immunology of the skin

8/13/2019 Immunology of the Skin

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1-5-09 The Immunology of the skin

1. Describe the major components of the immune system. Describe the differences between

the innate and adaptive immune responses. Delineate the components of the adaptive and

innate immune systems of the skin and describe their methods of action. Understand

differences between the cellular and humoral components of the immune system. Describethe different immunoglobulins active in the immunology of the skin.

Recall that there is innateand adaptiveimmunity.

Innate immunity is rapidand non-specificwith no memory. It consists of:

o Neutrophils: rollalong the endothelium andphagocytosevia hagolysosomes!

where organisms are killed "y o#ygen-deendent and indeendent mechanisms.

The o#ygen-deendentmechanism involves respiratory burstthat

roduces hydrogen ero#ide! hydro#yl radicals! and singlet o#ygen.

The o#ygen-indeendentmechanisms involves cationic proteins and

enzymessuch as myeloero#idase and lyso$yme

%acrahages release G-!" and G#-!"to stimulate myeloid recursordivision in the "one marrow! resulting in the release of millions of

neutrohilsinto circulation.

o $osinophils:rotect the host from infection "yarasites! which associate with

antigen-secific Ig& 'eosinohils ( arasites and allergic reactions)

&osinohils "ind to Ig& via low-affinity receptorscalled "c-epsilon-%&&.

&osinohils are only weakly hagocytic 'unlike macrohages and

neutrohils)! "ut can have a athologic role in allergic reactions.

o N' cells: eliminate infected or malignant cells

o #ast ells: mast cells are located in tissues! while "asohils are in the "lood.

*oth bind avidly to IgEvia e#ression of high affinityrecetors for the anti"ody!called "c-epsilon-%&.

*inding causes immediateallergic reactions! such as anaphylaxis and

angioedema. That+s "ecause activated ,c-esilon-RI leads todegranulation and release of histamine! serotonin! prostaglandins!

leukotrienes'*! ! /! &! and ,)2which enhance vascular

permeability! bronchoconstriction! and induction of inflammatory

response.

o omplement: involves 30 serum glycoroteins that result in enhanced

phagocytosisandAPC recognition.

The roteins include the anaphylatoxins(a! )a! and *a4 all stimulate

mast cellsto increase vascular permeabilityto encourage antibodiestoenter tissue. 5a is a strong chemoattractant.

The #+comle# is comosed of 5"! ! 6! 7! 9. It unches holes

in mem"rane causing death "y osmotic lysis.

o antimicrobial peptides: includes defensinslike human "eta-defensin 'h,D-)

and catheliecidins

o cytokines: low molecular eight messenger su"stances that can act autocrine!

aracrine! or endocrinevia "inding to cell surface recetors. They include


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interleukins 'I8) which are leukocyte oriented! colony-stimulating factors',) that act as hematopoeitic progenitors! and interferons'I,) which

interfere with viral replication

o toll-like receptors: recognition of micro"ial and viral comonents. They"ridge

the ga"etween innate and adative immunity. /endritic cells e#ress toll-like

recetors dative immunity: defined "y memory'secificity! imrovement with each encounter)

and antigen presentation'/+s stimulating na;ve T cells! initiating rimary immune

resonse). It consists of:

o Dendritic cells: function in stimulating na;ve T cells and initiating a rimary

immune resonse. They have to main locations:

/+s in the T cell areas of thespleen and lymph nodesare the mosteffective s

/+s in the epidermisare known as angerhans cells

8angerhans cells are derived from the *%! desite their eidermal

location.

They can "e identified with electron microscoy or histochemicalanalysis that stains forAPaseand has anti"odies directed against

8 antigenic moieties 'D1ais the most useful marker). They aredistinctive in having ,irbeck granules in histochem.

