1. Antigen-binding site Hinge region Stem region (a) Heavy chain
variable region
Hinge
region
Heavy chain
constant region
Stem
region
Light chain
variable region
Light chain
constant region
Disulfide bond
(a)
Figure 21.14a

2. Classes of Antibodies IgM IgA (secretory IgA) first antibody released
Readily fixes and activates complement
IgA (secretory IgA)
In mucus and other secretions
Helps prevent entry of pathogens

3. Table 21.3

4. Classes of Antibodies IgD IgG
Attached to surface of B cells as a receptor
IgG
75–85% of antibodies
From secondary
Crosses the placental barrier

5. Classes of Antibodies IgE Active in allergies and parasitic infections
Causes mast cells and basophils to release histamine

6. Table 21.3

7. (cell-bound antigens)
Adaptive defenses
Humoral immunity
Antigen-antibody
complex
Antigen
Antibody
Inactivates by
Fixes and activates
Neutralization
(masks dangerous
parts of bacterial
exotoxins; viruses)
Agglutination
(cell-bound antigens)
Precipitation
(soluble antigens)
Complement
Enhances
Enhances
Leads to
Phagocytosis
Inflammation
Cell lysis
Chemotaxis
Histamine
release
Figure 21.15

8. Monoclonal Antibodies
Commercially prepared pure antibody
Produced by hybridomas
Cell hybrids: fusion of a tumor cell and a B cell
Proliferate indefinitely and have the ability to produce a single type of antibody
Used in research, clinical testing, and cancer treatment

9. Cell-Mediated Immune Response
Major types of T cells
CD4 cells helper T cells (TH) when activated
CD8 cells cytotoxic T cells (TC) that destroy cells harboring foreign antigens
Other types of T cells
Regulatory T cells (TREG)
Memory T cells

10. (or regulatory T cells)
Adaptive defenses
Cellular immunity
Immature
lymphocyte
Red bone marrow
T cell
receptor
T cell
receptor
Maturation
Class II MHC
protein
Class I MHC
protein
CD4
cell
CD8
cell
Thymus
Activation
Activation
APC
(dendritic cell)
Memory
cells
APC
(dendritic cell)
CD4
CD8
Lymphoid
tissues and
organs
Effector
cells
Helper T cells
(or regulatory T cells)
Cytotoxic T cells
Blood plasma
Figure 21.16

11. T cells must simultaneously recognize
Antigen Recognition
Immunocompetent T cells are activated when their surface receptors bind to a recognized antigen (nonself)
T cells must simultaneously recognize
Nonself (the antigen)
Self (an MHC protein of a body cell)

12. Two types of MHC proteins are important to T cell activation
Class I MHC proteins - displayed by all cells except RBCs
Class II MHC proteins – displayed by APCs (dendritic cells, macrophages and B cells)
Both types are synthesized at the ER and bind to peptide fragments

13. Cytoplasm of any tissue cell Cisternae of endoplasmic reticulum (ER) 2
Endogenous antigen peptides enter ER via transport protein.
Endogenous antigen is degraded by protease. 1
Endogenous antigen peptide is loaded onto class I MHC protein. 3
Endogenous antigen— self-protein or foreign (viral or cancer) protein
Loaded MHC protein migrates in vesicle to the plasma membrane, where it displays the antigenic peptide. 4
Transport protein (ATPase)
Antigenic peptide
Plasma membrane of a tissue cell
Extracellular fluid
(a) Endogenous antigens are processed and displayed on class I MHC of all cells.
Figure 21.17a

14. Class II MHC is synthesized in ER.
Cytoplasm of APC 1a
Class II MHC is synthesized in ER.
Invariant chain prevents class II MHC from binding
to peptides in the ER. 3
Vesicle fuses with phagolysosome. Invariant chain is removed, and antigen is loaded. 2a
Class II MHC is exported from ER in a vesicle.
Cisternae of endoplasmic reticulum (ER)
Phagosome 1b
Extracellular antigen (bacterium) is phagocytized. 4
Vesicle with loaded MHC migrates to the plasma membrane.
Phagosome merges with lysosome, forming a phagolysosome; antigen is degraded. 2b
Lysosome
Extracellular antigen
Plasma membrane of APC
Antigenic peptide
Extracellular fluid
(b) Exogenous antigens are processed and displayed on class II MHC of antigen-presenting cells (APCs).
Figure 21.17b

