1. basic components of the immune system

Cell Biology

1. Basic Components of the Immune System Themba Hospital FCOG(SA) Part 1 Tutorials By Dr N.E Manana

2. INTRODUCTION It is generally believed that the immune system evolved as the host’s defence against infectious agents However , it may well play a larger role in the elimination of other foreign substances , tumour cells and antibodies that attack self . An immune response may be conveniently divided into two parts : (1) A specific response to a given antigen (2) A more nonspecific augmentation to that response

3. Fig 1.1

4. Macrophages Divided into two main groups : the dendritic cell and the mature macrophage. The dendritic cell’s major function is to present antigen to the lymphocyte , and it is the earliest cell to recognize foreign antigen There are two forms of dendritic cells : immature and mature The induction of an adaptive immune response begins when a pathogen is ingested by an immature dendritic cell This immature cell carries receptors on its surface that recognize common features of many pathogens such as cell wall carbohydrates of bacteria

5. Macrophages The mature macrophage also derives from primitive stem cells in the bone marrow , but unlike the lymphocyte , it matures in the tissues Thus monocytes , the precursors of mature macrophages , circulate for only a few hours before entering the tissues Where they live for months as mature macrophages There is great variety in the tissue macrophages ; they are heterogeneous in appearance and metabolism . The primary function of these mononuclear cells is to phagocytose invading organisms , dead cells , immune complexes , and antigens

6. Neutrophils These cells produce adhesin molecule receptors , permitting them to adhere to and migrate from the blood vessels to the site of infection They are attracted to the site by IL-8, C3a , and C3b , cytokines released by TH1 cells, and mast cells These cells are also phagocytic cells , and the process of phagocytosis is similar to that seen in macrophages . They are particularly effective when the invading organism becomes coated with antigen-specific antibodies ( opsonins ) along with activated complement components

7. Others NK cells also can kill target cells in the absence of either antigen or antibody stimulation Their lineage is not known, but they are probably in some manner related to T cells . Unlike other cells, they can be non-specifically activated by mitogens, interferon, and IL-12 . These cells are particularly useful in the early response to viral infection NK cells have a broad range of specificity and no real memory

8. INITIATION OF THE IMMUNE RESPONSE The first step must involve modification of the antigen , and these specialized cells are called APCs (Antigen presenting cells) Without such processing , T cells cannot recognize antigen Secretion of cytokines by APCs activated by antigen presentation that further activates antigen specific T cells Antigen is presented to the T cells in the MHC complex present on the surface of APCs The most efficient APCs are the dendritic cells

9. CYTOKINES They are secreted by macrophages (and T , B , epithelial cells and fibriblast ) and may act as stimulatory or inhibitory signals between cells Cytokines that initiate chemotaxis of leucocytes are called chemokines, other are interferons, interleukins, lymphokines and TNFs Interleukins 1 (IL-1) and 2 (IL-2) are of particular importance secondary to their role in amplifying the immune response IL-1 acts on a wide range of cells including T and B cells . In contrast, IL-2 primarily acts on lymphocytes

10. Specific immune response The specific immune response may be divided into two parts (mediated through the lymphocyte) : (1) The humoral response (2) The cellular response to a given antigen. Humoral responses are antibodies produced in response to a given antigen These antibodies are proteins , have similar structures , and can be divided into various classes ( immunoglobulins) Cellular immune responses require an intact Thymus , and are mediated by T (Thymus) lymphocytes , While antibody producing cells are dependent on the bone (bursa) marrow , are known as B cells .

11. Specific immune response Antigens , both foreign and self , are substances that may or may not provoke an immune response Both T cells and B cells have receptors that recognize these antigens . In the case of B cells , antibodies on the surface are a major source of antigen recognition , and once activated , they differentiate into plasma cells that produce large quantities of antibodies T cells have similar receptors known as T-cell receptors (TCR), and in the context of the major histocompatibility complex (MHC) molecules provide a means of self-recognition functions . Some functions are carried out by messages transmitted between these cells ( interleukins or cytokines)

12. ANTIBODY FIG 1.2A 1.2B

13. Antibodies The IgM molecule is the oldest class of immunoglobulins , and it is a large molecule consisting of five basic units held together by a J chain . The reason for this important physiological role is that it contains five complement-binding sites , resulting in excellent complement activation Because of its size , it does not usually penetrate into tissues In contrast, IgG is a smaller molecule that penetrates easily into tissues.

14. Antibodies The major mucosal immunoglobulin , IgA , consists of two basic units joined by a J chain IgA2 is the major IgA molecule in secretions and is quite effective in neutralizing antigens that enter via these mucosal routes IgD is synthesized by antigen-sensitive B cells and is involved in the activation of these cells by antigen IgE is produced by plasma cells and binds to specific IgE receptors on most cells and basophiles

15. T CELLS AND THEIR RECEPTORS Each T cell is also committed to a given antigen and recognizes it by one of two TCRs . They may have TCR2s composed of gamma (γ) and delta (δ) chains or TCR2s composed of another heterodimer of alpha (α) and beta (β) chains These TCR2s are associated with a group of transmembrane proteins on the CD3 molecule , which takes the antigen recognition signal inside the cell The TCR complex recognizes small peptides presented to it by the MHC class I and II

16. MAJOR HISTOCOMPATIBILITY COMPLEX Human histocompatibility antigens are also known as human leucocyte antigens (HLA) , synonymous with the MHC complex . These antigens are cell surface glycoproteins classified as type I or type II. They can produce genetic polymorphism with multiple alleles at each site, thus permitting a great deal of genetic variability between given individuals Recognition of antigen by T cells is MHC restricted .

17. Table 1.1

18. ANTIBODY PRODUCTION To achieve antibody production , at least four types of cells are required : APCs , B cells , and two types of regulating cells Antibodies are produced by naïve B cells and are called plasma cells In the early stages , B cells first show surface IgM These cells can later express IgG, IgA, or IgE , a phenomenon known as isotype switching S urface immunoglobulin act as its antigen-receptor site

19. ANTIBODY PRODUCTION A number of these B cells become memory cells so that a greater number of antigen specific B cells are available on a secondary contact with the same antigen . This phenomenon is known as clonal expansion and helps to account for the greater secondary response B cells alone do not respond to antigen directly , even in the presence of APC cells . They must have a second signal , normally provided by the T cells

20. Cellular Immunity Cell-mediated responses are implemented by T lymphocytes The major functions of T cells can be divided into two categories the first ( cytotoxicity ) is to lyse cells expressing specific antigens ( CD8 + cells is a potent killer of virally infected cells ) -The second ( delayed hypersensitivity ) is to release cytokines , thereby triggering an inflammatory response

21. COMPLEMENT The complement component system consists of a series of heat-liable proteins , and they normally exist as inactive precursors However, once activated each component may act as an enzyme and cleaves the next component in the sequence The control of the sequence relies on either spontaneous decay or specific inactivation Minor fragments play a role chemotaxis The major function of the complement system is to help in the opsonization of microorganisms and immune complexes

22. COMPLEMENT The critical step in complement activation is the cleavage of the C3 component by complement-derived enzymes called C3 convertases . This results in the presence of C3b , which mediates a number of vital biological activities Individuals who are deficient in C3 are obviously predisposed to bacterial infections and immune complex disease

23. Figure 1.9

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