White Blood Cells Flashcards Preview

Module 103: Theme 2 > White Blood Cells > Flashcards

Flashcards in White Blood Cells Deck (63):
1

Lymphoid Progenitors

Differentiate into B lymphocytes, T lymphocytes and NKC (aka large granular lymphocyte)
Differentiate from pluripotent stem cells

2

T lymphocytes

Mature in thymus

3

Myeloid Progenitor cell

Differentiate into Erythroid CFU (colony forming unit), megakaryocytes, basophil CFU, eosinophil CFU, granulocyte monocyte CFU

4

Granulocyte - monocyte CFU

Differentiates into neutrophils and monocytes

5

Erythroid CFU differentiates into

Erythrocytes

6

Megakaryocytes differentiate into

platelets

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Basophil CFU differentiate into

Basophils

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Eosinophils CFU differentiates into

Eosinophils

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Leukocytes

Lymphocytes: B cells, T cells, large granular lymphocyte

Phagocytes: monocular phagocytes, neutrophil, eosinophil

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Cells that produce inflammatory mediators

Basophils, mast cells, platelets

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Tissue cells

Produce interferons and cytokines

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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)

13

Monocular phagocytes

Complement the immune system and produce cytokines

14

B cells

Produce antibodies

15

Auxillary cells

Mast cells and platelets are important in the inflammatory response
Drawn to site of tissue injury or invasion

16

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

17

RBC adult count
Platelet count
Leukocyte count

5 * 10^6
2.5 * 10^5
7.3 * 10^3

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Percentage of neutrophils

50-70%
60% of circulating leukocytes

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Percentage of lymphocytes

20-40%

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Percentage of circulating monocytes

3-10%

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Percentage of circulating basophils

<1%

22

B + T

Antigen specific, NKC no antigen specific receptors

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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

24

Effector mediators produced by basophils

Histamine: increases vascular permeability and smooth muscle contraction

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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

26

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

27

Neutrophils

Multilobed nucleus
Found in the blood
Rapidly recruited to sites of infection/injury
First responders to infection
Numbers increase during bacterial infection

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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

29

Macrophages

Found in tissues
5-10 fold larger than monocytes
Contains many more organelles compared to monocytes

30

Bacterial infection causes

Increased neutrophils and increased monocytes in chronic infection

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Viral infection causes

increased lymphocytes, sometimes increased monocytes

32

Parasite infection causes

Increased eosinophils + activation of mast cells

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Fungal infections causes

Increased monocytes

34

Allergy causes

increased basophils and activation of mast cells
increased eosinophils in chronic phase

35

Ares of atherosclerotic pathogenesis (3)

Dysregulation of lipid metabolism
Endothelial cell dysfunction
Inflammation

36

Inflammation

A response of vascularised tissue to infections and damaged tissue
Characterised by heat, redness, pain and swelling

37

Purpose of inflammation

Brings cells and molecules involved in host defence and repair to the site of infection/injury

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Components of inflammatory response

Blood vessels, phagocytic leukocytes, plasma proteins

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Acute inflammation

Initial rapid response
Develops within minutes
Lasts hours/days
Predominantly mediated by neutrophils
Resolves once stimulus is removed

40

Chronic inflammation

Lasts weeks/months
Predominantly mediated by mononuclear cells (macrophages, lymphocytes)Tissue destruction
Attempts at healing (fibrosis)

41

Overview of inflammatory response (5)

1. Blood vessels dilate
2. Blood vessels become more permeable
3. Circulating leukocytes migrate into tissue
4. Leukocytes are activated
5. Activated leukocytes destroy microbes and unwanted material

42

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

43

Important monocyte chemokine

Monocyte chemotactic protein 1 - aka CCL2

44

Chemotaxis

movement of cells in a direction corresponding to a gradient of increasing or decreasing concentration of a particular substance

45

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

46

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

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Initial contact (Cell adhesion to endothelium)

P and E selectin on endothelium recognised by oligosaccharides on leukocytes

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Oligosaccharides

Sulfated sialyl-lewis^x

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Tighter adhesion (Cell adhesion to endothelium)

Intercellular adhesion molecules (ICAMs) on the endothelium recognise integrins on leukocytes

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ICAM1

intercellular adhesion molecule

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VCAM1

Vascular cell adhesion molecule

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VLA

Very late antigen

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LFA

Lymphocyte function associated antigen

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Endothelium activation

Absolute requirement for inflammation

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How adherent/ activated platelets recruit and inflame monocytes

Release tissue factor, differentiate to macrophage, activate interleukins, adhere, chemotaxis, proteolysis

56

Pattern recognition receptors

Macrophage mannose receptors, scavenger receptors, toll like receptors

57

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

58

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

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Macrophage mannose receptor ligand

Conserved carbohydrate structures

60

Scavenger receptor ligands

Anionic polymers, acetylate and oxidised LDL

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Toll like receptors ligand

Range of ligands for various TLRs

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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

63

Atherogenesis

Damage of endothelium and deposition of lipid:

1. production of chemokines and cytokines
2. Recruitment of monocytes
3. Develop into macrophages/foam cells

1. Potential exposure of collagen
2. Platelet activation and coagulation