Physiology of Normal White Blood Cells

Question 1

Leukopoiesis

Answer 1

form of haemotopoiesis that forms WBCs

Question 2

Haematopoiesis

Answer 2

Question 3

Myeloid cells are innate immunity.

True or False?

Answer 3

True

Question 4

Granulocytes:

• names of cells
• nuclei features
• function
• contain

Answer 4

• neutrophils, eosinophils, basophils,
  mast cells
• nuclei have many lobes
• innate immunity
• contain cytoplasmic granules that
  carry proteins and other molecules
  essential for the immune response
  to infection

Question 5

pAPCs are

Answer 5

• professional antigen presenting
  cells
• monocytes, macrophages, dendritic
  cells

Question 6

Lymphoid cells are adaptive immunity.

True or False?

Answer 6

True

Question 7

Haematopoiesis

Answer 7

Question 8

White blood cells numbers table (the pictures are more important)

Answer 8

Question 9

White Blood Cell Receptors are called

Answer 9

• Pattern Recognition Receptors
  (PRRs)

Question 10

PRRs

Answer 10

• pattern recognition receptors
• present on all myeloid white blood
  cells
• their ligands are Pathogen
  Associated Molecular Patterns
  (PAMPs)
• and Damage Associated Molecular
  Patterns (DAMPs)
• also present in skin cells, epithelial,
  mucosal, vascular endothelial,
  fibroblasts
• eg Toll like receptors
• essential for the recognition of a
  variety of microorganisms and
  pathogens by the myeloid WBC and
  initiation of the immune response

Question 11

What % of WBCs do monocytes make up?

Answer 11

2-12%

Question 12

Monocytes

Answer 12

• enter circulation as monocytes
  (patrolling monocytes)
• can migrate to tissues
  (inflammatory monocytes)
• and differentiate into macrophages
  in response to infection

Question 13

Tissue Resident Phagocytes:

Answer 13

• can be macrophages
• do not circulate but carry specific
  phagocytic functions and continue
  to act as pAPC
• eg: Kupffer cells (liver), microglia
  (nervous system)

Question 14

Macrophages

Answer 14

• bridge between adaptive and
  innate
• pAPCs
• antigen presentation after a
  macrophage has come in contact
  with a pathogen, is achieved
  through the MHC II molecules
• Fc receptors on macrophages:
  opsonisation, the enhancement of
  antigen recognition through
  antibody binding, significantly
  increases rate of phagocytosis

Question 15

Monocytes have a short half life, tissue macrophages are ———

Answer 15

self-replicating and have a much longer life span (months or years)

Question 16

Toll Like Receptors interact with

Answer 16

MyD88 protein
activates a signalling cascade leading to inflammatory cytokines and inflammation

Question 17

Macrophage receptors

Answer 17

Question 18

LPS receptors:
- stands for
- found on
- recognises

Answer 18

• liposaccharide receptor
• on macrophage
• recognises bacterial cell wall
  liposaccharides

Question 19

Scavenger Receptors:

Question 20

Neutrophils:

Answer 20

• short life span (hours)
• in infection neutrophils:
  - release signalling molecules
  that will reach the bone
  marrow and initiate the
  production of more
  neutrophils
  - phagocytose infect patho
  - tissue remodelling (elastin and
  collagen fibres) leading to
  wound healing and repair

Question 21

Which cytokine causes migration of neutrophils? Which cells produce this cytokine?

Answer 21

Interleukin 8
macrophages, dendritic cells, endothelial cells

Question 22

Neutrophils are essential for resolving —— infections. They kill microbes ———————-.

Answer 22

• fungal
• inside phagosomes with ROS
  (reactive oxygen species) and
  hydrolytic enzymes

Question 23

What is the main component of pus?

Answer 23

Neutrophils

Question 24

Phagocytosis

Answer 24

pathogens are killed inside phagosome due to low pH, activity of lysosomal enzymes, ROS (neutrophils) and NO (macrophages)

Question 25

Eosinophils

Answer 25

- characteristic granules - defence against parasites - circulate in the blood and migrate to tissues - abundant in the small intestine - IgE (FcepsilonR) contribute to allergy and asthma - release signalling molecules which influence the adaptive immune response

Question 26

Basophils

Answer 26

- contain histamine granules - histamine is released in response to basophils binding to antibody/antigen complexes - histamine increases blood vessel permeability and allows immune cell in circulation to enter the site of infection - release signalling molecules - in abscence of infection, release of histamine is linked to allergy symptoms

Question 27

Mast cells

Answer 27

- immature mast cells leave the bone marrow and circulate in the blood - released to tissues, where they mature - mast cells can be found in the skin, connective tissue, mucosal epithelial tracts, and resp and GI tract - contain granules with histamine and are contributors to the allergy response

Question 28

Dendritic Cells

Answer 28

- resemble dendrites - capture antigens by phagocytosis and internalise those through r eceptor mediated endocytosis, followed by subsequent presnetation fo the antigen to other immune cells (T cells) - links innate and adaptive - antigen presenting function can cuase their migration to lymphoid organs once an antigen has been captured

Question 29

Lymphocytes (T, B, Natural Killer)

Answer 29

- T cells have T cell receptors - T cells are either cytotoxic or helpers - B cells are lymphoid pAPCs and present to T cells - B cells can mature to antibody producing plasma cells - both interact with pAPCs - natural killer cells contain a varierty of antigen recognition receptors as well as cytotoxic granules that kill target cells

Question 30

Inflammation overview

Answer 30

Question 31

Mechanisms of Inflammation

Answer 31

- basophil receptors recognise PAMPs and DAMPs and release histamine as a response - PRRs on tissue resident dendritic cells and macrophages initiate the signalling cascade to release pro- inflammatory cytokines for neutrophil recruitment - circulating leukocyte adhesion to the vascular endothelium is essential in their recruitment and tissue migration - achieved through cell adhesion molecules CAMS: selectin, integrin

Question 32

Excessive inflammation can lead to

Answer 32

sepsis, which is can lead to septic shock - blood infection involving gram negative and gram positive bacteria - activation of TLR4 receptor and other PRRs causes an increaded production of cytokines and increased vasodilation

Question 33

Regulation of inflammation (3):

Answer 33

- IL-10: anti-inflammatory cytokine produced by macrophages, inhibits inflamm cytokines and promotes wound healing - negative feedback loops involving proteins that act in the PRR signalling pathways (MyD88) - inhibitors of inflammtory cytokines TNF alpha and IL-1 beta in the form of soluble receptors can sequestrate excess cyotkines

Question 34

Acute vs Chronic inflammation

Answer 34

Question 35

Artherogenesis Steps:

Answer 35

- endothelial dysfunction - macrophage adhesion - smooth muscle migration - fibro/lipid plaque - inflammation

Question 36

Macrophages in atherogenesis

Answer 36

- blood circulating monocytes can ingest oxidised LDL through SCAVENGER RECEPTROS - these monocytes can migrate to subendothelial tissue and differentiate into macrophages that accumulate oxidised LDL becmoing FOAM CELLS - foam cells cna rupture releasing their molecular content, incluuding chemokines, recuiting more monocytes, ampkifying the inflammation process around the endothelilal lesion

Question 37

Atherosclerosis Risks

Answer 37