1、淋巴系統與免疫淋巴系統與免疫淋巴系統與免疫The Lymphatic System and ImmunityThe human body recognizes anything other than its own as an invader.When these foreign bodies are capable of living in the human body and are harmful, they are called pathogens.Plasma contains antibodies against cells other than its own. These an

2、tibodies are formed when the infants are about three months old. Recall when the blood types were formed.Thus, there is the lymphatic system in the body to identify and destroy foreign bodies. (by forming antibodies)But, how do they distinguish our own from the others?淋巴系統與免疫淋巴系統與免疫淋巴系統與免疫The LymphT

3、he Lymphatic System and ImmunityThe human body recognizes anything other than its own as an invader.When these foreign bodies are capable of living in the human body and are harmful, they are called pathogens.Plasma contains antibodies against cells other than its own. These antibodies are formed wh

4、en the infants are about three months old. Recall when the blood types were formed.Thus, there is the lymphatic system in the body to identify and destroy foreign bodies. (by forming antibodies)But, how do they distinguish our own from the others?When the reaction is against each specific foreign bo

5、dy, it is called immune response or immunity.2021/1/122The Lymphatic System and ImmunOrganization and Functions of the Lymphatic SystemIn the lymphatic system there are:Lymphatic fluid, lymph, that contains lymphocytesVessels that transport lymphAnd sites where large contents of lymphocytes are held

6、: lymph nodes, spleen, and thymus.Functions of the lymphatic systemThe lymph system has three major functions:1. Fluid Balance. Circulating blood release about 30 L of fluid into interstitial space each day. Of the 27 L are returned to the circulation. The remaining 3L will enter the lymphatic syste

7、m as lymph. The lymph passes through the lymphatic system and enter back to the blood vessels. In addition to water, lymph contains substances as in plasma and substances extracted from cells.2. Fat Absorption. Fats and other substances are absorbed from the digestive tract and carried through the l

8、ymphatic system.3. Defense. Immune system (lymphocytes, B-cells, T-cells)2021/1/123Organization and Functions of Lymphatic VesselsLymphatic vessels are spread out throughout the body except in the CNS (Fig 22.1)They originate from within lymphocyte producing organs and empty into the thoracic duct.

9、They contain many lymphatic nodes and nodules.Like blood vessels, they have small vessels called lymphatic capillaries which lay close to the blood capillaries.Lymph soluble fluid will be picked up through the capillaries and pushed back to larger truck.They even have valves to control the flow of l

10、ymph through very low pressure of fluid.2021/1/124Lymphatic Vessels2021/1/124Lymphatic OrgansDiffuse lymphatic tissueDispersed lymphocytes, macrophages and other cells. No clear boundaries. (Fig. 22.2)Lymphoid NodulesPacked with lymphocytes.Flexible in size depending upon the number of lymphocytesSp

11、read in loose C.T. of the digestive, respiratory and urinary systems. Larger patches in intestinal system call Peyers patches.In lymph nodes they are called follicles, there they contain a germinal center, where lymphocytes divide.Though filled with lymphocytes, lymphoid nodules could be infected: t

12、onsillitis, appendicitis.2021/1/125Lymphatic Organs2021/1/125Tonsils Large groups of lymph nodules and diffuse lymphatic tissue located in the oral cavity (Fig. 22.3)Protection against bacteria, etc. In the nose and mouth. Three types of tonsils: pharyngeal, palatine, and lingualEnlarged pharyngeal

13、tonsil is called adenoid.Lymph Nodes ( Fig. 22.1 and Fig. 22.4)Found throughout the body except in the brain.They are encapsulation of lymphocytes, macrophages and reticular cells with blood vessels1-25mm in diameter and are subdivided into two regions called, a medulla and cortex. Within the cortex

14、 germinal centers are found. This is where lymphocyte division takes place.Act as sieve and removal of 99% of antigens while reactivating T- cells and B-cells.2021/1/126Tonsils 2021/1/1262021/1/1272021/1/1272021/1/1282021/1/128The SpleenUpper and posterior part of the abdominal cavity.Largest of the

15、 lymphatic tissue, 160g. (Fig. 22.5)Contains two types of lymphatic tissue: white pulp (arterial supply) and red pulp (venous supply).The spleen detects and responds to foreign substances in the blood, destroys worn-out RBCs and acts as a blood reservoir.2021/1/129The Spleen2021/1/1292021/1/12102021

16、/1/1210Thymus GlandOn top of the heartT-cells mature hereBecomes large during the first or second year.Intrinsic size is largest at puberty and then decreases. Produces lymphocytes which then move to other lymphatic tissues.Blood-thymic barrier - reticular cells wrap around capillaries and prevent l

17、arge molecules from entering the cortex of the thymus.2021/1/1211Thymus Gland2021/1/12112021/1/12122021/1/1212ImmunityHow the human body defends itself against damage from foreign substances such as microorganisms and harmful chemical as toxins.Innate (non-specific) and adaptive (specific) immunity.

