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1、Evasion of Immunity IVertebrate and invertebrate immune systems.Dr.Jo HamiltonParasitology BSIntroduction.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
2、 next host.lThe goal of the parasitised host is to cure or limit the infection.lDuring the next three lectures 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.Objectives and le
3、arning outcomes.lBy the end of this session students should be:lFamiliar with fundamental biology of vertebrate&invertebrate immune systems.lFamiliar with the concept of innate and acquired immunity in vertebrates.lRecognise that there is only innate immunity in invertebrates.lRecognise the key play
4、ers in both vertebrate and invertebrate immune systems.Immunity.lResistance to infection is called immunity.lThe term“immunity”is derived from the Greek word“immunis”meaning exempt.lThere are two types of immunity in vertebrates.Innate immunity present from birth.Acquired immunity result of infectio
5、n or vaccination.lInvertebrates only posses innate immunity.Innate immunity in vertebrates(also(also known as non-specific or natural immunity).known as non-specific or natural immunity).Characteristics:lPresent from birth.lNon-specific-acts on many organisms and does not show specificity.lDoes not
6、become more efficient on subsequent exposure to same organisms.Innate immunity in vertebrates.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.Innat
7、e immunity in vertebrates.lChemical defences-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.Innate immunity in vertebrates.Some
8、of the key players in innate immunity to consider in more detail are:lComplement.lOpsonization.lPhagocytosis&the oxidative burst.lInflammation.Innate immunity in vertebrates complement.lComplement.-complex of 17 proteins present in normal serum.l2 pathways classical&alternative.Innate immunity in ve
9、rtebrates classical complement pathway.lAntigen-antibody complex forms,constant region of antibody changes shape.lActivates C1,acquires esterase activity.lActivated C1 activates C2&C4 which activates C3,etc.lEventually,C8&C9 activated forming membrane attack complex(MAC)-pores in target cell membran
10、e-lysis.Innate immunity in vertebrates-alternative complement pathway.lAlternative pathway-C3 can interact directly with certain chemicals(teichoic acids,LPS)found in bacterial cell walls and activate the alternative pathway.Innate immunity in vertebrates opsonization.lOpsonization-process of coatin
11、g 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.lOpsonization and phagocytosis are
12、more efficient in immune individuals.Innate immunity in vertebrates cellular defence.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
13、 cells).Innate immunity in vertebrates White blood cells.Role of white blood cells in cellular defence.lWhite blood cells(WBCs)are major components of immune system.Blood smear showing different blood cell types.Innate immunity in vertebrates phagocytosis.lCertain WBCs highly mobile&carry out phagoc
14、ytosis.lWBCs chemotactically attracted to foci of disease or tissue damage.lPhagocytosis begins with engulfment of particulate matter(e.g.bacteria,clumps of virions,cell debris,etc.)into a phagosome.Innate immunity in vertebrates phagocytosis contd.lThe phagosome fuses with lysosomes to form the pha
15、golysosome.lLysosomes contain number of enzymes including acid hydrolases,lysozyme,neutral proteases,myeloperoxidase,lactoferrin,&phospholipase A.lThese enzymes can degrade biomolecules.Human macrophage engulfing the fungus Candida albicans.Innate immunity in vertebrates oxidative burst.lOnce engulf
16、ed,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.NeutrophilYeast Human neutrophil kills yeast cell using oxidative burst.The dye shows the extent of the reactions.Innat
17、e immunity in vertebrates inflammation.lInflammation-(or inflammatory response)mechanism by which phagocytes and complement are recruited to site of tissue invasion.lNon-specific reaction to tissue damage.Cell damage initiates a complex series of steps leading to inflammation.Innate immunity in vert
18、ebrates inflammation.Inflammation involves:Vasodilation-swelling.adhesion of leukocytes to endothelial cells of post-capillary venule,&emigration of phagocytes into tissues.redness(blood flow).pain(prostaglandins bind to nerve receptors).heat(pyrogens).Inflammation localised to area of infection/inj
19、ury 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 inflammation settles down(resolves).Acquired immunity(only in vertebrates).Also known as adaptive immunity/specific immunity.lDevelops as
20、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.Acquired immunity.lInduction of immunity by infection,or with vaccine,called active immunity.lNon-immune individ
21、ual 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.Acquired immunity.Characteristics of acquired immunity:lImmunological recognition.lDiscrimi
22、nation between self and non-self.lImmunological specificity.lImmunological memory.Acquired immunity.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-self)as distinct from self.lRespond
23、to the presence of a foreign organism by production of specific antibodies and specific lymphocytes.lMediate the elimination of such organisms.Acquired immunity.There are two types of acquired immunity.lCell-mediated immunity-this is immunity mediated by T-cells.T cells secrete lymphokines(e.g.inter
