10-12-09 Immunology I: intro to the immune system 1. Describe the types of leukocytes in the blood.

Leukocytes are white blood cells and include monocytes, dendritic cells*, neutrophils, eosinophils, basophils, NK cells, T cells, B cells, and plasma cells. he breakdown o! how each leukocyte is deri"ed is as !ollows: #ommon hemato$oeitic $rogenitor #ommon lym$hoid $rogenitor %& cells'''' cells' ( cells' )endritic cells'' #ommon myeloid $rogenitor *osino$hils''' (aso$hils''' %eutro$hils''' +onocytes,macro$hages )endritic cells'' *-ecall how ( and cells were re!erred to as lymphocytes. hey com$rise the com$onents o! ada$ti"e immunity. which is di"ided into humoral and cell-mediated immunity. /ll lym$hocytes0 *1$ress a diverse array of antigen receptors 2a"e e1treme specificity !or antigen /re sub3ect to mechanisms that ensure tolerance to self 4ndergo clonal selection on antigen binding 5enerate a memory res$onse ( cells make u$ humoral immunity. 4$on encountering an extracellular microbial antigen. the ( cells e1$and clonally and di!!erentiate into $lasma cells to make antibodies against that antigen. /ntibodies target microbes $resent at mucosal sur!aces and in the blood i.e. $roduction o! Ig/ !or mucosal-associated lym$hoid tissues 6+/L 7 antibodies cannot gain access to microbes that li"e and di"ide within cells cells make u$ cell-mediated immunity. hey can be acti"ated in two ways: 4$on encountering an intracellular microbial antigen 6i.e. "iruses re$licating within an in!ected cell7. the cells e1$and clonally 4$on encountering an /8# ''''%ote that NK cells ha"e granules but are classi!ied as agranular leukocytes. %& cells are non-s$eci!ic !or antigens 6in contrast to antigen s$eci!ic ( and cells7. #onse9uently. they are considered a com$onent o! innate immunity des$ite their common myeloid lineage with ( and cells.

)es$ite the lack o! antigen s$eci!icity. %&:s are ca$able o! recogni;ing aberrant cells such as tumors and "irus-in!ected cells using low amounts o! class I molecules. heir granules contain $er!orin and gran;yme that make 8<-*= in the cyto$lasm o! the cell. resulting in apoptosis.

''Dendritic cells are $rimarily deri"ed !rom the myeloid lineage. 2owe"er. a small minority o! )#:s also arise !rom the common lym$hoid $rogenitor. )#:s act as antigen $resenting cells 6/8#:s7 and are res$onsible !or initiating ada$ti"e immunity. 4$on recogni;ing and endocytosing an antigen. an immature )# is stimulated to migrate "ia lym$hatics to the nearest lym$h node. where they activate na ve antigenspecific T-cells. )#s are also $resent within the $aracortical areas o! the lym$h node itsel!. where they can sam$le antigens that $ass through the organ. '''%eutro$hils. baso$hils. and eosino$hils are considered granulocytes. /ll other leukocytes mentioned abo"e are considered agranular. Neutrophils are the most abundant leukocyte. making u$ about >0? o! $eri$heral blood leukocytes. and are considered the !irst line o! de!ense against $athogens. hey normally circulate in blood. but u$on encountering sites o! in!ection or in!lammation. are recruited to phagocytose bacteria. Eosinophils work in de!ense o! $arasitic in!ections and are res$onsible !or asthma. Basophils ha"e a key role in allergic reactions. 2. What is the distribution of lymphoid tissue in the body and how does it function? here are two ty$es o! lym$hoid tissues: 1. central lym$hoid organs a. com$onents: bone marrow and thymus b. !unction: central lym$hoid organs are generati"e@ in other words. bone marrow and thymus are where ( and cells mature and become com$etent to res$ond to antigens. res$ecti"ely 2. $eri$heral lym$hoid tissues a. com$onents: lym$h nodes. s$leen. mucosa. tonsils. 8eyer:s $atches. a$$endi1 i. structure o! the lym$h node: ( cells in !ollicles. cells and )#:s in $aracortical areas b. !unction: o$timi;e interactions o! antigens. /8#s. and lym$hocytes to $romote the de"elo$ment o! ada$ti"e immune res$onses. i. Aor e1am$le. lym$h nodes !unction to concentrate antigens and ser"e as a site !or nai"e lym$hocytes to locate and res$ond to these antigens. +oreo"er. lym$hoid organs bring rare cells together. such as hel$er :s interacting with ( cells s$eci!ic !or the same antigen to $roduce antibodies. . !ompare and contrast innate to specific"adapti#e immunity. $nnate immunity: B main com$onents

