Recognition of T cell epitopes (Abbas Chapter 6)

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1 Recognition of T cell epitopes (Abbas Chapter 6)

2 Functions of different APCs (Abbas Chapter 6)!!! Directon

3 Routes of antigen entry (Abbas Chapter 6) Flow of Information Barrier APCs LNs Sequence of Events Sensing Migration Activation Differentiation Remigration and Group Predation

4 Dendritic cells (Abbas Chapter 6) Conventional DCs (previously called myeloid DCs) stimulate strong T cell responses are the most numerous DC subset in lymphoid organs are derived from bone marrow progenitors can be cultured from bone marrow, blood cells, including blood monocytes constitute the resident tissue population of DCs On activation, DCs in epithelia and tissues mature and migrate into draining lymph nodes and initiate T cell responses Conventional DCs are also sometimes classified into the Langerhans cell type (representing DCs in epithelia and in skin-draining lymph nodes) and into the interstitial/dermal typ (representing DCs in most other tissues) Prototypes of epithelial DCs are Langerhans cells of the epidermis DCs in intestinal epithelia can send out processes that traverse the epithelial cells and project into the lumen, where they capture microbial antigens

5 Dendritic cells (Abbas Chapter 6) Plasmacytoid DCs resemble plasma cells morphologically acquire the morphology and functional properties of DCs only after activation develop in the bone marrow from a common precursor (with myeloid DCs) are found in the blood and in small numbers in lymphoid organs (T cell zones) Their major function is the secretion of antiviral type I interferons They also play a role in antigen presenting

6 Dendritic cells (Abbas Chapter 6) Dendritic cells are heterogeneous, including many subpopulations A, Light micrograph of cultured dendritic cells derived from bone marrow precursors. B, A scanning electron micrograph of a dendritic cell showing the extensive membrane projections. C, D, Dendritic cells in the skin, illustrated schematically (C) and in a section of the skin (D) stained with an antibody specific for Langerhans cells (which appear blue in this mmunoenzyme stain). E, F, Dendritic cells in a lymph node, illustrated schematically (E) and in a section of a mouse lymph node (F) stained with fluorescently labeled antibodies against B cells in follicles (green) and dendritic cells in the T cell zone (red).

7 Antigen capture and DC maturation (Abbas Chapter 6)

8 MHC (restriction) MHC I and II presentation of self and non-self nobody is histocompatible with anybody MAPs are decisive

9 Experimental evidence for MHC-I restriction

10 Human and mouse MHC loci (Abbas Chapter 6) short arm of chromosome 6 chromosome 17

11 Map of the human MHC (Abbas Chapter 6)

12 From sensing microbes to increased MHC expression Class II expression: Several transcription factors may be assembled and bind a protein called the class II transcription activator (CIITA), and the entire complex binds to the class II promoter and promotes efficient transcription. By keeping the complex of transcription factors together, CIITA functions as a master regulator of class II gene expression. CIITA is synthesized in response to IFN-γ,explaining how this cytokine increases expression of class II MHC molecules

13 Structure of class I MHC molecule (Abbas Chapter 6) binding site of CD8

14 Structure of class II MHC molecule (Abbas Chapter 6) binding site of CD4

15 Polymorphic residues of MHC molecules

16 Peptide binding (Abbas Chapter 6)

17 Pathways of processing and presentation

18 Some experiments

19 Class I MHC pathway (Abbas Chapter 6)

20 Class II MHC pathway (Abbas Chapter 6)

21 Functions of the invariant chain and HLA-DM

22 Cross-presentation (Abbas Chapter 6)

23 Presentation of extracellular and cytosolic antigens

24 Immunogenicity (immunodominance) of certain peptides

25

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