Cell-Mediated Immunity - Immunology

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

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

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