• IMUNITAS • SISTEM LIMFATIKA • ANTIGEN • IMUNITAS ALAMIAH VS ADAPTIF • IMUNITAS ADAPTIF IMUNITAS
• Immunity : kemampuan untuk menangkal
kerusakan atau penyakit . • Imunitas : (1) innate = alamiah = nonspecific (2) adaptive = acquired = specific - cell mediated immunity - antibody mediated immunity • Small lymphocytes are unique among blood cells in traveling through the body in the lymph as well as the blood. That is why they were named lymphocytes. • Lymphocytes leave the blood through the walls of fine capillaries in secondary lymphoid organs. • A lymph node is illustrated here. After spending some time in the lymph node, lymphocytes leave in the efferent lymph and return to the blood at the left subclavian vein. If a lymphocyte in a lymph node encounters a pathogen to which its cell-surface receptor binds, it stops recirculating. • Jumlah limfosit dalam tubuh manusia sekitar 2 x 10¹² ANTIGEN • Self and nonself substances that elicit an immune response and react with products of that response. • Non-self dapat berupa mikroorganisme atau parasit yang masuk kedalam tubuh host (manusia). • Most large molecules, including virtually all proteins and many polysaccharides, can act as antigens. • Antigenic determinants (or epitopes)= the parts of an antigen that bind to the antigen-binding site on either an antibody molecule or a lymphocyte receptor. • Most antigens have a variety of antigenic determinants that can stimulate the production of antibodies, specific T cell responses, or both. • Hapten: small organic molecules, not antigenic but may become antigenic when bound to larger carrier molecule,–e.g., penicillin,– may elicit hapten specific and carrier specific responses ANTIBODY • Antibodi dihasilkan oleh sel plasma (sel B yang telah berdeferensiasi). • Polyclonal antibody= production of hundreds species of antibodies, each made by a different B cell clone. • Oligoclonal antibody= a few clones of B cells production. • Monoclonal antibody= only a single B cell production. • Monoclonal antibodies are widely used as tools in biology and medicine, but they have to be produced in a special way. Innate vs adaptive immunity
Adaptive immune responses generally give rise
to long-lived immunological memory and protective immunity. Professional Antigen Presenting Cells • Dendritic cells are the most important APC, with a central role in the initiation of adaptive immune responses • Macrophages are specialized to internalize extracellular pathogens, especially after they have been coated with antibody, and to present their antigens. • B cells have antigen-specific receptors that enable them to internalize large amounts of specific antigen, process Photographs courtesy of R.M. Steinman (a); N. Rooney (b, c, it, and present it. e, f); S. Knight (d, g); P.F. Heap (h, i). • DC are found at Cortex (T cell area) • Makrofag: throughout but mainly the marginal sinus and medullary cords • B cells mainly in the follicle • Collection of genes that code for self/nonself recognition potential of a vertebrate • In humans, called human leukocyte antigen (HLA) complex –on chromosome 6 –three classes of MHC molecules –one paternal allele and one maternal allele Major Histocompatibility Complex (MHC) • Located in the membrane of body cells (except red blood cells). • “selfantigens,” = major histocompatibility complex (MHC) antigens = human leukocyte antigens (HLA). • Function: help T cells recognize that an antigen is foreign, not self. • MHC antigens are the reason that tissues may be rejected when they are transplanted from one person to another, • MHC molecules are membrane their normal proteins whose outer extracellular • The two types of MHC antigens: domains form a cleft in which a peptide 1. Class I MHC molecules are built into the fragment is bound. plasma membranes of all body cells • These fragments, which are derived except red blood cells. from proteins degraded inside the cell, 2. Class II MHC molecules appear on the including foreign protein antigens, are surface of antigen-presenting cells (dendritic cells, macrophages, and B bound by the newly synthesized MHC cells). molecule before it reaches the surface. APCs present exogenous antigens in association with MHC-II molecules Infected body cells present endogenous antigens in association with MHC-I molecules Cluster of Differentiation Molecules (CDs)
• Membrane proteins on lymphocytes and
