White Blood Cells Flashcards
Lymphoid Progenitors
Differentiate into B lymphocytes, T lymphocytes and NKC (aka large granular lymphocyte)
Differentiate from pluripotent stem cells
T lymphocytes
Mature in thymus
Myeloid Progenitor cell
Differentiate into Erythroid CFU (colony forming unit), megakaryocytes, basophil CFU, eosinophil CFU, granulocyte monocyte CFU
Granulocyte - monocyte CFU
Differentiates into neutrophils and monocytes
Erythroid CFU differentiates into
Erythrocytes
Megakaryocytes differentiate into
platelets
Basophil CFU differentiate into
Basophils
Eosinophils CFU differentiates into
Eosinophils
Leukocytes
Lymphocytes: B cells, T cells, large granular lymphocyte
Phagocytes: monocular phagocytes, neutrophil, eosinophil
Cells that produce inflammatory mediators
Basophils, mast cells, platelets
Tissue cells
Produce interferons and cytokines
Cytokines
Produced by T cells, large granular lymphocytes, mononuclear phagocytes
Low molecular weight
Act as messenger molecules of the immune system
Secreted by WBC
Assist in regulating the development of immune effector cells
Act locally (paracrine signalling)
Monocular phagocytes
Complement the immune system and produce cytokines
B cells
Produce antibodies
Auxillary cells
Mast cells and platelets are important in the inflammatory response
Drawn to site of tissue injury or invasion
Mast cells
Located: tissues only
Release granules containing histamine that affects vascular permeability
Prominent in mucosal and epithelial tissue
Express: FceRI that binds to IgE
RBC adult count
Platelet count
Leukocyte count
5 * 10^6
- 5 * 10^5
- 3 * 10^3
Percentage of neutrophils
50-70%
60% of circulating leukocytes
Percentage of lymphocytes
20-40%
Percentage of circulating monocytes
3-10%
Percentage of circulating basophils
<1%
B + T
Antigen specific, NKC no antigen specific receptors
Basophils
Non -phagocytic
Lobed nuceli, heavily granulated
Function: Release pharmacologically active substances from cytoplasmic granules
Recruited to site of allergic reaction or ectoparasite infection
Express FcERI
Allergen bind to allergen specific IgE bound to the cell surface of basophils causing degranulation of effector mediators
Effector mediators produced by basophils
Histamine: increases vascular permeability and smooth muscle contraction
FcERI
Cell surface receptor that binds to the Fc region of IgE so that IgE is tethered to the surface of the basophil where it can then bind to allergens
Eosinophils
Have bi-lobed and granulated cytoplasm
Mobile phagocytic cells that can migrate from the blood into the tissues
Play a role in defence against parasitic organisms
Located in tissues
Express FcERI upon activation
Granules in eosinophils contain toxins and peroxidases
Attack parasites in GI, resp and genitourinary tracts
Neutrophils
Multilobed nucleus
Found in the blood
Rapidly recruited to sites of infection/injury
First responders to infection
Numbers increase during bacterial infection
Monocytes
Kidney shaped nucleus
Reservoir of monocytes in spleen
Circulate in bloodstream where they enlarge
Migrate to tissues approx. 8 hours after released from bone marrow
Precursors to macrophages
Blood-bourne phagocytes
Macrophages
Found in tissues
5-10 fold larger than monocytes
Contains many more organelles compared to monocytes
Bacterial infection causes
Increased neutrophils and increased monocytes in chronic infection
Viral infection causes
increased lymphocytes, sometimes increased monocytes
Parasite infection causes
Increased eosinophils + activation of mast cells
Fungal infections causes
Increased monocytes
Allergy causes
increased basophils and activation of mast cells
increased eosinophils in chronic phase
Ares of atherosclerotic pathogenesis (3)
Dysregulation of lipid metabolism
Endothelial cell dysfunction
Inflammation
Inflammation
A response of vascularised tissue to infections and damaged tissue
Characterised by heat, redness, pain and swelling
Purpose of inflammation
Brings cells and molecules involved in host defence and repair to the site of infection/injury
Components of inflammatory response
Blood vessels, phagocytic leukocytes, plasma proteins
Acute inflammation
Initial rapid response Develops within minutes Lasts hours/days Predominantly mediated by neutrophils Resolves once stimulus is removed
Chronic inflammation
Lasts weeks/months
Predominantly mediated by mononuclear cells (macrophages, lymphocytes)Tissue destruction
Attempts at healing (fibrosis)
Overview of inflammatory response (5)
- Blood vessels dilate
- Blood vessels become more permeable
- Circulating leukocytes migrate into tissue
- Leukocytes are activated
- Activated leukocytes destroy microbes and unwanted material
Chemokines
Type of cytokine that induce directed chemotaxis in local responsive cells
Function: attractants for leukocytes, recruiting monocytes and neutrophils to the site of infection
Important monocyte chemokine
Monocyte chemotactic protein 1 - aka CCL2
Chemotaxis
movement of cells in a direction corresponding to a gradient of increasing or decreasing concentration of a particular substance
Stages of recruitment of monocytes to the site of inflammation
Bind to adhesion molecules on vascular endothelium near sites of infection and gets chemokine signal
Migrates into surrounding tissue
Differentiates into a macrophage +migrate to infection site
Cell adhesion to endothelium
2 types of contact between endothelium and circulating cells : Initial contact and tighter adhesion
Adhering monocytes are stimulated by MCP-1 to cross the endothelium and lodge in intima
Initial contact (Cell adhesion to endothelium)
P and E selectin on endothelium recognised by oligosaccharides on leukocytes
Oligosaccharides
Sulfated sialyl-lewis^x
Tighter adhesion (Cell adhesion to endothelium)
Intercellular adhesion molecules (ICAMs) on the endothelium recognise integrins on leukocytes
ICAM1
intercellular adhesion molecule
VCAM1
Vascular cell adhesion molecule
VLA
Very late antigen
LFA
Lymphocyte function associated antigen
Endothelium activation
Absolute requirement for inflammation
How adherent/ activated platelets recruit and inflame monocytes
Release tissue factor, differentiate to macrophage, activate interleukins, adhere, chemotaxis, proteolysis
Pattern recognition receptors
Macrophage mannose receptors, scavenger receptors, toll like receptors
Activation of phagocytic cells
Phagocytic cells can recognise, ingest and destroy many pathogens
These cells recognise by cell surface receptors that can discriminate between the surface molecules displayed by pathogens and host cells
Activation of macrophages by pathogen
Macrophage expresses receptors for many bacterial constituents
Bacteria binding to macrophage receptors initiate the release of cytokines and small lipid mediators of inflammation
Release of pro-inflammatory cytokines from activated macrophages, e.g. IL-1B, TNF -a, IL-6
Macrophage mannose receptor ligand
Conserved carbohydrate structures
Scavenger receptor ligands
Anionic polymers, acetylate and oxidised LDL
Toll like receptors ligand
Range of ligands for various TLRs
Phagocytosis
Macrophages and neutrophils produce a number of toxic products that help kill the engulfed microbe
Neutrophils are short-lived cells, dying soon after phagocytosing: dead and dying neutrophils are a major component of the pus that forms in some infections
Macrophages are long-lived and continue to generate new lysosomes
The microbicidal machinery of the phagocyte is in the organelles known as lysosomes. This compartmentalisation is necessary to protect the cell, but also to maintain an environment in which the molecules perform effectively
Atherogenesis
Damage of endothelium and deposition of lipid:
- production of chemokines and cytokines
- Recruitment of monocytes
- Develop into macrophages/foam cells
- Potential exposure of collagen
- Platelet activation and coagulation
