cemm mediated t cells humoral antibodies from b cells (plsma cells) thymus t cell ; bone marrow and fetal

liver for b cell maturation lymph nodes initiate immune resonpse; enter medulla where t cells, activate b cells i follicles; germinal centers contain stimulated b cells immune response to blood antigens takes place in sleen mucosa lymphoid tissue- gut including m cell (door keeper to peyer patch) peyer patch (mini lymph node); and tonsil and adenoid tissue antibodies activate complement which together enhance phago (opsonization) pluripotent divides into two groups myeloid and lymphoid progenitors mhc II on apc, mhc I on all cells (all 6 types expressed on every cell 3 from each parent both classes ) lymphoid progenitors il17 nk cell huge granular; igg, killer cell receptors, different than b or t cells, reduced mhc in virus and tumor cells; cd 16, 56 large agranular little cytoplasm; membrane IG, MHC II small nucleus lots ot cytoplasm and golgi low cytoplasm; cd4, TCR, cd3 kill virus/tumor cells with perforin (antigen independent, MHC turns off) or Fas (tumor necrosis factor apoptosis) or antibody dependent present antigens to MHC II t cells, cd 19/20/21, igm/d on naive secrete ab, memory recognize antigen, generate memory Th cell, cytokine effector cells

b cell plasma cells th cells Tc

low cytoplasm, CD8 (reacts with recognize mhc 1, memory cells that destroy all MHC I everywhere), TCR, virus, cancer, and foreign cells cd3 cd45ro generated on first exposure to make following exposures more quickly

memory

vdj for variable region of heavy chain in ABs (tip of heavy; also B chain TCR) just vj in light and a chain TCR. pick d,v,j, terminal deoxyribonucleotidyl transferase (TDT also part of ALL workup and immaturity marker, once cd10 CALLA and cd20 show up mu chains in cytoplasm) inserts random bases in heavy and tcr light and heavy randomly join allelic exclusion- if first chromosome fails try the other. apoptosis if 2nd failure. if success shut off the other. one specificity per cell constant region m or d closest to vdj, initially only one used. cell has to be activated for other types. cell can have d and m with same idiotype myeloid gmcsf il3 pmn multilobed, c3b and ig receptors natural bacteria killer, adcc

eosinophil basophil/ mast macropha ge dendritic

bilobe, ige receptor large blue, i g3e receptor mononuclear, large, tissues; MHC II; ig receptors, comp recept, TLR, activated by inteferon y (t & NK)

allergies, adcc parasites release histamine, anaphylaxis eat bacteria, debris, adcc, presewnt to Th

long arms, mononuclear, langerhans in skin; mhc present to Th, cytokines II direct and initiate T cell response blood stream, kidney bean CD14 phagocytic, in tissue become marcophage, predominate in mononucleosis

monocyte

complement kills, opens vasculatrure and chemotaxis (c5a), opsonization (c3b) and clear complexes and all forms end in c3a c5a (analyphylotoxins directly) and MAC alternate pathway- spontaneous c3b finds microbe, activated by microbial surgace or components (LPS, teichoic acid), does not need ab, activated by factor d lecitin pathway- mannose on microbes activates binding protein and associated serine protease MASP classical - activated by anitbodies with igm/igg binding by c1 then c4/2 activating etc need to make c3 convertase and c5 convertase c5-8 makes hole but c9 is what kills (defiency leads to niserria) regulated by - c1 esterase inhibitor (stops classical and bradikinin); decay-accelerating factor, factor h/i (all inactivated c3/5 convertase) anaphylotoxin inhibitor (stops c3a/5a anaphylaxis) c3b helps clear immune complexes, defiency leads to complex deposition c3d also activates b cells defiency often seen in lupus and glomerulonepthritis; nesseria (c5-c9), staph and strep infections common (especially c1,2,4 classical) c1 esterase inhibitor defiency- herditary angioedema, recurrenc skin and mucosal edema DAF defiency (paroxysmal nocturanal hemoglobulinuria, by hemolysis) phagocytes bind AB, c3b/4b and opsonins; lysosome fuses and kill, sometimes release nearby to kill. macrophages need intefereon y by t cells to kill. oxy (h202, superoxide anion, hydroxyl radical, hocl, no) formed by nadh/nadph oxidase and myelperoxidase acids, lysozymes, defensin (membrane damage) proteases, lactoferrin (iron chelation) chediak higashi reduced storage and release by phagocytes staph and strep of toxins chronic granulomatous job syndrome nadph deficient in PMN, so no h202 or superoxide anion; see phagocotyzed bugs reduced pmn response, high ige catalase producing infections (staph) and fungal staph abscesses, excema;

