cells and organs of the immune system 2015 sv(1

7/25/2019 Cells and Organs of the Immune System 2015 SV(1

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Cells and Organs of the Immune System:


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Cells and Organs of the Immune System:

Immune System= network of cells and organs that extendsthroughout body and functions as the last line of defense

against infection (also called Lymphoid System)

Lymph= interstitial fluid derived from blood plasma

Leukocytes= white blood cells; participate in immune

response; carried within blood and lymph and populating thelymphoid organs


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Types of Leukocytes (WC!:

"# $ranulocytes:contain obvious cytoplasmic granules

%eutrophils

asophils

&ast cells

'osinophils

# &yeloid )ntigen*+resenting Cells ()+C!:

&onocytes , macrophages

-endritic cells

.# &egakaryocytes , +latelets

/# Lymphocytes:

cells0 T cells0 natural killer (%1! cells0 %1T cells


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Irregularly*shaped0 multi*lobed nucleus

$ranulescontaining anti-microbial chemicals and

enzymes

Subdi2ided into / categoriesbased on cellular

morphology and staining characteristics of granulesa! %eutrophils

b! asophils

c! &ast cellsd! 'osinophils

$ranulocytes


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%eutrophils

!ulti-lobed nucleus

"ranulated cytoplasm

#tain with acidic or basic dyes

$nly live a few days

%& to '& of leukocytes in circulation

$ften called polymorphonuclear leukocyte (+&%! erform phagocytosis(cellular uptake of particulate

matter by engulfment - more later)

*mong the first cells recruited to the site of infection

+Leukocytosis= transient increase in , circulating ./

+%eutrophilia 3indication of infection (increase may be0-1 fold)


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asophils

2obed nucleus

3eavily granulated cytoplasm

#tain blue with basic methylene blue

45 of circulating leukocytes

%ot phagocytic

6ndergo degranulation(discharge contents of cytoplasmic

granules following appropriate stimulus)

+7elease pharmacologically active substances from

cytoplasmic granules (ex8 histamine) 9 defense againstlarger parasites (ex8 helminths) andallergic response

()llergy= malfunction of body:s defense in which

harmless agents (ex8 pollen) 9 inappropriate immune

reaction)


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&ast Cells

Share many features with basophils

2arge numbers cytoplasmic granules

45 of circulating leukocytes

recursors form in bone marrow are released into blood

and differentiate when enter tissue


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'osinophils

.ilobed nucleus

"ranulated cytoplasm #tain red with acidic dye >osin 7ed

5 to 1 of circulating leukocytes

+hagocytic (minor role! mportant in defense against parasiteswhich are too

large to be phagocytosed (secreted contents of

eosinophilic granules damages parasite membrane)

+>x8 defense against protozoal parasites fungi worms


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&yeloid )ntigen*+resenting Cells

+hagocytic cells that ha2e professional antigen*

presenting cell function

+&onocytes

+&acrophages

+-endritic cells

+rofessional antigen*presenting cells ()+Cs! ingest

pathogen0 digest pathogenic proteins into peptides0then present these peptide antigens on their

membrane surfaces to acti2ate other immune cells

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&onocytes , &acrophages:

/ompact nucleus +hagocytic

&onocytes are generated in the bone marrow and canmigrate to the tissues to differentiate into macrophages

or dendritic cells

&acrophages are 4 to "5 times larger thanmonocytes0 ha2e increased number and comple6ity of

organelles0 and are more immunologically acti2e


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&onocyte -e2elopment:

$ranulocyte , monocyte progenitor(in bone marrow)

?

+romonocyte

?>nters blood and circulates @ A hours while

differentiating into mature monocyte


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Two types of monocytes:

"# Inflammatory monocytes (more common) enter tissuesBuickly in response to infection

+$nce in the tissue monocytes can differentiate intomacrophages ordendritic cells

# +atrolling monocytes (less common) crawl along bloodvessels; provide reservoir for tissue-resident monocytes inabsence of infection; may Buell rather than initiate immune

responses


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&acrophages:

+hagocytic !ay survive months in tissue

Wanderingmacrophages travel to infected tissue

7i6edmacrophages reside permanently in a particulartissue

+)l2eolar macrophages (lung!

