immunology 2.

Adaptive (acquired(diperoleh)) immune system Spesific and has memory May be weak / absent on first exposure Increases with subsequent exposures to same specific pathogen Specialist cells, cytokines, antibodies Specialised mucosal lymphoid tissue The adaptive immune response are plays as supplements of non adaptive or innate response Adaptive immunity mediated by LYMPHOCYTES The growth, development and activities of granulocytes and lymphocytes are interconnected and often co-operative. Components of the Adaptive Immune System antigens antibodies lymph system lymphocytes B cells T cells NK cell (Natural Killer) Acquired Immunity responds to, distinguishes between and remembers specific pathogen it has encountered. Four Important Attributes: Specificity Antigens are microbes or microbe parts that provoke an immune response

Immune system recognizes small parts of the antigen called antigenic determinants or epitopes Immune deficiency is the loss of the bodys ability to respond to antigens and epitopes Tolerance of Self Regulatory T cells prevent other T cells from attacking self cells Autoimmune diseases occur when selftolerance breaks down If nonimmunogenic molecules (haptens) are linked to proteins, they may not be recognized as self Thus they might provoke an immune response (allergies)

Minimal Self Damage An immune response must be strong enough to eliminate the pathogen, yet controlled so as not to cause extensive damage

Immunological Memory Immunological memory is the ability to remember past pathogen exposures The body fights off any subsequent infections Two types of Adaptive or Acquired immunities in recieving immunity i.e.: via active and passive mechanism a.Active: resistance developed by an individual as a result of an antigenic stimulus. This involves the synthesis of antibodies and/or the production of immunologically active cells. b.Passive: resistance that is

transmitted to a recipient in a readymade form as passive immunity. Therefore preformed antibodies are administered. There are also two types of effector mechanisms that mediate specific immune response: a) Humoral Immune Response b) Cell-mediated Immune Response Humoral Immune Response The humoral immune response involves: activation of B cells production of antibodies against the identified antigen Highly specific, body can generate antibodies against any antigen or epitope

rapidly regenerating surfaces, peristaltic movement, mucociliary escalator, vomiting, flow of urine/tears, coughing Cellular and humoral defences lysosyme, sebaceous/mucous secretions, stomach acid, commensal organisms,complement proteins, phagocytosis, NK cells Cellular and humoral defences Antibodies, cytokines, T helper cells, cytotoxic T cells What is autoimmunity? Normally, the immune systems are able to differentiate: one antigen to other or self antigen and foreign Ag. If the immune system fail to differentiate self against foreign, the immune response become against their own Ag or called as Autoantibody or Autoimmunity. Generally is prevented by selftolerance, where self-reactive antigens are eliminated But, the body cannot eliminate all self-reactive antigens because some help protect against foreign antigens! This means that everyone has some self-reactive antigens, only, they have not activated our antibodiesyet When body mounts immune response against self, it is impossible for immune mechanism to eliminate antigen completely Result: a sustained response, chronic inflammation, tissue damage and sometimes death!

Cell Mediated Immune Response If the microbes enter cells, antibodies are less effective Then the cell mediated immune response is activated to eliminate nonself cells T cells have receptor proteins; the highly specific receptor proteins on the lymphocyte surface implies that even before an antigen enters the body, immunocompetent B and T cells are already waiting.

Skin & Mucous membranes

Types of Autoimmune Disease

Autoimmune disease is generally classified into systemic or organ specific diseases Most of Autoimmunity are harmful, the only normal or positive autoimmune response are recognition off cell surface Ag encoded by Major Histocompatibility complex (MHC) of anti-idiotypic response against self idiotypes (The antigen combining portion of the receptor or set of antigenic or epitope determinant of Ig V domain) Innate immunity - Involved in innate immunity are : 1.Epithelial surfaces : intact skin and mucous membrane Protection against invasion by microorganism. Eg: Mucosa of respiratory tract, mucopolysaccharides capable of neutralizing the bacterial products The mouth is constantly bathed in saliva, contain antibodies, IgA, Thelper and suppressor cell, macrophages. 2.Antibacterial substance in blood and tissues : The complement system possess bactericidal activity Destroys pathogenic bacteria invading the blood and tissues. Substances possessing antibacterial property include: Beta lysine active against anthrax, and related bacteria Basic polypeptides such leukins Acidic substances such as lactic acid found in muscle tissue, has anti bacterial action.

