Download - Chapter 14 Cell-Mediated Effector Responses
![Page 1: Chapter 14 Cell-Mediated Effector Responses](https://reader035.vdocuments.us/reader035/viewer/2022062222/56814bd0550346895db8a9d1/html5/thumbnails/1.jpg)
Chapter 14
Cell-Mediated Effector Responses
![Page 2: Chapter 14 Cell-Mediated Effector Responses](https://reader035.vdocuments.us/reader035/viewer/2022062222/56814bd0550346895db8a9d1/html5/thumbnails/2.jpg)
Cell-mediated immunity:
Detect and eliminate cells that harbor intracellular pathogens.
Ag-specific cells – CD4+ T cells, CD8+ T cells
Ag-nonspecific cells – NK cells macrophages neutrophils eosinophils
![Page 3: Chapter 14 Cell-Mediated Effector Responses](https://reader035.vdocuments.us/reader035/viewer/2022062222/56814bd0550346895db8a9d1/html5/thumbnails/3.jpg)
Cytotoxic T Cells
![Page 4: Chapter 14 Cell-Mediated Effector Responses](https://reader035.vdocuments.us/reader035/viewer/2022062222/56814bd0550346895db8a9d1/html5/thumbnails/4.jpg)
Two major categories of cell-mediated immune responses:
- Effector cells that have direct cytotoxic activity.
- Effector cells that mediate delayed-type hypersensitivity (DTH) reactions
![Page 5: Chapter 14 Cell-Mediated Effector Responses](https://reader035.vdocuments.us/reader035/viewer/2022062222/56814bd0550346895db8a9d1/html5/thumbnails/5.jpg)
Three types of effector T cells:
1. CD4+ TH1cells 2. CD4+ TH2 cells 3. CD8+ CTLs
Characteristics:
- less stringent activation requirements - increased expression of cell-adhesion molecules - production of both membrane-bound and soluble effector molecules
![Page 6: Chapter 14 Cell-Mediated Effector Responses](https://reader035.vdocuments.us/reader035/viewer/2022062222/56814bd0550346895db8a9d1/html5/thumbnails/6.jpg)
- The CD45RO isoform associates with the TCR complex and CD4/CD8 much better than does the CD45RA isoform.- CD2 LFA-3, LFA-1 ICAMs
![Page 7: Chapter 14 Cell-Mediated Effector Responses](https://reader035.vdocuments.us/reader035/viewer/2022062222/56814bd0550346895db8a9d1/html5/thumbnails/7.jpg)
- The FasL, perforins, and granzymes mediate target cell destruction by the CTLs.- Membrane-bound TNF and soluble IFN and GM-CSF promote macrophage activation by the TH1 cell.- The membrane-bound CD40L and soluble IL-4, IL-5, IL-6, and IL-10 play a role in B cell activation by the TH2 cell.
![Page 8: Chapter 14 Cell-Mediated Effector Responses](https://reader035.vdocuments.us/reader035/viewer/2022062222/56814bd0550346895db8a9d1/html5/thumbnails/8.jpg)
Generation of Effector CTLs
CD28B7
![Page 9: Chapter 14 Cell-Mediated Effector Responses](https://reader035.vdocuments.us/reader035/viewer/2022062222/56814bd0550346895db8a9d1/html5/thumbnails/9.jpg)
Tumor-Cell Destruction by a CTL
CTL
tumor cell
![Page 10: Chapter 14 Cell-Mediated Effector Responses](https://reader035.vdocuments.us/reader035/viewer/2022062222/56814bd0550346895db8a9d1/html5/thumbnails/10.jpg)
CTL-Mediated Killing of Target Cells
perforin monomers&
granzyme proteases
![Page 11: Chapter 14 Cell-Mediated Effector Responses](https://reader035.vdocuments.us/reader035/viewer/2022062222/56814bd0550346895db8a9d1/html5/thumbnails/11.jpg)
Cell-Mediated Pore Formation in Target-Cell Membrane
iCa++
fusion
release
insertion
![Page 12: Chapter 14 Cell-Mediated Effector Responses](https://reader035.vdocuments.us/reader035/viewer/2022062222/56814bd0550346895db8a9d1/html5/thumbnails/12.jpg)
Perforin Pore on a Red Blood Cell
- Perforin exhibits sequence homology with C9, and the pores formed by perforin are similar to those observed in complement-mediated lysis.
