Disease of The Immune System

The Normal Immune System

Function : Protect the host from invasion of foreign organism by distinguish self from nonself Prevent and repels attacks by endogenous factors (such as tumors or autoimmune phenomena Eliminate /neutralized the perceived invader The mechanisms of protection against infections fall into two broad categories 1. Innate Imunity Innate immunity is present from birth and is nonspesific in its activity. Innate immunity (also called natural, or native, immunity) refers to defense mechanisms that are present even before infection and that have evolved to specifically recognize microbes and protect individuals against infections. Innate immunity is the first line of defense, because it is always ready to prevent and eradicate infections The major components of innate immunity are - epithelial barriers, block entry of microbes -phagocytic cells (mainly neutrophils and macrophages) - dendritic cells, produce type I interferons, anti-viral cytokines that inhibit viral infection and replication - natural killer (NK) cells, provide early protection against many viruses and intracellular bacteria; -several plasma proteins, including the proteins of the complement system The two most important cellular reactions of innate immunity are: - inflammation : the process in which phagocytic leukocytes are recruited and activated to kill microbes -anti-viral defense, : mediated by dendritic cells and NK cells. 2. Adaptive Immunity Adaptive immunity (also called acquired, or specific, immunity) consists of mechanisms that are stimulated by (adapt to) microbes and are capable of recognizing microbial and nonmicrobial substances. Adaptive immunity develops later, after exposure to microbes, and is even more powerful than innate immunity in combating infections. There are two types of adaptive immunity a. Humoral Immunity protects against extracellular microbes and their toxins. Mediated by soluble antibody proteins that are produced by B cells and their secreted products, antibodies (also called immunoglobulins, Ig) b. Cellular Immunity responsible for defense against intracellular microbes. mediated by T (thymus-derived) lymphocytes.

Hummoral Immunity

Cellular Immunity

Component of The Immune System

Naive Effector Cells & Memory Cells Naive: Immunologically Inexperienced Effector cells : perform the function of eliminating microbes memory cells : which live in a state of heightened awareness and are better able to combat the microbe in case it returns Cells of The Immune System - T Lymphocytes T lymphocytes develop from precursors in the thymus Mature T cells are found in the blood Each T cell recognizes a specific cell-bound antigen by means of an antigenspecific T-cell receptor (TCR) TCR consists of a disulfide-linked heterodimer made up of an and a polypeptide chain ,each having a variable (antigenbinding) region and a constant region.

The TCR recognizes peptide antigens that are displayed by major histocompatibility complex (MHC) molecules on the surfaces of antigenpresenting cells (APCs).

B Lymphocyte B lymphocytes develop from precursors in the bone marrow constitute 10% to 20% of the circulating peripheral lymphocyte population and are also present in peripheral lymphoid tissues such as lymph nodes, spleen, and mucosa-associated lymphoid tissues. recognize antigen via monomeric membrane-bound antibody of IgM and IgD, associated with signaling molecules to form the B-cell antigen receptor complex Dendritic Cells There are two types of cells with dendritic morphology that are functionally quite different : 1. interdigitating dendritic cells, or just dendritic cells Most important antigen-presenting cells (APCs) for initiating primary T-cell responses against protein antigens 2. follicular dendritic cell present in the germinal centers of lymphoid follicles in the spleen and lymph nodes. These cells bear Fc receptors for IgG and can trap antigen bound to antibodies or complement proteins Macrophages Macrophages are a part of the mononuclear phagocyte system. Function : as APCs in T-cell activation key effector cells in certain forms of cell-mediated immunity. Has ability to kill ingested microbes participate in the effector phase of humoral immunity. efficiently phagocytose and destroy microbes that are opsonized (coated) by IgG or C3b Natural Killer Cells NK cells are endowed with the ability to kill a variety of infected and tumor cells, without prior exposure to or activation by these microbes or tumors. This ability makes NK cells an early line of defense against viral infections and, perhaps, some tumors The functional activity of NK cells is regulated by a balance between signals from activating and inhibitory receptors. The inhibitory receptors prevent NK cells from killing normal cells.

Tissues of the Immune System - Generative Lymphoid organs The principal generative lymphoid organs are the thymus, where T cells develop, and the bone marrow, the site of production of all blood cells and where B lymphocytes mature. - Peripheral Lymphoid Organs The peripheral lymphoid organs consist of the lymph nodes, spleen, and the mucosal and cutaneous lymphoid tissues. These tissues are organized to concentrate antigens,

APCs, and lymphocytes in a way that optimizes interactions among these cells and the development of adaptive immune responses

Cytokines : Messenger Molecules of the Immune System

Some of these interactions depend on cell-to-cell contact; however, many interactions and effector functions of leukocytes are mediated by short-acting secreted mediators called cytokines. 1. Cytokines that mediate innate immunity :IL-I, TNF, Type I interferon,IL-6. 2. Cytokines that regulate lymphocyte growth, activation, and differentitiation. : IL-2, 4,12,15,TGF B 3. .Cytokines that active inflamatory cell : IFN- gamma,TNF, IL-5 4. Cytokinesthat afffect leucocyte movement (callled chemokines : C-C and C-X-C chemokines. 5. Cytokines that stimulate hematopoisis: CSFs (colony stimulating factor)

The Immune Response

The Display and Recognition of Antigens - Lymphocytes specific for a large number of antigens exist before exposure to the antigen, and when an antigen enters, it selects the specific cells and activates them (clonal selection hypothesis) - Microbes and their protein antigens are captured by dendritic cells that are resident in epithelia and tissues. These cells carry their antigenic cargo to draining lymph nodes. Here the antigens are processed and displayed complexed with MHC molecules on the cell surface Cell-Mediated Immunity: Activation of T Lymphocytes and Elimination of Intracellular Microbes Naive T lymphocytes are activated by antigen and costimulators in peripheral lymphoid organs, and proliferate and differentiate into effector cells that migrate to any site where the antigen (microbe) is present secretion of the cytokine IL-2 and expression of high-affinity receptors for IL-2 When CD4+ helper T cells recognize antigens being displayed by macrophages or B lymphocytes, the T cells express CD40L, which engages CD40 on the macrophages or B cells and activates these cells. Cells of the TH1 subset secrete the cytokine IFN-, which is a potent macrophage activator. The combination of CD40- and IFN- mediated activation results in the induction of microbicidal substances in macrophages, leading to the destruction of ingested microbes. Activated CD8+ lymphocytes differentiate into CTLs that kill cells harboring microbes in the cytoplasm. By destroying the infected cells, CTLs eliminate the reservoirs of infection.

Humoral Immunity: Activation of B Lymphocytes and Elimination of Extracellular Microbes

B cells ingest protein antigens into vesicles, degrade them, and display peptides bound to MHC molecules for recognition by helper T cells. The helper T cells express CD40L and secrete cytokines, which work together to activate the B cells.

Decline of Immune Responses and Immunological Memory The majority of effector lymphocytes induced by an infectious pathogen die by apoptosis after the microbe is eliminated, thus returning the immune system to its basal resting state, called homeostasis. The initial activation of lymphocytes also generates long-lived memory cells, which may survive for years after the infection, and that respond faster and more effectively when re-exposed to the antigen than do naive cells