1. broad range of microbes
Chapter 43: The Immune System
non-specific & specific immunity
(innate & acquired immunity)
INNATE IMMUNITY
Rapid responses to a
broad range of microbes
ACQUIRED IMMUNITY
Slower responses to
specific microbes
External defenses
Internal defenses
Skin
Mucous membranes
Secretions
Phagocytic cells
Antimicrobial proteins
Inflammatory response
Natural killer cells
Humoral response
(antibodies)
Cell-mediated response
(cytotoxic
lymphocytes)
Invading
microbes
(pathogens)

2. Phagocytic cells (leukocytes):
Ingest microbes, trigger inflammatory response
Neutrophils – 60-70%
Monocytes/macrophages – reside in tissue
Eosinophils – secretes enzymes that damage invader
Dendritic cells – stimulate acquired immunity

3. Microbial debris can either be released or presented for immune system
Figure 43.4 Phagocytosis
Microbes
MACROPHAGE
Vacuole
Lysosome
containing
enzymes 1 2 3 4 5 6
Pseudopodia
surround
microbes.
are engulfed
into cell.
microbes
forms.
and lysosome
fuse.
Toxic
compounds
and lysosomal
destroy microbes.
Microbial
debris is
released by
exocytosis.
Microbial debris
can either be
released or
presented for
immune system
to “see.”

4. Lymphatic system – mostly Tissues & organs
Macrophages Reside:
Lymphatic system – mostly
Tissues & organs 1 2 3 4
Interstitial fluid bathing the
tissues, along with the white
blood cells in it, continually
enters lymphatic capillaries.
Fluid inside the
lymphatic capillaries,
called lymph, flows
through lymphatic
vessels throughout
the body.
Within lymph nodes,
microbes and foreign
particles present in
the circulating lymph
encounter macro-
phages, dendritic cells,
and lymphocytes,
which carry out
various defensive
actions.
Lymphatic vessels
return lymph to the blood via two large ducts that drain into veins near the
shoulders.
Adenoid
Tonsil
Lymph
nodes
Spleen
Peyer’s patches
(small intestine)
Appendix
Lymphatic
vessels
node
Masses of
lymphocytes and
macrophages
Tissue
cells
vessel
Blood
capillary
Interstitial
fluid

5. broad range of microbes
Antimicrobial proteins include:
Lysozyme – enzyme attach bacterial
Cell walls; tears, sweat
Complement system – serum proteins
Interferons – induces neighboring cells
resistance
INNATE IMMUNITY
Rapid responses to a
broad range of microbes
ACQUIRED IMMUNITY
Slower responses to
specific microbes
External defenses
Internal defenses
Skin
Mucous membranes
Secretions
Phagocytic cells
Antimicrobial proteins
Inflammatory response
Natural killer cells
Humoral response
(antibodies)
Cell-mediated response
(cytotoxic
lymphocytes)
Invading
microbes
(pathogens)

6. Figure 43.6 Major events in the Local Inflammatory Response
Pathogen
Pin
Macrophage
Chemical signals
Capillary
Phagocytic cells
Red blood cell
Blood
clotting
elements
Blood clot
Phagocytosis
Fluid, antimicrobial proteins,
and clotting elements move
from the blood to the site.
Clotting begins. 2
Chemical signals released
by activated macrophages
and mast cells at the injury
site cause nearby capillaries
to widen and become more
permeable. 1
Chemokines released by various
kinds of cells attract more
phagocytic cells from the blood
to the injury site. 3
Neutrophils and macrophages
phagocytose pathogens and
cell debris at the site, and the
tissue heals. 4
Chemicals released:
Histamine – causes dilation & increased
permeability of capillaries
Prostaglandins – increase blood flow to deliver
clotting elements thrombin, fibrin, etc.

7. Clotting - Fig. 42.17 FIBRIN Platelets adhere to collagen fibers
Clotting factors stimulate
prothrombin conversion to thrombin
Thrombin converts
Fibrinogen – sealant (inactive) 
FIBRIN

8. broad range of microbes
Non-specific – innate:
NK – natural killer cells
binds to virus infected cell/cancer cell
releases chemicals causing apoptosis
INNATE IMMUNITY
Rapid responses to a
broad range of microbes
ACQUIRED IMMUNITY
Slower responses to
specific microbes
External defenses
Internal defenses
Skin
Mucous membranes
Secretions
Phagocytic cells
Antimicrobial proteins
Inflammatory response
Natural killer cells
Humoral response
(antibodies)
Cell-mediated response
(cytotoxic
lymphocytes)
Invading
microbes
(pathogens)

