Download Chapter 43

Chapter 43: The Immune System
1. What is the difference between non-specific & specific immunity….aka
innate & acquired immunity?
INNATE IMMUNITY
Rapid responses to a
broad range of microbes
External defenses
Invading
microbes
(pathogens)
Internal defenses
Skin
Phagocytic cells
Mucous membranes
Antimicrobial proteins
Secretions
Inflammatory response
Phagocytic cells include:
-Neutrophils
-Monocytes/macrophages
-Eosinophils
-Dendritic cells
ACQUIRED IMMUNITY
Slower responses to
specific microbes
Natural killer cells
Humoral response
(antibodies)
Cell-mediated response
(cytotoxic
lymphocytes)
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.
Microbial debris can either be released or presented for immune system to “see.”
Chapter 43: The Immune System
1. What is the difference between non-specific & specific immunity….aka
innate & acquired immunity?
INNATE IMMUNITY
Rapid responses to a
broad range of microbes
External defenses
Invading
microbes
(pathogens)
Internal defenses
Skin
Phagocytic cells
Mucous membranes
Antimicrobial proteins
Secretions
Inflammatory response
Phagocytic cells include:
-Neutrophils
-Monocytes/macrophages
-Eosinophils
-Dendritic cells
ACQUIRED IMMUNITY
Slower responses to
specific microbes
Natural killer cells
Antimicrobial proteins include:
- Lysozyme
- Complement system
- Interferons
Humoral response
(antibodies)
Cell-mediated response
(cytotoxic
lymphocytes)
Figure 43.6 Major events in the local inflammatory response
Blood clot
Pin
Pathogen
Macrophage
Chemical signals
Phagocytic cells
Capillary
Blood
clotting
elements
Phagocytosis
Red blood cell
1 Chemical signals released
by activated macrophages
and mast cells at the injury
site cause nearby capillaries
to widen and become more
permeable.
2 Fluid, antimicrobial proteins,
and clotting elements move
from the blood to the site.
Clotting begins.
3 Chemokines released by various
kinds of cells attract more
phagocytic cells from the blood
to the injury site.
4 Neutrophils and macrophages
phagocytose pathogens and
cell debris at the site, and the
tissue heals.
Chemicals released:
- Histamine – causes dilation & increased permeability of capillaries
- Prostaglandins – increase blood flow to deliver clotting elements
thrombin, fibrin, etc.
Chapter 43: The Immune System
1. What is the difference between non-specific & specific immunity….aka
innate & acquired immunity?
INNATE IMMUNITY
Rapid responses to a
broad range of microbes
External defenses
Invading
microbes
(pathogens)
Internal defenses
Skin
Phagocytic cells
Mucous membranes
Antimicrobial proteins
Secretions
Inflammatory response
Phagocytic cells include:
-Neutrophils
-Monocytes/macrophages
-Eosinophils
-Dendritic cells
ACQUIRED IMMUNITY
Slower responses to
specific microbes
Natural killer cells
Antimicrobial proteins include:
- Lysozme
- Complement system
- Interferons
Natural killer cells
Humoral response
(antibodies)
Cell-mediated response
(cytotoxic
lymphocytes)
Chapter 43: The Immune System
1. What is the difference between non-specific & specific immunity….aka
innate & acquired immunity?
2. Where do these phagocytic cells reside?
- Lymphatic system – most
- Tissues & organs – macrophages
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
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.
Chapter 43: The Immune System
1. What is the difference between non-specific & specific immunity….aka
innate & acquired immunity?
2. Where do these phagocytic cells reside?
- Lymphatic system – most
- Tissues & organs – macrophages
3. How does the body mount a 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
External defenses
Invading
microbes
(pathogens)
ACQUIRED IMMUNITY
Slower responses to
specific microbes
Internal defenses
Skin
Phagocytic cells
Mucous membranes
Antimicrobial proteins
Secretions
Inflammatory response
Natural killer cells
Humoral response
(antibodies)
Cell-mediated response
(cytotoxic
lymphocytes)
Figure 43.7 Epitopes (antigenic determinants)
Antigenbinding
sites
Antibody A
Epitopes
(antigenic
determinants)
Antigen
Antibody B
Antibody C
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
Info for you
-Test Tuesday, 2/14
-Labs – Thurs, Fri, Mon
-Pre-labs – Thurs & Fri
-Bring essays tomorrow
-CC Registration Open House – Thurs, 2/9: 6:30 – 8:30
Chapter 43: The Immune System
1. What is the difference between non-specific & specific immunity….aka
innate & acquired immunity?
