脊椎和无脊椎动物免疫系统课件(PPT 47页)

1、Evasion of Immunity IVertebrate and invertebrate immune systems.Dr. Jo HamiltonParasitology BS第1页，共47页。Introduction. Successful parasites have evolved strategies for survival & development in both invertebrate and vertebrate hosts.The goal of a parasite is to propagate within the host and be transmi

2、tted to the next host. The goal of the parasitised host is to cure or limit the infection.During the next three lectures we will investigate strategies used by parasites to evade the host immune response. In this session we will revisit the immune system of both vertebrates and invertebrates.第2页，共47

3、页。Objectives and learning outcomes. By the end of this session students should be:Familiar with fundamental biology of vertebrate & invertebrate immune systems. Familiar with the concept of innate and acquired immunity in vertebrates.Recognise that there is only innate immunity in invertebrates.Reco

4、gnise the key players in both vertebrate and invertebrate immune systems.第3页，共47页。Immunity.Resistance to infection is called immunity. The term “immunity” is derived from the Greek word “immunis” meaning exempt.There are two types of immunity in vertebrates.Innate immunity present from birth.Acquire

5、d immunity result of infection or vaccination.Invertebrates only posses innate immunity. 第4页，共47页。Innate immunity in vertebrates (also known as non-specific or natural immunity).Characteristics:Present from birth. Non-specific - acts on many organisms and does not show specificity. Does not become m

6、ore efficient on subsequent exposure to same organisms. 第5页，共47页。Innate immunity in vertebrates.Non-specific Host Defences include:Mechanical / physical barriers skin, mucosal surfaces.Prevention of stasis peristalsis, flow of urine, upward movement of secretions in bronchial tree, coughing, vomitin

7、g. 第6页，共47页。Innate immunity in vertebrates.Chemical defences - Low pH of stomach contents, secretion of fatty acids in the skin.Biological defence complement, lysozyme, interferons, antimicrobial peptides, kinins, adhesion molecules, hormones, lactoferrin.Cellular defence - e.g. phagocytes.第7页，共47页。

8、Innate immunity in vertebrates.Some of the key players in innate immunity to consider in more detail are:Complement.Opsonization.Phagocytosis & the oxidative burst.Inflammation.第8页，共47页。Innate immunity in vertebrates complement.Complement. - complex of 17 proteins present in normal serum. 2 pathways

9、 classical & alternative. 第9页，共47页。Innate immunity in vertebrates classical complement pathway.Antigen-antibody complex forms, constant region of antibody changes shape. Activates C1, acquires esterase activity.Activated C1 activates C2 & C4 which activates C3, etc. Eventually, C8 & C9 activated for

10、ming membrane attack complex (MAC) - pores in target cell membrane - lysis. 第10页，共47页。Innate immunity in vertebrates - alternative complement pathway.Alternative pathway - C3 can interact directly with certain chemicals (teichoic acids, LPS) found in bacterial cell walls and activate the alternative

11、 pathway. 第11页，共47页。Innate immunity in vertebrates opsonization.Opsonization - process of coating micro-organisms with plasma proteins to make them more easily phagocytosable. It is stimulated by complement bound to antibody-antigen targets. Opsonization promotes adhesion between opsonized cell & ma

12、crophages. The opsonin binds to receptors on phagocyte membrane. Opsonization and phagocytosis are more efficient in immune individuals. 第12页，共47页。Innate immunity in vertebrates cellular defence.Cellular defence involves:Granulocytes (also known as the polymorphonuclear leukocytes e.g. eosinophils,

13、basophils etc). The reticulo endothelial system (e.g. macrophages, Kupffer cells of the liver and natural killer (NK cells). 第13页，共47页。Innate immunity in vertebrates White blood cells.Role of white blood cells in cellular defence.White blood cells (WBCs) are major components of immune system. Blood

14、smear showing different blood cell types. 第14页，共47页。Innate immunity in vertebrates phagocytosis.Certain WBCs highly mobile & carry out phagocytosis.WBCs chemotactically attracted to foci of disease or tissue damage. Phagocytosis begins with engulfment of particulate matter (e.g. bacteria, clumps of

15、virions, cell debris, etc.) into a phagosome. 第15页，共47页。Innate immunity in vertebrates phagocytosis contd.The phagosome fuses with lysosomes to form the phagolysosome. Lysosomes contain number of enzymes including acid hydrolases, lysozyme, neutral proteases, myeloperoxidase, lactoferrin, & phosphol