+&icroglial cells (brain!

+Osteoclasts (bone!


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lay role in eliminating bacteria during early stages of

infection (via phagocytosis-- see section on

phagocytosis under Cnon-specific interior defensesD)

Eery efficient at scavenging dead cells and debris during

inflammatory repair

!acrophages activated by various stimuli (phagocytosis

cell to cell contact chemical stimulus) 9 activemacrophage with increased phagocytic killing and

secretory capability)

)lso participate in body8s S+'CI7IC I&&9%'

-'7'%S'S as antigen presenting cells (phagocytose

)g0 then present the )g on their surface to show;

)g to other immune cells (T! < increased response!


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-endritic Cells:

/overed in maze of long membrane e6tensions(resemble

dendrites of nerve cells)

Fhere are many types of dendritic cells

+-eri2e from either myeloid or lymphoid lineage

*ll dendritic cells except follicular are antigen*presenting

cells

%ote: 7ollicular dendritic cells

+-o not arise in bone marrow

+)re in2ol2ed in maturation of cells ()b*producingcells = more later!


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&egakaryocytes:

>eside in bone marrow

Eery large cells that produce plateletsby cytoplasmic

budding

+latelets= small anucleate cells or cell fragments that

contain vasoactive substances and clotting factors +

important in formation of blood clots

latelets are also called thrombocytes


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Lymphocytes:

3 +rimary cells of the adapti2e immune system

0&-1& of circulating white blood cells

Three types of lymphocytes

+ cells+T cells

+%atural killer (%1! cells

#mooth round relatively small lack visible granules

. cells and F cells are difficult to distinguish

morphologically and may appear identical under

microscopy


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Lymphocytes:

One way to tell them apart is to look at the surface

protein e6pressed:

+CL9ST'> O7 -I77'>'%TI)TIO% (C-!= a

collection of monoclonal antibodies that all recogni?e

an antigen found on a particular differentiated celltype or types+ each of the antigens recognized by such a

collection of antibodies is called a C- &arker;and is

assigned a uniBue identifying number

+>x8 /GH F cells

+>x8 /GA F cells


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)gents of @umoral or )b*mediated Immunity

)rise and mature in bone marrow

>ach express a uniAue antigen*binding receptor (*cell

receptor or C>! on its membrane

+C> 3 membrane bound immunoglobulin (antibody!

+'ach of the B"#46"54 molecules of )b on the membrane of

a single cell is identical

>espond to antigen by di2iding rapidly to create memory

cells and effector cells called plasma cells (plasma cells

produce a secreted form of the antibody!

Lymphocytes: Cells


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)gents of Cell*mediated Immunity

)rise in bone marrow0 but migrate to thymus for

maturation

!ature F cells e6press a uniAue antigen*binding molecule

(T*cell receptor or TC>! on their membrane

+TC> must recogni?e antigen in association with a

self; molecule (&aor @istocompatibility Comple6

or &@C!

>espond to )g by directly killing marked cells (TC! or

indirectly by regulating immune system (T@!

Lymphocytes: T Cells


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Two maor types of T cells:

+T helper (T@! cells

+C-/D

+T cytoto6ic (TC! cells

+C-ED


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Large0 granular (grainy appearance under microscope!

art of innate immune system

4*"5F of lymphocytes in human peripheral blood

Gisplay cytoto6ic acti2ity against wide range of tumor

cells and against cells infected with 2iruses

-o not ha2e T* or *cell receptors (must recogni?eabnormal cells in a different way = more later!

Lymphocytes: %atural 1iller (%1! Cells


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Lymphocytes: %1T

%1T cells ha2e characteristics of both T cells and

%1 cells

+3ave a TC>

ut0 not a lot of di2ersity between TC>s ofdifferent %1Ts (unlike regular F cells)

+#ome express C-/ (like F3cells)

+3ave some of the receptors associated with %1cells (more later!

+Iot well understood (area of active research)

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+Self*renewingby cell division

+Can differentiate into other cell types

+-isplay enormous proliferati2e anddifferentiati2e capacity

)ll lood Cells (>C0 WC! )rise from@ematopoietic Stem Cells (@SC!


