Theme 2: Lecture 5 - Physiology of normal white blood cells Flashcards
Which cells make up the leukocytes
- B cells
- T cells
- Large granular lymphocytes (includes NK cells)
- Mononuclear phagocytes
- Neutrophils
- Eosinophils
- Basophils
Which cells make up the lymphocytes
- B cells
- T cells
- Large granular lymphocytes
Which cells make up the phagocytes
- Mononuclear phagocytes
- neutrophils
- eosinophils
What are the axillary cells of the immune system
- Basophils
- mast cells
- platelets
Which cells make up the granulocytes
- Neutrophils
- Eosinophils
- Basophils
What % of WBCs are neutrophils
50-70%
What % of WBCs are lymphocytes
20-40%
What % of WBCs are monocytes
3-10%
What % of WBCs are eosinophils
1-3%
What % of WBCs are basophils
< 1%
What % of lymphocytes are NK cells
5%
Basophil appearance
Lobed nuclei and heavily granulated cytoplasm
What are basophils
-Non-phagocytic cells
-Function by releasing pharmacologically active
substances from their cytoplasmic granules
-Express Fc epsilon RI
-Allergen can bind to allergen-specific IgE bound to the cell surface of basophils causing degranulation of effector mediators
Where are basophils found
circulating in the blood
Fc epsilon RI
An IgE receptor that binds to the Fc portion of IgE
Where are basophils recruited to
Recruited to sites of allergic reactions or ectoparasite infection
Eosinophil appearance
Have bilobed nuclei and granulated cytoplasm
What are eosinophils
- Motile phagocytic cells that can migrate from the blood into the tissues
- granules containing toxins e.g. peroxidases
- Attack parasites in GI, respiratory and genito-urinary tracts
Where are eosinophils found
majority located in tissues
Where are eosinophils recruited to
sites of allergic reactions
What do eosinophils express on activation
Fc epsilon RI
Neutrophil appearance
Polymorphonuclear cells
Where are neutrophils found
circulating in the blood
Neutrophil lifespan
- short
- 8 hours to 4 days
What are neutrophils
- Phagocytic cells
- first responders to infection, rapidly recruited to site
- numbers increased in bacterial infection
What do neutrophils produce
- myeloperoxidase (an enzyme)
- ROS
Monocyte appearance
kidney shaped nucleus
Where are monocytes found
- Reservoir of monocytes in the spleen
- Also circulate in bloodstream where they enlarge
When do monocytes migrate to tissues after being released from the bone marrow
one day
What are monocytes
- Blood-bourne phagocytes
- Precursors to macrophages
Where are macrophages found
in the tissues (they are tissue specific)
What are macrophages
tissue resident phagocytes
Macrophage lifespan
months to years
Macrophage appearance
- 5-10-fold larger than monocytes
- Contain many more organelles compared to monocytes e.g. lysosomes
Which WBCs are increased in bacterial infection
- neutrophils
- monocytes too in chronic infection
Which WBCs are increased in viral infection
- lymphocytes
- monocytes sometimes
Which WBCs are increased in parasite infection
- eosinophils
- activation of mast cells too
Which WBCs are increased in fungal infection
monocytes
Which WBCs are increased in allergy
- basophils
- eosinophils in chronic phase
- activation of mast cells
What are cytokines
- Act as the messenger molecules of the immune system
- Also assist in regulating the development of immune effector cells
- Have a low molecular weight (<30 kDa) regulatory proteins or glycoproteins
What are cytokines secreted by
primarily by WBCs
Where to cytokines act
generally locally (paracrine signalling)
What are chemokines
These are a type of cytokine that induce directed chemotaxis in local responsive cells
What do chemokines function mainly as
attractants for leucocytes, recruiting monocytes and neutrophils to the site of infection
MCP-1
- Monocyte chemotactic protein 1
- AKA CCL-2
- Important monocyte chemokine, key for recruiting monocytes to sites of injury/infection
What is inflammation characterised by
- heat
- redness
- swelling
- pain
What is inflammation
A response of vascularised tissue to infections and damaged tissue
What is the purpose of inflammation
To bring cells and molecules involved in host defence and repair the site of infection/injury
Process of inflammation
- Bacteria trigger macrophages to release cytokines and chemokines
- This causes vasodilation and increased vascular permeability which causes redness, heat and swelling
- Inflammatory cells (leukocytes) migrate into the tissue releasing inflammatory mediators which cause pain
- Leucocytes destroy microbes and unwanted material
Describe acute inflammation
- Initial, rapid response
- Develops within minutes
- Lasts hours – days
- Resolves once stimulus is removed
What is acute inflammation predominantly mediated by
neutrophils
Describe chronic inflammation
- Lasts weeks – months
- Can lead to tissue destruction
- Attempts at healing (fibrosis)
What is chronic inflammation predominantly mediated by
-mononuclear cells (macrophages, lymphocytes)
How are monocytes recruited to the site of infection
- Monocyte binds adhesion molecules (in the absence of these adhesion molecules, the monocytes aren’t going to be recruited into the tissue) on vascular endothelium near sites of infection and gets chemokine signal
- Monocyte migrated into surrounding tissues
- Monocyte differentiates into a macrophage and migrates to the site of infection
What are the 2 types of cell adhesion to endothelium
- Initial contact
- Tighter adhesion
What are adhering monocytes stimulated by to cross the endothelium and lodge in the intima
MCP-1
Initial contact
P-selectin and E-selectin (adhesion molecules) on endothelium recognised by oligosaccharides (sulfated sialyl-Lewis x ) on leucocytes
Tighter contact
intercellular adhesion molecules (ICAMs) on the endothelium recognised integrins (a type of receptor) on leucocytes
ICAMs
Intercellular adhesion molecules
When are ICAMs present
- When the endothelium is activated
- In normal circumstances these molecules aren’t present so don’t facilitate binding of the endothelium to leukocytes
Name 2 intercellular adhesion molecules
ICAM-1 (CD54)
VCAM-1 (CD106)
Which integrin molecules do ICAM-1 bind to
LFA-1
Mac1
What integrin molecule does VCAM-1 bind to
VLA-4
Describe the interaction between platelets and monocytes
Activated or adhered platelets can recruit and inflame monocytes
How do phagocytic cells recognise pathogens or damaged host molecules
By pattern recognition receptors (cell surface receptors) that can discriminate between the surface molecules displayed by pathogens and host cells
Name 3 pattern recognition receptors
- Macrophage mannose receptor
- Scavenger receptors
- Toll like receptors
What is the ligand for macrophage mannose receptors
conserved carbohydrate structures
What are the ligands for scavenger receptors
- anionic polymers
- acetylated and oxidised LDL
What are the ligands for toll like receptors
various ligands for various toll like receptors
Opsonization
Pathogens are coated by circulating receptors to make them more visible to phagocytes
Describe phagocytosis
- Occurs via actin-based mechanism and interaction with various cell surface receptors
- Foreign particles internalized to form phagosomes
- Fusion of phagosomes with lysosomes leads to formation of phagolysosomes where foreign particles are enzymatically degraded
- Lysosome regenerated afterwards