2. Where do these phagocytic cells reside?
3. How does the body mount a specific/acquired immune response?
4. How are the B cell & T cell receptors similar?
Figure 43.8 Antigen receptors on lymphocytes
Antigenbinding
site
Disulfide
bridge
Light
chain
C C
Heavy chains
B cell
Cytoplasm of B cell
Antigenbinding
site
Antigenbinding site
Variable
regions
Constant
regions
Transmembrane
region
V V
C C
Plasma
b chain
membrane a chain
Disulfide bridge
Cytoplasm of T cell
(a) A B cell receptor consists of two identical heavy
chains and two identical light chains linked by
several disulfide bridges.
T cell
(b) A T cell receptor consists of one
a chain and one b chain linked by
a disulfide bridge.
- Constant regions embedded in membrane
- Variable regions that bind to epitopes (vary)
- Quarternary proteins
- B cells – 2 heavy & 2 light chains
T cells – α and β chains
- “Y”
- “I”
Chapter 43: The Immune System
1. What is the difference between non-specific & specific immunity….aka
innate & acquired immunity?
2. Where do these phagocytic cells reside?
3. How does the body mount a specific/acquired immune response?
4. How are the B cell & T cell receptors similar?
5. How do T cell receptors recognize antigens?
Figure 43.9 The interaction of T cells with MHC molecules
Infected cell
Antigenpresenting
cell
Microbe
Antigen
fragment
1
1 A fragment of
foreign protein
(antigen) inside the
cell associates with
an MHC molecule
and is transported
to the cell surface.
Class I MHC
molecule
Antigen
fragment
1
2
2
T cell
receptor
Class II MHC
molecule
T cell
receptor
2 The combination of
MHC molecule and
antigen is recognized
by a T cell, alerting it
to the infection.
Helper T cell
(a)
Cytotoxic T cell
(b)
- Class I MHC molecule of an infected cell - Class II MHC of a phagocytic cell
- MHC usually empty but now filled
- Antigen-presenting cell (APC)
- TC recognizes filled MHC & tries to form
complementary receptor
Chapter 43: The Immune System
1. What is the difference between non-specific & specific immunity….aka
innate & acquired immunity?
2. Where do these phagocytic cells reside?
3. How does the body mount a specific/acquired immune response?
4. How are the B cell & T cell receptors similar?
5. How do T cell receptors recognize antigens?
6. How does our body recognize “self” from “non-self?”
- MHC – Major Histocompatibility Complex
- Cell markers that must be compatible for organ & tissue donations
7. How do B cells & T cells get their name?
- Where they mature
- B cells – bone
- T cells – thymus
Figure 43.10 Overview of lymphocyte development
Bone marrow
Lymphoid
stem cell
Thymus
T cell
B cell
Blood, lymph, and lymphoid tissues
(lymph nodes, spleen, and others)
Chapter 43: The Immune System
1. What is the difference between non-specific & specific immunity….aka
innate & acquired immunity?
2. Where do these phagocytic cells reside?
3. How does the body mount a specific/acquired immune response?
4. How are the B cell & T cell receptors similar?
5. How do T cell receptors recognize antigens?
6. How does our body recognize “self” from “non-self?”
7. How do B cells & T cells get their name?
8. How is the variable region of a receptor formed?
- Gene rearrangement aka activation
- NOT ALL CELLS IN OUR BODY HAVE THE SAME DNA
Figure 43.11 Immunoglobulin gene rearrangement
V4–V39
DNA of
undifferentiated
B cell
V2
V1
V40
V3
J1 J2 J3 J4 J5 Intron
C
1 Deletion of DNA between a V segment
and J segment and joining of the segments
DNA of differentiated
B cell
V1
V3 J5 Intron
V2
C
2 Transcription of resulting permanently rearranged,
functional gene
V3 J5 Intron
pre-mRNA
C
3 RNA processing (removal of intron; addition of cap
and poly (A) tail)
V3 J5
mRNA Cap
C
Poly (A)
4 Translation
Light-chain polypeptide
V
C
Variable Constant
region region
B cell receptor
B cell
- All variable regions do gene rearrangement – heavy & light (B), α and β (T)
- Analogous to alternative mRNA splicing but DNA is completely deleted
- Self-reactive receptors are eliminated
Chapter 43: The Immune System
1. What is the difference between non-specific & specific immunity….aka
innate & acquired immunity?
2. Where do these phagocytic cells reside?
3. How does the body mount a specific/acquired immune response?
4. How are the B cell & T cell receptors similar?
5. How do T cell receptors recognize antigens?
6. How does our body recognize “self” from “non-self?”
7. How do B cells & T cells get their name?
8. How is the variable region of a receptor formed?
9. What happens after a receptor binds to an antigen?
- Clonal selection
Figure 43.12 Clonal selection of B cells
Antigen molecules
B cells that
differ in
antigen
specificity
Antigen molecules
bind to the antigen
receptors of only one
of the three B cells
shown.
Antigen
receptor
The selected B cell
proliferates, forming
a clone of identical
cells bearing
receptors for the
selecting antigen.