- The perforin pores facilitate entry of granzyme proteases into the cell.
- Granzymes activate an apop- totic pathway within the cell.
![Page 13: Chapter 14 Cell-Mediated Effector Responses](https://reader035.vdocuments.us/reader035/viewer/2022062222/56814bd0550346895db8a9d1/html5/thumbnails/13.jpg)
CTL Can Use Fas to Lyze a Target Cell
![Page 14: Chapter 14 Cell-Mediated Effector Responses](https://reader035.vdocuments.us/reader035/viewer/2022062222/56814bd0550346895db8a9d1/html5/thumbnails/14.jpg)
CTL-mediated Killing Depends on Perforin, Fas, or A Combination of the Two
![Page 15: Chapter 14 Cell-Mediated Effector Responses](https://reader035.vdocuments.us/reader035/viewer/2022062222/56814bd0550346895db8a9d1/html5/thumbnails/15.jpg)
CTL-Mediated Apoptotic Pathways
Caspase:cysteine, aspartate protease
![Page 16: Chapter 14 Cell-Mediated Effector Responses](https://reader035.vdocuments.us/reader035/viewer/2022062222/56814bd0550346895db8a9d1/html5/thumbnails/16.jpg)
Natural Killer Cells
![Page 17: Chapter 14 Cell-Mediated Effector Responses](https://reader035.vdocuments.us/reader035/viewer/2022062222/56814bd0550346895db8a9d1/html5/thumbnails/17.jpg)
Natural Killer (NK) Cells:
- 5 - 10% of the recirculating lymphocyte population- No immunization is required. No memory- a population of large granular lymphocytes- constitutively cytotoxic, always having large granules- involved in the defense against viruses and tumors- Activity is stimulated by IFN, IFN, and IL-12.- express CD16 (FcRIII)- do not express TCR/CD3- Recognition is not MHC-restricted.- normal in RAG-1, RAG-2, and SCID mice- Cytotoxicity depends on perforin and granzymes.
![Page 18: Chapter 14 Cell-Mediated Effector Responses](https://reader035.vdocuments.us/reader035/viewer/2022062222/56814bd0550346895db8a9d1/html5/thumbnails/18.jpg)
Time Course of Viral Infection
![Page 19: Chapter 14 Cell-Mediated Effector Responses](https://reader035.vdocuments.us/reader035/viewer/2022062222/56814bd0550346895db8a9d1/html5/thumbnails/19.jpg)
NK-Cell Receptors
Activation Receptors: NKR-P1 (a C-type lectin recognizing carbohydrates)
Inhibitory Receptors: CD94/NKG2 (recognizing HLA-E with an HLA peptide) KIR (> 50 members; specific for one or a limited number of polymorphic products of particular HLA loci)
![Page 20: Chapter 14 Cell-Mediated Effector Responses](https://reader035.vdocuments.us/reader035/viewer/2022062222/56814bd0550346895db8a9d1/html5/thumbnails/20.jpg)
Opposing-signals Model of NK Activity
AR: activation receptor
KIR:killing inhibitory receptor
![Page 21: Chapter 14 Cell-Mediated Effector Responses](https://reader035.vdocuments.us/reader035/viewer/2022062222/56814bd0550346895db8a9d1/html5/thumbnails/21.jpg)
Ab-Dependent Cell-Mediated Cytotoxicity (ADCC)
![Page 22: Chapter 14 Cell-Mediated Effector Responses](https://reader035.vdocuments.us/reader035/viewer/2022062222/56814bd0550346895db8a9d1/html5/thumbnails/22.jpg)
Experimental Assessment of Cell-mediated Cytotoxicity
Mixed Lymphocyte Reaction (MLR)
Cell-mediated Lympholysis (CML)
Graft versus Host Reaction (GVHR)
![Page 23: Chapter 14 Cell-Mediated Effector Responses](https://reader035.vdocuments.us/reader035/viewer/2022062222/56814bd0550346895db8a9d1/html5/thumbnails/23.jpg)
