100
Wild type 75
Mutant + drosomycin
% survival 50
Mutant
Mutant + defensin 25 24 48 72 96
120
Hours post-infection
Fruit fly survival after infection by N. crassa fungi
100 75
Wild type
Mutant +
defensin
% survival 50
Mutant +
drosomycin
Mutant 25 24 48 72 96
120
Hours post-infection
Fruit fly survival after infection by M. luteus bacteria

7. 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

8. Cellular Innate Defenses
White blood cells (leukocytes) engulf pathogens in the body
Groups of pathogens are recognized by TLR, Toll-like receptors

9. Toll-like receptor or TLR
Fig. 43-6
EXTRACELLULAR
FLUID
Lipopolysaccharide
Toll-like receptor or TLR
Helper
protein
Flagellin
TLR4
WHITE
BLOOD
CELL
TLR5
VESICLE
TLR9
CpG DNA
Inflammatory
responses
TLR3
ds RNA

10. Toll-like receptor From Wikipedia,
The curved leucine-rich repeat region of Toll-like receptors, represented here by TLR3
Toll-like receptors (TLRs) are a class of proteins that play a key role in the innate immune system. They are single membrane-spanning non-catalytic receptors that recognize structurally conserved molecules derived from microbes. Once these microbes have breached physical barriers such as the skin or intestinal tract mucosa, they are recognized by TLRs which activates immune cell responses.
They receive their name from their similarity to the protein coded by the Toll gene identified in Drosophila in 1985 by Christiane Nüsslein-Volhard.[1]

11. Signaling pathway of Toll-like receptors.
Dashed grey lines represent unknown associations

13. There are different types of phagocytic cells:
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

15. Interstitial fluid Adenoid Tonsil Blood capillary Lymph nodes Spleen
Fig. 43-7
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

16. Antimicrobial Peptides and Proteins
Peptides and proteins function in innate defense by attacking microbes directly or impeding their reproduction
Interferon proteins provide innate defense against viruses and help activate macrophages
About 30 proteins make up the complement system, which causes lysis of invading cells and helps trigger inflammation

17. Inflammatory Responses
Following an injury, mast cells release histamine, which promotes changes in blood vessels; this is part of the inflammatory response
These changes increase local blood supply and allow more phagocytes and antimicrobial proteins to enter tissues
Pus, a fluid rich in white blood cells, dead microbes, and cell debris, accumulates at the site of inflammation

18. Pathogen Splinter Chemical signals Macrophage Mast cell Capillary
Fig
Pathogen
Splinter
Chemical
signals
Macrophage
Mast cell
Capillary
Red blood cells
Phagocytic cell

19. Pathogen Splinter Chemical signals Macrophage Fluid Mast cell
Fig
Pathogen
Splinter
Chemical
signals
Macrophage
Fluid
Mast cell
Capillary
Red blood cells
Phagocytic cell

20. Pathogen Splinter Chemical signals Macrophage Fluid Mast cell
Fig
Pathogen
Splinter
Chemical
signals
Macrophage
Fluid
Mast cell
Capillary
Phagocytosis
Red blood cells
Phagocytic cell

21. Specific immunity

22. Fig. 43-9 Antigen- binding site Antigen- binding site Antigen- bindingV
Disulfide
bridge V V V
Variable
regions C V V C
Constant
regions C C C C
Light
chain
Transmembrane
region
Plasma
membrane
Heavy chains
 chain
 chain
Disulfide bridge
B cell
Cytoplasm of B cell
Cytoplasm of T cell
T cell
(a) B cell receptor
(b) T cell receptor

23. Antigen- binding site Antigen- binding site V Disulfide bridge V V V
Fig. 43-9a
Antigen-
binding
site
Antigen-
binding site V
Disulfide
bridge V V V
Variable
regions C C
Constant
regions C C
Light
chain
Transmembrane
region
Plasma
membrane
Heavy chains
B cell
Cytoplasm of B cell
(a) B cell receptor

24. Antigen- binding site Variable regions V V Constant regions C C
Fig. 43-9b
Antigen-
binding
site
Variable
regions V V
Constant
regions C C
Transmembrane
region
Plasma
membrane
 chain
 chain
Disulfide bridge
Cytoplasm of T cell
T cell
(b) T cell receptor

