1. General Microbiology (Micr300)
Lecture 15
Adaptive Immunity
(Text Chapter: )

2. Lymphocytes: The Cellular Arms of Adaptive Immunity
T-lymphocytes
Mature in thymus
Interact with other defense cells (T helper cells, TH) or kill abnormal cells (cytotoxic T cells, Tc)
B-lymphocytes
Mature in bone marrow
Produce antibodies

3. The Adaptive Immune Response
In adaptive immunity, phagocytes present antigen to specific T cells, triggering the proliferation of effector T cells and subsequently the production of antibodies. Immune T cells and antibodies attack directly or indirectly the antigen.
The adaptive immune response is characterized by specificity for the antigen, the ability to respond more vigorously when reexposed to the same antigen (memory), and the ability to discriminate self antigens from nonself antigens (tolerance) (Figure 22.8).

4. Specific Interactions

5. Memory

6. Tolerance

7. Immunogens
Immunogens are foreign macromolecules that induce an immune response. Molecular size, complexity, and physical form are intrinsic properties of immunogens.
Molecular size is an important component of immunogenicity. For example, low-molecular-weight compounds called haptens cannot induce an immune response but can bind to antibodies. Because haptens are bound by antibodies, they are antigens even though they are not immunogenic.

8. Structure of the T-cell
Receptor (TCR)

9. Antigenic Determinants

10. Epitope
The antibody or TCR does not interact with the antigenic macromolecule as a whole but only against a distinct portion of the molecule called an antigenic determinant or epitope.

11. Presentation of Antigen to T Lymphocytes
T cells recognize digested antigens presented by antigen-presenting cells (APCs) or by pathogen-infected cells.
At the molecular level, TCRs bind peptide antigens presented by major histocompatibility complex (MHC) proteins. Class I MHC proteins are found on the surfaces of all nucleated cells.
Class II MHC proteins are found only on the surface of B lymphocytes, macrophages, and dendritic cells, all of which are APCs (Figure 22.11).

12. Class I MHC
Class II MHC

13. T-Cytotoxic Cells and Natural Killer Cells
T-cytotoxic (TC) cells recognize antigens presented via MHC I on virus-infected host cells and tumor cells through antigen-specific TCRs. Antigen-specific recognition triggers killing via perforin and granzymes (Figure 22.13).
TC use a special molecule called CD8 to dock onto MHC I.

14. T-Cytotoxic Cells

15. T-Helper Cells
T helper cells secrete cytokines to direct the function of other immune cells.
Depending on the cytokine profile T helper cells are dived into subgroups
TH1 cells enhance phagocyte function in destroying pathogens and promote inflammation
TH2 cells stimulate B cells to proliferate, augment antibody production and develop into plasma cells (Figure 22.14).

16. T-Helper Cells
Pro-inflammatory
cytokines

17. T cell – B cell Interaction
Antibody inducing cytokines
T cell – B cell Interaction

18. Antibodies (Immunoglobulins)
Immunoglobulin (Ig) (antibody) proteins consist of four chains, two heavy and two light (Figure 22.15). Each chain consists of different domains.
The amino-terminal region is a variable domain, meaning that the amino acid sequence in this structural region differs in each different antibody. The antigen-binding site is formed by the interaction of variable regions of heavy and light chains.
The constant regions are very uniform among groups of antibodies
There are 5 major groups of antibodies (isotypes) that differ in the make up of their constant region of the heavy chain (IgG, IgM, IgA, IgD, IgE)

19. Immunoglobulin G Structure
Fab
(antigen-binding fragment) Fc
(constant fragment)
L: light chain
H: heavy chain

20. The Antigen Binding Groove: Lock-Key Principle

21. Antibody Isotypes IgG IgM IgA IgD IgE g m a d e Isotype
Heavy chain type g m a d e
Main function
Phagocytosis
AgglutinationComplement activation
Placenta-transfer
Neutralization
Agglutination
Complement activation
Mucosal protection ?
B cell maturation marker
Allergies

22. Effector Functions of Antibodies
Neutralization (blocking)
Opsonization (enhancing phagocytosis)
Complement Activation (direct killing, enhancing phagocytosis)

23. Antibody Production
Antibody production is initiated by antigen contact with an antigen-specific B cell and is always IgM (Primary antibody response)
B cells require support from T helper cells for full production of antibodies including other isotypes
B cells take up and process antigen, present it to T helper cells, which in turn secrete cytokines to signal large scale production and isotype switch

24. Antibody Production
Some activated B cells develop into plasma cells and produce and secrete large amounts of antibody of isotypes other than IgM
Some activated B cells develop into long living memory cells and can rapidly produce large quantities (high titers) of antibodies upon reexposure to antigen (secondary antibody response, Figure 22.21).
Memory B cells do not need T cell activation

25. Primary & Secondary Antibody Responses

26. Antibodies As Tool
Inject antigen into rabbit (with immune stimulator = adjuvant)
Re-inject for 2 or 3 times
Rabbit will make antibodies against the antigen
Draw blood, prepare serum = polyclonal antibodies

27. Antibodies in Immunoassays: ELISA