gingers lazy leukocyte leukocyte adhesion neutrophils cant get to where theyre needed recurrent low grade infection nothing gets where it needs to bacterial and fungal infections, poor wound healing, delayed umbilical fall off staph and candida

myeloperoxids ae

low hocl, other oxy compounds,

acute inflammation- blood flow, vessel permeability, phagocytes. c3a/5a cause histamine and serotonin and prostaglandins. endothelial activates plasma enzymes, bradykinin, and fibrin. il1/6 tnf a activate acute phase response, fever response, c reactive chronic inflammation- infiltration with macrophage, lymphocytes, plasma, eosinophils, activated by cytokines from acute, fibrosis, granulomas t cells tcr associates with cd3, works like IG, each t cell expresses one type of individual tcr, only binding to MHC peptides cd4 class II of apc while cd8 on cytotoxic bind mhc 1 of nucleated cells bone marrow to thymus (outside in cortex to medulla), rearrangement of vdj segments; thymus elimiates those who self react or dont react to anything by having apcs and MHC exposure in thymus antigen dependent (memory system)- antigen specific tcr binds to peptide mhc, cd4/8 cobind, general cd28 on tcell binds to b7 co receptor is generic but allows process to continue; APC releases cytokines and detmines t cell response. additional selectins icam and integrin help maintain adhesions and bind in immune organ walls mhc1- comes from self antigens, labeled with ubiquitin, go into TAP transporter to ER binds to mhc I is shuttled to golgi then surface (viral, tumor activates killing). presented to cd8 CTL mhc II- b cells, monocytes, macrophages, dendritic. gets invariant chain in er to prevent binging in site until fusion with lyossome. goes to surface, and lymph channels to try and meet cd4 tcell. in serious damage go to spleen by hematogenous spread cross presentation- instead of fusing lysosomes, products bind mhc 1 in ER taken to lymphnode where naive tcell, macrophages b cells are activated, make effector cells (plasma, cd8, cd4 mature cells) leave lymphnode and are attracted to inflammatory site t cell activated by macrophage TCR with MHC, cd4 also binds MHC activates; costimulation is by cd 28 on tcell binding to b7 (also produed by TLR innate response) triggering cytokine production (triggers own growth IL2 most important); cd2/igcam binds integrin on apc, macrophage secretes IL1 which triggers activation. and causes ifn-y to activate macrophage ctla4/cd152 competes with cd28 to bind b7 on apc and is downregulation start as CD4 th0 and activated by dc il12, ifn-y gives us th1.- fighting intracellular

il2- t b cell growth; ctl activity ifn y- , less th2 macrophages, IfG reinforce local, promotoes inflmmatory responses, cell mediated; type IV rxn; good for viral, fungi and tumors il 4 gives us Th2- making antibodies il10- less th1 il4,5,6- b cell stimulate, igg/e/a synthesis, eosinophil activation more systemic, humoral and allergic responses (type 1), parasites and extracullular bacteria limit th1 inflammation th reg caused by il10- shoots tgfb, suppressing further response, needed to stop autoimmune (of th1) il 6 and tgfb gives th17 il17- activate pmn, promote infllmation and autoimmune leprosy- th1 tuberculoid eradicate by granuloma. in lepromatoud th2 happens, antibodies dont help and mycobacteria proliferate inside macrophages as th1 is shut down. serious disfiguring disease occurs superantigens- cross link bchain on tcr to achain on MHC. this activates t cells even thoughnothing is in MHC cleft. polyclonal activation and ifn-y. macrophages go nuts releasing all cytokines. staph enterotoxins, toxis shock syndrome toxin, strep pyrogenic exotoxins