1.Inflammation : Tissue injury & irritation by the entry of pathogens or other irritation Causes inflammation, as important non-specific mech. of defence. Help in the initial defense. 3.Fever : Rise in temperature following infection is a nat. defense mechanism Help to accelerate physiological processes & in many other cases Actually destroy the infecting pathogens. 5.Acute phase proteins : Infection or injury leads to sudden increase in plasma concentration of certain proteins, collectively called acute phase proteins. Include C-reactive protein, mannose binding protein, alpha 1-acid glycoprotein, serum amyloid p component and many others. Believed to enhance host resistance & prevent tissue injury . Promote repair of inflammatory lesions. Phagocytes : Phagocytes belong to two major lineage : 1.Monocyte / macrophage / Mononuclear phagocyte 2.PMN granulocyte : a. Neutrophil; b. Basophil; c. Eosinophil The other family of phagocytes consists of : a) circulating cells, the monocytes and

b) cells residing in interstitium of various organs.

throughout the connective tissue and around the basement membrane of small blood vessel, particularly in the lung. Polymorphonuclear granulocytes: a. Neutrophils Play an important role in acute inflammation provides a primary nonspecific internal defense mechanisms. comprise over 95% of circulating granulocytes. Chemotactic stimuli result in neutrophil margination and diapedesis. Neutrophils have two main types of granules: Primary granules-lysosomes containing acid hydrolysis, myeloperoxidase and muranidase (lysozyme). The secondary granules contain lactoferrin and lysozyme. In addition the granules also contain the antibiotic proteins defensins, seprocidins, cathelicidins and bacterial permeability inducing proteins

Mononuclear phagocytes Professional phagocytic macrophages: remove particulate antigens. APC: take up, process and present antigenic peptide to T cells.

The term macrophages is applied to the cells found free in body cavities While histiocytes is applied to cells found fixed in tissues. Macrophages : 1. Phagositic. Highly phagocytic cells reticuloendothelial system.

2. Present digestive Ag into membrane surface as super Ag , and so called as antigen presenting cells (APC) 3. Secrete active molecules, engulf and remove antigen. 4.Determined the induction of immune response of presenting determinants to T cells, which type will be induced 5.Possess: CR1, CR3, CR4, C5aR receptors and molecules important in antigen presentation (MHC class II receptor, CD1). Macrophage finally settle in the tissue as mature macrophage where they constitute the so-called reticuloendothelial system. Present

c. Basophils: Found in very small numbers in the circulation. Accounting for less than 0.2% of leucocytes. Basophilic granules contain primarily histamine and leukotrienes LTC4, LTD4, LTC4, which are potent spasmogenic agents causing constriction of smooth muscle. The granules of basophils contain

heparin, leukotrienes, histamine and eosinophil chemotactic factor for anaphylaxis. The stimulus basophil degranulation is often an allergen. Mediators such as histamine released by degranulation Cause the adverse symptoms of allergy but, on the positive side, they also play a role in immunity against parasites by enhancing inflammation. d. Mast cells : The mast cell, which is not found in the circulation. There are two kinds of mast cell: a) mucosal mast cell b) connective tissue mast cell. Important in immediate inflammation. Possess receptors for complement components (C3a and C5a) as well as receptors for the Fc portion of the antibody molecules IgE and IgG . Secretion of vasoactive substances that increase vascular permeability and dilation, the important signs of anaphylaxis. Feature prominent cytoplasmic granules, termed lysozymes, which store inflammatory mediators such as histamine, eosinophil chemotactic factor, neutrophil chemotactic factor and heparin. Can synthesize denovo, other inflammatory mediators, such as (SRS-A) tumor neurosis factor (TNF) and leukotriene. In addition mast cell interleukin has been shown to enhance collagenase activity and heparin may augment bone resorption