other cells • have specific roles in intercellular communication • used to identify and differentiate between leukocyte subpopulations • e.g., CD4 is the cell surface receptor for HIV KARAKTERISTIK • = defenses that involve specific recognition of a microbe once it has breached the innate immunity defenses. • slow to respon • involves lymphocytes (a type of white blood cell) called T (cell-mediated immunity) and B (antibody-mediated immunity) lymphocytes. FUNCTIONS • recognize nonself • respond to nonself • remember nonself MACAM • Cell-mediated immunity is • Antibody-mediated particularly effective against : immunity= humoral (fluid) 1. intracellular pathogens, which immunity, works mainly include any viruses, bacteria, against extracellular or fungi that are inside cells; pathogens, which include any 2. some cancer cells; viruses, bacteria, or fungi that are in body fluids 3. foreign tissue transplants. outside cells (blood or • cells attacking cells. lymph). • Developing B cells= immature B cells • Developing T cells= thymocytes • T cells and B cells are activated by foreign antigens mainly in peripheral LYMPHOCYTES • Three stages of lymphocytes maturation in the peripheral lymphoid organs: naïve cells, effector cells, and memory cells. • Resting T and B cells look very similar (small, only marginally bigger than red blood cells, and contain little cytoplasm ), even in an electron microscope. • After activation by an antigen, both proliferate and mature into effector cells. • Effector B cells secrete antibodies. In their most mature form, called plasma cells, they are filled with an extensive rough endoplasmic reticulum that is busily making antibodies. • In contrast, effector T cells contain very little endoplasmic reticulum and secrete a variety of signal proteins called cytokines, which act as local mediators. T CELLS • T cells can migrate to distant sites, but, once there, they act only locally on neighboring cells. • Three main classes of T cells: 1. cytotoxic T cells, directly kill infected host cells. 2. helper T cells, help activate macrophages, dendritic cells, B cells, and cytotoxic T cells by secreting a variety of cytokines and displaying a variety of co-stimulatory proteins on their surface. 3. regulatory (suppressor) T cells, are thought to use similar strategies to inhibit the function of helper T cells, cytotoxic T cells, and dendritic cells. B CELLS • B cells can act over long distances by secreting antibodies that are widely distributed by the bloodstream. • B cells can make more than 10¹² different antibody molecules that react specifically with the antigen that induced their production. THE CLONAL SELECTION THEORY • An antigen activates only those lymphocytes that are already committed to respond to it. • A cell committed to respond to a particular antigen displays cell- surface receptors that specifically recognize the antigen. • The human immune system is thought to consist of many millions of different lymphocyte clones, with cells within a clone expressing the same unique receptor. • Before their first encounter with antigen, a clone would usually contain only one or a small number of cells.
• A particular antigen may activate hundreds of different clones.
• Although only B cells are shown here, T cells operate in a similar way. • Note that the receptors on B cells are antibody molecules and that those on the B cells labeled “Bb” in this diagram bind the same antigen as do the antibodies secreted by the effector “Bb” cells. ANTIBODY • Antibody belong to a group of glycoproteins globulins, so called immunoglobulins (Igs). • Antibody Actions: 1. Neutralizing antigen. 2. Immobilizing bacteria. 3. Agglutinating and precipitating antigen cross-link pathogens to one another, causing agglutination (clumping together) and form a more-easily phagocytized. 4. Activating complement. Antigen– antibody complexes initiate the classical pathway of the complement system (discussed shortly). 5. Enhancing phagocytosis acts as a flag that attracts phagocytes. Antibodies can participate in host defense in three main ways ANTIBODY Comparison of primary and secondary immune responses The levels of antibodies against pathogen A are shown in blue, B in yellow.
• The immune response develops during an experimental immunization of a laboratory animal.
• The response is measured in terms of the amount of pathogen-specific antibody present in the animal’s blood serum, shown on the vertical axis, with time being shown on the horizontal axis. • On the first day the animal is immunized with a vaccine against pathogen A. • The primary response reaches its maximum level 2 weeks after immunization. • After the primary response has subsided, a second immunization with vaccine A on day 60 produces an immediate secondary response, which in 5 days is orders of magnitude greater than the primary response. • In contrast, a vaccine against pathogen B, which was also given on day 60, produces a typical primary response to pathogen B, demonstrating the specificity of the secondary response to vaccine A. Successful vaccination campaigns • Diphtheria, and poliomyelitis have been virtually eliminated from the USA, as shown by these three graphs. Cytokines • small protein hormones that stimulate or inhibit many normal cell functions, such as proliferation of progenitor blood cells in red bone marrow, cell growth, differentiation, and regulate activities of cells involved in innate or adaptive immune responses. • Lymphocytes and APC secrete cytokines TNF-α, IL-1, and IL-6 have a wide cytokines, as do fibroblasts, spectrum of biological activities that help to endothelial cells, monocytes, coordinate the body's responses to infection. hepatocytes, and kidney cells.