T3 L5: Physiology of normal white blood cells

• What are the lymphoid white blood cells?

  B lymphocytes

  T lymphocytes

  Natural killer cells
• What are the myeloid white blood cells?

  basophils

  Eosinophils

  neutrophils

  monocytes

  
• What are mast cells?

  White blood cells that play a role in allergic reactions and inflammation

  found in tissue, no blood
• What is the distribution of different lymphocytes?

  majority are B and T (both have antigen specific receptors)

  around 5% is NK - do NOT have antigen specific receptors
• What are neutrophils?

  first responders to infection

  numbers increased during bacterial infection

  • polymorphonuclear (multi-lobed nucleus)
  • found in blood
  • rapidly recruited to sites of infection
  • contain Myeloperoxidase (MPO) - oxidative enzyme
  • and ROS

  
• What are monocytes and macrophages?

  Monocytes: blood-bourn phagocytes; precursors to macrophages

  • kidney shaped nucleus
  • in spleen and bloodstream

  Macrophages:

  • in tissue (tissue-specific)
  • larger than monocytes

  
• What are eosinophils?

  motile phagocytic cells that can migrate from blood into tissues

  structure: bilobed nuclei, granulated cytoplasm

  functions:

  • release highly toxic granule proteins / free radicals
  • synthesise and release prostoglandins, cytokines to amplify inflammatory response

  
• What are basophils?

  non-phagocytic cells that circulate in blood

  structure: lobed nuclei, heavily granulated cytoplasm

  Functions:

  • express FceRI (antibody receptor)
  • release pharmacologically active substances from cytoplasmic granules
  • promote inflammation

  
• What are the leucocytes that increase in numbers in a bacterial infection?

  high neutrophils

  (high monocytes if chronic)
• What are the leucocytes that increase in numbers in a viral infection?

  high lymphocytes

  (sometimes high monocytes)
• What are the leucocytes that increase in numbers in a parasite infection?

  high eosinophils

  activation of mast cells
• What are the leucocytes that increase in numbers in an allergic reaction?

  high basophils

  (high eosinophils in chronic phase)

  activation of mast cells
• Interaction of leucocytes with blood vessels is key to the recruitment of leucocytes from blood to tissue.
• What are cytokines?

  immune messenger molecules

  secreted primarily by white blood cells

  act locally (paracrine)
• What are chemokines?

  cytokines that induce directed chemotaxis

  attractants for leucocytes

  Important example: CCL-2 (MCP-1: monocyte chemotactic protein-1)
• What is 'sterile inflammation'?

  Non-infectious inflammation.
• Why does inflammation cause heat, redness, pain and swelling?

  Heat and redness: caused by blood vessel dilation to allow increased blood flow to area

  Pain: dilation of blood vessels is mediated by histamine and bradykinin, which can irritate nerve endings

  Swelling: increase in blood vessel permeability also allows more fluid to enter tissue from blood
• What is the basic process of inflammation?

  1.Blood vessels dilate

  2.Blood vessels become more permeable

  3.Circulating leucocytes migrate into tissue

  4.Leucocytes are activated

  5.Activated leucocytes destroy microbes and unwanted material
• What are the two important vasodilators?

  histamine, bradykinin
• What are the characteristics of acute inflammation?

  predominantly mediated by neutrophils

  resolves once stimulus removed

  rapid
• What are the characteristics of chronic inflammation?

  predominantly mediated by mononuclear cells (macrophages, lymphocytes)

  tissue destruction

  attempts at healing (fibrosis)

  lasts weeks
• How does the recruitment of monocytes to sites of inflammation work?

  1. Monocyte binds adhesion molecules on vascular endothelium near sites of infection and gets chemokine signal
  2. Monocyte migrates into surrounding tissue
  3. Monocyte differentiates into macrophage and migrates to site of infection

  
• What are the two types of contact between endothelium and circulating cells?

  1. Initial contact: P-selectin & E-selectin recognised by leucocytes
  2. Tighter adhesion: ICAMs (intercellular adhesion molecules) on endothelium recognised by integrins on leucocytes
• What is monocyte adhesion to endothelium stimulated by?

  MCP-1
• What are Sulfated sialyl-Lewisx?

  oligosaccharides that are constitutively expressed on monocytes

  recognise P-selectin and E-selectin on endothelium during initial contact
• What are the important adhesion molecules for tighter binding (expressed by activated endothelium)?

  Mac1 – Macrophage 1 antigen

  LFA-1 – Lymphocyte function-associated antigen 1

  VLA-4 – Very Late Antigen-4 (Integrin alpha4beta1)

  VCAM-1 – Vascular cell adhesion molecule
• What is VCAM-1?

  adhesion molecule on endothelium

  binds monocytes and lymphocytes
• What are some pattern-recognition receptors that lead to phagocytosis?

  Macrophage mannose receptor

  • ligand: conserved carbohydrate structures

  Scavenger receptors

  • ligand: oxidised LDL

  Toll-like receptors (TLRs)

  • ligand: various
• What is opsonization of pathogens?

  coating with circulating receptors
• What are some proinflammatory cytokines released from activated macrophages?

  IL-1 beta, TNF-alpha, IL-6