18、 These two types are distinguished by the way they respond to specific stimulations and how they memorize the events.Specificity. Innate immunity can act against bacteria in genera. (no memory)Memory. Adaptive immunity can distinguish among different kinds of bacteria and generally get more sensitiv

19、e with each new encounter.2021/1/1213Immunity2021/1/1213Innate ImmunityMechanical MechanismPhysical barriers, such as the skin and membranesChemical Mediators (Table 22.1)Molecules which contribute to develop immunity.Kill bacteria: lysozyme and sebum mucusOthers: histamine and kinins by vasodilatio

20、n; interferon production, etc.ComplementIs a group of approximately 20 proteins that makes up approximately 10% of the globulin part of serum. They are a group of proteins activated in the form of a cascade and provide protection by attacking the bacterial membrane. They attach to and form holes in

21、the membranes. The proteins can also attach to bacteria membrane and stimulate macrophages to phagocytize the bacteria.2021/1/1214Innate Immunity2021/1/12142021/1/12152021/1/1215Interferons: proteins that protect the body against viral infection and possibly cancer.Cells for Innate ImmunityReview th

22、e major functions of, neutrophils, monocytes, macrophages, basophils, mast cells, eosinophils, and natural killer cells. (Table 22.2)Inflammatory ResponseTissue damage caused by bacteria or others may induce inflammation of tissue as it releases histamine, prostaglandins, kinins, etcVasodilation att

23、racts chemotatic phagocytes and other leukocytes to the region as well as fibrinogen to form fibrin in order to localize damage.2021/1/1216Interferons: proteins that pro2021/1/12172021/1/1217Adaptive ImmunitySubstances to stimulate adaptive immunity are antigens, of which molecule weights could be a

24、s large as 10,000 or more. (produce antibodies)Haptens are small molecules capable of combining with larger molecules to stimulate adaptive immunity response.Two type of antigens: foreign antigens (allergen) are from outside of the body, and self antigens (auto-immune) are molecules of its own body.

25、For example. Allergic reaction is by foreign antigens, while autoimmune disease is from self antigens.2021/1/1218Adaptive Immunity2021/1/1218Immunity has been divided into two types: humoral (body fluid) immunity and cell mediated immunity.Specificity : recognition of antigenThe specificity is estab

26、lished because of the specific receptors located on the surface of T and B cells.Versatility: there are many antigens.And there are many different forms of lymphocytes that are made against them.Memory: the adaptive immune system has a memory. With the presence of the foreign body, lymphocytes respo

27、nding to it begin to initiate cell divisions.The presence of antigen leads to the formation of active and memory cells.The active cells respond to antigens, while the memory cells wait until the next onslaught.In this manner, the second response to the same antigen will be fast.2021/1/1219Immunity h

28、as been divided intoLymphocytes25% of circulating white cells.The majority of lymphocytes are in peripheral tissues.Types of lymphocytesWe have already seen that there are three types of lymphocytes. (Fig. 22.9)T cells: 80% of circulating lymphocytes (cell mediated immunity)B cells: 10-15% , plasma

29、cells produce antibodies (immunoglobulins) and react antigenic pathogens. ( antibody-mediated immunity)Natural killer cell: the remainder: they attack foreign cells, normal cells infected with viruses and cancer cells. They immunologically survey peripheral tissues.2021/1/1220Lymphocytes2021/1/1220C

30、ytotoxic T cells attack foreign cells or cells infected with viruses. Provide cell-mediated immunity.Helper T cells stimulate the activities of T cells and B cells.Suppressor T cells inhibit T cells and B cells.2021/1/1221Cytotoxic T cells attack forei2021/1/12222021/1/1222Origin and development of

31、lymphocytesLymphocytes travel around the entire body and have significantly long life span.80% survive up to 4 years and some to 20 years.As we have seen: lymphocytes are made in the red bone marrow and some continue to develop in the thymus. (Fig. 22.9)Pre-B cells and pre-T cells are in the red bon

32、e marrow. Pre-B cells mature in the red bone marrow into B cells. T cells mature in the thymus.2021/1/1223Origin and development of lympA positive selection process keep cells capable of immune response. Those which are incapable will die.Each group of B or T cells capable of responding to a specifi

33、c antigen is a cloneEach clone is capable of responding to a particular antigen and there are many different clones.When the clones respond to self-antigens, negative selection eliminates such clones.Most of this process occurs during prenatal development, but continues throughout life.2021/1/1224A

34、positive selection process kActivation of LymphocyteLymphocytes are made in response to a specific antigen and in a large quantity.Antigenic Determinants and Antigens ReceptorsAn antigen may have many antigenic determinants (epitopes) (Fig. 22.10) to which lymphocytes can respond.Each antigenic dete

35、rminate can activate a specific lymphocyte. Thus is possible that an antigen with many epitopes can activate many different (clones) lymphocytes.Each lymphocyte from the same clone will have the same antigen receptor.For example, a t cell receptor has a variable and constant regions. (Fig. 22.11). T

