Updated: 8/7/2017

Lymphocyte Development and Structure

Topic
Review Topic
0
0
Questions
2
0
0
Evidence
2
0
0
Videos
3
Introduction
  • Lymphocyte development is complex and has several features including
    • localization to primary lymphoid organs such as
      • the bone marrow for B-cell development
      • the thymus for T-cell development
    • VDJ recombination in order to
      • rearrange genetic material
      • generate a unique B- or T-cell receptor
    • positive selection in order to
      • ensure all cells have functional receptors
    • proliferation in order to
      • expand the pool of potential lymphocytes
      • allow for broad protection against different types of antigens
    • negative selection in order to
      • remove cells that target self-antigens
      • protect against autoimmunity
  • There are many mechanisms to increase diversity during lymphocyte development such as
    • random recombination of genetic material during
      • VDJ recombination
    • random nucleotide addition to hypervariable regions by
      • the protein TdT
    • random assortment of different chains in receptor assembly
      • heavy chains with light chains in B-cells
      • alpha chains with beta chains in T-cells
    • somatic hypermuation after antigen exposure
      • only occurs in B-cells
B-Cell Development
  • B-cells develop in the bone marrow
    • develop a unique B-cell receptor
    • are tested to ensure that the receptor is functional
    • are further tested for self-reactivity to prevent autoimmunity
  • This development cycle is coordinated by the orderly progression through stages where
    • supporting cells give feedback at every stage
    • interaction strength of the B-cell receptor is monitored
Stages of B-Cell Development
Cell Type
Developmental Steps
Surface Receptor
Associations
Lymphoid stem cell
  • Commitment to B-cell lineage
  • None
  • Pleuripotent
Pro B-cell
  • Heavy chain VDJ recombination
  • Additional diversity from TdT modification
  • Heavy chain only
  • Recombination mediated by RAG proteins
  • Defect in RAG leads to Omenn syndrome with no mature B cells
Pre B-cell
  • Allelic exclusion to ensure only one heavy chain expressed
  • Positive selection
  • Proliferation
  • Pre B-cell receptor
  • Key step in monitoring activity of the recombined heavy chain
Immature B-cell
  • Light chain VJ recombination
  • Negative selection
  • IgM receptor
  • Inactivation of recombination machinery
  • Key step in tolerance
Mature B-cell
  • Exit into blood stream
  • IgM receptor
  • IgD receptor
  • Circulates and awaits activation by antigen
T-Cell Development  
 

 
  • T-cells migrate from the bone marrow to the thymus where they
    • develop a unique T-cell receptor
    • are tested to ensure that the receptor is functional
    • are further tested for self-reactivity to prevent autoimmunity
  • This development cycle is coordinated by the orderly progression through stages where
    • supporting cells give feedback at every stage
    • receptors that bind too strongly lead to developing T-cell death
    • the T-cell receptor undergoes selection in distinct compartments
Stages of T-Cell Development
Cell Type
Developmental Steps
Surface Proteins
Associations
T-cell precursor
  • Commitment to T-cell lineage
  • Migration to thymus
  • None
  • Lack of thymic development in DiGeorge syndrome
Double negative
  • Rearrangement of the β T-cell receptor chain
  • Proliferation
  • Pre T-cell receptor
  • Occurs in the thymic cortex
Double positive
  • Rearrangement of the α T-cell receptor chain
  • Expression of both CD4 and CD8
  • Positive selection against both class I and class II MHC
  • CD4
  • CD8
  • T-cell receptor
  • Key step in determining type of T-cell that develops
  • MHC II binding leads to CD4+ cells
  • MHC I binding leds to CD8+ cells
Single positive
  • Migration to medulla of thymus
  • Negative selection against self antigens
  • T-cell receptor
  • Either CD4 or CD8
  • The transcription factor AIRE allows medullary cells to express proteins from all areas of body
  • This ensure tolerance to vast majority of self antigens
Mature T-cell
  • Exit into blood stream
  • Awaits peripheral activation
  • T-cell receptor
  • Either CD4 or CD8
  • Circulates and awaits activation by antigen
 

Please rate topic.

Average 4.9 of 7 Ratings

Thank you for rating! Please vote below and help us build the most advanced adaptive learning platform in medicine

The complexity of this topic is appropriate for?
How important is this topic for board examinations?
How important is this topic for clinical practice?
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

Question locked
Sorry, this question is for
PEAK Premium Subscribers only
Upgrade to PEAK

(M1.IM.74) A thymic sample from a fetus is examined. One cell type found was double-positive for the CD4 and CD8 receptors. What is the identity of these double-positive cells? Review Topic

QID: 100495
1

T-cell progenitors cells in the bone marrow

6%

(2/36)

2

B-cells

0%

(0/36)

3

Immature T-cells of the thymic cortex

81%

(29/36)

4

Immature T-cells of the thymic medulla

11%

(4/36)

5

Macrophages

3%

(1/36)

M1

Select Answer to see Preferred Response

PREFERRED RESPONSE 3
ARTICLES (2)
VIDEOS (3)
Topic COMMENTS (12)
Private Note