Updated: 1/3/2019

T-Cell Activation

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Introduction
  • The activation of T-cells must be tightly controlled to allow for
    • selective proliferation of pathogen specific T-cells
    • anergy of self-reactive T-cells
    • prevention of autoimmune disorders
  • Four events are required for proper T-cell activation including
    • antigen processing and presentation by antigen presenting cells that
      • display antigens as peptides bound to MHC
      • migrate to draining lymph nodes
    • specific binding of the T-cell receptor to the antigen concurrently with
      • binding of CD4 coreceptors to MHC class II in helper T-cells
      • binding of CD8 coreceptors to MHC class I in killer T-cells
    • costimulation of the T-cell by antigen presenting cells through interaction between
      • B7 (CD80/CD86) on dendritic cells
      • CD28 on T-cells
    • differentiation through cytokine signaling pathways at the time of activation
  • After T-cell activation, activated cells migrate to the periphery where
    • killer T-cells identify infected cells and release toxic substances
    • helper T-cells undergo further differentiation into subtypes
Three Signal Hypothesis
  • Antigen presenting cells interact with naive T-cells in secondary lymphoid organs where
    • they allow T-cells to recognize their ingested antigens
    • they provide costimulatory input
  • T-cells require all signals to be present in order to activate
  • T-cells will undergo apoptosis or become anergic (state of inactivity) if
    • they receive only one of the activation signals so that
      • autoreactive cells can be removed
      • benign materials are not mistakenly recognized as harmful
    • they receive signals that the infection is cured and inflammation has subsided
Three Signal Hypothesis
Feature Signal 1 Signal 2
Signal 3
Function
  • Leverage specificity of T-cell receptors to detect antigen
  • Ensure binding to antigen presenting cell with antigen of interest
  • Distinguish between erroneous binding of T-cell receptors and real pathogenic recognition
  • Ensure that the recognized antigen is on an activated antigen presenting cell
  • Convey information about the surrounding environment of the activation site
  • Ensure proper differentiation of the activated T-cells
Interacting proteins
  • Antigen bound to MHC type I or II proteins 
  • T-cell receptor
  • CD4 or CD8
  • B7 (CD80 and CD86) that are only expressed on activated antigen presenting cells
  • CD28
  • IL-2 (T-cell survival signal)
  • Diverse cytokines
  • Cytokine receptors
Associations
  • Super antigens can artificially induce binding of T-cell receptor with MHC
  • Induced anergy or apoptosis if not present in conjuction with signal 1
  • Killer T-cells require cytokine help from helper T-cells to activate
 
Helper T-Cell Differentiation
  • After activation, helper T-cells further differentiate in response to
    • cytokine signals released by the innate immune system
    • the inflammatory environment of the activation site
    • cross talk with other adaptive cells such as regulatory T-cells
  • Each helper T-cell subtype differs in several ways including
    • general function of the class
    • signals (usually cytokines) required for differentiation
    • secreted factors produced
Helper T Cell Subtypes
Feature Th1 Th2
Th17
Function
  • Promote cell based immunity
  • Activate macrophages and cytotoxic T-cells
  • Promotes humoral immunity
  • Recruits eosinophils as part of parasite defence
  • Activate neutrophils
Differentiation
  • IFN-γ
  • IL-12
  • IL-2
  • IL-4
  • IL-6
  • TGF-β
Associations
  • Granuloma formation
  • Tuberculous leprosy
  • Lepromatous leprosy
  • IgE production by B cells
  • Chronic inflammatory conditions
Secreted Factors
  • IFN-γ
  • IL-2
  • IL-4
  • IL-5
  • IL-13
  • IL-17
  • IL-21

Reference

 

 

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Questions (2)
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
Calculator

(M1.IM.4822) A researcher is studying the interactions between foreign antigens and human immune cells. She has isolated a line of lymphocytes that is known to bind antigen-presenting cells. From this cell line, she has isolated a cell surface protein that binds the constant portion of the class I major histocompatibility complex molecule. The activation of this specific cell line requires co-activation via which of the following signaling molecules? Review Topic

QID: 109422
1

Interleukin 1

8%

(7/92)

2

Interleukin 2

67%

(62/92)

3

Interleukin 4

10%

(9/92)

4

Interleukin 6

3%

(3/92)

5

Interleukin 8

11%

(10/92)

M1

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PREFERRED RESPONSE 2

(M1.IM.77) A 25-year-old woman presents to the ED with a diffuse, erythematous rash in the setting of nausea, vomiting, and fever for 2 days. Physical exam reveals a soaked tampon in her vagina. Blood cultures are negative. The likely cause of this patient's disease binds to which molecule on T cells? Review Topic

QID: 101031
1

CD3

11%

(2/18)

2

Gamma chain of the IL-2 receptor

11%

(2/18)

3

CD40 ligand

17%

(3/18)

4

Variable beta portion of the T-cell receptor

39%

(7/18)

5

Fas ligand

17%

(3/18)

M1

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PREFERRED RESPONSE 4
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