WHITE BLOOD WHITE BLOOD CELLSCELLS

LEUKOCYTESLEUKOCYTES

Dr. Dr. TajTaj

PLASMA

CELLS

WHITE BLOOD CELLS ARE VERY IMPORTANT

WHY?

PATHOGENS

INFECTIONS

IMMUNITY

Innate immunity

(non specific)

Examples:•Phagocytes•Complement•Barriers

Acquired immunity(specific)

Humoral Antibody mediated

B lymphocytes

Cell mediatedT lymphocytes

GGranulocytesranulocytes Polymorphonuclear leukocytes Polymorphonuclear leukocytes

(PMNs)(PMNs) NeutrophilsNeutrophils EosinophilsEosinophils BasophilsBasophils

AgranulocytesAgranulocytes LymphocytesLymphocytes

T lymphocyte T lymphocyte B lymphocyteB lymphocyte

Monocytes Monocytes macrophage system macrophage system

TYPES TYPES (CLASSIFICATION) (CLASSIFICATION)

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CLASSIFICATIONCLASSIFICATION

GRANULOCYTES AGRANULOCYTES

Cell ApproximateNormal range(/µL)

Percentage of Total WBC

Total WBC 4000-11000 - - -

Granulocytes

Neutrophils Eosinophils Basophils

3000-6000150-3000-100

50-701-40.4

Lymphocytes 1500-4000 20-40

Monocytes 300-600 2-8

Concentration (Normal Counts)

Granulocytes 4-8 hours

Monocytes 10-20 hours

Lymphocytes & macrophages

months & years

Life span of leukocytes:

FORMATIONGENESIS

Genesis of blood cells

Genesis of white blood cells

BARRIERS

Lines of DefenseLines of DefenseResponse to InflammationResponse to Inflammation

11stst line of defense – Tissue macrophages & line of defense – Tissue macrophages & Physical Barriers Physical Barriers

22ndnd line of defense – Neutrophil Invasion of the line of defense – Neutrophil Invasion of the inflamed areainflamed area

33rdrd line of defense – Monocytes –macrophage line of defense – Monocytes –macrophage invasion of inflamed areainvasion of inflamed area

44thth line of defense – Increased production of line of defense – Increased production of granulocytes and Monocytes by Bone marrowgranulocytes and Monocytes by Bone marrow

MONOCYTESMONOCYTES

No Granules but VacoulesNo Granules but Vacoules Size: 15-20 µmSize: 15-20 µm More Efficient than More Efficient than

NeutrophilsNeutrophils Life span: 10-20 hours in Life span: 10-20 hours in

bloodblood Two types: Mobile & FixedTwo types: Mobile & Fixed

RESTING MACROPHAGE

ACTIVATED MACROPHAGE

ACTIVATED MACROPHAGE

Reticuloendothelial Reticuloendothelial SystemSystem

Monocyte/Macrophage Monocyte/Macrophage SystemSystem

MonocytesMonocytes Mobile macrophages Mobile macrophages Fixed tissue macrophages Fixed tissue macrophages Specialized endothelial cells Specialized endothelial cells

in bone marrow, spleen and in bone marrow, spleen and lymph nodeslymph nodes

TISSUE MACROPHAGE SYSTEM

Reticuloendothelial Reticuloendothelial SystemSystem

Monocytes/Macrophage Monocytes/Macrophage SystemSystemExamples are: -Examples are: -

1.1. Skin and Subc tissues Skin and Subc tissues (Histiocytes)(Histiocytes)

2.2. Lymph NodesLymph Nodes3. 3. Alveolar macrophagesAlveolar macrophages4.4. Liver sinuses (Kupffer Cells) Liver sinuses (Kupffer Cells)

5.5. Spleen & Bone marrowSpleen & Bone marrow6. Microglia in Brain6. Microglia in Brain

Tissue macrophages in Tissue macrophages in Liver sinusesLiver sinuses

Tissue macrophages in Lymph Tissue macrophages in Lymph NodesNodes

Tissue macrophages in SpleenTissue macrophages in Spleen

NEUTROPHILSNEUTROPHILS

Most Abundant WBCs 60-70 Most Abundant WBCs 60-70 %%

Size: 15-20 µmSize: 15-20 µm Nucleus: Multilobed 2-5 lobesNucleus: Multilobed 2-5 lobes Life span: 6-8 hoursLife span: 6-8 hours

