Innate Immunity By Dr Obied

Immunology Lecture 4 Innate immunity Not specific –has no memory – it is the first line of defense

Lecture objective Definition and characteristic important of innate immunity * The main component of innate immunity and it function *

(Component of innate immunity (4 External and internal body surface * Phagocytes * Soluble (humeral) mediators of innate immunity * Extracellular killing *

(External body surface (skin It is physical barrier prevents entry of pathogen(if you have patient with 70% Burn in addition to electrolyte imbalance, the main cause of death severe infection….. bacteremia and these because the intakes skin is non intake the physical barrier is non there and pathogen work freely in around) so, . the main function of skin as Physical barrier -1 Has secretion like sweet which contain lactic acid and fatty -2 .acid which effect ph make it unpleasant for pathogen

(Internal body surface (mucosal surface .has mucous prevent the attachment of pathogen to surfaces`-1 There is rapid passage of air.so, sneezing- coughing and -2 .movement of cilia all of these remove ( tard ) the microb :Washing action -3 Tear = eye washing Saliva = washing the mucous membrane of .mouth Urine = washing the mucous membrane of .urinary tract

.So, all these are washing action in certain fluid in your body There is certain enzyme and acid for bactericidia ( cidia -4 .means kill Bactericidia = kill bacteria × Bacteristatic = stop the growth of bacteria it does not . Kill the bacteria. Some antibiotic is the bacteria static There is certain substance in your body kill the bacteria. Starting from the H C L which in stomach – other enzyme lactoperoxidase in milk – lysozyme in tears .nasal secretion and saliva

:Concept of normal flora or commensals It is the bacteria present normally in certain location in your body. Their jobs to prevent pathogenic bacteria from occupy their surface. .It found in surface of skin and intestine NOTE: there is normal flora where they are. But if you take some bacteria from .intestine and put it in peritoneum you will end with peritonitis .So, the concept of flora is in it location

: Diagram will summarize -Skin-secretion

.phagocytes: we talked about it -2

Humeral (soluble) innate immunity…*complement -3 interferon* acute phase proteins* So, soluble mediator for acquired immunity = antibody

:Complement Has part of innate immunity and part of acquired immunity .Group of 20 serum proteins serum _ .These are pro- enzyme _ Pro-enzyme: enzyme which not active yet Activation of one of are proenzyme will activate the one on the line ‫عبارة عن سلسة من النزيمات البدائية‬ The activation of one proenzyme will activate the next one on line and the next one on line, cascade like the blood clotting system. At the center of all path way which all pathway will pass on it is C3 the most important and the most central. .It concentration in plasma 1.3 mg lml and it is activated by two pathway (Alternative pathway (part of innate immunity -1 (Classical pathway (part of acquired immunity -2

microorgamism

Alternative .path

)C3)proenzyme Antibody

Classical path. pathway

)C3)enzyme If you look at these diagram it will tell you exactly what we have been taken. This is so complicated war. The most important which I want from you to know: C3 all the pathway pass on it .C3 enzyme: I do not want you to know the details just the outline

We said the alternative path way is the part of innate immunity. Which starts when we meet the microb).reverse to classical pathway which need anti body to bigan. C3 is the starting point, C3 spontaneously work with out organism without antigen without any thing. C3 convert to C3a and C3b by little bit quantity C3b = will be acted on by factor B and factor D to give C3bBb C3BbB = come bake to C3a and c3b…. these called positive feed back mechanism C3

C3a

C3b

+ + + +

C3bBb

?Is this need microbes

NO Act spontaneous. In healthy individual we do not want this happened in large quantity because these lead to and using up of protein and.lead to inflammation We must put .faramel)in these process) These (faramel)…

factor H and factor I which break down C3bBb to C3bH

By: Dr. Areej Mansour

‫بسم الله الرحمن الرحيم‬ 2nd part of the 4th lec of immuno U will find this in healthy individual 'cause he doesn't needs the complement to be activated he need every things put in brake to prevent using of energy than prevent the body from being in continuous . inflammation

