PALOMAR COLLEGE PALOMAR COLLEGE PALOMAR COLLEGE PALOMAR COLLEGE Biology 201 Biology 201 Fundamentals of Fundamentals of Biology II Biology II Rob Mustard Rob Mustard Adjunct Faculty Adjunct Faculty
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Biology 201Biology 201Fundamentals of Biology IIFundamentals of Biology II
Rob MustardRob Mustard
Adjunct FacultyAdjunct Faculty
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Leukocytes & Immune ResponseLeukocytes & Immune Response
Blood cells are one of the “fluid” Connective Blood cells are one of the “fluid” Connective TissuesTissues
Red blood cells Red blood cells (erythrocytes)(erythrocytes) Mammalian RBCs lack Mammalian RBCs lack
nuclei and mitochondrianuclei and mitochondria ~7 ~7 m diameterm diameter
White blood cellsWhite blood cells(leukocytes)(leukocytes) Giemsa stain to Giemsa stain to
differentiate WBCsdifferentiate WBCs6-7 million erythrocytes / ml6-7 million erythrocytes / ml33
7,000 leukocytes / ml7,000 leukocytes / ml33
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Immune Response ModesImmune Response Modes
Innate ImmunityInnate Immunity Rapid (and general) response to a broad Rapid (and general) response to a broad
range of microbial invasionrange of microbial invasion Acquired (Adaptive) ImmunityAcquired (Adaptive) Immunity
Secondary (and highly-specific) response to Secondary (and highly-specific) response to previously-encountered pathogenspreviously-encountered pathogens
Vertebrates have Vertebrates have bothboth forms of immune- forms of immune-response mechanismsresponse mechanisms
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Innate ImmunityInnate Immunity External defenses include:External defenses include:
Skin:Skin: impenetrable to most viruses & bacteria impenetrable to most viruses & bacteria Mucous:Mucous: viscous fluid that traps microbes viscous fluid that traps microbes Cellular secretions:Cellular secretions: sebaceous (oil) & sweat sebaceous (oil) & sweat
glands reduce skin’s pH to 3-5; lysozyme glands reduce skin’s pH to 3-5; lysozyme digests Gram + cell wallsdigests Gram + cell walls
Internal defenses begin after bacteria Internal defenses begin after bacteria invade, typically through a break in skin or invade, typically through a break in skin or other epidermal layerother epidermal layer
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Inflammatory ResponseInflammatory Response Tissue damage from physical injury leads to Tissue damage from physical injury leads to
cascade of chemical signalscascade of chemical signals Histamine, stored in mast cells in connective Histamine, stored in mast cells in connective
tissuetissue Nearby capillaries become dilated and leaky, Nearby capillaries become dilated and leaky,
allowing passage of macrophages and increased allowing passage of macrophages and increased blood flowblood flow
Increased local blood supply leads to redness, Increased local blood supply leads to redness, heat and swelling (inflammation)heat and swelling (inflammation)
Macrophages move out into damaged tissues, in Macrophages move out into damaged tissues, in interstitial spaces between cellsinterstitial spaces between cells
Nonspecific Inflammatory Response
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Leukocytes Involved in Leukocytes Involved in Innate Immunity: Innate Immunity: PhagocytesPhagocytes
NeutrophilsNeutrophils 60-70% of all leukocytes, 60-70% of all leukocytes,
live only a few dayslive only a few days Big: 12-15 Big: 12-15 m (2x m (2x
erythrocytes)erythrocytes) Nucleus has 2-5 lobes Nucleus has 2-5 lobes
(polymorphic)(polymorphic) MonocytesMonocytes
5% of all leukocytes5% of all leukocytes Biggest:Biggest: 20 20 mm Lighter, “frothy” horseshoe-Lighter, “frothy” horseshoe-
shaped nucleusshaped nucleus
Neutrophils are Neutrophils are granulargranular
Monocytes are Monocytes are agranularagranular
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Leukocytes Involved in Leukocytes Involved in Innate Immunity: Innate Immunity: PhagocytesPhagocytes
EosinophilsEosinophils RareRare in blood smears (2-4%) in blood smears (2-4%) Big: 12-15 Big: 12-15 m (same size as m (same size as