Mixed Lymphocyte Reaction (MLR)
![Page 24: Chapter 14 Cell-Mediated Effector Responses](https://reader035.vdocuments.us/reader035/viewer/2022062222/56814bd0550346895db8a9d1/html5/thumbnails/24.jpg)
Cell-Mediated Lympholysis (CML)
![Page 25: Chapter 14 Cell-Mediated Effector Responses](https://reader035.vdocuments.us/reader035/viewer/2022062222/56814bd0550346895db8a9d1/html5/thumbnails/25.jpg)
Delayed-Type Hypersensitivity
![Page 26: Chapter 14 Cell-Mediated Effector Responses](https://reader035.vdocuments.us/reader035/viewer/2022062222/56814bd0550346895db8a9d1/html5/thumbnails/26.jpg)
Overview of the DDelayed TType HHypersensitivity (DTH) Response
![Page 27: Chapter 14 Cell-Mediated Effector Responses](https://reader035.vdocuments.us/reader035/viewer/2022062222/56814bd0550346895db8a9d1/html5/thumbnails/27.jpg)
![Page 28: Chapter 14 Cell-Mediated Effector Responses](https://reader035.vdocuments.us/reader035/viewer/2022062222/56814bd0550346895db8a9d1/html5/thumbnails/28.jpg)
Formation of Granuloma
![Page 29: Chapter 14 Cell-Mediated Effector Responses](https://reader035.vdocuments.us/reader035/viewer/2022062222/56814bd0550346895db8a9d1/html5/thumbnails/29.jpg)
Role of IFN in Host Defense against Intracellular Pathogens
![Page 30: Chapter 14 Cell-Mediated Effector Responses](https://reader035.vdocuments.us/reader035/viewer/2022062222/56814bd0550346895db8a9d1/html5/thumbnails/30.jpg)
![Page 31: Chapter 14 Cell-Mediated Effector Responses](https://reader035.vdocuments.us/reader035/viewer/2022062222/56814bd0550346895db8a9d1/html5/thumbnails/31.jpg)
Survival of the Intracellular Pathogen
![Page 32: Chapter 14 Cell-Mediated Effector Responses](https://reader035.vdocuments.us/reader035/viewer/2022062222/56814bd0550346895db8a9d1/html5/thumbnails/32.jpg)
Chapter 15
Leukocyte Migration and Inflammation
![Page 33: Chapter 14 Cell-Mediated Effector Responses](https://reader035.vdocuments.us/reader035/viewer/2022062222/56814bd0550346895db8a9d1/html5/thumbnails/33.jpg)
Lymphocyte Recirculation Routes
![Page 34: Chapter 14 Cell-Mediated Effector Responses](https://reader035.vdocuments.us/reader035/viewer/2022062222/56814bd0550346895db8a9d1/html5/thumbnails/34.jpg)
General Structures of the 4 Families of CCell-AAdhesion MMolecules (CAM)
![Page 35: Chapter 14 Cell-Mediated Effector Responses](https://reader035.vdocuments.us/reader035/viewer/2022062222/56814bd0550346895db8a9d1/html5/thumbnails/35.jpg)
CCell AAdhesion MMolecules (CAM)
![Page 36: Chapter 14 Cell-Mediated Effector Responses](https://reader035.vdocuments.us/reader035/viewer/2022062222/56814bd0550346895db8a9d1/html5/thumbnails/36.jpg)
Four Sequential but overlapping Steps in Neutrophil ExtravasationExtravasation
![Page 37: Chapter 14 Cell-Mediated Effector Responses](https://reader035.vdocuments.us/reader035/viewer/2022062222/56814bd0550346895db8a9d1/html5/thumbnails/37.jpg)
Cell-Adhesion Molecules and Chemokines Involved in the 1st 3 Steps of Neutrophil extravasation
![Page 38: Chapter 14 Cell-Mediated Effector Responses](https://reader035.vdocuments.us/reader035/viewer/2022062222/56814bd0550346895db8a9d1/html5/thumbnails/38.jpg)