(arriers: e$ithelial cells. mucus. and secretions 6stomach acid. lyso;yme in tears. betade!ensins in skin7 8hagocytosis: neutro$hils and macro$hages ingest and kill microbes. +acro$hages also secrete cytokines that initiate an inflammatory response #om$lement 6alternati#e pathway7: microbes se9uentially acti"ate $lasma $roteins 6known as a com$lement cascade7 and $roduce $roducts that kill microbes "ia three mechanisms: 17 early ste$s in"ol"e opsini!ing 6coat7 microbes with #Cb !or $hagocytosis o! the microbe by macro$hages and neutro$hils 27 late ste$s in"ol"e a #9 membrane attac" complex #$%&' that causes lysis o! the microbe C7 chemoattractants #Da and #Db $romote leukocyte recruitment and cause in!lammation at the site o! com$lement acti"ation %& cells: kill "irus-in!ected cells and $roduce interferon-gamma. a macro$hage acti"ating cytokine. In addition. innate immune res$onses stimulate subse9uent ada$ti"e immunity in ( and cells.

%dapti#e immunity: C main com$onents /ntibodies: !unction in binding to e1tracellular microbes. blocking their ability to in!ect cells. and $romoting their ingestion,destruction by $hagocytes 8hagocytosis: kills o!! microbes@ hel$er :s $lay a role in enhancing microbicidal acti"ities o! the $hagocytes #ytoto1ic cells: destroys intracellular microbes that cannot be accessed by antibodies ( cells 6antibodies7 and cells 6e!!ectors7 are res$onsible !or humoral and cell-mediated immunity. res$ecti"ely. as described below. &. 'ow do different types of lymphocytes mediate humoral and cellular immunity? (asic !ramework: /da$ti"e immunity 2umoral ( cells
/ntibodies 6Ig+. Ig5. Ig/. Ig*7 #ell-mediated immunity #ytoto1ic cells 6# Ls7 #)E 2el$er cells #)B

'umoral immunity: acti"ation o! ( cells and elimination o! *F -/cellular microbes ( cells are acti"ated u$on encountering $rotein and $olysaccharide antigens.' hese antigens ha"e multi$le identical antigenic determinants known as epitopes. (inding initiates proliferation and differentiation into $lasma cells that secrete di!!erent classes o! antibodies with distinct !unctions. he ability to $roduce di!!erent antibodies is known as hea#y chain class switchin(. It allows !or $lasticity in the antibody res$onse. Ig+: secretion stimulated by $olysaccharides and li$ids Ig5. Ig/. Ig*: secretion stimulated by $roteins 6"ia hel$er :s''7

*ach ( cell secretes antibodies that ha"e the same antigen binding site as the cell sur!ace rece$tors. ''=ide note: globular $rotein antigens do not bind to many antigen rece$tors@ conse9uently !ull ( cell res$onse re9uires #)B hel$er :s.

!ell)mediated immunity: acti"ation o! cells and elimination o! I% -/cellular 6cellassociated7 microbes 2ow do cells track down in!ected cellsG (y recogni;ing $athogens associated with +2#I and +2#II molecules. -ecall that $rotein antigens' taken u$ by /8#:s and $resented to naH"e cells on +2#s. /s these naH"e :s are being acti"ated. they secrete cytokine growth !actors and res$ond to other cytokines secreted by /8#:s. he ultimate result is proliferation and differentiation o! naH"e cells to e!!ector cells. #)E 6cytoto1ic7 cells recogni;e +2#I. hey directly kill cells harboring microbes in the cyto$lasm. #)B 6hel$er7 cells recogni;e +2#II. hey $roduce cytokines and e1$ress cell sur!ace molecules that bind to rece$tors on ( cells and macro$hages. thereby $romoting antibody $roduction and $hagocytosis. res$ecti"ely. '=ide note: $rotein antigens can be recogni;ed by both ( and antigens can only be recogni;ed by ( cells. cells. while $olysaccharide

*. What are the differences between na+#e, effector, and memory - and B cells? %aH"e ( and cells are lym$hocytes that ha"e not yet encountered an antigen. hey are specific to only <%* antigen. and such s$eci!icity is determined genetically during lym$hocyte de"elo$ment in the thymus and bone marrow. #onse9uently. there is tremendous di"ersity o! antigen rece$tors but also e1treme s$eci!icity amongst naH"e lym$hocytes. *!!ector ( and cells are generated u$on antigen binding. <nce a single lym$hocyte encounters an antigen. it is acti"ated to divide and $roduce many identical progeny. all o! which ha"e identical s$eci!icity to the $arent lym$hocyte. his $rocess is known as clonal selection and generates a whole set o! e!!ector lym$hocytes with identical s$eci!icity. +emory ( and cells are the conse9uence o! a $re-e1isting. clonally e1$anded. and long-li"ed $o$ulation o! antigen-s$eci!ic cells.