:In infected individual When there is infection by microorganisms, this brake )framel) will be* . remove ‫) سوف تزال هذه الفرامل‬infection) ‫في حاله اصابه الجسم ب‬ :The brake )framel) is . Factor H and factor I The polysaccharide of the microorganisms will protect C3bBb from * .factor H This result in formation more C3bBb which work and form more of C3a .and C3b C3b and C3bBb will act on factor 5. then factor 5 when it activated will * act on factor 6. then factor 6 act on factor 7 .then factor 7 act on factor 8 . . then factor 8 act on factor 9 .and all this factor will be converted in to C5B-9 This C5B-9 will be inserted in the surface of the micro to act as osmatic* lysis of this micro : Again We start from spontaneous break down of C3 in to C3a and C3b. two .factors )factor B and D ) work on C3b and converted it in to C3bBb .In healthy individual : at this point they will brake by factor H and I In infected individual : we have bacteria which attach to factor H and . remove it This result more formation of C3bBb --gives – C3a and C3b in large .amount C3bBb and C3b will act on factor 5. then factor 5 when it activated will act on the next factor 6. and so on up to 9 All these will give us acomplex called C5B-9 which inserted in the .surface of the micro and will lead to lysis the bacteria If u think that the whole process done only to make this lysis complex * C5B-9 ,ur mistaken The things that form throughout formation of this lysis such us C3a, C3b . and C5b are important in inflammation C5B-9 - ‫) ليس فقط تكوين‬complement ) ‫يعني الغرض من تفعيل ال‬ ‫ هو الغرض النهائي لكن‬C5B-9 The things that form in the way have important = the important of C5B-9 The othe name of C5B-9 is MAC = membrane attack complex*

It's complex form from factor 5 upto 9 inserted in the membrane and attack this membrane. That's why it called MAC :Function of the complement .Not only lysis but there is other function important more than lysis opsonization done by C3 \1 chemotaxis and inflammation= chemical attraction of the cell to site of \2 .inflammation ) tissue damage) and this done by C3a and C5a .lysis done by C5B-9 MAC \3 .figure: electromicrogaphs of the MAC inserted in membrane of micro :HUMORAL INNATE IMMMUNITY acute phase proteins ; are plasma protein that increase in the \2 concentration in acute phase of the inflammation) infection), of tissue .damage, of surgery , of truma and certain tumor change .This result in activation of complement , opsonization and other function Eg. of proteins: CRP c- reactive protein ) one of the acute phase protein* . it's indicate that there is an active acute process taken place in the patient . Other protein include cerulopasmin, haptoglobin, manose binding protein .)) MBP) and serum amyloid p )SAP ?agirls ask the doctor ; what is the meaning of opsonization _ It's like eating food without salt and pepper and when u eat it with salt and .pepper the eating will be better .Opsonization= phagocytosis in present of antibody and complement the complement C3b is the factor that upto the opsonization not the * .whole complement ;In a table Some of protein increase dramaticly in very large quantitive as the CRP. Some of them increase modernity like the other proteins. So, in hospital .they depend on CRP :HUMERAL INNATE IMMUNITY ;Interferons \3 .It's antiviral agent . these are the original describe as antiviral agent Now, we are know that there are antiviral agent and they do important . function for the immune system

So,interferon are antiviral agent that secreted by viral infected cell and other cell . when it secreted the neighbor cell are protected against this . virus This interferon does not help in the infected cell ,it will help the* .neighbor cell from not getting infected with the same virus ;There are 3 type* ) interferon alpha ) IFN \1 ) interferon beta )IFN \2 ) interferon gamma )IFN \3 ;figure the figure explain what we said : that the interferon are secreted by viral infected cell and other cell and once it secreted it provide resistance against this virus NOT in the infected cell " because it is already it .infected " but in the neighbor cells ;EXTRACELLULAR KILLING \4 Q: what is the intracellular killing ? Phagocytosis Some time the phagocytosis can't take place 'cause the organism is big * .to be phagocytosis it * .it's not able to eat up the whole parasite warm of 25 cm length : So, we need other mechanism Extracellular killing : sending killing signal to make target cell dead * )..…) like bo * :And this innate immunity done by NK \1 .eosinophils \2 Boisen will lead to death of the cell by apoptosis ) progrsmed cell* . ) "death " nucleus fragmentation The signal that come out from NK and eosinophils make the target cell * . undergo apoptosis this signal "the signal send by receptor " that kill the cell = mechanism* :that lead to apoptosis "they secrete perforin " come from perforation = holes \1 make holes in the surface of the cell which allow the entry of enzyme . like gamazymes which damage the nucleus and lead to apoptosis binding of two … one of them is Fas which found on the infected or \2 tumor cell and receptor called ) Fsa L) this binding lead to apoptosis ,binding TNF to TNF receptor ) TNFR ) lead to apoptosis \3 . TNF = tumor necrosis factors Figure ? Q: what is the cytotoxic cell in innate immunity .NK and eosinophils

;NOTE .The cell that produce perforin the same cell that produce gramazymes

‫لتنسونا من صالح الدعاء‬ Zainab al-haddad