Platelets:

In addition to their role in blood clotting are induced in immune responses and especially in inflammation. Derived from megakaryocytes in the bone marrow following injury to endothelial cells, Platelets adhere to, and aggregate at, the endothelial surface of damaged vascular tissue. They release two types of granules which include serotonin and fibrinogen. This result in an increased permeability, activation of complement and hence attraction of leucocytes. Cells, tissues and organs of the immune system: Lymphoid cells : The cells involved in the immune response are organized into tissues and organs in order to perform their functions most effectively. These structure are collectively reformed to as the lymphoid system. The lymphoid system comprises lymphocytes, accessory cells (macrophages and APCs) and in some tissues, epithelial cells. It is arranged into either discreetly encapsulated organs or accumulations of diffuse lymphoid tissue. The major lymphoid organs and tissues are classified into either primary (central) or secondary (peripheral).

In essence, lymphocytes are produced in the primary lymphoid organs and function within the secondary lymphoid organs and tissues. Primary lymphoid organs : Primary lymphoid organs are the major sites of lymphocyte development. The primary or central lymphoid organs include the thymus, fetal lines and fetal bone marrow. Secondary lymphoid organs : The generation of lymphocytes in primary lymphoid organs followed by their migration into peripheral secondary tissues. The secondary lymphoid tissues comprise well organized encapsulated organs, the spleen and lymphnodes and non-encapsulated accumulations of lymphoid tissue (MALT) The lymphocytes of the immune system migrate from primary to secondary lymphoid tissues. Once in the secondary tissues, the lymphocytes move from one lymphoid organ to another through the blood and lymphatic. All lymphocytes return to the circulation from the lymph node. Lymphnodes and the lymphatic system The formation of lymphocytes in central lymphoid organs and their migration to peripheral organs is accomplished by two circulatory networks the blood and lymphatic systems. Lymphocytes make up 70 to 80 percent of the nucleated cells in the

blood and more than 99 percent of the nucleated cells in the lymphatic fluid (lymph). The lymphoid system has three principal functions : To concentrate antigens into distinct structures. To circulate lymphocytes through tissues. To carry the products of the immune responses to the bloodstream and tissues. Lymphoid organs Organised tissue in which lymphocytes interact with nonlymphoid cells Sites of maturation & initiation of adaptive immune responses Lymphocyte recirculation NAIVE LYMPHOCYTES circulate from the blood into lymph nodes through high endothelial venules (HEV)

EFFECTOR CELLS exit lymph nodes and traffic to inflamed tissue.

MEMORY LYMPHOCYTES recirculate from blood into tissue, and then into lymph nodes through afferent lymphatics. Some may reside in tissue. Basic term of lymphatic system Circulatory System Blood fluid and components

in vessels Lymph fluid in tissues around vessels Haemolymph fluid in insects Cells: erythrocytes, lymphocytes, monocytes, neutrophils, basophils, eosinophils Lymphatic system Lymphatic vessels pervade the body Interrupted by lymph nodes filtering stations Fluid component is called lymph Initially cell free, the lymph collects cells (lymphocytes) and proteins as it moves through the lymph nodes Aggregated lymphoid follicles Tonsils Peyers patches Follicles of the appendix GALT, BALT,MALT Gut-associated lymphoid tissue (GALT) Bronchial-associated lymphoid tissue (BALT) Mucosa-associated lymphoid tissue (MALT) Lymph nodes Perform three functions in addition to providing a place for lymphocyte and macrophage residence Trap infectious agents from lymph Process foreign matter phagocytically