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@ematopoiesis:

@ematopoiesis formation J development of red J white

blood cells

Eia stemcelldifferentiation

2ocation of development of stem cells into mature immune

cells+one marrow: 3#/s primarily reside here and give rise

to all cell type progenitors in this location

+Thymus: here F cells complete their maturation (Fcell precursors travel via blood from bone marrow to

thymus where they complete maturation)

'arly in hematopoiesis @SC differentiates along one of


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'arly in hematopoiesis0 @SC differentiates along one of

two pathways:

9 Lymphoid progenitor cell(gives rise to . F natural killercells dendritic cells)

9 &yeloid progenitor cell(gives rise to 7./ neutrophilseosinophils basophils monocytes K macrophages

megakaryocytes K platelets dendritic cells)

Fhese lymphoid and myeloid progenitor cellsare

+%o longer self*renewing

+Committed to particular cell lineage


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>egulation of @ematopoiesis:

3ematopoiesis is continuous process that mustmaintain a steady state(production of blood cells

eBuals loss)


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Steady*state regulation of hematopoiesis achie2ed

through:

58 7egulation by cytokines(chemical messengers) that

stimulate proliferation and K or differentiation of

various hematopoietic cells

08 7egulation of expression of receptors for cytokines

in stem and progenitor cells

18 7emoval of some cells by controlled induction ofcell death (apoptosis!


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+rogrammed Cell -eath ()poptosis!:

Induced0 ordered process in which cell acti2ely bringsabout its own demise

/ells undergoing programmed cell death often exhibit

distinctive morphological changes referred to as

apoptosis+Gecrease in cell 2olume

+!odification of cytoskeleton 9 membrane blebbing

+/ondensation of chromatin+Gegradation of -%)

+#hedding of tiny membrane-bounded apoptotic

bodies

)poptotic bodies and cells in advanced apoptosis are


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)poptotic bodiesand cells in advanced apoptosis are

phagocytosed(taken up) by macrophages (a2oids release

of cellular en?ymeswhich may cause local damage and

inflammatory response)


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Laboratory Count -efinitions:

Complete blood cell count (/./) = total count

./ and 7./

Leukocyte differential count = , of each type ofleukocyte (given as of total , of leukocytes)

-iagnostic as acute infection can increase G

leukocytes (especially neutrophils!


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Lymphoid Organs:

+rimary Lymphoid Organs:

+ro2ide appropriate

microen2ironment for

de2elopment and maturation of

lymphocytes

Two primary lymphoid organs:

+ one marrow+ Thymus

S d L h id O


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Secondary Lymphoid Organs:

Trap antigen generally from nearby tissues orvascular spaces

&ature and T cells congregateand interact within

these organs

Sites where mature lymphocytes can interacteffecti2ely with antigen

Three types of secondary lymphoid organs:

+ Lymph nodes+ Spleen

+ &ucosal*associated lymphoid tissue (&)LT!


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+rimary Lymphoid Organs: one &arrow

Where hematopoietic stem cells produce progenitorsof all blood cell types

Site of cell origin and de2elopmentin humans mice

(bursa of


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Lymphatic System:


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y p y

*s blood circulates under pressure its fluid component

(plasma) seeps through thin wall of capillaries intosurrounding tissue (3 interstitial fluid!

++ermeates all tissues and bathes the cells

Interstitial fluidthat does not return to blood throughcapillary membranes is called lymph J flows from spaces

in connective tissue into network of tiny open lymphatic

capillaries then into series of progressively larger collecting

vessels called lymphatic 2essels Lymphatic Circulation= system of vessels that collects

excess lymph from tissues and returns it to bloodstream


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Lymphatic capillaries pick up interstitial fluid0 particulate and solubleproteins0 as well as immune cells from the tissue surrounding the

blood capillaries


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+rimary organs (thymus0 bone

marrow! in red#

Secondary organs and tissues in blue#

Lymphatic 2essels in purple#

&ost of the body8s lymphatics

e2entually drain into the thoracic

duct which empties into the left

subcla2ian 2ein near the heart to

return lymph to blood#

@owe2er0 2essels draining right arm

and right side of head con2erge to

form the right lymphatic duct0 which

empties into the right subcla2ian

2ein#


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Lymph nodes- located throughout body on lymphatic

vessels

Spleen

&ucosal*associated lymphoid tissue(!*2F) in

various body sites )denoids(nose)

