1、lSuccessful parasites have evolved strategies for survival&development in both invertebrate and vertebrate hosts.lThe goal of a parasite is to propagate within the host and be transmitted to the next host.lThe goal of the parasitised host is to cure or limit the infection.lDuring the next three lect
2、ures we will investigate strategies used by parasites to evade the host immune response.lIn this session we will revisit the immune system of both vertebrates and invertebrates.lBy the end of this session students should be:lFamiliar with fundamental biology of vertebrate&invertebrate immune systems
3、.lFamiliar with the concept of innate and acquired immunity in vertebrates.lRecognise that there is only innate immunity in invertebrates.lRecognise the key players in both vertebrate and invertebrate immune systems.lResistance to infection is called immunity.lThe term“immunity”is derived from the G
4、reek word“immunis”meaning exempt.lThere are two types of immunity in vertebrates.Innate immunity present from birth.Acquired immunity result of infection or vaccination.lInvertebrates only posses innate immunity.Characteristics:lPresent from birth.lNon-specific-acts on many organisms and does not sh
5、ow specificity.lDoes not become more efficient on subsequent exposure to same organisms.Non-specific Host Defences include:lMechanical/physical barriers skin,mucosal surfaces.lPrevention of stasis peristalsis,flow of urine,upward movement of secretions in bronchial tree,coughing,vomiting.lChemical d
6、efences-Low pH of stomach contents,secretion of fatty acids in the skin.lBiological defence complement,lysozyme,interferons,antimicrobial peptides,kinins,adhesion molecules,hormones,lactoferrin.lCellular defence-e.g.phagocytes.Some of the key players in innate immunity to consider in more detail are
7、:lComplement.lOpsonization.lPhagocytosis&the oxidative burst.lInflammation.lComplement.-complex of 17 proteins present in normal serum.l2 pathways classical&alternative.lAntigen-antibody complex forms,constant region of antibody changes shape.lActivates C1,acquires esterase activity.lActivated C1 ac
8、tivates C2&C4 which activates C3,etc.lEventually,C8&C9 activated forming membrane attack complex(MAC)-pores in target cell membrane-lysis.lAlternative pathway-C3 can interact directly with certain chemicals(teichoic acids,LPS)found in bacterial cell walls and activate the alternative pathway.lOpsoni
9、zation-process of coating micro-organisms with plasma proteins to make them more easily phagocytosable.lIt is stimulated by complement bound to antibody-antigen targets.lOpsonization promotes adhesion between opsonized cell¯ophages.The opsonin binds to receptors on phagocyte membrane.lOpsonizati
10、on and phagocytosis are more efficient in immune individuals.Cellular defence involves:lGranulocytes(also known as the polymorphonuclear leukocytes e.g.eosinophils,basophils etc).lThe reticulo endothelial system(e.g.macrophages,Kupffer cells of the liver and natural killer(NK cells).Role of white bl
11、ood cells in cellular defence.lWhite blood cells(WBCs)are major components of immune system.Blood smear showing different blood cell types.lCertain WBCs highly mobile&carry out phagocytosis.lWBCs chemotactically attracted to foci of disease or tissue damage.lPhagocytosis begins with engulfment of pa
12、rticulate matter(e.g.bacteria,clumps of virions,cell debris,etc.)into a phagosome.lThe phagosome fuses with lysosomes to form the phagolysosome.lLysosomes contain number of enzymes including acid hydrolases,lysozyme,neutral proteases,myeloperoxidase,lactoferrin,&phospholipase A.lThese enzymes can de
13、grade biomolecules.lOnce engulfed,the white cell must kill the organisms by some means such as the“respiratory(or oxidative)burst.lMany pathogens and parasites succeed because they are able to avoid phagocytosis.lInflammation-(or inflammatory response)mechanism by which phagocytes and complement are
14、 recruited to site of tissue invasion.lNon-specific reaction to tissue damage.Cell damage initiates a complex series of steps leading to inflammation.Inflammation involves:Vasodilation-swelling.adhesion of leukocytes to endothelial cells of post-capillary venule,&emigration of phagocytes into tissue
15、s.redness(blood flow).pain(prostaglandins bind to nerve receptors).heat(pyrogens).Inflammation localised to area of infection/injury by release of substances from micro-organisms or chemical mediators released from cells in tissues,e.g.histamine from mast cells.Once organisms are destroyed inflammat
16、ion settles down(resolves).Also known as adaptive immunity/specific immunity.lDevelops as response to an infection.lCalled adaptive as immune system adapts itself to previously unseen molecules.lThe induction of immunity by infection,or with a vaccine,is called active immunity.lInduction of immunity