25. Antigen-binding sites
Fig
Antigen-
binding
sites
Epitopes
(antigenic
determinants)
Antigen-binding sites
Antibody A
Antigen V V
Antibody C V V C C C C
Antibody B

26. Class I MHC molecules are found on almost all nucleated cells of the body
They display peptide antigens to cytotoxic T cells
Class II MHC molecules are located mainly on dendritic cells, macrophages, and B cells
Dendritic cells, macrophages, and B cells are antigen-presenting cells that display antigens to cytotoxic T cells and helper T cells

27. Top view: binding surface exposed to antigen receptors
Fig
Top view: binding surface
exposed to antigen receptors
Antigen
Class I MHC
molecule
Antigen
Plasma
membrane of
infected cell

28. Infected cell Microbe Antigen- presenting cell 1 Antigen associates
Fig
Infected cell
Microbe
Antigen-
presenting
cell 1
Antigen
associates
with MHC
molecule
Antigen
fragment
Antigen
fragment 1 1
Class I MHC
molecule
Class II MHC
molecule 2 2
T cell
receptor
T cell
receptor 2
T cell
recognizes
combination
(a)
Cytotoxic T cell
(b)
Helper T cell

29. Ig gene rearrangement DNA of undifferentiated B cell V37 V38 V39 V40
Fig
DNA of undifferentiated B cell
V37
V38
V39
V40 J1 J2 J3 J4 J5
Intron C 1
DNA deleted between randomly selected V and J
segments
DNA of differentiated B cell
V37
V38
V39 J5
Intron C
Functional gene
Ig gene rearrangement 2
Transcription
pre-mRNA
V39 J5
Intron C 3
RNA processing
B cell receptor
mRNA
Cap
V39 J5 C
Poly-A tail V V 4
Translation V V C C
Light-chain polypeptide V C C C
Variable
region
Constant
region
B cell

30. The mechanism of Ig diversity
1. DNA recombination
2. The joining V, D, and J domains is not always precise
3. The DNA coding for hypervariable region is hypermutation
CU

31. Origin of Self-Tolerance
Antigen receptors are generated by random rearrangement of DNA
As lymphocytes mature in bone marrow or the thymus, they are tested for self-reactivity
Lymphocytes with receptors specific for the body’s own molecules are destroyed by apoptosis, or rendered nonfunctional

32. Amplifying Lymphocytes by Clonal Selection
Fig
Antigen molecules
B cells that
differ in
antigen
specificity
Antigen
receptor
Conal selection of B calla
Antibody
molecules
Clone of plasma cells
Clone of memory cells

33. Antibody concentration
Fig
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
Antibody concentration
(arbitrary units)
Antibodies
to A
102
Antibodies
to B
101
100 7 14 21 28 35 42 49 56
Time (days)
Exposure
to antigen A
Exposure to
antigens A and B
The specifity of immunological memory

34. Fig. 43-16 Humoral (antibody-mediated) immune response
Cell-mediated immune response
Key
Antigen (1st exposure) +
Stimulates
Gives rise to
Engulfed by
Antigen-
presenting cell + + +
B cell
Helper T cell
Cytotoxic T cell + +
Memory
Helper T cells + + +
Antigen (2nd exposure) +
Memory
Cytotoxic T cells
Active
Cytotoxic T cells
Plasma cells
Memory B cells
Secreted
antibodies
Defend against extracellular pathogens by binding to antigens,
thereby neutralizing pathogens or making them better targets
for phagocytes and complement proteins.
Defend against intracellular pathogens
and cancer by binding to and lysing the
infected cells or cancer cells.