![Page 39: Chapter 14 Cell-Mediated Effector Responses](https://reader035.vdocuments.us/reader035/viewer/2022062222/56814bd0550346895db8a9d1/html5/thumbnails/39.jpg)
A Lymph-Node Postcapillary Venule with High Endothelium
![Page 40: Chapter 14 Cell-Mediated Effector Responses](https://reader035.vdocuments.us/reader035/viewer/2022062222/56814bd0550346895db8a9d1/html5/thumbnails/40.jpg)
Numerous Lymphocytes Bound to the Surface of a High Endothelial Venule (HEV)
![Page 41: Chapter 14 Cell-Mediated Effector Responses](https://reader035.vdocuments.us/reader035/viewer/2022062222/56814bd0550346895db8a9d1/html5/thumbnails/41.jpg)
NaïveNaïve T Cells Tend to Home to Secondary Lympoid Tissues through Their HEV Regions
![Page 42: Chapter 14 Cell-Mediated Effector Responses](https://reader035.vdocuments.us/reader035/viewer/2022062222/56814bd0550346895db8a9d1/html5/thumbnails/42.jpg)
EffectorEffector T Cells Expressing Particular Homing Receptors Will Home to particular Tertiary Extralymphoid Tissues
![Page 43: Chapter 14 Cell-Mediated Effector Responses](https://reader035.vdocuments.us/reader035/viewer/2022062222/56814bd0550346895db8a9d1/html5/thumbnails/43.jpg)
Extravasation of a Naïve T Cell through aHigh Endothelial Venule into a Lymph Node
![Page 44: Chapter 14 Cell-Mediated Effector Responses](https://reader035.vdocuments.us/reader035/viewer/2022062222/56814bd0550346895db8a9d1/html5/thumbnails/44.jpg)
Mediators of Inflammation
1. Chemokines
2. Plasma Enzyme Mediators kinin system clotting system fibrinolytic system complement system
3. Lipid Inflammatory Mediators
4. Cytokine Inflammatory mediators
![Page 45: Chapter 14 Cell-Mediated Effector Responses](https://reader035.vdocuments.us/reader035/viewer/2022062222/56814bd0550346895db8a9d1/html5/thumbnails/45.jpg)
![Page 46: Chapter 14 Cell-Mediated Effector Responses](https://reader035.vdocuments.us/reader035/viewer/2022062222/56814bd0550346895db8a9d1/html5/thumbnails/46.jpg)
Tissue Damage Induces Formation of Plasma Plasma Enzyme MediatorsEnzyme Mediators by the Kinin System, the Clotting System, and the Fibrinolytic System
![Page 47: Chapter 14 Cell-Mediated Effector Responses](https://reader035.vdocuments.us/reader035/viewer/2022062222/56814bd0550346895db8a9d1/html5/thumbnails/47.jpg)
The Breakdown of Membrane Phospholipids Generates Mediators of Inflammation
![Page 48: Chapter 14 Cell-Mediated Effector Responses](https://reader035.vdocuments.us/reader035/viewer/2022062222/56814bd0550346895db8a9d1/html5/thumbnails/48.jpg)
(proinflammatory cytokines)
![Page 49: Chapter 14 Cell-Mediated Effector Responses](https://reader035.vdocuments.us/reader035/viewer/2022062222/56814bd0550346895db8a9d1/html5/thumbnails/49.jpg)
Overview of the Cells and Mediators Involved in a Local Acute Inflammatory Response
![Page 50: Chapter 14 Cell-Mediated Effector Responses](https://reader035.vdocuments.us/reader035/viewer/2022062222/56814bd0550346895db8a9d1/html5/thumbnails/50.jpg)
Overview of the Organs and Mediators Involved in a Systemic Acute-Phase Response
![Page 51: Chapter 14 Cell-Mediated Effector Responses](https://reader035.vdocuments.us/reader035/viewer/2022062222/56814bd0550346895db8a9d1/html5/thumbnails/51.jpg)
The End