24、leukin-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).Acquired immunity cell mediated immunity.Acquired immunity cell mediated immunity.lKey cells involved in acquired immunity res
25、ponse are lymphocytes.lTwo types lymphocyte develop in bone marrow 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).Acquired immunity cell mediated i
26、mmunity,B lymphocytes.B lymphocytes(B cells):lFound fixed in the lymph nodes,liver and spleen.lThey are bone marrow-derived 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
27、B cells excrete antibody.Acquired immunity cell mediated immunity,T lymphocytes.T lymphocytes (T-cells):lFound in lymph nodes,liver,spleen,also freely circulating in the blood.lMatures in thymus.They have cell surface receptor of a pre-determined specificity.lThese cells regulate cellular immunity.l
28、Two main T cell types:helper T cells(Th cells have the CD4+receptor)&suppressor/cytotoxic T cells(Tc cells display the CD8+receptor).Acquired immunity cell mediated immunity,macrophages.A third important cell type are macrophages.lThese cells play essential role in processing&presenting immunogens t
29、o 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 phagocytosing them.Acquired immunity generation of immune response.In order for a
30、n 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 any molecule that is capab
31、le of generating an antibody response(antigen=antibody generating).Acquired immunity generation of immune response.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 i
32、nto IgG producing cells.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
33、 response.lMemory can last for few weeks or can last for years.Acquired immunity generation of immune response.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 cytot
34、oxicity mediated by CD4+and CD8+T cells.lTolerance-non-specific response 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.Humoral immunity antibodies
35、.Large glycoproteins released by B cells.Antibodies(Abs)specifically interact with antigens.Body can 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 complem
36、ent,agglutinate and immobilise antigens.lIgG-this is the main serum Ab.This is synthesized during the secondary immune response.Able to do all Ab mediated functions.Humoral immunity antibodies contd.lIgA-is mucosal antibody.Sometimes called secretory Ab as mucosal cells secrete them when mucosal pat
37、hogens begin to establish colonies.lIgD-is receptor antibody found on the surface of immunocompetent cells.This functions in the afferent 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.Hu
38、moral immunity antibodies contd.Abs are important for us in five ways.lneutralisation-an Ab molecule covers up sites on toxic molecule or virus.lopsonization-this is Ab-mediated phagocytosis.Macrophages have antibody receptor sites on surface,able to bind to antigen-antibody complexes before phagocy
39、tosing them.lcomplement fixation-a complicated system that reacts to antigen/antibody complexes(see also complement notes in innate immunity).Humoral immunity antibodies contd.lagglutination/precipitation-Abs cross-link antigens into large complexes making them easier to phagocytose&destroy.limmobil
40、ization-Abs bind to flagella etc.&prevent organisms from escaping macrophage death.Cellular immunity Th and Tc cells.lOften directed against intracellular parasites&cancer.Infected cells killed by macrophages under directions of CD4+Th cells.Cytotoxic T cells(CD8+directed)also participate by releasi
41、ng 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 effort to rid the infection.Self recognition is mediated by the Ma
42、jor Histocompatibility Complex antigens(MHC antigens).All our cells display these MHC antigens in specific patterns on the cell surface.Cellular immunity Major Histocompatibility Complex.lMacrophages must process the antigen&then display pieces of the antigen on its cell surface.They then present th
43、is 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+cells(i.e.they
44、 make cytotoxic T cells)when they displayed antigen plus Class II MHC they stimulate CD4+cells(i.e.helper T cells).Invertebrate immune system.Comparison of vertebrate&invertebrate immunity.VertebratesInvertebrates Innate ImmunityInnate Immunity(e.g.antimicrobial peptides)(e.g.antimicrobial peptides)
45、Acquired immunity-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 compone
46、nt.Vertebrate immune system both innate and acquired components.Invertebrate immunity.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
47、macrokines(these are similar to cytokines).lThe cellular response includes phagocytosis(haemocytes),encapsulation and nodulation.Invertebrate immunity humoral response.lAntimicrobial peptides.Wide range including defensins,cecropins,andropins,ceratotoxins,drosomycin&penaeidins etc.Their action leads
48、 to lysis of invading organism e.g.bacteria&protozoa.lMacrokines.There is growing 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 t
49、o phagocytose.Invertebrate immunity cellular response.lPhagocytosis-Haemocytes(amoebocytes)front line of invertebrate 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 macrophage
50、s).Bacteria and yeast(10microns)can be phagocytosed.Invertebrate immunity cellular response contd.lEncapsulation-If invader too large for phagocytosis(e.g.the egg of a parasitic wasp),encapsulation might ensue.Invader is compacted under layer of haemocytes.This is accompanied by melanization.The mel