35. Humoral (antibody-mediated) immune response
Fig a
Humoral (antibody-mediated) immune response
Key
Antigen (1st exposure) +
Stimulates
Gives rise to
Engulfed by
Antigen-
presenting cell + +
B cell
Helper T cell +
Memory
Helper T cells + +
Antigen (2nd exposure)
Memory
B cells
Plasma cells +
Secreted
antibodies
Defend against extracellular pathogens

36. Fig
The central role of helper T cells in humoral and cell-mediated immune response
Antigen-
presenting
cell
Peptide antigen
Bacterium
Class II MHC molecule
CD4
TCR (T cell receptor)
Helper T cell
Cytokines +
Humoral
immunity
(secretion of
antibodies by
plasma cells) +
Cell-mediated
immunity
(attack on
infected cells) + +
B cell
Cytotoxic T cell

37. Cell-mediated immune response
Fig b
Cell-mediated immune response
Antigen (1st exposure)
Key +
Stimulates
Gives rise to
Engulfed by
Antigen-
presenting cell + +
Helper T cell
Cytotoxic T cell +
Memory
Helper T cells + +
Antigen (2nd exposure)
Active
Cytotoxic T cells +
Memory
Cytotoxic T cells
Defend against intracellular pathogens

38. Cytotoxic T cell Perforin Granzymes CD8 TCR Class I MHC molecule
Fig
Cytotoxic T cell
Perforin
Granzymes
CD8
TCR
Class I MHC
molecule
Target
cell
Peptide
antigen

39. Cytotoxic T cell Perforin Granzymes CD8 TCR Class I MHC molecule Pore
Fig
Cytotoxic T cell
Perforin
Granzymes
CD8
TCR
Class I MHC
molecule
Pore
Target
cell
Peptide
antigen

40. The killing action of cytotoxic T cells
Fig
The killing action of cytotoxic T cells
Released cytotoxic T cell
Cytotoxic T cell
Perforin
Granzymes
CD8
TCR
Dying target cell
Class I MHC
molecule
Pore
Target
cell
Peptide
antigen
----A response to infected cells

41. B cell activation in the humoral immune response
Fig
B cell activation in the humoral immune response
Antigen-presenting cell
Bacterium
Peptide
antigen
B cell
Class II MHC
molecule +
Clone of plasma cells
Secreted
antibody
molecules
TCR
CD4
Cytokines
Endoplasmic
reticulum of
plasma cell
Activated
helper T cell
Helper T cell
Clone of memory
B cells
2 µm
----A response to extracellular pathogens

42. Antigen-presenting cell Bacterium
Fig
Antigen-presenting cell
Bacterium
Peptide
antigen
Class II MHC
molecule
TCR
CD4
Helper T cell

43. Antigen-presenting cell Bacterium
Fig
Antigen-presenting cell
Bacterium
Peptide
antigen
B cell
Class II MHC
molecule +
TCR
CD4
Cytokines
Activated
helper T cell
Helper T cell

44. Antigen-presenting cell Bacterium
Fig
Antigen-presenting cell
Bacterium
Peptide
antigen
B cell
Class II MHC
molecule +
Clone of plasma cells
Secreted
antibody
molecules
TCR
CD4
Cytokines
Activated
helper T cell
Helper T cell
Clone of memory
B cells

45. Fig a
Endoplasmic
reticulum of
plasma cell
2 µm

46. The five ab , or immunoglobulin (Ig) classes
Fig
Class of Immuno-
globulin (Antibody)
Distribution
Function
IgM
(pentamer)
First Ig class
produced after
initial exposure to
antigen; then its
concentration in
the blood declines
Promotes neutraliza-
tion and cross-
linking of antigens;
very effective in
complement system
activation
The five ab , or immunoglobulin (Ig) classes
J chain
IgG
(monomer)
Most abundant Ig
class in blood;
also present in
tissue fluids
Promotes opsoniza-
tion, neutralization,
and cross-linking of
antigens; less effec-
tive in activation of
complement system
than IgM
Only Ig class that
crosses placenta,
thus conferring
passive immunity
on fetus
IgA
(dimer)
Present in
secretions such
as tears, saliva,
mucus, and
breast milk
Provides localized
defense of mucous
membranes by
cross-linking and
neutralization of
antigens
J chain
Presence in breast
milk confers
passive immunity
on nursing infant
Secretory
component
IgE
(monomer)
Present in blood
at low concen-
trations
Triggers release from
mast cells and
basophils of hista-
mine and other
chemicals that cause
allergic reactions
IgD
(monomer)
Present primarily
on surface of
B cells that have
not been exposed
to antigens
Acts as antigen
receptor in the
antigen-stimulated
proliferation and
differentiation of
B cells (clonal
selection)
Trans-
membrane
region