CTL activated in lymphnode by dc cross presenting on MHC I, bind viral, tumor, transplanted cells with perforins, granzymes (serine proteases which trigger caspases) cytokines triggering apoptosis (TNFa), or FAS actiavtes apoptosis; and il2 by helper MHCI with nonself will bind a tcr (tumor, virus, intracellular bacteria) th1 activate with il2, and inteferon will make more mhc for tcr to bind recognize and kill hyperacute rxn- allograft rejection by preexisting antibodies within hours. previous transfusions, trnasplants, pregnancies. abs trigger complement destruction of graft acute- t cells about 10 days after transplant. chronic- fibrosis, vascular injury after months/years by type iv and complement systems gvhd- graft lymphocytes attack host cells. BMT is common. host has immunosuppression usually. jaundice, diarrhea, dermatitis HLA typing with abs test, also mixed lymphocyte rcn of host t cells to donor cells high il 1/6/ tnf- blood pressure drop, shock fever, clotting and septic shock; cytokine storm cytokine storm by tsst-1 superantigen stimulation il6 by myxoma and tumors give fever, weight loss, il2 and receptor in htlv-1 leads to leukemia

hot t bone steak, 1= fever, 2 = t cells, 3 = bone marrow, 4 = ige, 5= iga il8= neutrophils tnf a- macrophages secrete. il2 receptor synthesis for helper t cells, b cells, pmns inf y- stimulates macrophages, by helper cells inteferons- activate nk cells, inhibit viral synthesis, increase mhc1/2 expression, degrade viral mrna preventing infection cyclosporine tacrolimus inhibits il2, B cells constant heavy chain determines class, constant light chain detremine k or g bone marrow has clonal deletion, b cells escape but get shut off by cloncal anergy (antigen in serum turns of igm) papain- gives an fc and two fab, pepsin gives one fc and one fab can still bridge and precipitate (cup for pepsi) immautre and pregoneitors- tdt and rag,, mature can have d igm- first, pentamer, stays in serum due to size, complement activator, held by j(joining) chain and disulfide bonds, great at trapping free ag and activating complement (igg other) found in rheumatoid factor (igm against fc of igg) cytokines by th2 prompt isotype switching. where idiotype is joined to a constant region after other piece looped and excised giving new effectors, excised dna is degraded commiting you to a type

igd-activates b cells, igg- long half life, most common in serum, crosses placenta (receptor mediated), fixes complmenent, opsonines and chemotaxis/ adcc iga- secretions/ submucosa, il5, j chain in secretions dimer, prevents mucous adherence MALT specializes in protecting these surfaces. tonsils, peyer patches, TH2 is ready to make iga. secreted through the cell by endocytosis binding the polyig receptor; comes out with a secretory piece which prevents cleavage by mucosal enzymes. igm can cross first time with j chain ige- hypersensitivity, antparasite, binds mast cells and basophils without antigen t cells guide stimulate ig differentiation/splicing igm- can be stimulated besides t cells, by repetitive polymers (lps, dextran) doesnt produce memory b cell matures when ab binds triggering tyrosine kinase cascade, endocytosed and mhc II and B7 made, once mhcII/b7 binds with TCR/cd28 makes th2 cell; b cells bind cd40l on th2 increasing cytokine receptors and cytokine release (il4/5/6) creating plasma cell memory cell and type switching. only works with peptides in MHCII. sugars directly stimulate igm and no memory (cd40 system needed for class switching) clonal expansion- there are winners in recombination they eventually become predoinant isotype switching- t cells trigger heavy chain change from igm to igg inteferon y ; il4/5 for other class b cell proliferation creates germinal centers in follicles of lymphnodes cortex, they are clones but mutations can happen and no real repair system is in place (somatic hypermutation) higher affinity will be selected and in hyperigm- no germinal centers are made and you cant class switch because no cd40l present to activate b system