Some proliferating cells
develop into long-lived
memory cells that can
respond rapidly upon
subsequent exposure
to the same antigen.
Antibody
molecules
Clone of memory cells
Clone of plasma cells
Future infections
Current infection
- T cells also go through clonal selection
- T receptors not released like Ab from B cells
- Note the ER in plasma/effector cells – secreting cell
Some proliferating
cells develop into
short-lived plasma
cells that secrete
antibodies specific
for the antigen.
Chapter 43: The Immune System
1. What is the difference between non-specific & specific immunity….aka
innate & acquired immunity?
2. Where do these phagocytic cells reside?
3. How does the body mount a specific/acquired immune response?
4. How are the B cell & T cell receptors similar?
5. How do T cell receptors recognize antigens?
6. How does our body recognize “self” from “non-self?”
7. How do B cells & T cells get their name?
8. How is the variable region of a receptor formed?
9. What happens after a receptor binds to an antigen?
10. What is the difference between a primary & secondary immune response?
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
28
35
Time (days)
42
49
56
Chapter 43: The Immune System
1. What is the difference between non-specific & specific immunity….aka
innate & acquired immunity?
2. Where do these phagocytic cells reside?
3. How does the body mount a specific/acquired immune response?
4. How are the B cell & T cell receptors similar?
5. How do T cell receptors recognize antigens?
6. How does our body recognize “self” from “non-self?”
7. How do B cells & T cells get their name?
8. How is the variable region of a receptor formed?
9. What happens after a receptor binds to an antigen?
10. What is the difference between a primary & secondary immune response?
11. Let’s consider the immune response….
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
(Gene rearrangement)
Helper
T cell
Gives rise to
Active and
memory
helper
T cells
(Clonal selection)
Figure 43.15 The central role of helper T cells in humoral and cellmediated 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.
B cell
Humoral
immunity
(secretion of
antibodies by
plasma cells)
3 The cells in this clone
secrete other cytokines
that help activate B cells
and cytotoxic T cells.
- 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
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
Activate
Secreted
cytokines
activate
Helper
T cell
Gives rise to
Active and
memory
helper
T cells
(Gene rearrangement)
Cytotoxic
T cell
Gives rise to
Memory
cytotoxic
T cells
(Clonal selection)
Active
cytotoxic
T cells
Defend against infected cells, cancer
cells, and transplanted tissues
Figure 43.16 The killing action of cytotoxic T cells
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
- 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)
Fig. 43.14 An overview of the acquired immune response – B cells
Cell-mediated immune response
Humoral immune response
First exposure to antigen
Intact antigens
Antigens engulfed and
displayed by dendritic cells
Antigens displayed
by infected cells
Activate
Activate
Activate
B cell
Gives rise to
Plasma
cells
Memory
B cells
Secreted
cytokines
activate
Helper
T cell
Gives rise to
Active and
memory
helper
T cells
Secrete antibodies that defend against
pathogens and toxins in extracellular fluid
Pathogens in fluid
(Gene rearrangement)
Cytotoxic
T cell
Gives rise to
Memory
cytotoxic
T cells
(Clonal selection)
Active
cytotoxic
T cells
Defend against infected cells, cancer
cells, and transplanted tissues
Infected cells
Figure 43.17 Humoral immune response
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
Chapter 43: The Immune System
1. What is the difference between non-specific & specific immunity….aka
innate & acquired immunity?
2. Where do these phagocytic cells reside?
3. How does the body mount a specific/acquired immune response?
4. How are the B cell & T cell receptors similar?
5. How do T cell receptors recognize antigens?
6. How does our body recognize “self” from “non-self?”
7. How do B cells & T cells get their name?
8. How is the variable region of a receptor formed?
9. What happens after a receptor binds to an antigen?
10. What is the difference between a primary & secondary immune response?
11. Let’s consider the immune response….
12. What are the 5 classes of antibodies?
- GAMED
Figure 43.18 The five classes of immunoglobulins
IgM
(pentamer)
First Ig class produced after initial exposure to
antigen; then its concentration in the blood declines
J chain
IgG
(monomer)
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)
IgA
(dimer)
Secretory
component
Present in secretions such as tears, saliva, mucus,
and breast milk
J chain
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
IgE
(monomer)
IgD
(monomer)
Transmembrane
region
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)
Chapter 43: The Immune System
1. What is the difference between non-specific & specific immunity….aka
innate & acquired immunity?