17、 by infection,or with vaccine,called active immunity.lNon-immune individual can be made immune by transferring serum or lymphocytes from immune individual.This is know as passive immunity and demonstrates that serum constituents(antibodies)and lymphocytes are involved in immunity.Characteristics of
18、acquired immunity:lImmunological recognition.lDiscrimination between self and non-self.lImmunological specificity.lImmunological memory.Immunity mediated by immune system,responds to infection by mounting immune response.An immune response must:lRecognise a micro-organism or parasite as foreign(non-
19、self)as distinct from self.lRespond to the presence of a foreign organism by production of specific antibodies and specific lymphocytes.lMediate the elimination of such organisms.There are two types of acquired immunity.lCell-mediated immunity-this is immunity mediated by T-cells.T cells secrete lym
20、phokines(e.g.interleukin-2)which interact with other cell types,and either activate or repress an immune response.lHumoral immunity-this is blood-specific immunity mediated by antibodies(Abs).lKey cells involved in acquired immunity response are lymphocytes.lTwo types lymphocyte develop in bone marr
21、ow from common precursor.lEach different response mediated by different sets of lymphocytes.lFollowing invasion by a foreign organism,lymphocytes proliferate(i.e.divide)and differentiate(i.e.specialize).B lymphocytes(B cells):lFound fixed in the lymph nodes,liver and spleen.lThey are bone marrow-der
22、ived lymphocytes,mature in Peyers Patches of the pancreas.lDuring maturation,antigen-specified antibody is displayed on the cell surface.lIf the cell is activated by an antigen,the B cells excrete antibody.T lymphocytes (T-cells):lFound in lymph nodes,liver,spleen,also freely circulating in the bloo
23、d.lMatures in thymus.They have cell surface receptor of a pre-determined specificity.lThese cells regulate cellular immunity.lTwo main T cell types:helper T cells(Th cells have the CD4+receptor)&suppressor/cytotoxic T cells(Tc cells display the CD8+receptor).A third important cell type are macrophag
24、es.lThese cells play essential role in processing&presenting immunogens to lymphocytes.lAlso important effector cells(i.e.they carry out destruction of foreign material e.g.phagocytosis).lCarry receptors for antibody molecules which allows them to attach to antibody-antigen complexes before phagocyt
25、osing them.In order for an immune response to be activated,an object must first be recognised as foreign.lAn immunogen is any molecule that stimulates an immune response.In general,proteins are the best immunogens,followed by carbohydrates and then nucleic acids.Lipids are very poor.lAn antigen is a
26、ny molecule that is capable of generating an antibody response(antigen=antibody generating).Upon an initial infection,it takes about 4-7 days to generate an immune response.lAfter seven days get primary immune response.Initially,IgM produced but B cells differentiate further into IgG producing cells
27、.After about three weeks primary immune response turned off.lDuring this initial period Ab producing cells and memory B cells are formed.lWhen same agent encountered by host again,body recognises it,stimulates the memory cells to secrete Abs.This is called the secondary immune response.lMemory can l
28、ast for few weeks or can last for years.There are three types of effector immune response.lHumoral(blood)-antibody response mediated by B cells®ulated by T cells.lCell-mediated(cellular)-delayed-type hypersensitivity and cytotoxicity mediated by CD4+and CD8+T cells.lTolerance-non-specific respons
29、e mediated by T cells.Healthy individuals tolerant to own tissues,sometimes immune response fails to recognise self giving rise to autoimmune diseases or transplant rejection in transplantation surgery.Large glycoproteins released by B cells.Antibodies(Abs)specifically interact with antigens.Body ca
30、n produce millions of antibody specificities genetically as the B cells mature.There are five classes of Ab:lIgM largest&first Ab to be made antibody response.IgM can mediate neutralisation,fix complement,agglutinate and immobilise antigens.lIgG-this is the main serum Ab.This is synthesized during t
31、he secondary immune response.Able to do all Ab mediated functions.lIgA-is mucosal antibody.Sometimes called secretory Ab as mucosal cells secrete them when mucosal pathogens begin to establish colonies.lIgD-is receptor antibody found on the surface of immunocompetent cells.This functions in the affe