complement pathways and bacterial killings, lead to inteferon and nk cell activation, pmns and phagocytes come, creating pamp to activate macrophages and cytokines; acute phase response for il1/6/tnf leading to dc maturation to lymphnodes, lymphocytes interact with apcs in nodes/ spleen etc. mhc II activate cd4th activating naive b cells. prolifereation into th1/2 cells and activation of cd8cl. lymphocytes exit and activates macrophages and dc by inteferon y at site memory inhibits new primary response to new epitopes could be why there are influenze epidemics. I, 30 mins ige, previously exposed, mast cells and basophil linkage by ige produced by switched b cell, allows it to last forever antiparasites, toxins allergies, hay fever, anaphylaxis, asthma, wheals, shock

II 8 hour

antibody and complement/adcc; non cytotoxic

opsonization, lysis of bacteria,

hemolytic anemia, drug induced thrombocytopenia goodpastures, AR fever; receptor activation by ab myasthenia, graves

III 8 hour

soluble deposits, induce inflammation delayed th1, activation of macrophages, lymphocytes

inflmmatory rxn at site arthrus, serum sickness, and clearance as farmers lung, leukocytes are activated glomerulonephritis, sle macrophage activation, granulomas, ctl contact dermatitis (poison ivy), granuloma, graft rejection, tb test

IV days

ACID- anaph, cytotoxic, immune complex, delayed allergic rhinitis- mucus from parasympathetic cholinergic pathways. antihistamine antagonize h1 receptors mast cells- histamine, heparin, eosinophil chemotactic factor a; prostaglandin, leukotrienes; smooth muscle contraction, permeability, anticoagulant II and III ends up being the same just complex vs direct HDNB- rh negative mom with abs sensitized by rh+ baby at membran rupture, 2nd pregnancy is affected and complement hemolyzes so we give rhogam to prevent mother from forming memory cells; coombs test contact dermatitis doesnt have ige RA diabetes ms/goodpasture sle ankylosing, psoriases, ibd, reiters celiac graves b8 dr4 dr3/4 dr2 dr2/3 b27 dq2/8

aids- viral syndrome, silent phase with replicatin in lymph nodes (especially monocytes); cd4/8 ratio inverts as 4 dies and is killed and 8 activates to do the killing; gp120 binds cd4. coreceptors of cytokine sites differe in stages, macrophages then t cells cxcr4 making synctium.. Once inside reverse transcriptase is errorprone on purpose leading to progresion, drug resistance, and inability to vaccinate. ccr5 defect have apparent immunity

CD4 absence= destruction of cd4 cells, immune system destroys infected cells, synctium formation (multinucleated giant cell by fusion), toxicity to precursors, apoptosis, cd4 loss leads to ctl loss (lack of il2) and viral overflow. aadditionally b cells defunct produing lots of unspecific losers; monocytes release cytokines, tnf wasting for systemic pathology pneumocysti- silver stain, broncholavage if suspected; thrush and hairy leukoplakia (EBV) infectious enterocolitis- fever w diarrhea; crypto bartonella - bacillary angiomatosis; tumor like endothelial fatal if not treated with erythromycin cns infections, dementia (inflammatory response) leuoencephopathy (jc demyleination) peripheral- direct toxiticty, cmv (retinitis) kaposi, nonhodjkins, lymphoma, cervical,