15. T cell activation is a two-step process
APCs (most often a dendritic cell) migrate to lymph nodes and other lymphoid tissues to present their antigens to T cells
T cell activation is a two-step process
Antigen binding
Co-stimulation

16. Adaptive defenses Cellular immunity Viral antigen Dendritic cell
engulfs an
exogenous antigen,
processes it, and
displays its
fragments on class
II MHC protein. 1
Class lI MHC
protein
displaying
processed
viral antigen
Dendritic
cell
CD4 protein
Immunocompetent
CD4 cell recognizes
antigen-MHC
complex. Both TCR
and CD4 protein bind
to antigen-MHC
complex. 2
T cell receptor
(TCR)
Immunocom-
petent CD4
T cell
Clone
formation
CD4 cells are
activated,
proliferate (clone),
and become memory
and effector cells. 3
Helper T
memory cell
Activated
helper
T cells
Figure 21.18

17. Helper T Cells
Interact directly with B cells
Stimulate B cells
B cells may be activated without TH cells

18. TH cell help in humoral immunity
Activated helper
T cell
TH cell binds with the
self-nonself complexes of a
B cell that has encountered
its antigen and is displaying
it on MHC II on its surface. 1
T cell receptor (TCR)
Helper T cell
CD4 protein
MHC II protein
of B cell displaying
processed antigen
TH cell releases
interleukins as
co-stimulatory signals to
complete B cell activation. 2
IL- 4 and other
cytokines
B cell (being activated)
(a)
Figure 21.19a

19. TH cell help in cell-mediated immunity
CD4 protein 1
Helper T cell
Previously
activated TH cell
binds dendritic cell.
Class II MHC
protein
APC (dendritic cell)
TH cell stimulates
dendritic cell to express
co-stimulatory
molecules (not shown)
needed to activate CD8
cell. 2
IL-2
Dendritic cell can
now activate CD8 cell
with the help of
interleukin 2 secreted
by TH cell. 3
Class I
MHC protein
CD8
protein
CD8 T cell
(b)
Figure 21.19b

20. Roles of Cytotoxic T(TC) Cells
Directly attack and kill other cells
Activated TC cells circulate in blood and lymph and lymphoid organs in search of body cells displaying antigen they recognize

21. Roles of Cytotoxic T(TC) Cells
Targets
Virus-infected cells
Cells with intracellular bacteria or parasites
Cancer cells
Foreign cells (transfusions or transplants)

22. Cytotoxic T Cells
Bind to a self-nonself complex
Can destroy all infected or abnormal cells

23. 1 2 3 4 5 Adaptive defenses Cellular immunity Cytotoxic T cell (TC)
TC binds tightly to
the target cell when it
identifies foreign antigen
on MHC I proteins. 1
TC releases perforin and
granzyme molecules from its
granules by exocytosis. 2
Granule
Perforin molecules
insert into the target
cell membrane,
polymerize, and form
transmembrane pores
(cylindrical holes)
similar to those
produced by
complement
activation. 3
Perforin
TC cell
membrane
Target
cell
membrane
Granzymes enter the
target cell via the pores.
Once inside, these
proteases degrade
cellular contents,
stimulating apoptosis. 4
Target
cell
Perforin
pore
Granzymes
The TC detaches and
searches for another prey. 5
(a) A mechanism of target cell killing by TC cells.
Figure 21.20a

24. Regulatory T (TReg) Cells
Dampen the immune response by direct contact or by inhibitory cytokines
Important in preventing autoimmune reactions

