脊椎和无脊椎动物免疫系统

1、脊椎和无脊椎动物免疫系统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 transmitted to the next host. The goal of the parasitised host is to cure or limit the infection.D

2、uring 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.Objectives and learning outcomes. By the end of this session students should be:Familiar with fund

3、amental 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.Recognise the key players in both vertebrate and invertebrate immune systems.Immunity.Resistance to infe

4、ction 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.Acquired immunity result of infection or vaccination.Invertebrates only posses innate immunity. Innate immunity in v

5、ertebrates (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 more efficient on subsequent exposure to same organisms. Innate immunity in vertebrates.Non-specific Host Defences incl

6、ude:Mechanical / physical barriers skin, mucosal surfaces.Prevention of stasis peristalsis, flow of urine, upward movement of secretions in bronchial tree, coughing, vomiting. Innate immunity in vertebrates.Chemical defences - Low pH of stomach contents, secretion of fatty acids in the skin.Biologic

7、al defence complement, lysozyme, interferons, antimicrobial peptides, kinins, adhesion molecules, hormones, lactoferrin.Cellular defence - e.g. phagocytes.Innate immunity in vertebrates.Some of the key players in innate immunity to consider in more detail are:Complement.Opsonization.Phagocytosis & t

8、he oxidative burst.Inflammation.Innate immunity in vertebrates complement.Complement. - complex of 17 proteins present in normal serum. 2 pathways classical & alternative. Innate immunity in vertebrates classical complement pathway.Antigen-antibody complex forms, constant region of antibody changes

9、shape. Activates C1, acquires esterase activity.Activated C1 activates C2 & C4 which activates C3, etc. Eventually, C8 & C9 activated forming membrane attack complex (MAC) - pores in target cell membrane - lysis. Innate immunity in vertebrates - alternative complement pathway.Alternative pathway - C

10、3 can interact directly with certain chemicals (teichoic acids, LPS) found in bacterial cell walls and activate the alternative pathway. Innate immunity in vertebrates opsonization.Opsonization - process of coating micro-organisms with plasma proteins to make them more easily phagocytosable. It is s

11、timulated by complement bound to antibody-antigen targets. Opsonization promotes adhesion between opsonized cell & macrophages. The opsonin binds to receptors on phagocyte membrane. Opsonization and phagocytosis are more efficient in immune individuals. Innate immunity in vertebrates cellular defenc

12、e.Cellular defence involves:Granulocytes (also known as the polymorphonuclear leukocytes e.g. eosinophils, basophils etc). The reticulo endothelial system (e.g. macrophages, Kupffer cells of the liver and natural killer (NK cells). Innate immunity in vertebrates White blood cells.Role of white blood

13、 cells in cellular defence.White blood cells (WBCs) are major components of immune system. Blood smear showing different blood cell types. Innate immunity in vertebrates phagocytosis.Certain WBCs highly mobile & carry out phagocytosis.WBCs chemotactically attracted to foci of disease or tissue damag

14、e. Phagocytosis begins with engulfment of particulate matter (e.g. bacteria, clumps of virions, cell debris, etc.) into a phagosome. Innate immunity in vertebrates phagocytosis contd.The phagosome fuses with lysosomes to form the phagolysosome. Lysosomes contain number of enzymes including acid hydr

15、olases, lysozyme, neutral proteases, myeloperoxidase, lactoferrin, & phospholipase A. These enzymes can degrade biomolecules. Human macrophage engulfing the fungus Candida albicans.Innate immunity in vertebrates oxidative burst.Once engulfed, the white cell must kill the organisms by some means such

16、 as the “respiratory (or oxidative) burst.Many 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.Innate immunity in vertebrates inflammation .Inflammation - (

17、or inflammatory response) mechanism by which phagocytes and 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.Innate immunity in vertebrates inflammation.Inflammation involves: Vasodila

18、tion - 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 / injury by release of substances from mic

19、ro-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.Develops as response to an infection.Calle

20、d adaptive as immune system adapts itself to previously unseen molecules. The induction of immunity by infection, or with a vaccine, is called active immunity. Acquired immunity.Induction of immunity by infection, or with vaccine, called active immunity. Non-immune individual can be made immune by t

21、ransferring 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:Immunological recognition. Discrimination between self and