Their function in the skin allows for initiation of sensitization

'as evidenced "y the lack of contact sensiti$ation in skin devoid of

8angerhans cells deleted "y class

II 'which resent exogenousantigens that result formendocytosis?rotein degradation in endolyso$omes)! while /7T

cells recogni$e antigens resented on %> class I'which resent

endogenousantigens that are either viral or tumor)

o The %>-II is critically dependent on dendiritic cells! "

cells! and monocytes#macrophagesunlike %>-I

o / cells: they develo in the *%! migrate to the thymus for selection.

positive selection 'only T cells that recogni$e self %>are allowed to

survive) occurs in the corte# of the thymus. 95@of T cells get selected out

in ositive selection.

negative selection'T cells that recogni$e selfetides dislayed on self-

%>s are eliminated) occurs in the medulla of the thymus Immature T cells e#ress "oth / and /7 'the Adou"le-ositiveB

stage). &ventually! one of the surface markers is lost! giving the T cell

secificity to %> II and %> I! resectively.

T cell signaling reCuires two signals:

"irst signal: TR "inding to etide-%> comle# on s

'"asically the antigen "eing resented)

o this determinesspecificity


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o "inding of first signal without the second costimulatory

signal results in anergyfollowed "y aototic cell death

!econd 0costimulatory signal: surface molecules and cytokines

o ,unctions in romoting clonal expansionof T cell as well

as T cell differentiationinto effectors and memories

T heler cells '/) recogni$e foreign antigens andactivate #&to eliminate athogens! as well as

activating , cells. There are three tyes of heler

effector cells:

/h2:precursorthat e#resses I8-3! I,-

gamma! T,-"eta! I, ! I8-! I8-5! I8-!

I8-9! I8-1D 'won+t really "e tested)

/h1: e#resses I,-gamma! T,-alha!

and I8-3 to induce a cell-mediated

inflammatory resonse

/h: e#resses I8-! I8-5! I8-! and I8-10

tofavor antibody production! cause allergic

disdease! cause atopic asthma! and systemiclupus erythematosus. I8- in articular

stimulates * cells to roduce Ig&! while I8-5romotes eosinohilsand I8-10 inhi"its

Th1.

ytoto#ic T cells '/7) focus on endogenousantiviral and antitumorresonses. They have two

athways for killing:

Inserting perforinsinto the cell mem"rane

ctivating death receptor "as'/95) viadeath ligand "as'/958) to trigger

aotosis

o ostimulator molecules include the ,3 family members

'*6-1 aka /70! or *603 aka /7)

ositively regulates D4recetor on T

cellscauses crosslinkinge#ression of anti-

aototic genes and roduction of cytokines like I8-

3

o / cell receptors 0/%s: defined "y their diversity.

ecific recetors for every ossi"le antigenare encoded "y fewer than

00 genesE This is made ossi"le "y recombination of varia"le regiongenes2

=aria"le '=)

/iversity '/)2only in TR and TR loci

Foining 'F)

onstant ')


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&ach TR uses a different com"o! with additional nucleotides "eing

inserted "y deo#yri"onucleotidyl-transferase

The maGority never encounter their antigen

o , cells and immunoglobulins: the maGor role of * cells isroduction of

immunoglo"ulins. D15! D2! and Dare the main markers. ctivation

leads to maturation! or the secretion of secific anti"odies. &ach Ig contains two identical light chainsand two identical heavy chains.

They are linked together "y disulfide "onds! and the-terminal functions

as the "inding site. The /R region of Ig+s recogni$e eitoes! so no

antigen presentation is re$uired. tensive gene rearrangement createsdiversity.

&g#: the largestIg at 900 k/a

ontains one F chain

Induces rimary immune resonse: romotes agglutination and

activates classical comlement

&gG: the most abundantIg! comrising of 65@ of all anti"odies. There are

su"classes 'IgH1-IgH)! with IgH1 and IgHD"eing activators ofclassical comlement. %oreover! autoimmuneanti"odies are mostly

mediated "y IgH.

&g+: this is the mucosalIg. It activates the alternativeathway. There are

3 su"classes 'Ig1 and Ig3). Ig is resonsi"le for athogenesis of"ullous autoimmune diseases.

&g$: this is the anahylacticanti"ody! for immediate anahylactic

reactions. resence of Gust a few are needed for sensiti$ation.

o U6, radiation '390-D30 nm) suresses the skin immune system and causes

reactivation of herpes simplex virus. Translant atients have increased chance of

skin cancer.

immunology of the skin

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