Cell-Mediated Immunity

Overview

Cell-mediated immunity is the result of cooperation between innate and adaptive immunity to
- destroy virus infected cells before they can produce more virus
- damage pathogenic bacteria, fungi, and parasites
- eliminiate cancerous cells that lack normal cell surface proteins
Cells involved in immunity can be divided into
- primary effector cells such as
  - granulocytes
  - macrophages
  - CD8+ T-cells
  - natural killer (NK) cells
- secondary support cells such as
  - CD4+ helper T-cells
  - dendritic cells
Cell-mediated immunity can result from
- innate immune response
- activation of T-cells
coordination of cells via cytokines

Important Cytokines in Cellular Immunity

Cytokines are key coordinators of the cellular immune response by promoting
- vascular changes near the site of inflammation
- recruiting of other target cells
- differentiation of target cells
- signaling to distant organs
Cytokines can be secreted by a variety of cells including
- activated macrophages
- helper T-cells
killer T-cells

Important Cytokines in Cellular Immunity
Cytokine	Function	Secreted by
Interleukin-1	Causes fever and acute inflammationActivates endothelial expression of adhesion molecules	Macrophages
Interleukin-2	Stimulates growth and survival of T-cells and NK cells	All T-cells
Interleukin-3	Stimulates the growth and differentiation of bone marrow cells	All T-cells
Interleukin-4	Induces differentiation of helper T-cells into Th2 subtype cellsPromotes growth of B-cells and enhances class switching to IgG and IgE	Th2 cells
Interleukin-5	Promotes growth and differentiation of B cells and eosinophilsPromotes class switching to IgA	Th2 cells
Interleukin-6	Stimulates feverCauses increased production of acute phase proteins by liver	Macrophages
Interleukin-8	Stimulates chemotaxis by neutrophils to sites of infection	Macrophages
Interleukin-10	Decreases inflammatory response by inhibiting macrophages and dendritic cellsDecreases expression of MHC molecules and Th1 cytokines	Regulatory T-cells
Interleukin-12	Promotes differentiation of T-cells into Th1 cellsActivates killing by NK cells	Macrophages
Tumor necrosis factor-α	Alters vascular endothelium to promote leakageRecruits diverse white blood cells to site of releaseInduce fever	Macrophages
Interferon-α/β	Activates antiviral defense system of cellsDown regulates protein synthesisUpregulates MHC expression for easy recognition of infected cells	All cells
Interferon-γ	Activates macrophages to kill ingested organisms Promotes granuloma formation Increases MHC and antigen presentation by all cellsIncreases killing by NK cells	Th1 cells

Effector Mechanisms

Macrophage and neutrophil killing depends upon
- oxygen-dependent mechanisms such as respiratory burst
- oxygen-independent mechanisms including
  - hydrolytic enzymes that destroy peptides
  - defensins that form holes in bacterial membranes
  - lactoferrin that binds iron and denies it to bacteria
  - lysozyme that cleaves bacterial peptidoglycan walls
NK and cytotoxic CD8+ T-cell killing depends upon three mechanisms including
- exocytosis of cytotoxic granules containing
  - granzymes that are apoptosis activating serine proteases
  - perforin that makes a hole in membranes
- Fas ligand that directly signals target cells to undergo apoptosis
- cytokine signaling mainly through TNF pathways that also induce apoptosis
Notably NK cells are inhibited by MHC complexes on the surface of cells

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