22、non-self. Immunological specificity. Immunological memory. 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

23、a foreign organism by production of specific antibodies and specific lymphocytes. Mediate the elimination of such organisms. 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) whi

24、ch interact with other cell types, and either activate or repress an immune response. Humoral immunity - this is blood-specific immunity mediated by antibodies (Abs).Acquired immunity cell mediated immunity.Acquired immunity cell mediated immunity.Key cells involved in acquired immunity response are

25、 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). Acquired immunity cell mediated immu

26、nity, 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 cell is activated by an antigen, th

27、e B cells excrete antibody. 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 specificity. These cells regulate cellular imm

28、unity. 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. These cells play essential role in processing & pre

29、senting 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 phagocytosing them. Acquired immunity generation of immune

30、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 carbohydrates and then nucleic acids. Lipids are very poor. An antigen

31、is any molecule that is capable 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.After seven days get primary immune response. Initially, IgM produced

32、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 host again, body recognises it, stimulates the memory cells to secrete A

33、bs. This is called the secondary immune response. Memory can last for few weeks or can last for years. Acquired immunity generation of immune response. There are three types of effector immune response. Humoral (blood) - antibody response mediated by B cells & regulated by T cells. Cell-mediated (ce

34、llular) - 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 fails to recognise self giving rise to autoimmune diseases or transplant rejection

35、 in transplantation surgery. Humoral immunity antibodies. 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: IgM largest & first Ab to be m

36、ade 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 do all Ab mediated functions. Humoral immunity antibodies contd. IgA - is mucosal antibody. S

37、ometimes 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 functions in the afferent response. IgE - binds to the surface of mast cells causing degranulation of the cell

38、 and release of histamine into circulation. This ab is involved with allergies. Humoral immunity antibodies contd. Abs are important for us in five ways.neutralisation - an Ab molecule covers up sites on toxic molecule or virus. opsonization - this is Ab-mediated phagocytosis. Macrophages have antib

39、ody 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 (see also complement notes in innate immunity).Humoral immunity antibodies contd. agglutination/precipitation - Ab

40、s cross-link antigens into large complexes making them easier to phagocytose & destroy.immobilization - Abs bind to flagella etc. & prevent organisms from escaping macrophage death. Cellular immunity Th and Tc cells.Often directed against intracellular parasites & cancer. Infected cells killed by ma

41、crophages under directions of CD4+ Th cells. Cytotoxic T cells (CD8+ directed) also participate by releasing toxic components which kill the cell.Cells 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.

42、 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 our cells display these MHC antigens in specific patterns on the cell surface. Cellular immunity Major Histocompatibility Complex.Ma

43、crophages 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 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” o

44、nly 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 displayed antigen plus Class II MHC they stimulate CD4+ cells (i.e. helper T cells). Invertebrate immune system.Comparison of vertebrate & inv

45、ertebrate immunity.VertebratesInvertebratesInnate ImmunityInnate Immunity(e.g. antimicrobial peptides)(e.g. antimicrobial peptides) Acquired immunity-Phagocytic cellsPhagocytic cells(Macrophages neutrophils etc)(Haemaocytes)-Melanization-Phenoloxidase cascadesCytokinesMacrokines Immune competent tis

46、suesImmune competent tissuesN.B. Invertebrate immune system comprises only innate system; it is non-specific and has no memory component. Vertebrate immune system both innate and acquired components. Invertebrate immunity.The invertebrate immune system is comprised of two branches:The humoral respon

47、se (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 cytokines).The cellular response includes phagocytosis (haemocytes), encapsulation and nodulation.Invertebrate immunity humor

48、al response.Antimicrobial peptides. Wide range including defensins, cecropins, andropins, ceratotoxins, drosomycin & penaeidins etc. Their action leads to lysis of invading organism e.g. bacteria & protozoa.Macrokines. There is growing evidence of these cytokine-like molecules. Haemolymph preparatio

49、ns have been shown to stimulate vertebrate immune effector cells (e.g. macrophages).Agglutinins (lectins). Agglutinate invading organisms making them easier to phagocytose.Invertebrate immunity cellular response.Phagocytosis - Haemocytes (amoebocytes) front line of invertebrate cellular. Foreign (non-self) invaders are taken into a