Activation of the Adaptivge Immunity

1. Adaptive Immunity- Activation

2. Overview
• In order to initiate an immune response antigen must be
recognized.
• Antigen recognition depends on detection of antigen by
special receptors.
• Antigen recognition depends on cellular cooperation.
• Cellular cooperation is controlled by recognition of MHC-
encoded receptors.

3. Clonal Selection Theory
(F. Macfarlane Burnet)
• Pre-existence of of many different potential
antibody producing cells
• Each cell displays surface receptors for specific
antigens
• Antigen encounter selects cells

4. Postulates of the Clonal Selection
Hypothesis
• Each lymphocyte bears a single type of receptor of a unique specificity
• Interaction between a foreign molecule and a lymphocyte receptor
capable of binding that molecule with high affinity leads to lymphocyte
activation
• The differentiated effector cells derived from an activated lymphocyte
will bear receptors of identical specificity to those of the parental cell
from which that lymphocyte was derived
• Lymphocytes bearing receptors specific for self molecules are deleted at
an early stage in lymphocyte development and are therefore absent
from the repertoire

5. First a Word About “Cluster of
Differentiation/Designation” (CD) Antigens
• What are they?
–Differentiation antigens
–Expressed by cells at distinct stages of
differentiation
–Expressed by cells having different functions
• How are they detected?

6. Fluorescence-Activated Cell Sorting (FACS)

7. Major Lymphocyte Populations
• B lymphocytes and plasma cells
• T lymphocytes
–Helper/Inducer (CD4)
–Suppressor (CD8)

8. T Cell Recognition of Antigen
• Recognize antigen peptide fragments bound to specialize cell
surface molecules on antigen-presenting cells (APC).
• Molecules are encoded by major histocompatibility complex
• Peptides are displayed to T cells as peptide:MHC complexes
• T cell antigen receptors recognize peptide:MHC complexes
• Each MHC molecule can bind numerous different peptides
• Two classes of MHC molecules

9. Major Histocompatibility Complex (MHC)
Gene Products
• Class I
– Antigen is usually endogenous (e.g. viral proteins).
– CD8+ cytotoxic T lymphocytes (CTLs) recognize antigen in
association with class I MHC gene product on APC.
• Class II Molecules
– Antigen is usually extracellular.
– CD4+ Helper T Lymphocytes recognize antigen in
association with class II MHC gene product on APC.

10. Cellular Cooperation and Antigen
Recognition
APC Extracellular
Antigen
CD4+ Helper T
Lymphocyte
Class II
MHC-
associated
antigen
+

11. B Cell Antigen Recognition
• Cell surface immunoglobulin receptor or B-cell
receptor (IgM and IgD)
• Antigen contact initiates B-cell activation, clonal
expansion, maturation to plasma cell
• Antigen receptor is identical to immunoglobulin that
will ultimately be produced

12. Antigen Presenting Cells
• Macrophages/monocytes
• Dendritic cells (e.g., Langerhan’s cells)
• B cells

13. Properties of
Antigen-
Presenting
Cells

14. Cellular Cooperation
TH B
antigen
Antibody secretion by
plasma cells
Plasma Cells
Antigen presenting cell
Antigen presentation to T
and B cells by APC
T cells elaborate cytokines to
facilitate B cell proliferation
and maturation

15. Adjuvants
• Freund's Complete Adjuvant (Water-in-oil emulsion)
– mineral oil
– emulsifying agent
– microbial preparation (eg. heat-killed extract of
Mycobacterium tuberculosis)
– aqueous phase containing antigen
• Aluminum Hydroxide Gel
• Microbial Adjuvants
– C. parvum
– BCG
• Peptides and Synthetic Polymers

16. Effector Mechanisms
• Mechanisms that are used by the immune system to
eliminate pathogens (or other substances) from the body
• Cellular effector mechanisms
– Activated T cells
– Natural killer cells
• Humoral effector mechanisms (antibody)
– Neutralization
– Opsonization
– Complement activation
– Antibody-dependent cell-mediated cytotoxicity (ADCC)

17. Effector Activity Against Pathogens

18. Clonal Expansion Following Antigen Exposure
Virgin lymphocyte pool
PRIMARY RESPONSE
SECONDARY RESPONSE
effector cells memory cell pool
effector cells memory cell pool

19. The Bottom Line
• In order to initiate an immune response antigen
must be recognized.
• Antigen recognition depends on detection of
antigen by special receptors.
• Antigen recognition depends on cellular
cooperation.
• Cellular cooperation is controlled by recognition
of MHC-encoded receptors.
• Antigen “drives” the process resulting in
“effector” cells and “memory” cells.

20. Thank you