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Chapter

PSL301H1 Chapter Notes -Pus, Warfarin, Spirometer


Department
Physiology
Course Code
PSL301H1
Professor
Gordon Richardson

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Lecture'1'Page'547/557'
'
Lecture'2'
The'Immune'System'
! Key'features'of'the'immune'system:'specificity'and'memory'–'together'these'processes'enable'body'to'distinguish'“self”'
from'“non/self”'and'mount'a'targeted'response'to'specific'invaders'
! Immune'system'serves'three'major'functions:'
o Protects(body(from(disease0causing(invaders'known'as'pathogens.'Microorganisms'(microbes)'that'act'as'
pathogens'(bacteria,'viruses,'fungi'and'one/celled'protozoans).'Larger'pathogens'include'multicellular'parasites'
(hookworms'and'tapeworms)'
! Virtually'any'exogenous'molecular'or'cell'has'potential'to'elicit'an'immune'response.'Pollen,'chemicals'
and'foreign'bodies'are'examples'of'substances'to'which'body'may'react.'Substances'that'trigger'body’s'
immune'response'and'can'react'with'products'of'that'response'are'known'as'antigens'
o It(removes(dead(or(damaged(cell'as'well'as'old'RBC.'Scavenger'cells'of'immune'system'patrol'extracellular'
compartment,'gobbling'up'and'digesting'dead'or'dying'cells'
o Tries(to(recognize(and(remove(abnormal(cells(created'when'normal'cell'growth'and'development'go'wrong'
! When'body’s'immune'system'fails'to'perform'its'normal'functions.'Pathologies'of'immune'system'generally'fall'into'one'of'
three'categories:'
o Incorrect(responses'if'mechanisms'for'distinguishing'self'from'non/self'fail'and'immune'system'attacks'body’s'
normal'cells'(autoimmune'disease)'
o Overactive(response'allergies'are'conditions'in'which'immune'system'creates'a'response'that'is'out'of'proportion'
to'the'threat'posed'by'antigen'
o Lack(of(response(–(Immunodeficiency(disease'arise'when'some'components'of'immune'system'fails'to'work'
properly.'Primary(immunodeficiency(is'a'family'of'genetically'inherited'disorders'that'range'from'severe'to'mild.'
Acquired(immunodeficiencies(may'occur'as'a'result'of'infection'(AIDS'caused'by'HIV)'
'
Pathogens'of'the'human'body'
Bacteria'and'viruses'require'different'defense'mechanisms'
! Bacteria'and'viruses'differ'from'each'other'in'several'ways'
! These'differences'require'body'to'have'variety'of'immune'response'
o Structure'–'bacteria'are'cell'with'cell'membrane'usually'surrounded'by'cell'wall.'Some'encapsulated'bacteria'also'
produce'additional'protective'outer'layer'(capsule).'Viruses'are'not'cells'–'they'consist'of'nucleic'acid'(DNA'or'
RNA)'enclosed'in'coat'of'viral'proteins'(capsid).'Some'viruses'add'an'envelop'of'phospholipid'and'protein'made'
from'host’s'cell'membrane'and'incorporate'viral'proteins'into'envelop'
o Living(conditions(and(reproduction'–'most'bacteria'can'survive'and'reproduce'outside'a'host'if'required'nutrients,'
temperature,'pH…'are'present.'Viruses'must'use'intracellular'machinery'of'host'to'replicate.'Location'of'
pathogens'in'both'major'compartments'of'body'requires'different'defense'mechanisms'for'each'compartment'
o Susceptibility(to(drugs'most'bacteria'can'be'killed'by'drugs'(antibiotics).'These'drugs'act'directly'on'bacteria'and'
destroy'them'or'inhibit'their'growth.'Viruses'cannot'be'killed'by'antibiotics'some'viral'infections'can'be'treated'
with'antiviral'drugs'which'target'specific'stages'of'viral'replication'
'
Viruses'can'replicate'only'inside'host'cells'
! Replication'cycle'of'virus'begins'when'virus'invades'host'cell'
! To'cross'human'cell'membrane,'virus'binds'to'membrane'receptors'triggering'endocytosis'of'entire'virus'particle'
! Or'virus'envelope'fuses'with'host'cell'membrane'allowing'core'of'virus'to'enter'cytoplasm'
! Once'inside'host'cell'and'free'of'capsid,'virus’s'nucleic'acid'takes'over'host'cell'resources'to'make'new'viral'nucleic'acid'and'
viral'protein'
! These'components'assemble'into'additional'virus'particles'that'are'released'from'host'cell'to'infect'other'cells'
! Viruses'can'be'released'from'host'cell'in'two'ways'
o Virus'can'cause'host'cell'to'rupture'releasing'virus'particles'into'ECF'
o Virus'particles'surround'themselves'with'layer'of'host'cell'membrane'and'then'bud'off'from'surface'of'host'cell'
! Viruses'do'other'kind'of'damage'to'host'cell'–'may'disrupt'cell’s'metabolism'so'cell'dies'–'some'causes'cold'sores'and'
chicken'pox'
'
The'Immune'Response'
! Body'has'two'lines'of'defense'–'physical'and'chemical'barriers'(skin,'mucus,'stomach'acid)'first'try'to'keep'pathogens'out'of'
body’s'internal'environment'
! If'first'line'of'defense'fails'then'internal'immune'response'takes'over'