9. broad range of microbes
Specific/acquired immune response:
B cells – humoral response
T cells – cell-mediated response
For both, the cells recognize specific shapes
INNATE IMMUNITY
Rapid responses to a
broad range of microbes
ACQUIRED IMMUNITY
Slower responses to
specific microbes
External defenses
Internal defenses
Skin
Mucous membranes
Secretions
Phagocytic cells
Antimicrobial proteins
Inflammatory response
Natural killer cells
Humoral response
(antibodies)
Cell-mediated response
(cytotoxic
lymphocytes)
Invading
microbes
(pathogens)

10. How microbes are detected

11. Figure 43.7 Epitopes (antigenic determinants)
binding
sites
Antibody A
Antigen
Antibody B
Antibody C
Epitopes
(antigenic
determinants)
Antigen – any foreign molecule recognized by the body – antibody generator
Epitope – specific shape recognized by an immune cells
Both B cells & T cells have receptors that must be complementary to the epitope

12. B cell & T cell receptors:
Fig. 43.8
Constant regions embedded in membrane
Variable regions that bind to epitopes (vary)
Quarternary proteins

13. Figure 43.8 Antigen receptors on lymphocytes
binding
site
binding site
Disulfide
bridge
Light
chain
Heavy chains
Cytoplasm of B cell
b chain
Disulfide bridge
a chain V C
T cell
A T cell receptor consists of one
chain and one b chain linked by
a disulfide bridge.
(b)
A B cell receptor consists of two identical heavy
chains and two identical light chains linked by
several disulfide bridges.
(a)
Variable
regions
Constant
Transmembrane
region
Plasma
membrane
B cell
Cytoplasm of T cell
B cells – 2 heavy & 2 light chains
“Y”
T cells – α and β chains
- “I”

14. Figure 43.8 Antigen receptors on lymphocytes
binding
site
Disulfide
bridge
Light
chain
Heavy chains
Cytoplasm of B cell
b chain
Disulfide bridge
a chain V C
T cell
A T cell receptor consists of one
chain and one b chain linked by
a disulfide bridge.
(b)
(a)
Variable
regions
Constant
Plasma
membrane
B cell
Cytoplasm of T cell
T cells – α and β chains
- “I”

15. Figure 43.8 Antigen receptors on lymphocytes
binding
site
binding site
Disulfide
bridge
Light
chain
Heavy chains
Cytoplasm of B cell
b chain
Disulfide bridge
a chain V C
T cell
A T cell receptor consists of one
chain and one b chain linked by
a disulfide bridge.
(b)
A B cell receptor consists of two identical heavy
chains and two identical light chains linked by
several disulfide bridges.
(a)
Variable
regions
Constant
Transmembrane
region
Plasma
membrane
B cell
Cytoplasm of T cell

16. T cell receptors recognize antigens: Figure 43.9

17. Figure 43.9 The interaction of T cells with MHC molecules
Infected cell
Antigen
fragment
Class I MHC
molecule
T cell
receptor
Cytotoxic T cell
(a)
Microbe
Antigen-
presenting
cell
Class II MHC
Helper T cell
(b) 1 2
The combination of
MHC molecule and
antigen is recognized
by a T cell, alerting it
to the infection.
A fragment of
foreign protein
(antigen) inside the
cell associates with
an MHC molecule
and is transported
to the cell surface.
Antigen-presenting cell (APC)

18. T cell receptors recognize antigens: Figure 43.9
Class I
MHC molecule of an infected cell
fills with an antigen fragment
TC recognizes filled MHC
forms complementary receptor
Class II
MHC of a phagocytic cell
Helper T binds

19. Figure 43.9 The interaction of T cells with MHC molecules
Infected cell
Antigen
fragment
Class I MHC
molecule
T cell
receptor
Cytotoxic T cell
(a)
Microbe
Antigen-
presenting
cell
Class II MHC
Helper T cell
(b) 1 2
The combination of
MHC molecule and
antigen is recognized
by a T cell, alerting it
to the infection.
A fragment of
foreign protein
(antigen) inside the
cell associates with
an MHC molecule
and is transported
to the cell surface.