16、ipase A. These enzymes can degrade biomolecules. Human macrophage engulfing the fungus Candida albicans.第16页，共47页。Innate immunity in vertebrates oxidative burst.Once engulfed, the white cell must kill the organisms by some means such as the “respiratory (or oxidative) burst.Many pathogens and parasi

17、tes 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.第17页，共47页。Innate immunity in vertebrates inflammation .Inflammation - (or inflammatory response) mechanism by which phagocytes a

18、nd complement are recruited to site of tissue invasion. Non-specific reaction to tissue damage. Cell damage initiates a complex series of steps leading to inflammation.第18页，共47页。Innate immunity in vertebrates inflammation.Inflammation involves: Vasodilation - swelling. adhesion of leukocytes to endo

19、thelial 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 / injury by release of substances from micro-organisms or chemical mediators released fro

20、m cells in tissues, e.g. histamine from mast cells. Once organisms are destroyed inflammation settles down (resolves). 第19页，共47页。Acquired immunity (only in vertebrates).Also known as adaptive immunity / specific immunity.Develops as response to an infection.Called adaptive as immune system adapts it

21、self to previously unseen molecules. The induction of immunity by infection, or with a vaccine, is called active immunity. 第20页，共47页。Acquired immunity.Induction of immunity by infection, or with vaccine, called active immunity. Non-immune individual can be made immune by transferring serum or lympho

22、cytes from immune individual. This is know as passive immunity and demonstrates that serum constituents (antibodies) and lymphocytes are involved in immunity. 第21页，共47页。Acquired immunity.Characteristics of acquired immunity:Immunological recognition. Discrimination between self and non-self. Immunol

23、ogical specificity. Immunological memory. 第22页，共47页。Acquired immunity.Immunity mediated by immune system, responds to infection by mounting immune response. An immune response must: Recognise a micro-organism or parasite as foreign (non-self) as distinct from self. Respond to the presence of a forei

24、gn organism by production of specific antibodies and specific lymphocytes. Mediate the elimination of such organisms. 第23页，共47页。Acquired immunity.There are two types of acquired immunity. Cell-mediated immunity - this is immunity mediated by T-cells. T cells secrete lymphokines (e.g. interleukin-2)

25、which interact with other cell types, and either activate or repress an immune response. Humoral immunity - this is blood-specific immunity mediated by antibodies (Abs).第24页，共47页。Acquired immunity cell mediated immunity.第25页，共47页。Acquired immunity cell mediated immunity.Key cells involved in acquire

26、d immunity response are lymphocytes.Two types lymphocyte develop in bone marrow from common precursor. Each different response mediated by different sets of lymphocytes. Following invasion by a foreign organism, lymphocytes proliferate (i.e. divide) and differentiate (i.e. specialize). 第26页，共47页。Acq

27、uired immunity cell mediated immunity, B lymphocytes.B lymphocytes (B cells):Found fixed in the lymph nodes, liver and spleen. They are bone marrow-derived lymphocytes, mature in Peyers Patches of the pancreas. During maturation, antigen-specified antibody is displayed on the cell surface. If the ce

28、ll is activated by an antigen, the B cells excrete antibody. 第27页，共47页。Acquired immunity cell mediated immunity, T lymphocytes.T lymphocytes (T-cells):Found in lymph nodes, liver, spleen, also freely circulating in the blood. Matures in thymus. They have cell surface receptor of a pre-determined spe

29、cificity. These cells regulate cellular immunity. Two main T cell types: helper T cells (Th cells have the CD4+ receptor) & suppressor / cytotoxic T cells (Tc cells display the CD8+ receptor). 第28页，共47页。Acquired immunity cell mediated immunity, macrophages.A third important cell type are macrophages

30、. These cells play essential role in processing & presenting immunogens to lymphocytes.Also important effector cells (i.e. they carry out destruction of foreign material e.g. phagocytosis). Carry receptors for antibody molecules which allows them to attach to antibody-antigen complexes before phagoc

31、ytosing them. 第29页，共47页。Acquired immunity generation of immune response. In order for an immune response to be activated, an object must first be recognised as foreign. An immunogen is any molecule that stimulates an immune response. In general, proteins are the best immunogens, followed by carbohyd

32、rates and then nucleic acids. Lipids are very poor. An antigen is any molecule that is capable of generating an antibody response (antigen = antibody generating).第30页，共47页。Acquired immunity generation of immune response. Upon an initial infection, it takes about 4-7 days to generate an immune respon

33、se.After seven days get primary immune response. Initially, IgM produced but B cells differentiate further into IgG producing cells. After about three weeks primary immune response turned off. During this initial period Ab producing cells and memory B cells are formed. When same agent encountered by

