Basic Immunology University of Tabuk Faculty of Applied Medical Science Department of Medical Laboratory Technology Mr.AYMAN.S.YOUSIF MSc.Medical Microbiology & Immunology Academic Year: ( )

Mr.AYMAN.S.YOUSIF /03/2013 Lecture 5: Acquired Immunity

Objectives At the end of this lecture, you should be able to: 1.To compare and contrast antigens recognized by the TCR and BCR. 2.To describe the pathways involved in processing endogenous and exogenous antigens. 3.To discuss self MHC restriction in antigen presentation to T cells. 4.To describe the major antigen presenting cells. 1

Comparison of BCR and TCR  B cells and T cells recognize different substances as antigens and in a different form.  The B cell uses cell surface-bound immunoglobulin as a receptor and the specificity of that receptor is the same as the immunoglobulin that it is able to secrete after activation.  B cells recognize the following antigens in soluble form:  Proteins.  Nucleic acids.  Polysaccharides.  Some lipids.  Small chemicals (haptens). 2

Comparison of BCR and TCR not  In contrast, the overwhelming majority of antigens for T cells are proteins, and these must be fragmented and recognized in association with MHC products expressed on the surface of nucleated cells, not in soluble form.  T cells are grouped functionally according to the class of MHC molecules that associate with the peptide fragments of protein: 1. Helper T cells recognize only those peptides associated with class II MHC molecules, and 2. cytotoxic T cells recognize only those peptides associated with class I MHC molecules. 3

Antigen Processing and Presentation  Antigen processing refers to the. ability of APCs to break down antigen into peptides and to associate those peptides with MHC molecules  Antigen presentation is he process of displaying peptide antigens associated with MHC molecules to a T cell.  MHC class I molecules present degradation products derived from intracellular (endogenous) proteins in the cytosol.  MHC class II molecules present fragments derived from extracellular (exogenous) proteins that are located in an intracellular compartment. 4

I. Class I MHC Pathway.  All nucleated cells express class I MHC. 1) Proteins are fragmented in the cytosol by proteosomes or by other proteases. 2) The fragments are then transported across the membrane of the endoplasmic reticulum by transporter proteins (TAP). 3) Synthesis and assembly of class I Within the endoplasmic reticulum. 4) The partial folded MHC class I complex binds to the TAP complex, and, after binding of peptide. The peptide/MHC complex is transported through the Golgi apparatus to the cell surface. 5

I. Antigen Processing and Presentation - Class I MHC Pathway. ( Transporter Antigen Processing (TAP) in the endoplasmic reticulum) 6

I. Antigen Processing and Presentation - Class I MHC Pathway. proteosomes (complex of proteins having proteolytic activity) 7

Activation of naïve CTL cell (CD8) 8

II. Class II MHC pathway  Whereas all nucleated cells express class I MHC, only a limited group of cells express class II MHC, which includes the professional Antigen Presenting Cells (APC).  The principal APC are Macrophages, Dendritic cells (Langerhans cells),and B cells.  The expression of class II MHC molecules is either constitutive or inducible ( especially by interferon-gamma (INF) in the case of macrophages ). 9

II. Antigen Processing and Presentation - Class II MHC Pathway. 1) Exogenous proteins taken in by endocytosis are fragmented by proteases in an endosome. 2) The alpha and beta chains of MHC class II, along with an invariant chain, are synthesized and assembled in the endoplasmic reticulum. 3) The invariant chain prevents endogenous peptides from the cytosol from associating with class II MHC molecules. 4) The class II MHC molecules with the associated invariant chain are transported through the Golgi and trans-Golgi apparatus to reach the endosome 5) where the invariant chain is digested, and the peptide fragments from the exogenous protein are able to associate with the class II MHC molecules, which are finally transported to the cell surface. 10

Invariant chain

II. Antigen Processing and Presentation - Class II MHC Pathway. 11

Activation of naïve T helper cell (CD4) 12

III. Self MHC Restriction In order for a T cell to recognize and respond to a foreign protein antigen, it must:-  Recognize the MHC on the presenting cell as self MHC. This is termed self MHC restriction.  Helper T cells recognize antigen in context of class II self MHC.  Cytotoxic T cells recognize antigen in context of class I self MHC. 13

Antigen Presenting Cells (APCs) The three main types of antigen presenting cells are :-  Dendritic cells.  Macrophages.  B cells.  although other cells, that express class II MHC molecules, (e.g., thymic epithelial cells) can act as antigen presenting cells in some cases. 14 B cellMacrophage Dendritic Cell

I. Dendritic cells  Are found in skin and other tissues.  Ingest antigens by pinocytosis and transport antigens to the lymph nodes and spleen.  Are the most effective antigen presenting cells and can present antigens to naïve (virgin) T cells.  They can present internalized antigens in association with either class I or class II MHC molecules (cross presentation).  The predominant pathway for internalized antigen is the class II pathway. 15

I. Dendritic cells  Constitutively express MHC I and MHC II (can stimulate both CD4+ and CD8+ T cells) as well as B7 (the co-stimulatory signal)  Antigen presentation appears to be the sole purpose of dendritic cells, and these cells can be infected by a wide variety of viruses.  They can present some viral peptides on their MHC II, and contribute to the induction of antibody against viruses.  Very efficient at stimulation of cytotoxic responses. 16

II. Macrophages  Are not as effective in presenting antigen to naïve T cells but they are very good in activating memory T cells.  Express little MHC II or B7, but have receptors for bacterial cell wall components which, upon binding, activate the macrophage to express high levels of B7 and MHC II.  Once activated, macrophages are efficient at stimulating CD4 + T cells, both for inflammatory responses and helper (antibody) responses. 17

III. B cell  B cells express high levels of MHC II, but not B7  These cells bind antigen via their surface Ig and ingest antigens by pinocytosis. Like macrophages  These cells are Not as effective as dendrite cells in presenting antigen to naïve T cells.  B cells are very effective in presenting antigen to memory T cells, especially when the antigen concentration is low because surface Ig on the B cells binds antigen with a high affinity. 18

Capture of circulating T cells in lymph nodes T cells enter lymph node across the walls of venules T cells monitor antigen presented by macrophages and dendritic cells T cells that do not encounter specific antigen leave the lymph node through lymphatic vessels T cells that encounter specific antigen proliferate and begin to differentiate into effector cells 20

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