1.1. DiapedesisDiapedesis2.2. ChemotaxisChemotaxis3.3. OpsonizationOpsonization4.4. DegranulationDegranulation5.5. Phagocytosis & Phagocytosis &

DigestionDigestion

DEFENSIVE PROPERTIES OF DEFENSIVE PROPERTIES OF MACROPHAGES & MACROPHAGES &

NEUTROPHILSNEUTROPHILS

PMNs Digestive SystemPMNs Digestive System(Antimicrobial system)(Antimicrobial system)

ENZYMATICGranulesGranules HeparinHeparin HistamineHistamine BradykininBradykinin SerotininSerotinin DefensinsDefensins Lysosomal enzymesLysosomal enzymes Slow reacting substance Slow reacting substance of anaphylaxisof anaphylaxis

PMNs Digestive SystemPMNs Digestive System(Antimicrobial system)(Antimicrobial system)

NON ENZYMATICrespiratory burstrespiratory burst O2 Free Radicals (O-2, H2O2, -OH)O2 Free Radicals (O-2, H2O2, -OH) NADPH-oxidaseNADPH-oxidase MyeloperoxidaseMyeloperoxidase Cl- Cl- HoCl HoCl Hypochlorous acid “very toxic”Hypochlorous acid “very toxic”

Feed Back Feed Back Control of Control of

MacrophageMacrophage& Neutrophil & Neutrophil

responseresponse

IMPORTANT TERMSIMPORTANT TERMS

LeukocytosisLeukocytosis NeutrophiliaNeutrophilia PusPus LeukopeniaLeukopenia LeukemiasLeukemias

Formation of PusFormation of Pus

Dead Neutrophils Dead Neutrophils Dead Macrophages Dead Macrophages Necrotic tissueNecrotic tissue

InflammatioInflammationn

Is an Innate responseIs an Innate response When tissue injury occurs by When tissue injury occurs by

bacteria, trauma, chemical or heat, bacteria, trauma, chemical or heat, multiple substances are released by multiple substances are released by injured tissue that cause dramatic injured tissue that cause dramatic secondary changes in the injured secondary changes in the injured tissue. The entire complex of tissue tissue. The entire complex of tissue changes is called changes is called InflammationInflammation

EOSINOPHILEOSINOPHIL

Granules contain arginine rich protein, which Granules contain arginine rich protein, which take acid dye (eosin)take acid dye (eosin)

Function: PhagocytosisFunction: Phagocytosis Chemotaxis: attracted towards chronic Chemotaxis: attracted towards chronic

inflammationinflammation Neutralises allergic products such histamine, 5-HT, Neutralises allergic products such histamine, 5-HT,

Ag-Ab complex, bradykinin (allergic disease of skin Ag-Ab complex, bradykinin (allergic disease of skin &lungs)&lungs)

Phagocytosis is same as neutrophil, but less Phagocytosis is same as neutrophil, but less efficientefficient

Eosinophils Eosinophils cont,cont,

High eosinophil count:High eosinophil count: Parasitic (hook worm, ascaris, Parasitic (hook worm, ascaris,

bilharzia)bilharzia) Allergic (asthma, rhinitis, drug Allergic (asthma, rhinitis, drug

reaction)reaction) Dermatological diseasesDermatological diseases

BASOPHILSBASOPHILS

Weak phagocytic cellsWeak phagocytic cells Granules contain polysaccharide Granules contain polysaccharide

granules > base methylene blue color.granules > base methylene blue color. Similar to mast cells releases its Similar to mast cells releases its

granules containing heparin, histamine, granules containing heparin, histamine, 5HT. Which causes inflammation 5HT. Which causes inflammation reactionreaction

IMMUNITY

Protect the body against damages caused by

foreign organism e.g. bacteria, viruses transplanted incompatible tissue or

organs

IMMUNE CELLSIMMUNE CELLS

Cells which recognized foreign Cells which recognized foreign organism (antigen) by receptors organism (antigen) by receptors on its surface and respondon its surface and respond to it:to it:

1.1. T-LymphocytesT-Lymphocytes

2.2. B-Lymphocytes B-Lymphocytes

Immune Immune responseresponse

Lymphocytes respondLymphocytes respond to to antigen either by:antigen either by:

1.1. Producing antibodies (B-Producing antibodies (B-lymphoctes) to attack foreign lymphoctes) to attack foreign antigen (humoral immunity)antigen (humoral immunity)

2.2. Cellular killing of foreign Cellular killing of foreign invading organism (cellular invading organism (cellular immunity) by T-lymphocytesimmunity) by T-lymphocytes

AntigensLarge > 8000, complex, unique molecule that triggers a specific immune response against

itself when it gains entry into body.

