1. Lecture Outline Antigens Definition Exogenous Endogenous
Antigen Presentation
Exogenous - APC, MHC II, T helper cells (CD4+)
Endogenous - Infected host cells, MHC I, cytotoxic T-cells (CD8+)
Antigen Presentation by B-cells
Co-stimulation

2. ANTIGENS
DEFINITION
-Antigens are molecules that elicit an immune response in the body.
-Antigens can be:
Proteins
Polysaccharides - sugars such as mannose.
Lipoproteins - conjugates of lipids (fats) with proteins.
-We will focus on how protein antigens are presented to the
immune system.
Antigen Presentation
-The display of digested bits of foreign molecules (i.e. antigens) on the
surface of Antigen Presenting Cells (e.g. macrophages).
-Antigens are often presented to T-cells and upon recognition the
T-cells become activated.

3. Antigen Presentation and “cell-mediated immunity”
The Immune Response
Activation of T helper cells
Activation of B cells
“humoral immunity”
TH2
Activation of Cytotoxic T-cells
“cell-mediated immunity”
TH1
CD4+
CD4+
CD8+

4. TYPES OF ANTIGENS EXOGNEOUS ANTIGENS
Antigens that enter the body from the environment;
Invading Pathogens
-Bacteria, Viruses, and Parasites INFECTIONS/DISEASE
Inhaled Antigens
-Proteins on cat hairs
-Dust ASTHMA ATTACK
-Pollen
Ingested Antigens
-Shellfish proteins
-Peanuts ALLERGIC RESPONSES
Antigens Introduced Beneath Skin
-Splinter
-Injected vaccine IMMUNIZATION

5. TYPES OF ANTIGENS ENDOGENOUS ANTIGENS
Antigens that are generated within cells of the body;
Proteins encoded by the genes of viruses (foreign)
Abnormal or altered ‘host’ proteins
-Encoded by mutant genes
(e.g. mutated proteins produced by cancer cells)

6. DETECTION OF ANTIGENS
Whether we encounter Exogenous or Endogenous Antigen;
-An effective immune response to any antigen requires that
the antigen is recognized by T-cells.
-Recognition of antigen(s) by T-cells is achieved by antigen
presentation resulting in the;
Activation of T helper (TH) cells CD4+
Activation of cytotoxic T cells CD8+
-The two categories of antigens (Exogenous and
Endogenous) are processed and presented to T-cells by
different mechanisms.

7. Cell-to-Cell Communication
Antigen Presentation
Cell-to-Cell Communication
T helper cell Macrophage

8. Presentation of EXOGENOUS Antigens
Players
APC (macrophage)
Antigen
MHC II
T helper cells
CD4+

9. Presentation of EXOGENOUS Antigens
Exogenous Antigens are taken up by two types of APC
Phagocytic cells (macrophages)
B lymphocytes (B cells)
Antigen-Presenting Cells (APC)
-Antigen is engulfed “eaten”; phagocytosis
-Antigen contained within the phagosome.
-Phagosome fuses with a lysosome.
-Antigen is then degraded into fragments (e.g. short peptides)
-These antigenic peptides are then displayed on the surface.
-Major Histocompatibility Class II (MHC II) is the receptor
responsible for presenting exogenous antigens.
-MHC II presented antigen is recognized by CD4+ T cells.
-Activated CD4+ T cells essential for controlling immune responses.

10. MHC class II
Presentation of Peptide

11. Generation of Antigen-MHC class II Complex
Presentation to
TH cells (CD4+)
[4]
[1]
Phagosome
[3]
[2]
Phagolysosome
APC (macrophage)

12. Presentation of Antigen to T helper cells

13. Presentation of Antigen to T helper cells

14. Presentation of ENDOGENOUS Antigens
Players
Infected Host Cell (or)
Altered Host Cell
Antigen
MHC I
Cytotoxic T cells
CD8+

15. Presentation of ENDOGENOUS Antigens
Antigens that are generated within a cell (e.g. viral proteins)
-Antigen is degraded into fragments (e.g. short peptides)
-These antigenic peptides are then displayed on the surface.
-Major Histocompatibility Class I (MHC I) is the receptor responsible for
presenting endogenous antigens.
-MHC I presented antigen is then recognized by CD8+ T cells.
-Most CD8+ T cells are cytotoxic.
-They have the ability to destroy the infected cell presenting viral peptides.
-Process helps to limit the spread of viruses (and cancer) .

16. MHC class I
Presentation of Peptide

17. Generation of Antigen-MHC class I Complex Cytotoxic T cells (CD8+)
Presentation to
Cytotoxic T cells (CD8+)
[4]
[3]
[2]
[1]

18. Presentation of Antigen to cytotoxic
T-cells (CD8+)

19. Presentation of Antigen to cytotoxic
T-cells (CD8+)
MHC I
Peptide
CD8
TCR
Cytotoxic
T cells (CD8+)

20. Comparison of antigen presentation to cytotoxic and T helper cells
CD8+
CD4+
CD8+
CD4+

21. Antigen-Presentation by B cells
Players
B cells, BCR, (endogenous) Antigen, MHC II, T helper cells
CD4+
Produce
Antibodies

22. Antigen-Presentation by B cells
B cells process and present EXOGENOUS antigens
-This process differs from macrophage antigen presentation.
-Antigen is engulfed “eaten” by receptor-mediated endocytosis.
-The B cell receptors for antigen (BCRs) are antibodies anchored on the
cell surface.
-Antigen is then degraded into fragments (e.g. short peptides)
-These antigenic peptides are then displayed on the surface.
-Major Histocompatibility Class II (MHC II) is the receptor
responsible for presenting exogenous antigens.
-MHC II presented antigen is recognized by CD4+ T cells.
-Activated CD4+ T cells are essential for helping B cells to proliferate
and produce antibodies that are released into the surroundings.

23. Antigen-Presentation by B cells

24. COSTIMULATION
-Binding of a TCR to a peptide-MHC complex is NOT sufficient to activate a T-cell.
-In order to become activated, the T-cell must bind to the presented peptide with its TCR and receive a second signal.
-This second signal is called costimulation.
-One of the most important costimulators are molecules on APC termed B7 that interact with CD28 on T cells.
-Binding of CD28 to B7 provides the necessary second signal required for the activation of the T-cell.

25. COSTIMULATION
-Although T-cells may encounter self-antigen in the body, they will not
respond unless they receive costimulation.
-Cells presenting the body’s own antigen do not provide signal two.
-This causes T cells that recognize self antigens to die.
-Protection from autoimmunity.