Physiology of normal White Blood Cells

Haematopoiesis - lymphoid cells

What are the components of the immune system?

What is the blood cell count in adults?

What are NEUTROPHILS?

What are MONOCYTES?

What are MACROPHAGES?

What are EOSINOPHILS?

• Have bilobed nuclei and granulated cytoplasm

• Motile phagocytic cells that can migrate from the blood into the tissues; majority are located in tissues

What is the function of eosinophils?

What are BASOPHILS?

• Lobed nuclei and heavily granulated cytoplasm

• Non-phagocytic cells that circulate in the blood

What is the function of basophils?

1) recruited to sites of allergic reactions or ectoparasite infection

• express FceRI

2) allergen can bind to allergen-specific IgE bound to the cell surface of basophils causing degranulation of effector mediators

3) Release pharmacologically active substances from cytoplasmic granules

4) Promote inflammation

Leucocytes and immunity

What are CYTOKINES?

• Low molecular weight (< 30 kDa) regulatory proteins or glycoproteins

• Act as the messenger molecules of the immune system

• Secreted primarily by white blood cells

• Also assist in regulating the development of immune effector cells

• Generally act locally (paracrine signalling)

What are CHEMOKINES?

• These are a type of cytokine that induce directed chemotaxis in local responsive cells

• Chemokines function mainly as attractants for leucocytes, recruiting monocytes and neutrophils to the site of infection

What is an important monocyte chemokine?

MCP-1 – Monocyte chemotactic protein-1 (Also known as CCL-2)

• Important for recruitment of monocytes

What is the function of MCP-1?

1) Recruit leucocytes (monocytes and neutrophils in particular)

2) Chemotaxis of blood leukocytes

3) Increase in expression of adhesion molecules

What is likely to happen in a tissue where MCP-1 is increased?

1) Increase in adhesion molecules on leucocytes

2) Chemotaxis of leucocytes from blood towards endothelium

3) Migration of leucocytes from blood into tissue

Inflammation

What are the components of the inflammatory response?

1) Blood vessels

2) Phagocytic leucocytes

3) Plasma proteins (e.g. complement, antibodies)

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

Acute VS Chronic inflammation

Recruitment of monocytes to sites of inflammation

Cell adhesion to endothelium

What is TRANSIENT INITIAL CONTACT?

What is TIGHTER BINDING?

Platelet/Monocyte interactions

Recognition leading to phagocytosis

1) Macrophage mannose receptor

• Ligand: Conserved carbohydrate structures

2) Scavenger receptors

• Ligand: anionic polymers, acetylated and oxidised LDL

• LDL is Low Density Lipoprotein which is a type of lipoprotein that contains high levels of cholesterol

3) Toll-like receptors (TLRs)

• Ligand: range of ligands for various TLRs

4) Opsonization of pathogens (coating with circulating receptors) also important

Phagocytosis

Example: activation of macrophages by pathogens

What is Atherosclerosis?

Build-up of plaque in lining of arteries

1) Involves 3 areas of pathogenesis:

• Endothelial cell dysfunction

• nflammation (mediated by monocytes/macrophages)

• Dysregulation of lipid metabolism

Atherogenesis (development of atherosclerotic plaque)