Chapter 10. Infection and Immunity

1. Chapter 10. Infection and Immunity • In this chapter, we will examine some of the principles of infection and immunity, the mechanisms by which pathogens cause disease, the body’s defenses against disease, and ways that infectious diseases can be prevented by immunization and controlled by drugs. That is to say, we will discuss the relationship between infection and immunity. • SOME IMPORTANT CONCEPTS: • Infection: refer to the process that the pathogens (pathogenic microbes ) invade or colonize in the host’s body. • pathogens: refer to the disease-causing microorganism

2. Disease (infectious disease): is an abnormal state resulted by an infection in which part or all of the body is not properly adjusted or incapable of performing its normal function and appear the clinical symptom. An infection may exist in the absence of detectable disease known as sub-clinical symptoms such as recessive infection or healthy vector. • Immunity: It used to refer the ability of the body’s defense to the pathogenic microbes or the infectious diseases. The update concept of immunity is recognized as both the function to recognize and eliminate the hetero-antigenic matter and the ability of maintaining the body’s stability and the balance of the functions. It may normally be helpful and harmful in abnormal case.

3. 免疫的功能 Immuno-functions 功能 正常 异常 过高 过低 免疫防护 抗传染免疫 超敏反应 免疫缺陷 自身稳定 清除衰老和死亡细胞 自身免疫 ------- 免疫监视 清除变异细胞 ------- 肿瘤发生 normal abnormal Functions high low Immuno-defense anti-infection hypersensitivety immuno- or allergy deficiency Homeostasis remove the dead or autoimmune decayed cell Surveillance remove the denatured cell tumor forming

4. Section A. Infection • Factors Responsible to Epidemic Infection Spreading • Factors that responsible to the spread of epidemic disease include: pathogens, immunity of the host’s body, and environments. • Pathogen or pathogenic microbe (including bacteria, yeasts, molds, viruses and protozoan) is one of the infectious factors and their pathogenicity as well. • The immunity or the defense of host’s body is related to the results of an infection • The environments or the conditions are important to the spread of an epidemic disease.

5. 2. Factors responsible to the invasion and infection • Factors that determine the invasion or the infection of bacteria into a host’s body are related to the • ① virulence or pathogenicity, ② the amount of pathogens and ③ the ways of transmission. • Virulence Adherence Organotropism Antiphagocytic factor Extrocellular enzymes Invasiveness toxin Diphtherin Tetanine Botulin Exotoxin endotoxin (Produced by G+) (Produced by G-)

7. Contact transmission Indirect contact transmission Droplet transmission Vehicle transmission Vectors Biological transmission • Transmission It can also be classified by the organs or tissues sensitive to the infectious microbes. • Numbers of infectious microbes: The numbers required for the infection of microbes is quite different according to the pathogens. Salmonella typhi and Vibrio cholerae＞108 , Shigella dysenteriae and Yersinia pestis < 10 ( only 7 ).

11. Section B. Defense to Infection and Pathogens From the discussion above, you can see that the results of an infection include at lest three kinds: the apparent infection (the infectious disease with clinical symptoms) including acute and chronic infection, the inapparent or recessive infection, and healthy carrier (vector). The reason why there are different results of the infection is related to both side of pathogens and the host’s body. That is to say, the host , like human has the ability to ward off disease which is called defence or resistance. The resistances can be divided into two general kinds: I.Nonspecific defence: including mechanical barriers (the first line of defence), phagocytes, antimicrobial factors, fever; and II. Specific resistance or immunity.

12. Part I: Non-specific resistance • Nonspecific resistance refers to the innate ability of defense that protect us against any pathogen, regardless of species. • Mechanical or Physical Barriers • Skin and mucous • Blood – brain barrier • Blood – placenta barrier • Chemical factors: including lysozyme, lactic acid, transferrins and sebum .

13. 3. Phagocytosis • Classification and Functions of Phagocytes • Type of Functional cells Functions Phagocyte • GranulocytesNeutrophils and • Monocytes Phagocytic against microbes during the initial phase of infection. Phagocytic against microbes as infection and against worn-out blood cells as infection subsides; also involved in cell-mediated immunity. Eosinophils Mononuclear phagocytes system: wandering / fixed macrophages

14. The Mechanism of Phagocytosis • Phagocytosis is the ingestion of a microorganism or any particulate matter by a Phagocyte. The process can be divided into four main phases: chemotaxis, adherence, ingestion and digestion. • 4. Inflammation • Inflammation refers to a defensive response triggered by the damage to the body’s tissues. It is usually characterized by four symptoms: redness, pain, heat, and swelling. The functions are: ⑴ to destroy and remove the injurious and its byproducts; ⑵ to limit the effects by confining or walling the agents; and ⑶ to repair or replace the damaged tissues.