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! Internal'immune'response'includes'same'basic'steps'
o Detection(and(identification'of'foreign'substance'
o Communication(with'other'immune'cells'to'rally'an'organized'response'
o Recruitment(of'assistance'and'coordination'of'the'response'among'all'participants'
o Destruction(or(suppression'of'invader'
! Not'all'invaders'can'be'destroyed'by'body’s'immune'system'–'some'cases'body'can'only'control'damage'and'keep'invader'
from'spreading'
! Antibodies'–'proteins'secreted'by'certain'immune'cells'bind'antigens'and'make'them'more'visible'to'immune'system'
! Cytokines'are'protein'messengers'released'by'one'cell'that'affect'growth'or'activity'of'another'cell'
! Human'immune'response'general'divided'into'two'categories:'nonspecific'innate'immunity'and'specific'acquired'immunity'
! Innate(immunity'present'from'birth'and'is'body’s'nonspecific(immune(response(to'invasion'
! Immune'cell'membrane'receptors'that'mediate'innate'immunity'have'broad'specificity'and'response'to'range'of'molecular'
signals'that'are'unique'and'common'to'pathogenic'microorganisms'
! Nonspecific'innate'response'does'not'target'particular'pathogen'–'it'begins'within'minutes'to'hours'
! Inflammation'apparent'on'skin'as'red,'warm,'swollen'area'–'hallmark'reaction'of'innate'immunity'
! Acquired(immunity(directed'at'specific'invaders'and'for'this'reason'is'the'body’s'specific(immune(response'
! The'immune'cell'membrane'receptors'that'mediate'acquired'immunity'are'highly'specific'and'can'distinguish'between'
different'pathogens'
! One'characteristic'of'acquired'immunity'is'that'specific'immune'response'to'first'exposure'to'a'pathogen'may'take'days'–'
with'repeated'exposures,'the'immune'system'“remembers”'prior'exposure'to'pathogen'and'reacts'more'quickly'
! Acquired'immunity'can'be'divided'into'cell/mediated'immunity'and'humoral'immunity'
o Cell0mediated(immunity'uses'contact/dependent'signaling'in'which'an'immune'cell'receptor'binds'to'a'receptor'
on'its'target'
o Humoral(immunity'(or'antibody0mediated(immunity)'uses'the'secreted'proteins'(antibodies)'to'carry'out'the'
immune'response'
! Innate'response'is'more'rapid'but'does'not'target'specific'invader''
! It'is'reinforced'by'antigen/specific'acquired'response'which'amplifies'the'efficacy'of'innate'response'
'
Anatomy'of'the'immune'system'
! The'immune'system'has'two'anatomical'components:'lymphoid'tissues'and'cells'responsible'for'immune'response'
'
Lymphoid'tissues'are'everywhere'
! Two'primary'lymphoid'tissues'are:'thymus(gland(and'bone(marrow'
! Both'have'an'outer'wall'formed'from'fibrous'collagenous'capsules'
! Spleen'contains'immune'cells'positioned'so'thy'monitor'blood'for'foreign'invaders'
! Phagocytic'cells'in'spleen'also'trap'and'remove'aging'RBC'
! Lymph'nodes'associated'with'lymphatic'circulation'–'this'filtered'fluid'is'picked'up'by'lymph'capillaries'and'passes'through'
encapsulated'lymph'nodes'on'its'journey'back'from'circulation'
! Inside'lymph'nodes,'clusters'of'immune'cells'intercept'pathogens'that'have'entered'ISF'through'breaks'in'skin'or'mucus'
membranes'
! Once'these'microbes'have'been'swept'into'lymph,'immune'cells'in'nodes'hep'prevent'their'spread'throughout'body'
! Unencapsulated'diffuse(lymphoid(tissues'are'aggregations'of'immune'cells'that'appear'in'other'organs'of'the'body'–'they'
include:'
o Tonsils'at'posterior'nasopharynx'
o Gut0associated(lymphoid(tissue((GALT)'which'lies'just'under'epithelium'of'esophagus'and'intestines'
o Clusters'of'lymphoid'tissue'associated'with'kin'and'respiratory,'urinary'and'reproductive'tract'
o These'tissues'contain'immune'cells'positioned'to'intercept'invading'pathogens'before'they'get'into'general'
circulation'
'
Leukocytes'mediate'immunity'
! Leukocytes'(WBC)'primary'cells'responsible'for'immune'responses'of'body'
! Most'are'larger'than'RBC'but'not'as'numerous'
! Most'leukocytes'circulate'blood'but'usually'leave'capillaries'and'function'extravascularly''
! Some'types'can'live'out'of'tissue'for'several'months'but'others'only'few'hours'or'days'
! Leukocytes'are'divided'into'six'basic'types'
o Eosinophils(
o Basophils'(in'blood'and'related'mast(cells'in'tissues)'
o Neutrophils'