34、 host again, body recognises it, stimulates the memory cells to secrete Abs. This is called the secondary immune response. Memory can last for few weeks or can last for years. 第31页，共47页。Acquired immunity generation of immune response. There are three types of effector immune response. Humoral (blood

35、) - antibody response mediated by B cells & regulated by T cells. Cell-mediated (cellular) - delayed-type hypersensitivity and cytotoxicity mediated by CD4+ and CD8+ T cells. Tolerance - non-specific response mediated by T cells. Healthy individuals tolerant to own tissues, sometimes immune response

36、 fails to recognise self giving rise to autoimmune diseases or transplant rejection in transplantation surgery. 第32页，共47页。Humoral immunity antibodies. Large glycoproteins released by B cells. Antibodies (Abs) specifically interact with antigens. Body can produce millions of antibody specificities ge

37、netically as the B cells mature. There are five classes of Ab: IgM largest & first Ab to be made antibody response. IgM can mediate neutralisation, fix complement, agglutinate and immobilise antigens. IgG - this is the main serum Ab. This is synthesized during the secondary immune response. Able to

38、do all Ab mediated functions. 第33页，共47页。Humoral immunity antibodies contd. IgA - is mucosal antibody. Sometimes called secretory Ab as mucosal cells secrete them when mucosal pathogens begin to establish colonies. IgD - is receptor antibody found on the surface of immunocompetent cells. This functio

39、ns in the afferent response. IgE - binds to the surface of mast cells causing degranulation of the cell and release of histamine into circulation. This ab is involved with allergies. 第34页，共47页。Humoral immunity antibodies contd. Abs are important for us in five ways.neutralisation - an Ab molecule co

40、vers up sites on toxic molecule or virus. opsonization - this is Ab-mediated phagocytosis. Macrophages have antibody receptor sites on surface, able to bind to antigen-antibody complexes before phagocytosing them. complement fixation - a complicated system that reacts to antigen/antibody complexes (

41、see also complement notes in innate immunity).第35页，共47页。Humoral immunity antibodies contd. agglutination/precipitation - Abs cross-link antigens into large complexes making them easier to phagocytose & destroy.immobilization - Abs bind to flagella etc. & prevent organisms from escaping macrophage de

42、ath. 第36页，共47页。Cellular immunity Th and Tc cells.Often directed against intracellular parasites & cancer. Infected cells killed by macrophages under directions of CD4+ Th cells. Cytotoxic T cells (CD8+ directed) also participate by releasing toxic components which kill the cell.Cells involved in cel

43、lular 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 Major Histocompatibility Complex antigens (MHC antigens). All

44、 our cells display these MHC antigens in specific patterns on the cell surface. 第37页，共47页。Cellular immunity Major Histocompatibility Complex.Macrophages must process the antigen & then display pieces of the antigen on its cell surface. They then present this antigen to T cells, which recognize the a

45、ntigen 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. When macrophages display antigen plus Class I MHC they stimulate CD8+ cells (i.e. they make cytotoxic T cells) when they

46、 displayed antigen plus Class II MHC they stimulate CD4+ cells (i.e. helper T cells). 第38页，共47页。Invertebrate immune system.Comparison of vertebrate & invertebrate immunity.VertebratesInvertebratesInnate ImmunityInnate Immunity(e.g. antimicrobial peptides)(e.g. antimicrobial peptides) Acquired immuni

47、ty-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. Vertebrat

48、e immune system both innate and acquired components. 第39页，共47页。Invertebrate immunity.The invertebrate immune system is comprised of two branches:The humoral response (N.B. this is not antibody mediated) is concerned with soluble components such as antimicrobial peptides (AMPs), agglutinins (lectins)

49、 and macrokines (these are similar to cytokines).The cellular response includes phagocytosis (haemocytes), encapsulation and nodulation.第40页，共47页。Invertebrate immunity humoral response.Antimicrobial peptides. Wide range including defensins, cecropins, andropins, ceratotoxins, drosomycin & penaeidins

50、 etc. Their action leads to lysis of invading organism e.g. bacteria & protozoa.Macrokines. There is growing evidence of these cytokine-like molecules. Haemolymph preparations have been shown to stimulate vertebrate immune effector cells (e.g. macrophages).Agglutinins (lectins). Agglutinate invading organisms making them easier to phagocytose.第41页，共47页。Invertebrate immunity cellular response.Phagocytosis - Haemocytes (amoebocytes) front line of invertebrate cellular. Foreign (non-self) invaders are taken into a pha