1 of 39

Cells and Organs of the Immune System�Chapter 2

2 of 39

Hematopoiesis

  • HSC (Hematopoietic Stem Cell)
    • Reside in Bone Marrow
    • Pluripotent
    • 1 HSC Per 50,000 BM Cells (~3x108 cells in Mouse Bone Marrow)
    • Extremely Proliferative If Need Arises
  • HSC Differentiates to LPC (lymphoid progentor cell) or MSC (myeloid stem cell)
  • Growth Factors and Cytokines Determine Path
  • Once LPC or MSC, Committed
  • Stromal Cells Are Supporting Cells In BM (endothelial, fat cells, fibroblasts, macrophages)

​

3 of 39

Hematopoietic Growth Factors

  • Colony Stimulating Factors
    • 4 types
      • Multi-CSF (IL-3)
      • M-CSF (Macrophage CSF)
      • G-CSF (Granulocyte CSF)
      • GM-CSF (Granulocyte Monocyte CSF)
  • EPO (erythropoietin)
    • Induces production of RBCs

​

​

4 of 39

5 of 39

6 of 39

Cell Death

  • Orderly Self Destruction and Disorderly
  • Neutrophils (5.0 x 1010) Last For a Few Days
  • Aberrant Apoptosis Can Give Rise To Leukemia
  • Apoptosis (orderly)
    • Reduction In Cell Volume
    • Chromatin Condensation
    • DNA Degradation
    • MΦ Ingest Membrane Bound Bodies
    • No Inflammation
  • Necrosis
    • Bursting of Cell Due To Injury
    • Contents Released To Environment
    • Inflammation

​

​

​

7 of 39

8 of 39

9 of 39

Genes Regulating Apoptosis

10 of 39

11 of 39

Detecting Apoptosis Using Flow Cytometry

Annexin V-FITC

Propidium Iodide

Ceramide Treatment

12 of 39

Cells of the Immune System

  • Lymphoid Cells
    • B-cells, T-cells and Null cells (NK cells)
    • 20-40% of body’s leukocytes
    • 99% of lymph node
    • If inactivated said to be naïve
    • Nucleus occupies almost entire cell
    • 6 μm diameter

​

13 of 39

Lymphoid Cells

14 of 39

Lymphoid Cells

15 of 39

Identifying Cell Using the CD Nomenclature

  • CD Cluster Of Differentiation
  • Over 300 CD Markers
  • T cells, CD4 or CD8 and CD3
  • B cells, CD19
  • NK cells, CD56
  • Monocytes/Macrophages CD14
  • Dendritic Cells, CD1c (Human), CD11c (mouse)

​

16 of 39

17 of 39

Null Cells

  • Do Not Express Classical Lymphocyte Markers
  • Predominantly NK Cells (CD56)
  • Eliminate Tumor Cells and Virally Infected Cells
  • Express Low Affinity FcγRIII (CD16)
  • Using CD16 They Can Carry Out ADCC
  • Reduction of MHC I Can Activate Them

​

18 of 39

Mononuclear Cells

  • Monocytes in Blood, MΦ in Tissues
    • Monocytes 5-10 times smaller than MΦ
  • MΦ Increases Phagocytic Ability
  • Secretes cytokines and Produces Hydrolytic Enzymes
  • Named Based on Tissue They Reside
    • Alveolar (lungs), Kupffer (liver), Microglial (brain), Osteoclasts (bone)
  • Activated By Phagocytosis or Cytokines (IFNγ)
  • Antigen Presenting Capacity Thru MHC II

Mononuclear Cells

19 of 39

Monocyte vs MΦ

20 of 39

MΦ Effective APC

21 of 39

MΦ Capturing Bacteria

22 of 39

Dendritic Cells

  • Professional APCs
  • Several Types
    • Langerhans (LC) found in skin
    • Circuilating DCs
      • Myeloid (MDC1 and MDC2)
      • Plasmacytoid
  • Interstitial DCs, populate organs such as heart, lungs, liver, intestines
  • Interdigitating DCs, T-cell areas of lymph nodes and Thymic medulla

​

​

23 of 39

Dendritic Cells

  • Scarce Cell Type
  • Discovered in 1972
  • Early 90s Using GM-CSF/IL4 and Later flt-3 limitation Was Overcome
  • Intense Area of Research
  • Seemed Promising for Tumor Treatment
  • Maybe Better for Tolerance

24 of 39

Dendritic Cells

http:www.coleypharma.com

25 of 39

Developmental Pathway of DCs

26 of 39

Follicular DCs

  • Do Not Express MHC II Molecules
  • Found in Lymph Follicles (Rich in B Cell)
  • Express FcR For Antibodies and Complement
  • Ag-Ab Complex Shown To Last Very Long (weeks to months)

27 of 39

Organs Of Immune System

  • Primary Lymphoid Organs
    • Bone Marrow and Thymus
    • Maturation Site
  • Secondary Lymphoid Organs
    • Spleen, lymph nodes,
    • MALT (mucosal associated lymph tissue)
    • GALT (gut associated lymph tissue)
    • Trap antigen, APC, Lymphocyte Proliferation

​

28 of 39

29 of 39

Thymus

  • Bilobed Organ on Top of Heart
  • Reaches Max. Size During Puberty
    • 70g infants, 3 g in adults
  • 95-99% Of T Cells Die in Thymus
    • self reactivity or no reactivity to Ag
  • Consists of Cortex and Medulla
  • Rat Thymocytes Sensitive to Glucorticoids

​

​

​

​

30 of 39

Thymus

31 of 39

Lymphatic System

  • Plasma From Blood Seeps Into Tissue
  • Interstitial Fluid Either Goes Back or Becomes Lymph
  • Lymph Enters Lymphatic Vessels
  • Thoracic Duct Is Largest Lymphatic Vessel Empties Into Left Subclavian Vein
  • Lymphatic Vessel Depends On Muscle Contractions For Movement
  • One Way Valves Ensure One Direction
  • Lymph Nodes Act As Filters For Antigens

​

32 of 39

Lymphatic System

33 of 39

34 of 39

Lymph Node

35 of 39

Lymph Node

  • Multiple Afferent Lymphatics
  • Cortex
    • B-cells, Follicular DCs, MΦ, GCs, Primary Follicles
  • Paracortex
    • TH, MΦ, DCs
  • Medulla
    • Plasma Cells
  • Post Capillary Venule
    • Allow Lymphocyte Migration From Circuilation Into Lymph Node
  • One Efferent Lymphatic
    • Rich In Abs and Lymphocytes

​

36 of 39

Mucosal Associated Lymphoid Tissue (MALT)

  • Mucous Membranes S.A=400m2
  • Mucous Membr. Most Common Pathogen Entry Site
  • M.M Protected by MALT
  • Organization Varies (most organized P.P, Tonsils, appendix
  • GI Tract, IEL Unique γδ TCRs
  • Lamina Propia (below epithelium) MΦ, B cells, TH
  • M Cell Allows Ag Entry, Unique Architecture

37 of 39

38 of 39

39 of 39