20. Naming B & T cells:
Where they mature
B cells – bone
T cells – thymus

21. Figure 43.10 Overview of lymphocyte development
Bone marrow
Lymphoid
stem cell
B cell
Thymus
T cell
Blood, lymph, and lymphoid tissues
(lymph nodes, spleen, and others)

22. Light-chain polypeptide
Formation of variable region of a receptor:
Gene rearrangement - activation
DNA of
undifferentiated
B cell
DNA of differentiated
pre-mRNA
mRNA
Cap
Transcription of resulting permanently rearranged, functional gene
RNA processing (removal of intron; addition of cap and poly (A) tail)
B cell receptor
Light-chain polypeptide
Intron
Variable
region
Constant V1 V2 V3
V4–V39
V40 J1 J2 J3 J4 J5 V C 2 3 4
Translation
Poly (A)
Deletion of DNA between a V segment and J segment and joining of the segments 1
Analogous to alternative mRNA splicing but DNA is completely deleted

23. What happens after a receptor binds to an antigen? Figure 43.12
Clonal selection
Very specific to:
Antigen epitopes on -
Microbe
infected body cell
cancer cell
interacts only w/WBC carrying complementary receptors

24. Figure 43.12 Clonal selection of B cells
Antigen molecules
Antigen
receptor
B cells that
differ in
antigen
specificity
Antibody
molecules
Clone of memory cells
Clone of plasma cells
Some proliferating cells
develop into long-lived
memory cells that can
respond rapidly upon
subsequent exposure
to the same antigen.
bind to the antigen
receptors of only one
of the three B cells
shown.
The selected B cell
proliferates, forming
a clone of identical
cells bearing
receptors for the
selecting antigen.
Some proliferating
cells develop into
short-lived plasma
cells that secrete
antibodies specific
for the antigen.
Future infections Current infection

25. Antibody concentration
difference b/t primary & secondary immune response:
Antibodies
to A
to B
Antibody concentration
(arbitrary units)
104
103
102
101
100 7 14 21 28 35 42 49 56
Time (days)
Day 1: First
exposure to
antigen A 1
Primary
response to
produces anti-
bodies to A 2
Day 28:
Second exposure
to antigen A; first
antigen B 3
Secondary response to anti-
gen A produces antibodies
to A; primary response to anti-
gen B produces antibodies to B 4
Figure 43.13 The specificity of immunological memory

26. The Immune Response….

27. Figure 43.14 An overview of the acquired immune response - TH
Humoral immune response
Cell-mediated immune response
First exposure to antigen
Antigens engulfed and displayed by dendritic cells
Activate
Gives rise to
Helper T cell
Active and memory helper T cells
B cells
T cells
(Gene rearrangement)
(Clonal selection)

28. CD4 on T cell keeps APC bound to T cell during gene rearrangement
Figure 43.15 The central role of helper T cells in humoral and cell-mediated immune responses
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.
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.
The cells in this clone
secrete other cytokines
that help activate B cells
and cytotoxic T cells.
Cell-mediated
immunity
(attack on
infected cells)
Humoral
(secretion of
antibodies by
plasma cells)
Dendritic
cell
Bacterium
Peptide antigen
Class II MHC
molecule
TCR
CD4
Helper T cell
Cytokines
Cytotoxic T cell
B cell 1 2 3
CD4 on T cell keeps APC bound to T cell during gene rearrangement
Cytokines from APC stimulate TH to secrete its own cytokines
TH cytokines exert (+) feedback on TH & stimulate TC & B cells

29. Figure 43.14 An overview of the acquired immune response - TC
Humoral immune response
Cell-mediated immune response
First exposure to antigen
Antigens engulfed and displayed by dendritic cells
Antigens displayed by infected cells
Activate
Gives rise to
Helper T cell
Cytotoxic T cell
Active and memory helper T cells
Memory cytotoxic T cells
Active cytotoxic T cells
Defend against infected cells, cancer cells, and transplanted tissues
Secreted
cytokines
activate
(Gene rearrangement)
(Clonal selection)

30. Figure 43.16 The killing action of cytotoxic T cells
Perforin
Granzymes
CD8
TCR
Class I MHC
molecule
Target
cell
Peptide
antigen
Pore
Released
cytotoxic
T cell
Apoptotic
target cell
Cancer
Cytotoxic
A specific cytotoxic T cell binds to a
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. 1
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. 2
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. 3
CD8 on T cell keeps infected cell bound to T cell during gene rearrangement
Granzymes released from TC digest a hole and allow perforins to create a pore
Infected cell commits suicide (apoptosis)