germinal centers where t and b cells interact and activate. high endothelial venules take lymphocytes to lymph nodes, using l selctins binding to addressins on naive cells cortex is b cell area, paracortex is t cell many drug allergies due to haptens combining with larger molecules (penicillin, strep, aspirin, sulfa, succinyl) 7 days later. the conjugation to proteins is the immunogenic comples acute inflammation- skin is breached. bacteria activate macrophage releasing cytokines (chart) and il1,6 tnf a (systemic fever response) to express selectin. phagocytes attach to e-selectin (endothelium) with mucin like cam. low affinity results in rolling. il8, complement and bacterial peptides trigger g protein signal and change in integrin to bind with IG superfamily CAM and this allows for exravasation through endothelium chemotaxis- more receptors so attraction to higher concentration, release own chemoattractants to call others il 8 mast cells, platelets, neutophils, macrophages, eosinophils basophils classical/alternative pathways recruit inflammatory molecules, neutorphils activation hageman and plasmin; mast cell degranuation (vasodilation, permeability) chemoattractant, hypersensitivity, product of cascade formyl on bacterial proteins is marker or foriegn

complement c5a

leukotrien b4

phospholipids of macrophages monocytes arachidonic acid cascade lipooxygenase pathway microbes

formyl methionyl peptides

phagocytosis- pseudopodia, phagosome fuse with lysosome and excocytotis opsonization- help phago, igg and c3b receptors, staph a uses protein a to block the igg fc receptor respiratory burst- membrane nadph oxidase activated creating superoxide anion hydroxyl (fenton reactino iron) and h202 )superoxide disumutase) granules with myeloperoxidase make hocl (bleach) iNO is activated and NO can join for ONOO (peroxynitrite) all attacking membrance inside phagolysosome lysosome also has- defensins, lysozymes, lactoferrin not needing oxygen to activate problems in system occur in ghronic granulomatous disease- extracellular bacteria and fungi. nadph oxidase problems so no oxy dependent systems work. catalase negative still make the h202 for other products but catalase positive (kleb, staph, asper) destroy h202 before it can be used against them. Nitroblue tetrazolium (disease remain yellow)and neutrophil oxidative index (flow cytometry) lack of killing leads to granulomas macrophage- resisting killing, needs to be activated by inf-y from th1. if tb is hiding then release enzymes and destroy everything in area NK- granzymes/perforins, viruses and tumor cells kill cells with no mhc I, stimulated by inf and il12, cd16 marker, activated by lecitins and inhibited by mhc1 adcc- fc receptors (on nk, macrophages, monocytes, pmn) for igg trigger perforins, tnf, works with ige on worms viral strategies- RNA replicate faster than ctl starts; turn off mhc until nk kills cmv- decoy mhc 1 tricking nk and stopping ctl. adcc can still kill, decoy attract abs plasma cells die in two weeks, no more stimulus to make them, memory cells in arrest stage of cell cycle. only go to inflammed tissues tcells undergo activation induced cell death by fas, defunct il2 rceptor til antigen dissemination of memory- adenovirus gastro causes iga and military proteted against pneumonia memory cells have lfa-1 which attracts to active inflamation instead of lymph nodes passive immuno risks- abs generate ige and anaphylaxis, type III hypersensitivity (abs against their abs generate complexes and complment rxn), may not recognize iga never give live to immunocompromised (MMR rotavirus, varicella/zoster, measles, adeno, polio, small pox, yellow fever) tend to be enveloped Rubella never in preggos flu and yellow fever no in egg allergies componenet hep b and hpv igm levels have to be detected in infants to determine their status (igg from mothers), still at year only 60% and iga level very low so mucosal infections adjuvant- prolong presence, costimulation, granulomas, lymphocyte proliferation isotype (heavy chain) idiot type (variable region) allotype variation person to person in their constant regions

transplant- blood type igms react large enough to agglutinate autografat; isograft (twins; allograft (same species) xenogenic (animal) direct coombs- take baby blood add anti antibody immunoglobulin see if it agglutinates indirect- take moms blood add rh positive blood, add antiantibody immunoglobulin see if it agglutinates (better mroe specific) direct fluro ab- fluro abs are mixed with patient tissue see if fluoresce indirect fluro- look for abs, we make ag add patient serum, then add abs against abs and look for fluorescense elisa- plates covered with ag p24, check their serum and dilute, then add fluorescent abs to see if their abs are sticking western- hiv proteins seperated, add patient serum and if positive they will react to every protein, add anti antibody and every band needs to react