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o Monocytes'and'their'derivatives'macrophages'
o Lymphocytes(and'their'derivatives'plasma(cells'
o Dendritic(cells'
! They'can'be'distinguished'by'stained'tissue'samples'by'size'and'shape'of'nucleus'
'
Immune'cell'names'
! Granulocytes('/'WBCs'whose'cytoplasm'contains'prominent'granules'–'names'of'different'cell'types'come'from'staining'
properties'of'granules'
! Basophils'granules'stain'dark'blue'with'basic'(alkaline)'dye'
! Eosinophils(granules'stain'dark'pink'with'the'acid'due'eosin'
! In'all'three'types'of'granulocytes'the'granule'contents'are'relased'from'cell'by'exocytosis'(degranulation)'
! Neutrophil'granules'do'not'stain'darkly'with'standard'blood'stains'and'are'therefore'“neutral”'
! Three'functional'groups:'
o Phagocytes'WBC'that'engulf'and'ingest'their'targets'by'phagocytosis'(neutrophils,'eosinophils,'macrophages'and'
monocytes'(macrophages'precursor)'
o Cytotoxic(cells'named'because'they'kill'cells'they'attack'
o Antigen0presenting(cells((APCs)'includes'macrophages,'monocytes,'certain'lymphocytes'and'dendritic'cells'
! Basophils('
o Rare'in'circulation'but'are'easily'recognized'in'stained'blood'smear'by'large'dark'blue'granules'in'cytoplasm''
o Very'similar'to'mast(cells'of'tissues'and'both'cell'types'release'mediators'that'contribute'to'inflammation'
o Granules'of'these'cells'contain'histamine'heparin'(an'anticoagulant'that'inhibits'blood'clotting),'cytokines'and'
other'chemicals'involved'in'allergic'and'immune'response'
o Mast'cells'are'concentrated'in'CT'of'skin,'lungs'and'GI'tract'
o Ideally'situated'to'intercept'pathogens'that'are'inhaled'or'ingested'or'that'enter'though'breaks'in'epidermis'
! Neutrophils'
o Phagocytic'cells'that'typically'ingest'and'kill'5/20'bacteria'during'programmed'life'span'of'one'or'two'days'
o Most'abundant'WBC'(50/70%)'and'most'easily'identified'by'segmented'nucleus'material'
o Form'in'bone'marrow'and'released'into'circulation'
o Most'remain'in'blood'but'can'leave'circulation'if'attracted'to'an'extravascular'site'of'damage'or'infection'
o In'addition'to'ingesting'bacteria'and'foreign'particles,'neutrophils'release'a'variety'of'cytokines'including'fever/
causing'pyrogens'and'chemical'mediators'of'inflammatory'response'
! Eosinophils''
o Easily'recognized'by'bright'pink/staining'granules'in'cytoplasm'
o These'immune'cells'are'associated'with'allergic'reactions'and'parasitic'diseases'
o Few'found'in'peripheral'circulation'where'the'account'for'1/3%'of'all'leukocytes'
o Lifespan'in'blood'~6/12'hours'
o Most'functioning'eosinophils'found'in'digestive'tract,'lungs,'urinary'and'genital'epithelia'and'CT'of'skin'
o These'location'reflect'their'role'in'defense'against'parasitic'invaders'
o They'are'known'to'attach'to'large'antibody/coated'parasites'and'release'substances'from'their'granules'that'
damage'or'kill'parasites''
o Because'they'kill'pathogens,'they'are'classified'as'cytotoxic'cells'
o Can'participate'in'allergic'reaction'–'the'contribute'to'inflammation'and'tissue'damage'by'releasing'toxic'enzymes,'
oxidative'substances'and'protein'called'eosinophil0derived(neurotoxin'
! Monocytes(and(macrophages'
o Monocytes'are'precursor'cells'of'tissue'macrophages'
o Not'very'common'in'blood'(1/6%)'
o Only'spend'8'hours'in'transit'from'bone'marrow'to'permanent'positions'in'tissue'
o Once'out'of'blood,'monocyte'enlarge'and'differentiate'into'phagocytic'macrophages'
o Some'tissue'macrophages'patrol'tissues'creeping'along'by'amoeboid'motion'
o Others'find'location'and'remain'fixed'in'place'
o Macrophages'are'primary'scavengers'within'tissue'
o Large'and'more'effective'than'neutrophils,'ingesting'up'to'100'bacteria'during'lifespan'
o They'also'remove'larger'particles'such'as'old'RBC'and'dead'neutrophils'
o Because'they'are'APCs,'macrophages'play'an'important'role'in'development'of'acquired'immunity'
o After'they'ingest'and'digest'molecular'or'cellular'antigens,'fragments'of'processed'antigen'are'inserted'into'
macrophage'membrane'as'part'of'surface'protein'complexes'
o In'addition,'dendritic'cells'and'lymphocytes'known'as'B(lymphocytes'also'act'as'APCs'
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