Tonsils(throat)

)ppendi6 (intestine) +eyer8s patches (intestinal wall)

Within mucous membranes lining upper

airways0 bronchi0 urogenital tract



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Secondary Lymphoid Organs: Lymph %odes


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Secondary Lymphoid Organs: Lymph %odes

>ncapsulated bean-shaped structures containing networkpacked with lymphocytes0 macrophages0 dendriticcells

/lustered at Lunctions of lymphatic vessels 9 therefore

are first organized lymphoid structure to encounter *gthat enter tissue

rovide ideal environment for filtration of foreign )gH subseAuent interaction of )g with lymphocytes

*ntigenic stimulation within node causes proliferationof lymphocytes as well as migration of existinglymphocytes from blood into node 9 2isible swelling ofnode in response to infection


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Lymph %ode Structure:


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Lymph %ode Structure:

Three ones:

"#Corte6 (contains lymphocytes

(mostly cells!0 macrophages0 and

follicular dendritic cells arranged in

follicles;!

#+aracorte6 (contains mostly T cells!

.#&edulla (site where lymphocytes0

plasma cells and )b e6it!


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S d L h id O S l


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Secondary Lymphoid Organs: Spleen

2arge ovoid organ situated high in left abdominal cavity

#pecializes in filtering blood and trapping blood*borne

)g (thus responds to systemic infection!

+.lood-borne *g and lymphocytesenter 2ia spenic

artery

+.loodlea2es 2ia spenic 2ein

resents trapped *g to lymphocytes populating K

circulating through spleen

#plenectomy 9 increase in blood-borne bacterial

infections (sepsis K bacteremia)


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Three ones:

"#>ed pulp (network of sinusoids populated by macrophages and >CsJ site ofdestruction of old and defecti2e >Cs!

#&arginal ?one (between red and white pulpJ contains mainly macrophages and

cells!

.#White pulp (surrounds the arteries0 forming a periarteriolar lymphoid sheath

(+)LS! = populated mainly by T cells and cell follicles!


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Laparoscopic Splenectomy



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y y p g

&ucosal*)ssociated Lymphoid Tissue (&)LT!

&ucous membraneslining digestive respiratory urogenitaltracts have large surface area (@H&& mM)

+&aor site of entry of for most pathogens

Fhese vulnerable surfaces defended by &)LT

+)LT 3 bronchus*associated lymphoid tissue

+$)LT 3 gut*associated lymphoid tissue

+%)LT 3 nasal*associated lymphoid tissue

#tructurally range from loose barely organized clusters oflymphoid cells (in intestinal villi) to well-organized

structures (tonsils appendix eyer:s patches)

3as large population of )b*producing cells


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& Cells:


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& Cells:

+n mucus membranes of digestive respiratory andurogenital tracts

+


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Skin )lso Contains Lymphoid Tissue

#kin = largest organ in human body Critical anatomic barrier against pathogens

$uter layer of skin composed largely of specialized

epithelial cells called keratinocytes

+#ecrete cytokines9 local inflammatory response

Langerhans cells(type of skin-resident dendritic cell)

phagocytose )g then migrate to regional lymph nodes

to act as )g*presenting cells 9 activate immuneresponse

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Tertiary; Lymphoid Tissues:


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Tertiary Lymphoid Tissues:

= Fissues that are the sites of infection

2ymphocytes activated by *g in secondary lymphoidtissue can return to these organs (ex8 lung liver brain) as

effector cells and can also reside there as memory cells

Fertiary lymphoid tissues can generate definedmicroenvironments that organize the returning lymphoid

cells

'2olutionary -istribution of Lymphoid Tissues:


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'2olutionary -istribution of Lymphoid Tissues:

cells and organs of the immune system 2015 sv(1

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