47. Class of Immuno- globulin (Antibody) IgM (pentamer)
Fig a
Class of Immuno-
globulin (Antibody)
Distribution
Function
IgM
(pentamer)
First Ig class
produced after
initial exposure to
antigen; then its
concentration in
the blood declines
Promotes neutraliza-
tion and cross-
linking of antigens;
very effective in
complement system
activation
J chain

48. Class of Immuno- globulin (Antibody) IgG (monomer)
Fig b
Class of Immuno-
globulin (Antibody)
Distribution
Function
IgG
(monomer)
Most abundant Ig
class in blood;
also present in
tissue fluids
Promotes opsoniza-
tion, neutralization,
and cross-linking of
antigens; less effec-
tive in activation of
complement system
than IgM
Only Ig class that
crosses placenta,
thus conferring
passive immunity
on fetus

49. Class of Immuno- globulin (Antibody) IgA (dimer)
Fig c
Class of Immuno-
globulin (Antibody)
Distribution
Function
IgA
(dimer)
Present in
secretions such
as tears, saliva,
mucus, and
breast milk
Provides localized
defense of mucous
membranes by
cross-linking and
neutralization of
antigens
J chain
Presence in breast
milk confers
passive immunity
on nursing infant
Secretory
component

50. Class of Immuno- globulin (Antibody) IgE (monomer)
Fig d
Class of Immuno-
globulin (Antibody)
Distribution
Function
IgE
(monomer)
Present in blood
at low concen-
trations
Triggers release from
mast cells and
basophils of hista-
mine and other
chemicals that cause
allergic reactions

51. Class of Immuno- globulin (Antibody) IgD (monomer)
Fig e
Class of Immuno-
globulin (Antibody)
Distribution
Function
IgD
(monomer)
Present primarily
on surface of
B cells that have
not been exposed
to antigens
Acts as antigen
receptor in the
antigen-stimulated
proliferation and
differentiation of
B cells (clonal
selection)
Trans-
membrane
region

52. Ab-mediated mechanisms of antigen disposal
Fig
Ab-mediated mechanisms of antigen disposal
Viral neutralization
Opsonization
Activation of complement system and pore formation
Bacterium
Complement proteins
Virus
Formation of
membrane
attack complex
Flow of water
and ions
Macrophage
Pore
Foreign
cell

53. Fig a
Viral neutralization
Virus

54. Fig b
Opsonization
Bacterium
Macrophage

55. Activation of complement system and pore formation
Fig c
Activation of complement system and pore formation
Complement proteins
Formation of
membrane
attack complex
Flow of water
and ions
Pore
Foreign
cell

56. Fig

57. Impact on public health
Fig
Impact on public health
IgE
Histamine
Allergen
Granule
Mast cell

58. include systemic lupus erythematosus, rheumatoid arthritis,
Fig
Autoimmune diseases
include systemic lupus erythematosus,
rheumatoid arthritis,
insulin-dependent diabetes mellitus, and
multiple sclerosis

59. Acquired immune system evasion by pathogens
Antigenic variation
Latency
Herpes simplex viruses: typeI and II
Sensory neurons express relatively few MHCI molecules
Attack on the immune system:HIV

60. ---- sleeping sickness (trypanosomiasis)
Fig
A change in epitope expression, which are called antigenic variation
1.5
Antibodies to
variant 1
appear
Antibodies to
variant 2
appear
Antibodies to
variant 3
appear
1.0
Variant 1
Variant 2
Variant 3
Millions of parasites
per mL of blood
0.5 25 26 27 28
Weeks after infection
---- sleeping sickness (trypanosomiasis)

61. Helper T cell concentration
Fig
Latency
AIDS
Relative antibody
concentration
800
Relative HIV
concentration
600
Helper T cell concentration
in blood (cells/mm3)
Helper T cell
concentration
400
200 1 2 3 4 5 6 7 8 9 10
Years after untreated infection