Updated: 6/2/2020

Cell-Mediated Immunity

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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 inflammation
  • Activates 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 cells
  • Promotes growth of B-cells and enhances class switching to IgG and IgE
  • Th2 cells
Interleukin-5 
  • Promotes growth and differentiation of B cells and eosinophils
  • Promotes class switching to IgA
  • Th2 cells
Interleukin-6
  • Stimulates fever
  • Causes 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 cells
  • Decreases expression of MHC molecules and Th1 cytokines
  • Regulatory T-cells
Interleukin-12
  • Promotes differentiation of T-cells into Th1 cells
  • Activates killing by NK cells
  •  Macrophages
Tumor necrosis factor-α
  • Alters vascular endothelium to promote leakage
  • Recruits diverse white blood cells to site of release
  • Induce fever
  •  Macrophages
Interferon-α/β
  • Activates antiviral defense system of cells
  • Down regulates protein synthesis
  • Upregulates 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 cells
  • Increases 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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(M1.IM.15.21) A 55-year-old Caucasian male presents for a routine colonoscopy. A polyp is found in the patient's transverse colon and is found to be cancerous on histological evaluation. Upon examination, it is found that these cancerous cells have decreased MHC class I expression on their surface. Which immune system cell is most capable of killing these tumor cells? Tested Concept

QID: 100442
1

Natural killer cells

77%

(47/61)

2

B-cells

0%

(0/61)

3

Macrophages

2%

(1/61)

4

Eosinophils

0%

(0/61)

5

Cytotoxic T-cells

21%

(13/61)

M 1 D

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(M1.IM.15.72) A 3-year-old recent immigrant is diagnosed with primary tuberculosis. Her body produces T cells that do not have IL-12 receptors on their surface, and she is noted to have impaired development of Th1 T-helper cells. Which of the following cytokines would benefit this patient? Tested Concept

QID: 100493
1

IL-4

13%

(14/109)

2

IL-17

1%

(1/109)

3

IL-22

2%

(2/109)

4

Interferon-gamma

81%

(88/109)

5

TGF-beta

2%

(2/109)

M 1 A

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(M1.IM.14.46) A 48-year-old immigrant from Vietnam presents with fever, weight loss, a persistent cough, and malaise. His symptoms began three months ago and have worsened over time. On exam, he is afebrile with BP 140/80, HR 78/minute, and RR 14/min. A sample of the patient's sputum is shown in Figure A, and chest radiograph is shown in Figure B. Which cell type is responsible for the formation of the granuloma? Tested Concept

QID: 100467
FIGURES:
1

Neutrophils

9%

(11/117)

2

TH2 lymphocyte

16%

(19/117)

3

CD8 T cell

12%

(14/117)

4

TH1 lymphocyte

57%

(67/117)

5

Natural killer cells

3%

(4/117)

M 1 D

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