Updated: 11/17/2018

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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Questions (6)
Lab Values
Blood, Plasma, Serum Reference Range
ALT 8-20 U/L
Amylase, serum 25-125 U/L
AST 8-20 U/L
Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca2+) 8.4-10.2 mg/dL
Cholesterol, serum Rec: < 200 mg/dL
Cortisol, serum 0800 h: 5-23 μg/dL //1600 h:
3-15 μg/dL
2000 h: ≤ 50% of 0800 h
Creatine kinase, serum Male: 25-90 U/L
Female: 10-70 U/L
Creatinine, serum 0.6-1.2 mg/dL
Electrolytes, serum  
Sodium (Na+) 136-145 mEq/L
Chloride (Cl-) 95-105 mEq/L
Potassium (K+) 3.5-5.0 mEq/L
Bicarbonate (HCO3-) 22-28 mEq/L
Magnesium (Mg2+) 1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)  
24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL
Ferritin, serum Male: 15-200 ng/mL
Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL
Female: premenopause: 4-30 mIU/mL
midcycle peak: 10-90 mIU/mL
postmenopause: 40-250
pH 7.35-7.45
PCO2 33-45 mmHg
PO2 75-105 mmHg
Glucose, serum Fasting: 70-110 mg/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative stimuli: > 7ng/mL
Immunoglobulins, serum  
IgA 76-390 mg/dL
IgE 0-380 IU/mL
IgG 650-1500 mg/dL
IgM 40-345 mg/dL
Iron 50-170 μg/dL
Lactate dehydrogenase, serum 45-90 U/L
Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL
Female: follicular phase: 5-30 mIU/mL
midcycle: 75-150 mIU/mL
postmenopause 30-200 mIU/mL
Osmolality, serum 275-295 mOsmol/kd H2O
Parathyroid hormone, serume, N-terminal 230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L
Phosphorus (inorganic), serum 3.0-4.5 mg/dL
Prolactin, serum (hPRL) < 20 ng/mL
Proteins, serum  
Total (recumbent) 6.0-7.8 g/dL
Albumin 3.5-5.5 g/dL
Globulin 2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL
Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h
Thyroxine (T4), serum 5-12 μg/dL
Triglycerides, serum 35-160 mg/dL
Triiodothyronine (T3), serum (RIA) 115-190 ng/dL
Triiodothyronine (T3) resin uptake 25%-35%
Urea nitrogen, serum 7-18 mg/dL
Uric acid, serum 3.0-8.2 mg/dL
Hematologic Reference Range
Bleeding time 2-7 minutes
Erythrocyte count Male: 4.3-5.9 million/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 12.0-16.0 g/dL
Hemoglobin, plasma 1-4 mg/dL
Leukocyte count and differential  
Leukocyte count 4,500-11,000/mm3
Segmented neutrophils 54%-62%
Bands 3%-5%
Eosinophils 1%-3%
Basophils 0%-0.75%
Lymphocytes 25%-33%
Monocytes 3%-7%
Mean corpuscular hemoglobin 25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration 31%-36% Hb/cell
Mean corpuscular volume 80-100 μm3
Partial thromboplastin time (activated) 25-40 seconds
Platelet count 150,000-400,000/mm3
Prothrombin time 11-15 seconds
Reticulocyte count 0.5%-1.5% of red cells
Thrombin time < 2 seconds deviation from control
Volume  
Plasma Male: 25-43 mL/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 19-31 mL/kg
Cerebrospinal Fluid Reference Range
Cell count 0-5/mm3
Chloride 118-132 mEq/L
Gamma globulin 3%-12% total proteins
Glucose 40-70 mg/dL
Pressure 70-180 mm H2O
Proteins, total < 40 mg/dL
Sweat Reference Range
Chloride 0-35 mmol/L
Urine  
Calcium 100-300 mg/24 h
Chloride Varies with intake
Creatinine clearance Male: 97-137 mL/min
Female: 88-128 mL/min
Estriol, total (in pregnancy)  
30 wks 6-18 mg/24 h
35 wks 9-28 mg/24 h
40 wks 13-42 mg/24 h
17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 6-15 mg/24 h
Osmolality 50-1400 mOsmol/kg H2O
Oxalate 8-40 μg/mL
Potassium Varies with diet
Proteins, total < 150 mg/24 h
Sodium Varies with diet
Uric acid Varies with diet
Body Mass Index (BMI) Adult: 19-25 kg/m2
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(M1.IM.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? Review Topic

QID: 100442
1

Natural killer cells

56%

(10/18)

2

B-cells

0%

(0/18)

3

Macrophages

6%

(1/18)

4

Eosinophils

0%

(0/18)

5

Cytotoxic T-cells

39%

(7/18)

M1

Select Answer to see Preferred Response

PREFERRED RESPONSE 1

(M1.IM.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? Review Topic

QID: 100493
1

IL-4

15%

(8/55)

2

IL-17

0%

(0/55)

3

IL-22

4%

(2/55)

4

Interferon-gamma

78%

(43/55)

5

TGF-beta

0%

(0/55)

M1

Select Answer to see Preferred Response

PREFERRED RESPONSE 4

(M1.IM.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? Review Topic

QID: 100467
FIGURES:
1

Neutrophils

7%

(4/58)

2

TH2 lymphocyte

22%

(13/58)

3

CD8 T cell

16%

(9/58)

4

TH1 lymphocyte

48%

(28/58)

5

Natural killer cells

3%

(2/58)

M1

Select Answer to see Preferred Response

PREFERRED RESPONSE 4
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