25. physical attack on the Ag
Cell-mediated
immunity
Humoral
immunity
Antigen (Ag) intruder
Inhibits
Inhibits
Triggers
Adaptive defenses
Innate defenses
Surface
barriers
Internal
defenses
Free Ags
may directly
activate B cell
Ag-infected
body cell engulfed
by dendritic cell
Antigen-
activated
B cells
Becomes
Clone and
give rise to
Ag-presenting cell
(APC) presents
self-Ag complex
Activates
Activates
Memory
B cells
Naïve
CD8
T cells
Naïve
CD4
T cells
Activated to clone
and give rise to
Activated to clone
and give rise to
Induce
co-stimulation
Plasma cells
(effector B cells)
Memory
cytotoxic T cells
Memory
helper T cells
Secrete
Activated
cytotoxic
T cells
Activated
helper
T cells
Cytokines stimulate
Antibodies (Igs)
Nonspecific killers
(macrophages and
NK cells of innate
immunity)
Circulating lgs along with
complement mount a chemical
attack on the Ag
Together the nonspecific killers
and cytotoxic T cells mount a
physical attack on the Ag
Figure 21.21

26. Organ Transplants Four varieties
Autografts: from one body site to another in the same person
Isografts: between identical twins
Allografts: between individuals who are not identical twins
Xenografts: from another animal species

27. Prevention of Rejection
Depends on similarity of tissues
Treated with immunosuppressive
Many of these have severe side effects

28. Immunodeficiencies
Congenital and acquired conditions that cause immune cells, phagocytes, or complement to behave abnormally

29. Severe Combined Immunodeficiency (SCID) Syndrome
Genetic defect
Marked deficit in B and T cells
SCID is fatal if untreated; treatment is with bone marrow transplants

30. Acquired Immune Deficiency Syndrome (AIDS)
HIV multiplies in lymph nodes throughout the asymptomatic period
Symptoms appear in a few months to 10 years
HIV-coated glycoprotein complex attaches to the CD4 receptor
HIV enters the cell and uses reverse transcriptase to produce DNA from viral RNA
The DNA copy (a provirus) directs the host cell to make viral RNA and proteins, enabling the virus to reproduce

31. Hypersensitivities
Immune responses to a perceived (otherwise harmless) threat
Causes tissue damage
Different types are distinguished by
Their time course
Whether antibodies or T cells are involved
Antibodies cause immediate and subacute hypersensitivities
T cells cause delayed hypersensitivity

32. Immediate Hypersensitivity
Acute (type I) hypersensitivities (allergies) begin in seconds after contact with allergen
Initial contact is asymptomatic but sensitizes the person
Reaction may be local or systemic

33. Immediate Hypersensitivity
The mechanism involves IL-4 secreted by T cells
IL-4 stimulates B cells to produce IgE
IgE binds to mast cells and basophils, resulting in a flood of histamine release and inducing the inflammatory response

34. Anaphylactic Shock
Systemic response to allergen that directly enters the blood
Basophils and mast cells are enlisted throughout the body
Systemic histamine releases may cause
Constriction of bronchioles
Sudden vasodilation and fluid loss from the bloodstream
Hypotensive shock and death
Treatment: epinephrine

35. Subacute Hypersensitivities
Caused by IgM and IgG transferred via blood plasma or serum
Slow onset (1–3 hours) and long duration (10–15 hours)
Cytotoxic (type II) reactions
Antibodies bind to antigens on specific body cells, stimulating phagocytosis and complement-mediated lysis of the cellular antigens
Example: mismatched blood transfusion reaction

36. Subacute Hypersensitivities
Immune complex (type III) hypersensitivity
Antigens are widely distributed through the body or blood
Insoluble antigen-antibody complexes form
Complexes cannot be cleared from a particular area of the body
Intense inflammation, local cell lysis, and death may result
Example: systemic lupus erythematosus (SLE)

37. Delayed Hypersensitivities (Type IV)
Slow onset (one to three days)
Mechanism depends on helper T cells
Cytokine-activated macrophages and cytotoxic T cells cause damage
Example: allergic contact dermatitis (e.g., poison ivy)