Basic Principles of the Immune System

Basic Principles of the Immune System

1. Immune System Dr. Hadi Munib Oral and maxillofacial surgery resident

2. Outline The Normal Immune Response Cells and Tissues of the Immune System Overview of Lymphocyte Activation and Adaptive Immune Response References

3. Immune System Immunity refers to protection against infections. The immune system is the collection of cells and molecules that are responsible for defending the body against the countless pathogens that individuals encounter. Immunodeficiency Diseases; Defects in the immune system render individuals easy prey to infections Hypersensitivity Disorders; when the immune system is itself capable of causing tissue injury and disease.

4. Normal Immune Response Defense against pathogens consists of two types of reactions Innate immunity ( Natural or Native immunity) is mediated by cells and proteins that are always present poised to react against infectious pathogens . Called into action immediately in response to infection Provide the first line of defense. Some of these mechanisms also are involved in clearing damaged cells and tissues. A major reaction of innate immunity is inflammation

5. Normal Immune Response Many pathogens have evolved to resist innate immunity, Adaptive Immunity (Acquired/ Specific); More specialized and powerful mechanisms of protection against these infections Adaptive immunity is normally silent and responds (or adapts ) to the presence of infectious agents by generating potent mechanisms for neutralizing and eliminating the pathogens . The terms immune system and immune response generally refer to adaptive immunity.

6. Innate Immunity The major components of innate immunity are: Epithelial barriers that block the entry of microbes. Phagocytic cells (mainly neutrophils and macrophages) Dendritic cells (DCs) Natural killer (NK) cells Other innate lymphoid cells, and several plasma proteins, including the proteins of the complement system

7. Innate Immunity Phagocytes, dendritic cells and many other cells express receptors that sense the presence of infectious agents and substances released from dead cells. The microbial structures recognized by these receptors are called pathogen-associated molecular patterns; They are shared among microbes of the same type, and they are essential for the survival and infectivity of the microbes The substances released from injured and necrotic cells are called damage-associated molecular patterns . The cellular receptors that recognize these molecules are often called pattern recognition receptors . It is estimated that innate immunity uses about 100 different receptors to recognize 1000 molecular patterns.

8. Reactions of Innate Immunity The innate immune system provides host defense by the following two main reactions: Inflammation. Cytokines and products of complement activation, are produced during innate immune reactions and trigger the vascular and cellular components of inflammation. Anti-viral defense. Type I interferons produced in response to viruses act on infected and uninfected cells and activate enzymes that degrade viral nucleic acids and inhibit viral replication.

9. Adaptive Immunity The adaptive immune system consists of lymphocytes and their products, including antibodies. The adaptive immune system can recognize a vast array of foreign substances. Humoral immunity, mediated by soluble proteins called antibodies that are produced by B lymphocytes Cell-mediated (or cellular) immunity, mediated by T lymphocytes Cytotoxic T Lymphocytes; directly killing infected cells Helper T Cells; activating phagocytes to kill ingested microbes, via the production of soluble protein mediators called cytokines

10. Cells and Tissues of the Immune System The cells of the immune system consist of lymphocytes, most of which have specific receptors for antigens and mount adaptive immune responses. Specialized APCs, which capture and display microbial and other antigens to the lymphocytes. Various effector cells, whose function is to eliminate microbes and other antigens.

11. Lymphocytes Present in the circulation and in various lymphoid organs. Although all lymphocytes are morphologically similar, they actually consist of several functionally and phenotypically distinct populations Lymphocytes develop from precursors in the generative (primary) lymphoid organs; T lymphocytes mature in the thymus, whereas B lymphocytes mature in the bone marrow. Each T or B lymphocyte and its progeny, which constitute a clone , express a single antigen receptor The total population of lymphocytes (numbering about 1012 in humans) can recognize tens or hundreds of millions of antigens.

