Theme 2: Lecture 5 - Physiology of normal white blood cells Flashcards
1
Q
Which cells make up the leukocytes
A
- B cells
- T cells
- Large granular lymphocytes (includes NK cells)
- Mononuclear phagocytes
- Neutrophils
- Eosinophils
- Basophils
2
Q
Which cells make up the lymphocytes
A
- B cells
- T cells
- Large granular lymphocytes
3
Q
Which cells make up the phagocytes
A
- Mononuclear phagocytes
- neutrophils
- eosinophils
4
Q
What are the axillary cells of the immune system
A
- Basophils
- mast cells
- platelets
5
Q
Which cells make up the granulocytes
A
- Neutrophils
- Eosinophils
- Basophils
6
Q
What % of WBCs are neutrophils
A
50-70%
7
Q
What % of WBCs are lymphocytes
A
20-40%
8
Q
What % of WBCs are monocytes
A
3-10%
9
Q
What % of WBCs are eosinophils
A
1-3%
10
Q
What % of WBCs are basophils
A
< 1%
11
Q
What % of lymphocytes are NK cells
A
5%
12
Q
Basophil appearance
A
Lobed nuclei and heavily granulated cytoplasm
13
Q
What are basophils
A
-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
14
Q
Where are basophils found
A
circulating in the blood
15
Q
Fc epsilon RI
A
An IgE receptor that binds to the Fc portion of IgE
16
Q
Where are basophils recruited to
A
Recruited to sites of allergic reactions or ectoparasite infection
17
Q
Eosinophil appearance
A
Have bilobed nuclei and granulated cytoplasm
18
Q
What are eosinophils
A
- 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
19
Q
Where are eosinophils found
A
majority located in tissues
20
Q
Where are eosinophils recruited to
A
sites of allergic reactions
21
Q
What do eosinophils express on activation
A
Fc epsilon RI
22
Q
Neutrophil appearance
A
Polymorphonuclear cells
23
Q
Where are neutrophils found
A
circulating in the blood
24
Q
Neutrophil lifespan
A
- short
- 8 hours to 4 days
25
What are neutrophils
- Phagocytic cells
- first responders to infection, rapidly recruited to site
- numbers increased in bacterial infection
26
What do neutrophils produce
- myeloperoxidase (an enzyme)
| - ROS
27
Monocyte appearance
kidney shaped nucleus
28
Where are monocytes found
- Reservoir of monocytes in the spleen
| - Also circulate in bloodstream where they enlarge
29
When do monocytes migrate to tissues after being released from the bone marrow
one day
30
What are monocytes
- Blood-bourne phagocytes
| - Precursors to macrophages
31
Where are macrophages found
in the tissues (they are tissue specific)
32
What are macrophages
tissue resident phagocytes
33
Macrophage lifespan
months to years
34
Macrophage appearance
- 5-10-fold larger than monocytes
| - Contain many more organelles compared to monocytes e.g. lysosomes
35
Which WBCs are increased in bacterial infection
- neutrophils
| - monocytes too in chronic infection
36
Which WBCs are increased in viral infection
- lymphocytes
| - monocytes sometimes
37
Which WBCs are increased in parasite infection
- eosinophils
| - activation of mast cells too
38
Which WBCs are increased in fungal infection
monocytes
39
Which WBCs are increased in allergy
- basophils
- eosinophils in chronic phase
- activation of mast cells
40
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
41
What are cytokines secreted by
primarily by WBCs
42
Where to cytokines act
generally locally (paracrine signalling)
43
What are chemokines
These are a type of cytokine that induce directed chemotaxis in local responsive cells
44
What do chemokines function mainly as
attractants for leucocytes, recruiting monocytes and neutrophils to the site of infection
45
MCP-1
- Monocyte chemotactic protein 1
- AKA CCL-2
- Important monocyte chemokine, key for recruiting monocytes to sites of injury/infection
46
What is inflammation characterised by
- heat
- redness
- swelling
- pain
47
What is inflammation
A response of vascularised tissue to infections and damaged tissue
48
What is the purpose of inflammation
To bring cells and molecules involved in host defence and repair the site of infection/injury
49
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
50
Describe acute inflammation
- Initial, rapid response
- Develops within minutes
- Lasts hours – days
- Resolves once stimulus is removed
51
What is acute inflammation predominantly mediated by
neutrophils
52
Describe chronic inflammation
- Lasts weeks – months
- Can lead to tissue destruction
- Attempts at healing (fibrosis)
53
What is chronic inflammation predominantly mediated by
-mononuclear cells (macrophages, lymphocytes)
54
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
55
What are the 2 types of cell adhesion to endothelium
- Initial contact
| - Tighter adhesion
56
What are adhering monocytes stimulated by to cross the endothelium and lodge in the intima
MCP-1
57
Initial contact
P-selectin and E-selectin (adhesion molecules) on endothelium recognised by oligosaccharides (sulfated sialyl-Lewis x ) on leucocytes
58
Tighter contact
intercellular adhesion molecules (ICAMs) on the endothelium recognised integrins (a type of receptor) on leucocytes
59
ICAMs
Intercellular adhesion molecules
60
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
61
Name 2 intercellular adhesion molecules
ICAM-1 (CD54)
| VCAM-1 (CD106)
62
Which integrin molecules do ICAM-1 bind to
LFA-1
| Mac1
63
What integrin molecule does VCAM-1 bind to
VLA-4
64
Describe the interaction between platelets and monocytes
Activated or adhered platelets can recruit and inflame monocytes
65
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
66
Name 3 pattern recognition receptors
- Macrophage mannose receptor
- Scavenger receptors
- Toll like receptors
67
What is the ligand for macrophage mannose receptors
conserved carbohydrate structures
68
What are the ligands for scavenger receptors
- anionic polymers
| - acetylated and oxidised LDL
69
What are the ligands for toll like receptors
various ligands for various toll like receptors
70
Opsonization
Pathogens are coated by circulating receptors to make them more visible to phagocytes
71
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