31. Fig. 43.14 An overview of the acquired immune response – B cells
Humoral immune response
Cell-mediated immune response
First exposure to antigen
Intact antigens
Antigens engulfed and displayed by dendritic cells
Antigens displayed by infected cells
Activate
Gives rise to
B cell
Helper T cell
Cytotoxic T cell
Plasma cells
Memory B cells
Active and memory helper T cells
Memory cytotoxic T cells
Active cytotoxic T cells
Secrete antibodies that defend against pathogens and toxins in extracellular fluid
Defend against infected cells, cancer cells, and transplanted tissues
Secreted
cytokines
activate
(Gene rearrangement)
(Clonal selection)
Pathogens in fluid Infected cells

32. Figure 43.17 Humoral immune response2 1 3
B cell
Bacterium
Peptide antigen
Class II MHC molecule
TCR
Helper T cell
CD4
Activated helper T cell
Clone of memory B cells
Cytokines
Clone of plasma cells
Secreted antibody molecules
Endoplasmic reticulum of plasma cell
Macrophage

33. 5 classes of antibodies:
GAMED
immunoglobulins

34. Figure 43.18 The five classes of immunoglobulins
First Ig class produced after initial exposure to
antigen; then its concentration in the blood declines
Promotes neutralization and agglutination of
antigens; very effective in complement activation
(see Figure 43.19)
Most abundant Ig class in blood; also present in
tissue fluids
Only Ig class that crosses placenta, thus conferring
passive immunity on fetus
Promotes opsonization, neutralization, and agglutination
of antigens; less effective in complement activation than
IgM (see Figure 43.19)
Present in secretions such as tears, saliva, mucus,
and breast milk
Provides localized defense of mucous membranes by
agglutination and neutralization of antigens (see
Figure 43.19)
Presence in breast milk confers passive immunity on
nursing infant
Triggers release from mast cells and basophils of
histamine and other chemicals that cause allergic
reactions (see Figure 43.20)
Present primarily on surface of naive B cells that have
not been exposed to antigens
Acts as antigen receptor in antigen-stimulated
proliferation and differentiation of B cells (clonal
selection)
IgM
(pentamer)
IgG
(monomer)
IgA
(dimer)
IgE
J chain
Secretory
component
Transmembrane
region
IgD

35. antigen disposal:
Antibodies inactivate antigens
1. enhances phagocytosis-
viral neutralization
agglutination
precipitation of soluble antigens
2. cell lysis-
complement sys. activation

36. Figure 43.19 Antibody-mediated mechanisms of antigen disposal
Binding of antibodies to antigens
inactivates antigens by
Viral neutralization
(blocks binding to host)
and opsonization (increases
phagocytosis)
Agglutination of
antigen-bearing particles,
such as microbes
Precipitation of
soluble antigens
Activation of complement system
and pore formation
Bacterium
Virus
Bacteria
Soluble
antigens
Foreign cell
Complement
proteins
MAC
Pore
Enhances
Phagocytosis
Leads to
Cell lysis
Macrophage
MAC – membrane attack complex
Figure 43.19 Antibody-mediated mechanisms of antigen disposal

37. passive vs. active immunity:
transfer of antibodies breastfeeding, injection (rabies)
Active –
body creates its own antibodies during an infection – vaccine

38. blood transfusions require a match: Type – A, B, AB or O Rh factor
Pregnancy issues – Rh- mom with prior Rh+ fetus having another Rh+
Based on Glycoproteins on RBC surface

39. Table 43.1 Blood Groups That Can and Cannot Be Safely Combined in Transfusion
Type O- : Universal donor
Type AB+ : Universal recipient

40. allergic response Allergies are hypersensitivities to allergens
Anaphylactic shock –
widespread mast cell degranulation causes abrupt dilation of peripheral capillaries & quick drop in BP

41. Figure 43.20 Mast cells, IgE, and the allergic response
IgE antibodies produced in
response to initial exposure
to an allergen bind to
receptors or mast cells. 1
On subsequent exposure to the
same allergen, IgE molecules
attached to a mast cell recog-
nize and bind the allergen. 2
Degranulation of the cell,
triggered by cross-linking of
adjacent IgE molecules,
releases histamine and other
chemicals, leading to allergy
symptoms. 3
Allergen
IgE
Histamine
Granule
Mast cell
Allergies are hypersensitivities to allergens
Anaphylactic shock – widespread mast cell degranulation causes abrupt
dilation of peripheral capillaries & quick drop in BP

42. autoimmune diseases: Lupus Rheumatoid arthritis
- Insulin-dependent diabetes
- MS – multiple sclerosis

43. AIDS:
- Acquired Immune Deficiency Syndrome