12. Lymphocytes All mature lymphocytes go through distinct phases during their lives Naïve lymphocytes; express antigen receptors but have not responded to antigens and do not serve any functions. Effector lymphocytes are induced by lymphocyte activation and perform the functions that eliminate microbes. Memory lymphocytes induced during activation survive in a functionally silent state even after the antigen is eliminated and respond rapidly upon subsequent encounters with the antigen.

13. T Lymphocytes Thymus-derived T lymphocytes develop into the effector cells of cellular immunity and “help” B cells to produce antibodies against protein antigens. T cells constitute 60% to 70% of the lymphocytes in peripheral blood and are the major lymphocyte population in splenic peri -arteriolar sheaths and lymph node inter-follicular zones. T cells cannot recognize free or circulating antigens; The vast majority (>95%) of T cells sense only peptide fragments of proteins displayed by molecules of the major histocompatibility complex (MHC).

14. B Lymphocytes B (bone marrow–derived) lymphocytes are the cells that produce antibodies, the mediators of humoral immunity . B cells make up 10% to 20% of the circulating peripheral lymphocyte population. They also are present in bone marrow and in the follicles of peripheral (secondary) lymphoid organs. After stimulation, B cells differentiate into plasma cells. Which secrete large amounts of antibodies. There are five classes, or isotypes, of immunoglobulins: IgG, IgM, and IgA constitute more than 95% of circulating antibodies. IgA is the major isotype in mucosal secretions.

15. B Lymphocytes IgE is present in the circulation at very low concentrations Also is found attached to the surfaces of tissue mast cells IgD is expressed on the surfaces of B cells but is secreted at very low levels.

16. Natural Killer Cells NK cells are innate immune cells, as they are functional without prior activation and do not express highly variable and clonally distributed receptors for antigens . NK cells have two types of receptors; inhibitory and activating. Inhibitory receptors recognize self class I MHC molecules, which are expressed on all healthy cells Activating receptors recognize molecules that are expressed or upregulated on stressed or infected cells Innate lymphoid cells (ILCs) are populations of lymphocytes that lack TCRs but produce cytokines similar to those that are made by T cells.

17. Dendritic Cells Dendritic cells (DCs) are the most important antigen presenting cells for initiating T-cell responses against protein antigens . Plasmacytoid They have numerous fine cytoplasmic processes that resemble dendrites. These cells are located at the right place to capture antigens—under epithelia, the common site of entry of microbes and foreign antigens, and in the interstitia of all tissues, where antigens may be produced. DCs within the epidermis are called Langerhans cells . DCs express many receptors for capturing and responding to microbes (and other antigens), including TLRs and C-type lectin receptors. In response to microbes, DCs are recruited to the T-cell zones of lymphoid organs, where they are ideally positioned to present antigens to T cells. DCs express high levels of MHC and other molecules needed for antigen presentation and activation of T cells.

18. Lymphoid Tissues The tissues of the immune system consist of the generative (primary, or central ) lymphoid organs. I n which T lymphocytes and B lymphocytes mature and become competent to respond to antigens. The peripheral (or secondary ) lymphoid organs, in which adaptive immune responses to microbes are initiated. The principal generative lymphoid organs are the thymus, where T cells develop. The bone marrow, the site of production of all blood cells and where B lymphocytes mature.

19. Lymph Nodes Encapsulated, highly organized collections of lymphoid cells and innate immune cells that are located along lymphatic channels throughout the body. As lymph passes through lymph nodes, resident APCs are able to sample antigens that are carried to the node in lymph derived from the interstitial fluids of tissues. DCs transport antigens from nearby epithelial surfaces and tissues by migrating through lymphatic vessels to the lymph nodes. Thus, antigens become concentrated in draining lymph nodes

20. Adaptive Immune Response Steps Antigen recognition; Activation, proliferation and differentiation of specific lymphocytes into effector and memory cells Elimination of the antigen. Decline of the response, with memory cells being the long-lived survivors

21. References Chapter 5: Overview of Lymphocyte Activation and Adaptive Immune Responses

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