2. Where do these phagocytic cells reside?
3. How does the body mount a specific/acquired immune response?
4. How are the B cell & T cell receptors similar?
5. How do T cell receptors recognize antigens?
6. How does our body recognize “self” from “non-self?”
7. How do B cells & T cells get their name?
8. How is the variable region of a receptor formed?
9. What happens after a receptor binds to an antigen?
10. What is the difference between a primary & secondary immune response?
11. Let’s consider the immune response….
12. What are the 5 classes of antibodies?
13. How are antigens removed?
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
Complement
proteins
Bacteria
Virus
Activation of complement system
and pore formation
MAC
Pore
Soluble
antigens
Bacterium
Foreign cell
Enhances
Leads to
Phagocytosis
Cell lysis
Macrophage
MAC – membrane attack complex
Chapter 43: The Immune System
1. What is the difference between non-specific & specific immunity….aka
innate & acquired immunity?
2. Where do these phagocytic cells reside?
3. How does the body mount a specific/acquired immune response?
4. How are the B cell & T cell receptors similar?
5. How do T cell receptors recognize antigens?
6. How does our body recognize “self” from “non-self?”
7. How do B cells & T cells get their name?
8. How is the variable region of a receptor formed?
9. What happens after a receptor binds to an antigen?
10. What is the difference between a primary & secondary immune response?
11. Let’s consider the immune response….
12. What are the 5 classes of antibodies?
13. How are antigens removed?
14. What is the difference between passive & active immunity?
- Passive – transfer of antibodies – breastfeeding, injection (rabies)
- Active – body creates its own antibodies during an infection – vaccine
15. What needs to match for blood transfusions?
- 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
Table 43.1 Blood Groups That Can and Cannot Be Safely
Combined in Transfusion
Type O- : Universal donor
Type AB+ : Universal recipient
Chapter 43: The Immune System
1. What is the difference between non-specific & specific immunity….aka
innate & acquired immunity?
2. Where do these phagocytic cells reside?
3. How does the body mount a specific/acquired immune response?
4. How are the B cell & T cell receptors similar?
5. How do T cell receptors recognize antigens?
6. How does our body recognize “self” from “non-self?”
7. How do B cells & T cells get their name?
8. How is the variable region of a receptor formed?
9. What happens after a receptor binds to an antigen?
10. What is the difference between a primary & secondary immune response?
11. Let’s consider the immune response….
12. What are the 5 classes of antibodies?
13. How are antigens removed?
14. What is the difference between passive & active immunity?
15. What needs to match for blood transfusions?
16. What needs to match for organ transplants?
- MHC
17. What happens with an allergic response?
Figure 43.20 Mast cells, IgE, and the allergic response
IgE
Allergen
Histamine
1
3
2
Granule
Mast cell
1 IgE antibodies produced in 2 On subsequent exposure to the 3 Degranulation of the cell,
triggered by cross-linking of
response to initial exposure
same allergen, IgE molecules
adjacent IgE molecules,
to an allergen bind to
attached to a mast cell recogreleases histamine and other
receptors or mast cells.
nize and bind the allergen.
chemicals, leading to allergy
symptoms.
- Allergies are hypersensitivities to allergens
- Anaphylactic shock – widespread mast cell degranulation causes abrupt
dilation of peripheral capillaries & quick drop in BP
Chapter 43: The Immune System
1. What is the difference between non-specific & specific immunity….aka
innate & acquired immunity?
2. Where do these phagocytic cells reside?
3. How does the body mount a specific/acquired immune response?
4. How are the B cell & T cell receptors similar?
5. How do T cell receptors recognize antigens?
6. How does our body recognize “self” from “non-self?”
7. How do B cells & T cells get their name?
8. How is the variable region of a receptor formed?
9. What happens after a receptor binds to an antigen?
10. What is the difference between a primary & secondary immune response?
11. Let’s consider the immune response….
12. What are the 5 classes of antibodies?
13. How are antigens removed?
14. What is the difference between passive & active immunity?
15. What needs to match for blood transfusions?
16. What needs to match for organ transplants?
17. What happens with an allergic response?
18. What are some autoimmune diseases?
- Lupus
- Insulin-dependent diabetes
- Rheumatoid arthritis
- MS – multiple sclerosis
Chapter 43: The Immune System
1. What is the difference between non-specific & specific immunity….aka
innate & acquired immunity?
2. Where do these phagocytic cells reside?
3. How does the body mount a specific/acquired immune response?
4. How are the B cell & T cell receptors similar?
5. How do T cell receptors recognize antigens?
6. How does our body recognize “self” from “non-self?”
7. How do B cells & T cells get their name?
8. How is the variable region of a receptor formed?
9. What happens after a receptor binds to an antigen?
10. What is the difference between a primary & secondary immune response?
11. Let’s consider the immune response….
12. What are the 5 classes of antibodies?
13. How are antigens removed?
14. What is the difference between passive & active immunity?
15. What needs to match for blood transfusions?
16. What needs to match for organ transplants?
17. What happens with an allergic response?
18. What are some autoimmune diseases?
19. What happens with AIDS?
- Acquired Immune Deficiency Syndrome