T lymphocyte biology part III Suggested Reading for

T lymphocyte biology part III Suggested Reading for Class #10 Abbas: pgs. 129 -146 I included 2 figures from Chapter 5 for review purposes only 9/22/2016

Learning Objectives for Class #10 part 1 • Compare the different functions of the CD 4+ T helper cell subsets: Tfh, Th 1, Th 2, Th 17 • Describe the importance of cell-mediated immunity, using L. monocytogenes as an example • Describe the different mechanisms by which IFN-γ secretion by Th 1 cells enhances the function of macrophages • Explain how cytokines produced at the site of infection influence T cell differentiation through subset-specific transcription factor activity, and how this determines the nature of the immune response, e. g. : IL-12, IFN gamma Th 1 cells IL-4 Th 2 cells, IL-1, IL-6, IL-23, TGF- Th 17 cells

Learning Objectives for Class #10 part II • Describe the mechanisms by which Th 2 cells protect the body against helminths • Compare and contrast classical and alternative macrophage activation • Explain the importance of proper balance between Th 1 vs. Th 2 activation, and how this can determine the outcome of an infection, using M. leprae as an example • Describe the mechanisms by which Th 17 cells protect against bacterial and fungal infections • Describe the mechanism of how CTLs and NK cells can kill diseased host cells • Explain the cooperation between Th 1 cells and CTLs in eradicating intracellular microbes • Discuss several examples of how microbes have evolved to become resistant to cell-mediated immunity, including T cell exhaustion

Induction and effector phases of cell-mediated immunity (review slide from Chapter #5) Abbas Fig. 5. 2

Cell-mediated immunity Abbas Fig. 6. 1

Cell-mediated immunity to an intracellular bacterium, Listeria monocytogenes Abbas Fig. 6 -2

Listeriosis causes food poisoning Listeria sp. -can grow in refrigerator (importance of TH 1 and CMI for Listeria sp. discussed on previous 2 slides) Additional information below on this slide is FYI, not on i. RAT or Block exam 2 -facultative intracellular pathogen that grows in host cells escape from phagolysosome, grow in cytosol cellular immunity important to eradicate -bacteria can “push” their way into adjacent host cell by cytoskeleton assembly http: //cmgm. stanford. edu/theriot/movies. html cool Listeria movement inside cell videos Murray Fig 26. 1 Listeria monocytogenes in Cerebral Spinal Fluid

Development of effector CD 4+ T cells review slide from Chapter #5 Notice Tfh cells represent an additional subset of effector T lymphocytes Abbas Fig. 5. 13

Characteristics of subsets of CD 4+ helper T lymphocytes Abbas Fig. 6 -3

Properties of the major cytokines produced by CD 4+ helper T lymphocytes Abbas Fig. 6 -4

Functions of cytokines involved in T cell-mediated immunity Abbas Fig. 6 -4

Functions of Th 1 cells Abbas Fig. 6 -5

Activation of macrophages by Th 1 lymphocytes Abbas Fig. 6 -6

Macrophage responses and their roles in cell-mediated immunity. Abbas Fig. 6 -6

Development of Th 1 effector cells Abbas Fig. 6 -7 A

Development of Th 2 effector cells Abbas Fig. 6 -7 B

Functions of Th 2 cells Abbas Fig. 6 -8

Classical and alternative macrophage activation Abbas Fig. 6 -9

Balance between Th 1 and Th 2 cell activation determines outcome of intracellular infections. Abbas Fig. 6. 10

Lepromatous leprosy-most severe form of M. leprae infection results from insufficient cell-mediated immunity -skin destruction, loss of sensation to extremities, fatal if untreated -repeated trauma and infections results from loss of sensation eventually resulting in loss of fingers & toes tuberculoid leprosy-better outcome- (on left) cellular immunity effective at localizing infection

Development of Th 17 effector cells Abbas Fig. 6 -7 C

Functions of Th 17 cells Abbas Fig. 6. 11

Mechanisms of killing of infected cells by CD 8+ cytotoxic T lymphocytes (CTLs). NK cells also use granzymes and perforin to kill altered host cells (that are stressed and lack MHC class I expression) Abbas Fig. 6 -12