Provide cellular scaffolding necessary for immune cell interactions Spleen Preceding description of splenic circulation combines the closed circulation and open circulation hypotheses This is the mixed circulation hypothesis Dispute is not yet resolved Only contains efferent lymphatics Ratio of white to red pulp varies depending on immune status of individual Not essential for survival but is important as a discriminatory filter for blood cells and lymph, as well as immune functions IMMUNE RESPONSE The immune system is an extremely complicated and has a dominant role as: Defense mechanism, Homeostasis, and surveillance and they are genetically controlled The core system of immunology are: Cells memories and specificity, however many cross reactivity may happen Antigenic determinants are such area which determine the specificity of the antigen With the exact memories, reaction on secondary inoculation or infection will be much faster and much higher

compared to those of primary response Determination of Self and Non-Self Antigen Burnet and Fenner postulated that soon after delivery (perinatal) the immune system will introduced into all bodys cells through lymphoid system development and therefore become tolerance On their development many cells were fail to be intoduced into the immune system till they finsally become mature human being. This problem merely due to: Blood organ barrier: 1. Brain barrier 2. Camera Occuli (eye) barrier 3. Reproductive Tract barrier e.g. Prostat gland The cell develop afterwrad i.e. After maturation e.g. 1. Ovum ; 2. Sperm When the immune system fail to recognize self Ag they develop autoimmmue Rx and the harmful effect are formerly named as horror autotoxicus & clinically divided into systemic or non-organ specific and organ specific Reminder of basic immunological terms ANTIGENS (Ag) are substances recognised by: ANTIBODIES (Immunoglobulin, Ig, Ab) Antibodies are made by B CELLS

T LYMPHOCYTES (T CELLS) T HELPER (Th) cells help B cells make antibodies: CYTOTOXIC T cells (CTL) kill infected cells/abn cells

two essential properties of antigens include Immunogenicity the ability to stimulate immune system Specificity or reactivity the ability to react with effector molecules (antibody) to form an antigen-antibody complex

Immunogenecity & Antigenic Specificity Immunogenicity is a property of substances that can induced a detectable immune response (humoral, cellular, or most commonly both when introduced into animal/human Chemical nature of Immunogens. The most potent are macromolecular protein, but polysaccharides, synthetic polypeptides, and other synthetic polymer such as polyviniylpyrrolidone are immunogenic under appropriate condition Although pure nucleic acids have not been shown to be immunogenic, Ab that react with nucleic acid may be induced by immunization. Immunogenecity Depend on its physicochemical characteristics, however

operationally dependent on the experimental condition of the system, e.g. gelatin was generally accepted as nonimmunogenic until the development of more sensitive methods The factor that confer immunogenecity on molecules are complex & incompletely understood , however certain conditions are really related A. Foreignness: protein from different spec. & injected to other vertebrate will evoke Ab depend on dose, route & frequency of injection B. Chemical complexity: more complex more potent C. Molecular size: extremely small molecules such as amino acids or monosaccharides are usually not immunogenic. In few instances, substances w MW < 1000 have proved to be immunogenic. But as general rule MW< 10,000 are only weakly/not immunogenic at all. The most potent are macroproteins with MW>100,000 D. Genetic constitution of the Animal: e.g polysaccharides are immunogenic for mice and Human but bot for Guinea pig. Even in one species, strain 2 G. pigs response readily to poly-LLysine, whereas strain 13 do not. The ability to response is inherited as an autosomal dominant trait E. Method of Ag Administration: An Ag that is ineffective when injected intravenously may evoke a copious Ab response when injected sub-cutaneously In general once threshold is exceeded, increasing doses led to increasing- but less than pro-proportionate-response.

However excessive Ag doses may not only fail to stimulate Ab formation, they can establish a state of specific unresponsiveness. Antigenic determinant: area that determine the specificity of Ag are designated Antigenic determinants Hapten: From Greek haptein (to fasten) small molecules (macromol may also function as hapten) which by itself cannot stimulate Ab synthesis, but will combine with Ab one formed. The protein to which hapten link called as Carrier, has its self set of native integral determinant as well as new determinant introduced by the conjugated hapten