1. The Immune System: Innate and Adaptive Body Defenses: Part B21
The Immune System: Innate and Adaptive Body Defenses: Part B

2. Antibodies
Immunoglobulins—gamma globulin portion of blood
Proteins secreted by plasma cells
Capable of binding specifically with antigen detected by B cells

3. Basic Antibody Structure
T-or Y-shaped monomer of four looping linked polypeptide chains
Two identical heavy (H) chains and two identical light (L) chains
Variable (V) regions of each arm combine to form two identical antigen-binding sites

4. Basic Antibody Structure
Constant (C) region of stem determines
The antibody class (IgM, IgA, IgD, IgG, or IgE)
The cells and chemicals that the antibody can bind to
How the antibody class functions in antigen elimination

5. 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

6. Classes of Antibodies IgM IgA (secretory IgA)
A pentamer; first antibody released
Potent agglutinating agent
Readily fixes and activates complement
IgA (secretory IgA)
Monomer or dimer; in mucus and other secretions
Helps prevent entry of pathogens

7. Table 21.3

8. Classes of Antibodies IgD IgG
Monomer attached to the surface of B cells
Functions as a B cell receptor
IgG
Monomer; 75–85% of antibodies in plasma
From secondary and late primary responses
Crosses the placental barrier

9. Classes of Antibodies IgE
Monomer active in some allergies and parasitic infections
Causes mast cells and basophils to release histamine

10. Table 21.3

11. Generating Antibody Diversity
Billions of antibodies result from somatic recombination of gene segments
Hypervariable regions of some genes increase antibody variation through somatic mutations
Each plasma cell can switch the type of H chain produced, making an antibody of a different class

12. Antibodies inactivate and tag antigens
Antibody Targets
Antibodies inactivate and tag antigens
Form antigen-antibody (immune) complexes
Defensive mechanisms used by antibodies
Neutralization and agglutination (the two most important)
Precipitation and complement fixation

13. Neutralization
Simplest mechanism
Antibodies block specific sites on viruses or bacterial exotoxins
Prevent these antigens from binding to receptors on tissue cells
Antigen-antibody complexes undergo phagocytosis

14. Cross-linked antigen-antibody complexes agglutinate
Agglutination
Antibodies bind the same determinant on more than one cell-bound antigen
Cross-linked antigen-antibody complexes agglutinate
Example: clumping of mismatched blood cells

15. Precipitation
Soluble molecules are cross-linked
Complexes precipitate and are subject to phagocytosis

16. Complement Fixation and Activation
Main antibody defense against cellular antigens
Several antibodies bind close together on a cellular antigen
Their complement-binding sites trigger complement fixation into the cell’s surface
Complement triggers cell lysis

17. Complement Fixation and Activation
Activated complement functions
Amplifies the inflammatory response
Opsonization
Enlists more and more defensive elements

18. (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

19. Cell-Mediated Immune Response
T cells provide defense against intracellular antigens
Two types of surface receptors of T cells
T cell antigen receptors
Cell differentiation glycoproteins
CD4 or CD8
Play a role in T cell interactions with other cells

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

21. (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

22. Comparison of Humoral and Cell-Mediated Response
Antibodies of the humoral response
The simplest ammunition of the immune response
Targets
Bacteria and molecules in extracellular environments (body secretions, tissue fluid, blood, and lymph)

23. Comparison of Humoral and Cell-Mediated Response
T cells of the cell-mediated response
Recognize and respond only to processed fragments of antigen displayed on the surface of body cells
Targets
Body cells infected by viruses or bacteria
Abnormal or cancerous cells
Cells of infused or transplanted foreign tissue

24. 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)

25. 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

26. Class I MHC Proteins
Bind with fragment of a protein synthesized in the cell (endogenous antigen)
Endogenous antigen is a self-antigen in a normal cell; a nonself antigen in an infected or abnormal cell
Informs cytotoxic T cells of the presence of microorganisms hiding in cells (cytotoxic T cells ignore displayed self-antigens)

27. 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

28. Class II MHC Proteins
Bind with fragments of exogenous antigens that have been engulfed and broken down in a phagolysosome
Recognized by helper T cells

29. 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

30. 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

31. T Cell Activation: Antigen Binding
CD4 and CD8 cells bind to different classes of MHC proteins (MHC restriction)
CD4 cells bind to antigen linked to class II MHC proteins of APCs
CD8 cells are activated by antigen fragments linked to class I MHC of APCs

32. T Cell Activation: Antigen Binding
Dendritic cells are able to obtain other cells’ endogenous antigens by
Engulfing dying virus-infected or tumor cells
Importing antigens through temporary gap junctions with infected cells
Dendritic cells then display the endogenous antigens on both class I and class II MHCs

33. T Cell Activation: Antigen Binding
TCR that recognizes the nonself-self complex is linked to multiple intracellular signaling pathways
Other T cell surface proteins are involved in antigen binding (e.g., CD4 and CD8 help maintain coupling during antigen recognition)
Antigen binding stimulates the T cell, but co-stimulation is required before proliferation can occur

34. 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

35. T Cell Activation: Co-Stimulation
Requires T cell binding to other surface receptors on an APC
Cytokines (interleukin 1 and 2 from APCs or T cells) trigger proliferation and differentiation of activated T cell

36. T Cell Activation: Co-Stimulation
Without co-stimulation, anergy occurs
T cells
Become tolerant to that antigen
Are unable to divide
Do not secrete cytokines

37. T Cell Activation: Co-Stimulation
T cells that are activated
Enlarge, proliferate, and form clones
Differentiate and perform functions according to their T cell class

38. Include interleukins and interferons
Cytokines
Mediate cell development, differentiation, and responses in the immune system
Include interleukins and interferons
Interleukin 1 (IL-1) released by macrophages co-stimulates bound T cells to
Release interleukin 2 (IL-2)
Synthesize more IL-2 receptors

39. Other cytokines amplify and regulate innate and adaptive responses
IL-2 is a key growth factor, acting on cells that release it and other T cells
Encourages activated T cells to divide rapidly
Used therapeutically to treat melanoma and kidney cancers
Other cytokines amplify and regulate innate and adaptive responses

40. Roles of Helper T(TH) Cells
Play a central role in the adaptive immune response
Once primed by APC presentation of antigen, they
Help activate T and B cells
Induce T and B cell proliferation
Activate macrophages and recruit other immune cells
Without TH, there is no immune response

41. Helper T Cells
Interact directly with B cells displaying antigen fragments bound to MHC II receptors
Stimulate B cells to divide more rapidly and begin antibody formation
B cells may be activated without TH cells by binding to T cell–independent antigens
Most antigens require TH co-stimulation to activate B cells

42. 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

43. 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

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

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