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

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.

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+

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

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)

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.

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

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

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.

MHC class II Presentation of Peptide

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

Presentation of Antigen to T helper cells

Presentation of Antigen to T helper cells

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

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) .

MHC class I Presentation of Peptide

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

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

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

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

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

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.

Antigen-Presentation by B cells

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.

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.