17. 5. Antimicrobial Substances in the normal Humor • The body produces certain antimicrobial substances in addition to the chemical factors mentioned earlier. Among the most important of these are the proteins of the complement system, interferon and lysozym. • the Complement system • Complement is a defensive system consisting of Serum proteins that participate in lysis of foreign cells,inflammation, and phagocytosis. It consists of a group about 30 interacting proteins found in normal serum. The major components of the complement are designated by a numbering system ranging from C1 ~ C9 . The C1 has 3 subcomponents: C1q ,C1r ,C1s

18. Interferon • Interferon ( IFNs ) are a class of similar proteins produced by certain animal cells after stimulations, especially by the virus, performing the function to interfere the multiplication of the foreign nuclear acids. One of the interesting features of IFNs is that they are host-cell-specific but not virus-specific. It means that IFNs produced by human cells protect human cells but produce little antivirial activity for cells of other species, such as mice or chickens. How ever, the IFNs of a species are active against a number of different viruses. • There are three types of IFNs in human: α – IFNs and β – IFNs (antivirial), and γ – IFNs (cause neutrophils to kill bacteria).

19. Part II: Specific Immunity Specific immunity is a specific defensive response when a host is invaded by foreign organisms or other foreign substances which should be called antigen.The immune system of the host recognizes antigen as not belonging to the body, and it develops an immune response against them. This immune response involves the production of proteins called antibodies and specialized lymphocytes. Both specialized lymphocytes and antibodies are specially targeted for the antigens that cause their formation, and they can destroy or inactive those antigens if they encounter them again. Specific immunity is also called acquired immunity since it is developed during an individual’s lifetime.

20. Immune System Immune system consists of immune organs, immunocytes, and immuno-molecules. • Immune organs: • central immune organ • peripheral organs Thymus ( T cell ) Bone marrow (stem & B cell ) Bursa of Fabricius ( B cell ) Lymph node Spleen Mucousal immune system Skin associated lymphoid system

23. Immunocytes RBC Platelets Granulocytes Monocyte - Macrophages Pro-T cell Pro-B cell Neutro- Basophils Eosino- T cell B cell Myeloid stem cell Lymphoid stem cell Multipotential stem cell marrow central immune organ peripheral organ

24. TH – helper, to help B cell (CD4+T cell) TS – suppressor, inhibit other T & B TDTH – delayed type hypersensitivity TC or CTL– cytotoxic T lymphocyte (CD8+ T cell) T cell TR– regulator TE – effecter B cell – plasma cell – produce antibodies NK cell and K cell ( natural killing or killer cell ) Other immunocytes such as: granulocytes, mast cell, monocytes, dendritic cell.

25. Immune molecules • Immune molecules refer to the molecules related to the immuno-response including: • ⑴ the surface immuno-molecules of membrane, such as MHC (major histocompetibility complex, MHC) I and II antigens, CD (cluster of differentiation, CD) antigens and so on. • ⑵ humoral immuno-molecules such as antibodies, complements, and cytokine (CK). CK like ILS (interleukin), CSF (colony stimulating factor), IFNs, TNF (tumor necrosis factor), TGF (transferming growth factor) etc.

27. 2. Antigen (Ag) • Concept: An antigen is any substance which induces an immune response in the form of proliferation of lymphocytes and production of antibodies specific for the introduced, and may have a reaction or combination with antibody and activated lymphocytes either in vivo or in vitro. It can be divided into two classes: Complete antigen which may not only introduce the antibodies and proliferate lymphocytes (immunogenicity) but also can react with them (reactinogenicity). Hapten (incomplete antigen) has only the reactinogenicity. Most of the proteins, viruses, bacteria are complete antigens, and nearly all the oligose, lipids, nuclear acids, and simple drugs are haptens.

28. The Features of Antigens: • Macromoleculariness : > 10000 • Complex construction: has more molecular groups • Foreignness: inter species, genus and organs or tissues • Specificity: determined by antigenic determinant or • epitope • Microbial Antigens: Fibria Ag O Ag Toxin Ag endo~ exo~ H Ag K or Vi

29. 3. Antibodies (Ab) • Concept: Antibodies are proteins that made in response to an antigen and can recognize and bind to that antigen, there for help neutralize or destroy the antigen. They are produced by plasma cells and identified as a group of globulins called immunoglobulins (Ig). • Ig classes and structure: The five classes of Igs are designated IgM, IgG, IgA, Igd, and IgE. Each class plays a different role in the immune response. The structures of Igs are similar resembled as monomer like IgG and IgE. IgA and IgM are usually dimer and pentamer of monomers joined together by disulfide bonds shown in next slide.

