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Chapter 14 Cell-Mediated Effector Responses - PowerPoint PPT Presentation

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Chapter 14 Cell-Mediated Effector Responses. 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

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Chapter 14

Cell-Mediated Effector


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




Three types of effector T cells:

1. CD4+ TH1cells

2. CD4+ TH2 cells

3. CD8+ CTLs


- less stringent activation requirements

- increased expression of cell-adhesion molecules

- production of both membrane-bound and

soluble effector molecules

  • - The FasL, perforins, and granzymes mediate target cell destruction by the CTLs.

  • - Membrane-bound TNFb and soluble IFNg 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.

CTL-Mediated Killing of Target Cells

perforin monomers


granzyme proteases

Cell-Mediated Pore Formation

in Target-Cell Membrane





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.

CTL-Mediated Apoptotic Pathways Combination of the Two


cysteine, aspartate protease

Natural Killer Cells Combination of the Two

  • Natural Killer (NK) Cells: Combination of the Two

  • 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 IFNa, IFNb, and IL-12.

  • express CD16 (FcgRIII)

  • 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.

Time Course of Viral Infection Combination of the Two

NK-Cell Receptors Combination of the Two

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)

Opposing-signals Model of NK Activity Combination of the Two


killing inhibitory receptor


activation receptor

Ab-Dependent Cell-Mediated Cytotoxicity Combination of the Two


Experimental Assessment of Combination of the Two

Cell-mediated Cytotoxicity

Mixed Lymphocyte Reaction (MLR)

Cell-mediated Lympholysis (CML)

Graft versus Host Reaction (GVHR)

Mixed Lymphocyte Reaction (MLR) Combination of the Two

Cell-Mediated Lympholysis (CML) Combination of the Two

Delayed-Type Hypersensitivity Combination of the Two

Overview of the Combination of the TwoDelayed Type Hypersensitivity

(DTH) Response

Formation of Granuloma Combination of the Two

Role of IFN Combination of the Twog in Host Defense against

Intracellular Pathogens

Chapter 15 Combination of the Two

Leukocyte Migration

and Inflammation

Lymphocyte Recirculation Routes Combination of the Two

General Structures of the 4 Families Combination of the Two

of Cell-Adhesion Molecules (CAM)

C Combination of the Twoell Adhesion Molecules (CAM)

Four Sequential but overlapping Steps Combination of the Two

in Neutrophil Extravasation

Naïve Endothelial Venule (HEV) T Cells Tend to Home to Secondary Lympoid Tissues through Their HEV Regions

Effector Endothelial Venule (HEV) T Cells Expressing Particular Homing Receptors Will Home to particular Tertiary Extralymphoid Tissues

Extravasation of a Naïve T Cell through a Endothelial Venule (HEV)

High Endothelial Venule into a Lymph Node

  • Mediators of Inflammation Endothelial Venule (HEV)

  • Chemokines

  • 2. Plasma Enzyme Mediators

  • kinin system

  • clotting system

  • fibrinolytic system

  • complement system

  • 3. Lipid Inflammatory Mediators

  • 4. Cytokine Inflammatory mediators

Tissue Damage Induces Formation of Endothelial Venule (HEV)Plasma Enzyme Mediators by the Kinin System, the Clotting System, and the Fibrinolytic System

The Breakdown of Membrane Phospholipids Endothelial Venule (HEV)

Generates Mediators of Inflammation

(proinflammatory cytokines) Endothelial Venule (HEV)

Overview of the Cells and Mediators Involved Endothelial Venule (HEV)

in a Local Acute Inflammatory Response

Overview of the Organs and Mediators Endothelial Venule (HEV)

Involved in a Systemic Acute-Phase Response

The End Endothelial Venule (HEV)