32、rent response.lIgE-binds to the surface of mast cells causing degranulation of the cell and release of histamine into circulation.This ab is involved with allergies.Abs are important for us in five ways.lneutralisation-an Ab molecule covers up sites on toxic molecule or virus.lopsonization-this is A
33、b-mediated phagocytosis.Macrophages have antibody receptor sites on surface,able to bind to antigen-antibody complexes before phagocytosing them.lcomplement fixation-a complicated system that reacts to antigen/antibody complexes(see also complement notes in innate immunity).lagglutination/precipitat
34、ion-Abs cross-link antigens into large complexes making them easier to phagocytose&destroy.limmobilization-Abs bind to flagella etc.&prevent organisms from escaping macrophage death.lOften directed against intracellular parasites&cancer.Infected cells killed by macrophages under directions of CD4+Th
35、 cells.Cytotoxic T cells(CD8+directed)also participate by releasing toxic components which kill the cell.lCells involved in cellular immunity must be able to recognise self,especially as many of their targets are cells infected by agents that are within them.This means killing ones own cells in an e
36、ffort to rid the infection.Self recognition is mediated by the Major Histocompatibility Complex antigens(MHC antigens).All our cells display these MHC antigens in specific patterns on the cell surface.lMacrophages must process the antigen&then display pieces of the antigen on its cell surface.They t
37、hen present this antigen to T cells,which recognize the antigen as being foreign as well as recognising the MHC antigens.If the T cell“sees”both antigen and MHC it becomes activated:if it“sees”only the MHC antigen nothing happens.lWhen macrophages display antigen plus Class I MHC they stimulate CD8+
38、cells(i.e.they make cytotoxic T cells)when they displayed antigen plus Class II MHC they stimulate CD4+cells(i.e.helper T cells).Comparison of vertebrate&invertebrate immunity.VertebratesInvertebratesInnate ImmunityInnate Immunity(e.g.antimicrobial peptides)(e.g.antimicrobial peptides)Acquired immun
39、ity-Phagocytic cellsPhagocytic cells(Macrophages neutrophils etc)(Haemaocytes)-Melanization-Phenoloxidase cascadesCytokinesMacrokines Immune competent tissuesImmune competent tissuesN.B.Invertebrate immune system comprises only innate system;it is non-specific and has no memory component.Vertebrate
40、immune system both innate and acquired components.The invertebrate immune system is comprised of two branches:lThe humoral response(N.B.this is not antibody mediated)is concerned with soluble components such as antimicrobial peptides(AMPs),agglutinins(lectins)and macrokines(these are similar to cyto
41、kines).lThe cellular response includes phagocytosis(haemocytes),encapsulation and nodulation.lAntimicrobial peptides.Wide range including defensins,cecropins,andropins,ceratotoxins,drosomycin&penaeidins etc.Their action leads to lysis of invading organism e.g.bacteria&protozoa.lMacrokines.There is g
42、rowing evidence of these cytokine-like molecules.Haemolymph preparations have been shown to stimulate vertebrate immune effector cells(e.g.macrophages).lAgglutinins(lectins).Agglutinate invading organisms making them easier to phagocytose.lPhagocytosis-Haemocytes(amoebocytes)front line of invertebra
43、te cellular.Foreign(non-self)invaders are taken into a phagocytotic vacuole where proteolytic enzymes&free oxygen radicals destroy the pathogen(in a similar way to vertebrate macrophages).Bacteria and yeast(10microns)can be phagocytosed.lEncapsulation-If invader too large for phagocytosis(e.g.the eg
44、g of a parasitic wasp),encapsulation might ensue.Invader is compacted under layer of haemocytes.This is accompanied by melanization.The melanized capsule adheres to host tissues but is walled off from the host.Phenoloxidases mediate melanization reaction but also have other tasks including wound hea
45、ling,cuticle pigmentation&sclerotisation.lNodulation-Microaggregates of haemocytes&bacteria encased in haemocytes are melanised&removed from circulation.lPhagocytosis,encapsulation and nodulation mediated by eicosanoids(prostaglandins,leukotrienes).lIn addition to the cellular&humoral defences,inver
46、tebrates also have mechanical or physical defences.lThese include the cuticle,epithelia and in the case of insects the peritrophic membrane.By the end of this session you should be:lFamiliar with fundamental biology of vertebrate&invertebrate immune systems.lFamiliar with the concept of innate and a
47、cquired immunity in vertebrates.lRecoginise that invertebrates have only innate immune system.lRecognise the key players in both vertebrate and invertebrate immune systems.We will:lDescribe immunity to particular parasites.lExplore the strategies that parasites use to evade the hosts immune system.谢谢！