36. Functions and distributions of Igs: • IgG: IgG account for about 80% of all antibodies in serum. They really cross the wall of blood vessels and enter tissue fluids. It’s the only antibody that can cross the placenta and confer passive immunity to a fetus. IgG protect against circulating bacteria and viruses, neutralize toxins, trigger the complement system, and, when bound to antigens, enhance the effectiveness of phagocytic cells. • IgM: IgM make up 5 –10% of the Abs in serum. It remain in blood vessels and do not enter surrounding tissues. It’s the first to appear in response to initial exposure to an antigen which makes it uniquely valuable in the diagnosis of infectious disease.

37. IgA: IgA account for only about 10 – 15% of the antibodies in serum, but it is by far the most common form in mucous membranes and in body secretions such as mucus, saliva, tears and breast milk. So it is the most abundant Ig in the body. It can be divided into two forms: the serum IgA as a monomer and the secretory IgA as a dimer. The main function of sIgA is to prevent the attachment of pathogens, particularly to respiratory pathogens, helps protect infants from gastrointestinal infections. IgE: IgE constitute only 0.002% of the total Abs. But they will help against parasitic worms. Some times they are associated with allergic reaction. IgD: IgD is about 0.2% and its function unknown.

38. Mechanism of Ab Formation • Primary and Secondary Response Concentration of Ab Primmary Secondary Time (days) IgM IgG Total amount of Ab Specific memorial reaction for IgG

39. Diversity of Antibody Formation: ⑴ Clonal selection theory: There may be 109-12 clones of immunocyte extant in the body. The antigen entered choose the right clone and triggered the cell proliferation and produce the relative antibodies. The clone may be forbidden once met the antigen at the fetus period and formed a forbidden clone which do not respond to that antigen any more. This phenomenon of immunological tolerance reasonably describes the mechanism that why the body’s immune system do not respond to the self components. ⑵ Somatic mutation. ⑶ Gene rearrangement. ⑷ Allelic exclusion. ⑸ Random combination of chains of L-, H-, C-, V-, and J-.

42. 神经系统 内分泌系统 免疫系统 可感知刺激 垂体激素 神经递质 神经肽 激素 细胞因子 激素 （病源、毒素等刺激） 细胞因子

43. Section C. Practical Application of Immunology 1. Diagnostic Immunology Precipitation reaction Agglutination reaction Complement-Fixation reaction Fluorescent-Antibody techniques Enzyme-Linked Immunosorbent Assay (ELISA) Radioimmunoassay 2. Vaccines and biological products

44. 免疫学检测方法与免疫技术 概述 免疫学检验方法和免疫化学技术主要包括： 抗原抗体的制备、纯化和鉴定，免疫扩散、免疫电泳、免疫凝集试验、补体结合试验，免疫细胞分离、纯化和鉴定，免疫功能检测，细胞因子检测，放射免疫检测，免疫酶标检测，荧光和发光免疫技术，免疫组化实验方法，原位杂交免疫组化，免疫PCR技术，免疫微球的应用，免疫电镜技术，细胞凋亡的检测方法，膜受体分析，胞内钙镁浓度的测定和细胞间通讯，流氏细胞仪技术及应用等。 从上述内容可以看出，免疫技术是免疫学和物理、化学及电子信息和分子生物学理论和技术的结合产物。其应用涉及生命科学的各个领域，已成为现代医学和生物学研究工作不可缺少的有效工具。

45. 免疫技术的原理和特点： • 基于免疫应答的理论，即抗原抗体的特异性反应。基于免疫细胞的结构、应答特性和分子基础。 具有特异性 高度灵敏性； 可重复性；广泛适用性；快速反应性；可观察性；可定性、定量，即可控性；组化定位特性等特点。 概括起来可分为： • 沉淀反应，即可溶性抗原和抗体间的反应。 • 凝集反应，即颗粒性抗原和抗体间的反应。 • 免疫标记，即用酶、同位素、荧光素或电子致密物质标记。 • 免疫印渍，即用标记抗体与待测蛋白质印迹结合。 • 单抗及工程抗体技术，即分子生物技术。 • 流氏细胞术，即荧光标记，流体喷射，激光和能谱检测，电 • 脑分析。