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1、,Chapter 22,Anatomy interferon production, etc. Complement Is 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
2、 and form holes in the membranes. The proteins can also attach to bacteria membrane and stimulate macrophages to phagocytize the bacteria.,Interferons: proteins that protect the body against viral infection and possibly cancer. Cells for Innate Immunity Review the major functions of, neutrophils, mo
3、nocytes, macrophages, basophils, mast cells, eosinophils, and natural killer cells. (Table 22.2) Inflammatory Response Tissue damage caused by bacteria or others may induce inflammation of tissue as it releases histamine, prostaglandins, kinins, etc Vasodilation attracts chemotatic phagocytes and ot
4、her leukocytes to the region as well as fibrinogen to form fibrin in order to localize damage.,Adaptive Immunity Substances to stimulate adaptive immunity are antigens, of which molecule weights could be as large as 10,000 or more. (produce antibodies) Haptens are small molecules capable of combinin
5、g 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. For example. Allergic reaction is by foreign antigens, while autoimmune disease is from self
6、 antigens.,Immunity has been divided into two types: humoral (body fluid) immunity and cell mediated immunity. Specificity : recognition of antigen The specificity is established because of the specific receptors located on the surface of T and B cells. Versatility: there are many antigens. And ther
7、e 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 responding to it begin to initiate cell divisions. The presence of antigen leads to the formation of active and memory cells. The
8、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.,Lymphocytes 25% of circulating white cells. The majority of lymphocytes are in peripheral tissues. Types of lymphocytes We have already seen t
9、hat there are three types of lymphocytes. (Fig. 22.9) T cells: 80% of circulating lymphocytes (cell mediated immunity) B cells: 10-15% , plasma cells produce antibodies (immunoglobulins) and react antigenic pathogens. ( antibody-mediated immunity) Natural killer cell: the remainder: they attack fore
10、ign cells, normal cells infected with viruses and cancer cells. They immunologically survey peripheral tissues.,Cytotoxic 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 in
11、hibit T cells and B cells.,Origin and development of lymphocytes Lymphocytes 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. (
12、Fig. 22.9) Pre-B cells and pre-T cells are in the red bone marrow. Pre-B cells mature in the red bone marrow into B cells. T cells mature in the thymus.,A positive selection process keep cells capable of immune response. Those which are incapable will die. Each group of B or T cells capable of respo
13、nding to a specific antigen is a clone Each 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 througho
14、ut life.,Activation of Lymphocyte Lymphocytes are made in response to a specific antigen and in a large quantity. Antigenic Determinants and Antigens Receptors An antigen may have many antigenic determinants (epitopes) (Fig. 22.10) to which lymphocytes can respond. Each antigenic determinate can act
15、ivate 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). The variable r
16、egion 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.,Major Histocompatibility Complex Antigens Some are direct
17、, but most lymphocyte activation involves glycoproteins on the surface of cells called MHC molecules. All cell membranes have MHC MHC class I molecules (Fig. 22.12a) On nucleated cells, foreign or self proteins are fragmented in the nucleated cells and become antigens. They combine with MHC class I
18、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. (cell mediated immunity), while self antigen/MHC I will not.,MHC class II Molecules (Fig 22.12b
19、) The more complex and advanced lymphocytes stimulation use MHC II molecules. These molecules are found in antigen-presenting cells, such as B cells, macrophages, monocytes and dendritic cells. Antigen-presenting cells phagocytically ingest unprocessed antigens, process them and let them combine wit
20、h 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 the antigen.,Costimulation In addition to the interaction between the presented MHC II/ antigen and antigen receptor, costimula
21、tion, with cytokinins for example, is needed (Fig.22 13a) Another costimulation (Fig. 23. 13b) is achieved cross 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 Cells Enhances more pr
22、oduction of T and B cells On activation helper T cells produce a variety of cytokins that coordinated specific and nonspecific 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,
23、such as interleukins, the number of helper T cells increase and thus stimulate B cells or effector T cells, which release perforin, produces hole in infected cells.,Inhibition of lymphocytes Inhibition of lymphocytes proliferation against its own self-antigen is achieved by tolerance. Deletion of se
24、lf-reactive lymphocytes During 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 lymphocytes By lack of costimulation Activation of suppresse
25、r T cell. This is not well understood. The suppressor T cells release suppressive cytokins.,Antibody-mediated Immunity When exposed to an antigen, the body activates B cells and produces antibodies. the antibodies are found in body fluids thus respond to extracellular antigens. Antibodies Antibodies
26、 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 types (Ta
27、ble 22.5) IgG, IgM, IgA, IgE, and IgD,They 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, etc. Effects of Antibodies The function of an
28、tibody 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 several ways (Fig. 22.17) Upon binding with a
29、n 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.,Antibody production The primary Response The first encounter with an antigen, an B cell
30、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
31、 cells. The primary process takes 1-14 days, the antigen may cause tissue damage during this period.,The secondary or memory response When the immune system is exposed to the same antigen after the primary response The memory cells quickly divide to produce plasma cells and large quantity of antibody is released, providing immune protection. the response is quick, hours to a few days, and the the quantity of antibody production is large. Good defense against the disease. The memory
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