Physiology of normal white blood cells Flashcards
what cells are from myeloid progeny
erythrocytes, platelets, basophils, eosinophils, neutrophils and monocytes
what cells are from lymphoid progeny
B and T lymphocytes and NK cells
what cells are leucocytes
B cell, T cell, large granular lymphocyte, mononuclear phagocyte, neutrophil, eosinophil and basophil
what cells are phagocytes
mononuclear phagocyte, neutrophil and eosinophil
what cells are auxiliary cells
basophil, mast cell and platelets
what cells are granulocytes
neutrophil, basophil and eosinophil
how many lymphocytes are NK cells
Approximately 5% of lymphocytes are NK cells – do not have antigen specific receptors
what are basophils
Lobed nuclei, heavily granulated cytoplasm
Non phagocytic cells
what do basophils do
Function by releasing pharmacologically active substances from their cytoplasmic granules
Circulate in blood
Recruited to sites of allergic reaction or parasitic infection
Express F epsilon R1 - can bind to allergen specific IgE so allergen can bind to basophils causing degranulation of effector mediators
what are eosinophils
Have bilobed nuclei and granulated cytoplasm
Motile phagocytic cells that migrate from blood into tissues
Majority are located in tissues
what do eosinophils do
Recruited to sites of allergic reaction
Express FC epsilom R1 upon activation (bind to IgE)
Granules containing toxins eg peroxidases
Attach parasites in GI, respiratory and genito-urinary tracts
what are neutrophils
(polymorphonuclear cells)
Multilobed nucleus
Found in blood (60% of circulating leucocytes)
what do neutrophils do
Rapidly recruited to sites of infection/injury (short lifespan (8hr-4days)
Phagocytic, myeloperoxidase and ROS
First responders, numbers increased in blood during bacterial infection
what are monocytes
Kidney shaped nucleus Blood born phagocytes
Precursors to macrophages
what do monocytes do
Reservoir of monocytes in the spleen
Circulate in bloodstream where they enlarge
Migrate into tissues approx. 1 day after release from bone marrow
what are macrophages
Found in tissues (tissue specific)
5-10 fold larger than monocytes and Contain many more organelles
Lifespan months to years
what do macrophages do
Tissue born phagocytes
what cells increase in bacterial infection
neutrophils (monocytes in chronic infection)
what cells increase in viral infection
lymphocytes, sometimes monocytes)
what cells increase in parasitic infection
eosinophils + activation of mast cells
what cells increase in fungal infection
monocytes
what cells increase in allergy
basophils (eosinophils in chronic phase), activation of mast cells
how is leucocyte function regulated
Recruitment of leucocytes from blood to tissues is key to their immune functions
(interactions with blood vessels is key to recruitment)
what are cytokines
Act as messenger molecules of immune system
Assist in regulating the development of immune effector cells
Generally act locally (paracrine signalling)
what do cytokines do
Low molecular weight (>30kDa) regulatory proteins or glycoproteins
Secreted primarily by WBCs
what are chemokine
Type of cytokine that induce directed chemotaxis in local responsive cells
what do chemokine do
Chemokines function mainly as attractant for leucocytes, recruit monocytes and neutrophils to site of infections
Important monocyte chemokines MCP-1 (monocyte chemotactic protein-1)
AKA CCL-2
what is inflammation
A response of vascularised tissue to infections and damaged tissues (heat redness pain and swelling)
`Aim is to bring cells and molecules involved in host defence and repair to site of infection/injury
what are the mechanisms of inflammation
Components: blood vessels, phagocytic leucocytes, plasma proteins (eg complement, antibodies)
Overview:
Blood vessels dilate
“ more permeable
Circulating leucocytes to migrate blood to tissue
Activated
destroy microbes and any unwanted material
what is the difference between acute and chronic infection
Time it lasts
Speed of development
Healing (resolved when stimulus removed in acute, attempts and tissue destruction in chronic)
acute- neutrophils
chronic- mononuclear cells (eg macrophages and lymphocytes)
what are the types of cell adhesion to the endothelium
Initial contact – P and E-selectin on endothelium recognised by oligosaccharides on leucocytes
Tighter adhesion – intercellular adhesion molecules (ICAMS) on the endothelium recognise integrins on leucocytes
what happens after cell adhesion to the endothelium
Adhering monocytes are stimulated by MCP-1 to cross endothelium and lodge in intima
Turn to macrophage once in tissue
what molecules are involved the transient initial contact
E and P-selectin expressed on activated endothelium (not activated in normal circumstances)
what molecules are involved the tighter binding
ICAM-1 and V-CAM1 present on activated endothelium, not under normal circumstances)
what is a requirement for inflammation
Ligands present on leucocytes
Activated endothelium a requirement for inflammation
how do platelets interact with monocytes
Adherent/activated platelets can recruit and inflame monocytes
how are recruited leucocytes activated
Phagocytic cells can recognise, ingest and destroy many pathogens
These cells recognise pathogens damaged host molecules by means of cell surface receptors that can discriminate between the surface molecules displayed by pathogens and host cells
Can also recognise damaged host molecules
Effect is to activate macrophages by pathogens
what are types of pattern recognition receptors
Macrophage mannose receptor: ligands: conserved carb structures
Scavenger receptors: ligand: anionic polymers, acetylated and oxidised LDL
Toll like receptors: Ligand: range of ligands for various TLRs
Opsonisation of pathogens (coating with circulating receptors) also important
what proinflammatory cytokines are released from macrophages
(IL-1B, TNF-a, IL-6)
what is atherosclerosis
build-up of plaque lining arteries
Involves 3 areas of pathogenesis
Endothelial cell dysfunction
Inflammation mediated by monocytes/macrophages)
Dysregulation of lipid metabolism
what is atherogenesis
development of atherosclerotic plaque
how does atherogenesis occur
damaged endothelium and lipid deposits
expose collagen - activate platelets or
produced cyto/chemokines, recruit monocytes to develop into macrophages and foam cells which further damages endothelium