36、he variable region will have specific antigen binding sites. Thus a clone of T cells can bind a specific antigenic determinant. The other T cells within the same clone could have different antigen binding sites.The B-cell receptor is similar, but larger.2021/1/1225Activation of Lymphocyte2021/12021/

37、1/12262021/1/12262021/1/12272021/1/1227Major Histocompatibility Complex AntigensSome are direct, but most lymphocyte activation involves glycoproteins on the surface of cells called MHC molecules. All cell membranes have MHCMHC class I molecules (Fig. 22.12a)On nucleated cells, foreign or self prote

38、ins are fragmented in the nucleated cells and become antigens.They combine with MHC class I molecule in the cell and the complex are transported on the surface of the cell.At the surface of the cell membrane, the foreign antigen/MHC I complex will attract T cells and the cell will be destroyed. (cel

39、l mediated immunity), while self antigen/MHC I will not.2021/1/1228Major Histocompatibility ComplMHC class II Molecules (Fig 22.12b)The more complex and advanced lymphocytes stimulation use MHC II molecules.These molecules are found in antigen-presenting cells, such as B cells, macrophages, monocyte

40、s and dendritic cells.Antigen-presenting cells phagocytically ingest unprocessed antigens, process them and let them combine with MCH II molecules. the complex will be presented on the surface of the cells.They stimulate the other (lymphocytes) immune cells to divide and to cause the destruction of

41、the antigen.2021/1/1229MHC class II Molecules (Fig 222021/1/12302021/1/1230CostimulationIn addition to the interaction between the presented MHC II/ antigen and antigen receptor, costimulation, with cytokinins for example, is needed (Fig.22 13a)Another costimulation (Fig. 23. 13b) is achieved cross

42、linking two cells with other molecules such as CD4, B7, CD28, etc.Other example of cytokinins are listed in Table 22.4. Note interferons and interleukins.Helper T CellsEnhances more production of T and B cellsOn activation helper T cells produce a variety of cytokins that coordinated specific and no

43、nspecific defenses and stimulate cell mediated immunity. Study Fig. 22.14 and 22.15 to find how proliferation of helper T cell can be achieved.In short, with the help of cytokinins, such as interleukins, the number of helper T cells increase and thus stimulate B cells or effector T cells, which rele

44、ase perforin, produces hole in infected cells.2021/1/1231Costimulation2021/1/12312021/1/12322021/1/12322021/1/12332021/1/12332021/1/12342021/1/1234Inhibition of lymphocytesInhibition of lymphocytes proliferation against its own self-antigen is achieved by tolerance.Deletion of self-reactive lymphocy

45、tesDuring prenatal development when immature lymphocytes are exposed to the self antigens, they die. Thus, no lymphocytes which respond to the self antigen will be found as the subject matures.Preventing activation of lymphocytesBy lack of costimulationActivation of suppresser T cell.This is not wel

46、l understood. The suppressor T cells release suppressive cytokins.2021/1/1235Inhibition of lymphocytes2021/Antibody-mediated ImmunityWhen exposed to an antigen, the body activates B cells and produces antibodies. the antibodies are found in body fluids thus respond to extracellular antigens.Antibodi

47、esAntibodies are produced in B cells in response to an antigen and are found in plasma.Plasma proteins have four major components: albumin, alpha, beta and gamma globulins.Antibodies are found in gamma globulins group, thus sometimes are called gamma globulins or immunoglobulins (Ig).There are five

48、types (Table 22.5)IgG, IgM, IgA, IgE, and IgD2021/1/1236Antibody-mediated Immunity2021They all consist of four peptides. (Fig 22.16) connected with disulfide bonds and have a constant region and a antigen binding variable region.The constant region may attach to cells, such as macrophages, basophils

49、, etc.Effects of AntibodiesThe function of antibody is to find antigen and destroy it.Neutralization, agglutination and precipitation, activation of complement. Attraction of phagocytes, enhancement of phagocytes, and stimulation of inflammation.Antibodies can counteract the action of antigens in se

50、veral ways (Fig. 22.17)Upon binding with an antigen, the antibody inactivates the antigen.Inactivation may lead to co-precipitation of antigen and antibodies.Binding of two may stimulate phagocytic activities and the release of inflammation chemicals.2021/1/1237They all consist of four pepti2021/1/1

51、2382021/1/12382021/1/12392021/1/1239Antibody productionThe primary ResponseThe first encounter with an antigen, an B cell divides and differentiate leading to antibodies production (Fig. 22.18a).Antibodies, IgM and IgD, are on the surface of B cells. B cells, which are small lymphocytes, activated by antigen starts cell divisions.Some become large plasma cells, which produce antibodies and other become small memory B cells.The primary process takes 1-14 days, the antigen may cause tissue damage during this period.2021/1/1240Antibody production2021/1/1240The secondary or memory res