1. The Adaptive Immune Response
Chapter 16

2. Strategy of Adaptive Immune Response
First response to particular antigen called primary response
May take a week or more to develop
Immune systems remembers pathogen on subsequent exposure
Termed secondary response
Adaptive immunity divided into
Humoral immunity
Eliminates extracellular pathogens
Cellular immunity
Eliminates intracellular pathogens

3. Strategy of Adaptive Immune Response
Overview of humoral immunity
Mediated by B lymphocytes
A.k.a B cells
Develops in bone marrow
B cells may be triggered to proliferate into plasma cells
Plasma cells produce antibodies
Antibodies produces when antigen bonds B cell receptor
Some B cells produce memory cells

4. Strategy of Adaptive Immune Response
Overview of cellular immunity
Mediated by T lymphocytes
A.k.a T cells
Matures in thymus
Divided into 2 subsets
Cytotoxic T cells
Helper T cells
T cell receptors help with antigen recognition

5. Anatomy of the Lymphoid System
Lymphoid system collection of tissues and organs designed to bring B and T cells in contact with antigens
In order for body to mount appropriate response immune cells must encounter antigen
Lymphoid system includes
Lymphatic vessels
Secondary lymphoid organs
Primary lymphoid organs

6. Anatomy of the Lymphoid System
Lymphatic vessels
Carry lymph to body tissues
Lymph formed as result of body’s circulatory system
Lymph travels through vessels to lymph nodes
Material such as protein is removes
Fluid portion empties back into blood stream

7. Anatomy of the Lymphoid System
Secondary lymphoid organs
Sites where lymphocytes gather to encounter antigens, organs include
Lymph nodes
Spleen
Tonsils
Adenoids
Appendix
Organs situated strategically
Allows for initiation of immune response from nearly any place in body

8. Anatomy of the Lymphoid System
Primary lymphoid organs
Bone marrow and thymus are primary lymphoid organs
Location where stem cells destined to become B and T cell mature
B cells mature in bone marrow
T cells mature in thymus
Once mature, cells leave primary lymphoid organs and migrate to secondary lymphoid organs

9. Nature of Antigens
Coined from compounds that elicit antibody production
Antibody generator
Includes an enormous variety of materials
Today term used to describe any compound that elicits and immune response
Antigen that causes immune response termed immunogen
Proteins and polysaccharides induce swong response
Lipids and nucleic acids often do not
Recognition of antigen directed at antigenic determinant or epitope

10. Nature of Antibody Two chains are heavy Two chains are light
Structure of the Ab
Basic unit is the monomer
Made of four chains of amino acids held together by disulfides bonds
Two chains are heavy
Two chains are light
Each heavy and light chain has a constant region
The constant region is known as Fc regions
Each heavy and light chain has a variable region
Variable region is unique to each Ab
This region binds to a specific Ag and is know as Fab region

11. Nature of Antibody Protective outcomes of antibody-antigen binding
Neutralization
Prevents virus or toxin from interacting with cell
Immobilization and prevention of adherence
Antibody bonding to cellular structures to interfere with function
Agglutination and precipitation
Clumping of bacterial cells by specific antibody
Bacteria more easily phagocytized

12. Nature of Antibody Protective outcomes of antibody-antigen binding
Opsonization
Coating of bacteria with antibody to enhance phagocytosis
Complement activation
Antibody bonding triggers classical pathway
Antibody-dependent cellular cytotoxicity
Multiple antibodies bind a cell which becomes target for certain cells

13. Nature of Antibody Ab divided into five classes
Class is based on constant region of the Ab
Classes include:
IgG
IgA
IgM
IgD
IgE

14. Nature of Antibody Five classes of antibody IgM
First Ab to respond to infection
5 – 13% of Ab in circulation
Structure: pentamer
Five monomer units joined together at the constant region
Found on the surface of b lymphocytes as a monomer
Only Ab that can be formed by the fetus

15. Nature of Antibody Five classes of antibody IgG IgA
Dominant Ab in circulation
80 – 85% Ab in circulation
Structure = monomer
Only Ab that can cross the placenta
The antibody of memory!!!!!
IgA
Found in secretions
% of Ab in circulation
Structure
Monomer in serum
Dimer in secreations
Breast milk, mucous, tears and saliva

16. Nature of Antibody Five classes of Ab IgD IgE
<1% of total Ab in circulation
Structure = monomer
Maturation of antibody response
IgE
Barely detectable in circulation
Active in allergic reaction

17. Clonal Selection of Lymphocytes
When antigen introduced into body only appropriate antibody bind
Initiates multiplication of specific antibody
Process called clonal selection
Repeated cycles of cell division generates population of copied cells
Termed clonal expansion
Without sustained stimulation cells undergo apoptosis

18. Clonal Selection of Lymphocytes
Lymphocyte characteristics include
Naïve
Have antigen receptor but have not encountered antigen
Activated
Able to proliferate
Have bound antigen
Effectors
Descendents of activated lymphocytes
Able to produce specific cytokines
Plasma cells, T helper and cytotoxic T cells effector cells
Memory lymphocytes
Long-lived descendents of activated lymphocytes
Memory cells responsible for speed and effectiveness of secondary response
Remembers antigen on subsequent exposure