Neutrophils)Neutrophils) Nucleus has 2 lobesNucleus has 2 lobes
Dendritic CellsDendritic Cells Patrol interstitial spaces of Patrol interstitial spaces of
skin & mucosal membranesskin & mucosal membranes Phagocytize invaders, Phagocytize invaders,
process & present antigen process & present antigen material (APCs)material (APCs)
Activate acquired immune Activate acquired immune systemsystem
Eosinophils are Eosinophils are granulargranular
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Leukocytes Involved in Innate Leukocytes Involved in Innate Immunity: Immunity: HypersensitivityHypersensitivity
BasophilsBasophils RarestRarest of the of the
leukocytes (<0.5%)leukocytes (<0.5%) 10-12 10-12 m diameterm diameter Respond to allergic Respond to allergic
reactions (reactions (e.g., e.g., bee & bee & wasp stings, pollen)wasp stings, pollen)
Very granular; nucleus Very granular; nucleus often obscuredoften obscured
Live for about 2 weeksLive for about 2 weeks
Basophils are Basophils are very granularvery granular
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Leukocytes Involved in Leukocytes Involved in Innate Immunity: Innate Immunity: CytotoxicityCytotoxicity
Natural Killer CellsNatural Killer Cells A specialized lymphocyteA specialized lymphocyte Attack virus-infected cellsAttack virus-infected cells Attack cancer cells (tumors)Attack cancer cells (tumors) NK cells recognize NK cells recognize
infected/defective cells via infected/defective cells via surface featuressurface features
Bind to target cells, release Bind to target cells, release chemicals (perforins) that chemicals (perforins) that lead to apoptosislead to apoptosis
An NK cell (N) attached to a "target" cell "T". The NK cell will kill the now helpless target cell quickly, by the injection of deadly perforin.
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Leukocytes Involved in Leukocytes Involved in Acquired ImmunityAcquired Immunity
LymphocytesLymphocytes Very common in blood; Very common in blood;
20-40% of WBCs20-40% of WBCs Slightly larger than Slightly larger than
RBCs (~10 RBCs (~10 m)m) Dark-staining, circular Dark-staining, circular
nucleusnucleus Agranular; cytoplasm Agranular; cytoplasm
is transparentis transparent
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Lymphocyte SpecializationLymphocyte Specialization Vertebrate lymphocytes take on specialized rolesVertebrate lymphocytes take on specialized roles Circulate through blood & lymph, concentrated in Circulate through blood & lymph, concentrated in
spleen & lymph nodesspleen & lymph nodes B & T cells bear ~100K antigen receptors (all the B & T cells bear ~100K antigen receptors (all the
same)same)
Lightchain
VV
C
C C
C
VV
Antigen-binding sites
Variable regions
Constant regions
C
V
C
V
T cell chain chainHeavy
chainsB cell
IgM IgM ReceptorsReceptors
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Acquired Immunity ResponsesAcquired Immunity Responses Humoral ResponseHumoral Response
Dendritic cell (APC) engulfs pathogen, presents Dendritic cell (APC) engulfs pathogen, presents antibody via cell-surface protein (MHC class II)antibody via cell-surface protein (MHC class II)
Helper T cell binds to presented antigenHelper T cell binds to presented antigen APC releases cytokines to stimulate production of APC releases cytokines to stimulate production of
more “activated” T cellsmore “activated” T cells Activated B cells secrete antibodies, which immobilize Activated B cells secrete antibodies, which immobilize
pathogens, marking them for destruction by pathogens, marking them for destruction by macrophagesmacrophages
Cellular Immune ResponseCellular Immune Response A cell other than a leukocyte takes up and kills a A cell other than a leukocyte takes up and kills a
microbe, presents antigen on surface (MHC class I)microbe, presents antigen on surface (MHC class I) Cytotoxic (activated) T cell binds to presented Cytotoxic (activated) T cell binds to presented
antigen, releases perforins, lyses infected cell antigen, releases perforins, lyses infected cell
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Questions??Questions??