ENEMIESBacterias, Viruses, Fungi, Parasites

•Foreign ness•Molecular size•Chemical structure •Antigenic determinants (Epitopes)

Antibody

Globulin molecules in plasma which are capable of attacking the invading agent.

EXAMPLES: IgG, IgA, IgM, IgD, IgE

Types of lymphocytes

1. Helper T-cells.

2. Cytotoxic T-cells.

3. Suppressor T-cells.

B-lymphocytes•Plasma cells•Memory Cells

B lymphocytesT lymphocytes

Humoral immunityHumoral immunity B-lymphocytes recognize foreign B-lymphocytes recognize foreign

organism by its surface receptorsorganism by its surface receptors Interact with antigen>>> proliferation Interact with antigen>>> proliferation

of B-lymphocytes to plasma cells of B-lymphocytes to plasma cells Plasma cells secrete the specific Plasma cells secrete the specific

antibody to destroy the antigen antibody to destroy the antigen Some of this plasma cells will be kept Some of this plasma cells will be kept

in marrow as memory cell ready for in marrow as memory cell ready for next exposure to same antigennext exposure to same antigen

Primary immune Primary immune responseresponse

The immune response of the The immune response of the body when exposed to antigen body when exposed to antigen for the first time >> antibodies for the first time >> antibodies are formed after a latent are formed after a latent period (1-2 w), time needed for period (1-2 w), time needed for multiplication and maturation multiplication and maturation of lymphocytes (vaccination)of lymphocytes (vaccination)

Secondary immune Secondary immune responseresponse

Upon the second exposure to the Upon the second exposure to the same antigen.same antigen.

immediate production of high immediate production of high titer antibodies titer antibodies

Due to the presence of memory Due to the presence of memory lymphocytes (from first exposure) lymphocytes (from first exposure) which react immediately when which react immediately when exposed to the same antigen exposed to the same antigen

Cellular immunityCellular immunity

T-cell react with antigen > proliferate to T-cell react with antigen > proliferate to give either:give either:

Cytotoxic T cells CD8 Cytotoxic T cells CD8 (Tc) destroy foreign (Tc) destroy foreign cell, removed by macrophage, monocytes, cell, removed by macrophage, monocytes, neutrophilsneutrophils

Helper T cell CD4Helper T cell CD4 (Th) secret lymphokinese (Th) secret lymphokinese to attract macrophages, stimulate B cell to to attract macrophages, stimulate B cell to secret antibodies against target cells infected secret antibodies against target cells infected with viruseswith viruses

Helper T-cells

• Most abundant.

• Secrete Cytokines (Interleukins)

• Stimulation of growth and proliferation of cytotoxic T cells and suppressor T cells.

• Stimulation of B cell growth and differentiation. Activation of macrophage system.

• Feedback stimulatory effect on helper T cells themselves.

Cytotoxic T-cells(Killer cells)

Bind with specific antigen

Secrete perforins (hole forming proteins)

Fluid flows into the cell

Cell swells and dissolves

Suppressor T-cells

•Suppress the function of Cytotoxic and helper T cells.

•Helper and Suppressor T-cells are called regulatory T-cells.

Function of Cellular Function of Cellular immunity immunity

1.1. Rejection of transplanted Rejection of transplanted tissues (kidney)tissues (kidney)

2.2. Delayed hypersensitivity Delayed hypersensitivity reaction (tuberculin)reaction (tuberculin)

3.3. Antitumor immunityAntitumor immunity4.4. Cooperation with B cell in Cooperation with B cell in

humoral immunityhumoral immunity

Clinical importanceClinical importance

The Acquired Immune Deficiency The Acquired Immune Deficiency Syndrome (AIDS)Syndrome (AIDS) AIDS virus selectively attack Th AIDS virus selectively attack Th

(CD4), reversing Th:Tc ratio 1:2(CD4), reversing Th:Tc ratio 1:2 Normal Th (CD4) : Tc (CD8) ratio 2:1Normal Th (CD4) : Tc (CD8) ratio 2:1 inhibition of immune responseinhibition of immune response prone to bacteria/ viruses infectionprone to bacteria/ viruses infection CancerCancer

ImmunizationActive immunity:

•Dead organism.

•Toxins.

•Live attenuated organism.

Passive immunity:

Infusion of antibodies, activated T-cells or both.

SUMMARY

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