19. B Lymphocyte and Antibody Response
Antigen binds to B cell receptor
Poises B cell to respond
In many cases B cell needs conformation from helper T cells
Ag enters the body and is phagocytized and processed by macrophages
These macrophages destroy Ag and present a portion on the surface of the macrophage next to self Ag
Macrophages are call antigen presenting cells (APC)

20. B Lymphocyte and Antibody Response
Processed Ag combines with specific TH with the appropriate receptor
APC releases substances to activate TH cell
TH cell activates B cells to divide and differentiate
Produce plasma cells and memory B cells

21. B Lymphocyte and Antibody Response
Characteristic of primary response
Lag period of 10 to 12 days occurs before antibody detection in blood
Activated B cell proliferate and differentiate into increasing numbers of plasma cells as long as antigen in present
Net result is slow steady increase in antibody titer
Overtime some B cells undergo changes enhancing immune response including
Affinity maturation
Class switching
Formation of memory cells

22. B Lymphocyte and Antibody Response
Affinity maturation
Form of natural selection
Occurs among proliferating B cells
Fine tunes quality of response with respect to specificity
B cell receptors more and more specific to antigen
Antibody binds antigen more tightly

23. B Lymphocyte and Antibody Response
Class switching
B cells initially programmed to differentiate into plasma cells
Plasma cells secrete IgM antibodies
Helper T cell produce cytokines
Some B cells switch programming
Differentiate to plasma cells that secrete other classes of antibody
Commonly IgG

24. B Lymphocyte and Antibody Response
Formation of memory
B cells that have undergone class switching
Produce IgG antibody
IgG is antibody of memory
IgG antibody can circulate in body for years allowing protection against specific antigens

25. B Lymphocyte and Antibody Response
Characteristics of secondary response
Memory cells responsible for swift effective reaction of secondary response
Often eliminating invaders before noticeable harm is done
Vaccine exploits phenomenon of immunologic memory
Some memory B cells will differentiate into plasma cells
Results in rapid production of antibodies

26. B Lymphocyte and Antibody Response
T-independent antigens
Can stimulate antibody response
Activate B cells without helper T cells
Few antigens are T-independent
B cell receptors bind antigen simultaneously
Leads to B cell activation
Some polysaccharides and lipopolysaccharides act as T-independent antigens

27. T Lymphocytes Antigen Recognition and Response
General characteristics of T cells
Have multiple copies of T cell receptors
Receptors have variable site of antigen bonding
Role of T cells different from B cells
T cells never produce antibody
T cells armed with effectors that interact directly with antigen
T cell receptor does not react with free antigen
Antigen must be presented by APC

28. T Lymphocytes Antigen Recognition and Response
General Characteristics
During antigen presentation antigen cradled in grove of major histocompatability complex molecule (MHC molecule)
Two types MHC
MHC class I
Bind endogenous antigen
MHC class II
Bind exogenous antigen

29. T Lymphocytes Antigen Recognition and Response
General characteristics
Two major function T cell populations
Cytotoxic T cells
Proliferate and differentiate to destroy infected or cancerous “self” cells
Have CD8 marker
Recognize MHC class I
Helper T cells
Multiply and develop into cells that activate B cells and macrophages
Stimulate other T cells orchestrate immune response
Have CD4 marker
Recognize antigen display by MHC class II

30. T Lymphocytes Antigen Recognition and Response
Functions of Tc (CD8) cells
Induce apoptosis in “self” cells
Cells infected with virus or intracellular microbe
Destroys cancerous “self” cells
Nucleated cells degrade portion of proteins
Load peptides into groove of MHC class I molecule
MHC class I molecule recognized by circulating Tc cell
Cell destroyed by lethal effector function of Tc cell
Tc cells releases pre-formed cytokines to destroy cell

31. T Lymphocytes Antigen Recognition and Response
Functions of TH (CD4) cells
Orchestrate immune response
Recognize antigen presented by MHC class II molecules
MHC class II molecules found only on APC
If TH cell recognizes antigen cytokines are delivered
Cytokines activate APC to destroy antigen

32. T Lymphocytes Antigen Recognition and Response
Role of TH cells in B cell activation
If TH cell encounters B cell bearing peptide: MHC class II complex
TH cell responds by producing cytokines
B cell is activated in response to cytokine stimulation
B cell proliferates and undergoes class switching
Also drive formation of B memory cells

33. T Lymphocytes Antigen Recognition and Response
Role of TH cells in macrophage activation
Macrophages routinely engulf invading microbes resistant to lysosomal killing
TH cells recognize macrophage with engulfed microbes resistant to killing
TH cells activate macrophages by delivering cytokines that induce more potent destructive mechanisms

34. Natural Killer Cells
Natural killer cell descend from lymphoid stem cells
They lack antigen specificity
No antigen receptors
Recognize antigens by means of Fc portion of IgG antibodies
Allows NK cells to attach to antibody coated cells
Actions augment adaptive immune response
Important in process of antibody dependent cellular toxicity
Enable killing of host cells with foreign protein in membrane
Natural killer cells recognize destroyed host cells with no MHC class I surface molecules
Important in viral infection

35. Lymphocyte Development
During lymphocyte development B and T cells acquire ability to recognize distinct epitopes
Once committed to specific antigen cell “checked out” to ensure proper function
B cells undergo developmental stages in bone marrow
T cell go through process in thymus