IMMUNITYPrior Concepts: 5th semester do read about topics like leucocytes, White blood cells, neutrophils,basophils, eosinophilsetcIMMUNITY: The ability of human body to resist almost all kinds of organisms and toxins that tends todamage the tissues and organs is called immunity. Immunity is the body’s ability to fight off harmful micro-organism –PATHOGENS – that invade it. Fungi, Protozoans, Bacteria and viruses are all potential pathogens.IMMUNE SYSTEM: It refers to a system composed of specialized cells that fight against diseaseproducing bacteria and toxins. The immune system produces antibiotics or cells that can deactivate pathogens. The immune system includes all parts of the body that help in the recognition and destruction of foreign materials. White blood cells, phagocytes and lymphocytes, bone marrow, lymph nodes, tonsils, thymus and your spleen are all part of the immune system.TYPES OF IMMUNITYAccording to ability of body to develop immunity, it is classified into two types: Active immunity Passive immunityActive immunity is further divided into two types with respect to body’s ability to develop specific ornon-specific immunity.Immunity Passive immunity Active immunityAcquired immunityInnate immunityAntibody mediated immunity Cell mediated immunityACTIVE IMMUNITY: occurs when one makes his / her own antibodies. This type of immunity is longterm. Getting the disease: if you get an infectious disease (like chicken pox), often times that stimulates the production of MEMORY CELLS which are then stored to prevent the infection in the future. VACCINATION: is an injection of a weakened form of the actual antigen that causes the disease. The injection is too weak to make you sick but your B-lymphocytes will recognize the antigen
and react as if it were the “real thing”. Thus, you produce MEMORY CELLS for long term immunity.PASSIVE IMMUNITY: occurs the antibodies come from some other source. This type of immunity isshort term. Breast milk: milk form a mother’s breast contains antibodies. The body is acquiring passive immunity. These antibodies will only last several weeks. Gamma globulin: A gamma globulin shot is pure an injection of antibodies to provide temporary immunity. You might receive a gamma globulin shot if you travel outside of the country.INNATE IMMUNITY (non-specific): the natural resistance of the body to various bacteria, toxins andother foreign agents without any specific immune process is called innate immunity. Body’s first linedefenses(physical and chemical barriers)Innate immunity can be obtained by: Cellular components: phagocytosis of bacteria and other invaders by white blood cells and tissue macrophage system. Non-cellular components: Destruction by the acid secretions of stomach and by the digestive enzymes of organisms swallowed into stomach. Resistance of skin to invasion by organisms. Presence in the blood of certain chemical compounds that attach to foreign organisms or toxins and destroy them e.g. lysozymes, basic polypeptide, complement complex. Other examples include tears, saliva, mucous, sweat etc.ACQUIRED IMMUNITY (specific): human body has ability to develop extremely powerful specificimmunity against invading agents and this is called the acquired immunity.TYPES OF ACQUIRED IMMUNITY: a- HUMORAL (ANTIBODY-MEDIATED) IMMUNITY: in this type of immunity, body develops circulating antibodies which are globulin molecules and are capable of attacking the invading agents. This type of immunity is composed of specific antibodies synthesized by plasma cells derived from B-lymphocytes. b- CELL-MEDIATED IMMUNITY: in this type of immunity body develops large number of lymphocytes which are specifically activated against foreign agent. These activated or sensitized lymphocytes have the ability to attach to a foreign agent and to destroy it. This type immunity is composed of sensitized T-lymphocytes.Acquired immunity is the second line defense of the body. If a pathogen is able to get past the body’s firstline of defense and an infection starts, the body can rely on its second line of defense. The results in whatis called an inflammatory response which cause: Redness and heat: due to capillary dilation resulting in increased blood flow. Swelling: due to passage of plasma from the blood stream into the damaged tissue. Pain: due mainly to tissue destruction and to a lesser extent swelling.
ANTIGEN: any invading agent like foreign proteins, organisms, or toxins that can produce an immuneresponse is called an antigen. OR a substance usually protein in nature which when introduced into thetissue, stimulate antibody production.ANTIBODY: (Immunoglobulin) the specific globulin protein formed in the blood plasma ass a reaction toantigen is called antibody. Blood contain three types of globulin: alpha, beta and gamma. Antibodies aregamma globulins.The antibodies that circulate in the blood stream are called as immunoglobulins (Ig)Each antibody is composed of two light chains and two heavy chains. Each chain has a constant andvariable portion. 1- Variable portion (Fab fragment) attaches specifically to a particular type of antigen. It determines antigen binding specificity. 2- Constant portion (Fc fragment) has receptors for attachment to complement complex. It determines physical properties.TYPES OF IMMUNOGLOBULIN: (acronym: GAMED)IgG: It is the most abundant type of immunoglobulin present in serum. It is main antibody in secondary response (while IgM in primary response) It provides an important defense against bacteria and viruses. It is the only antibody that can cross placenta. It is the most abundant immunoglobulin in newborn. It activates complement (IgM also) It acts as opsonin and therefore enhances phagocytosis.IgA: It is the main immunoglobulin in secretions such as colostrum, saliva, tears and respiratory, intestinal and genital tract secretions. It prevents attachment of microorganism to mucus membrane. It cannot cross placenta and does not activate complement.IgM: It is also known as monomeric IgM on B – cell surface and constitutes antigenic receptor. It is the main immunoglobulin produced early in the primary response. It provides defense against bacteria and viruses. It can activate complement. It does not cross placenta.
IgE: It is found in allergies and parasitic reactions. It mediates type I hypersensitivity reactions by causing release of mediators from mast cells and basophils upon exposure to antigen. It is the main host defense against helminth (worm) nfections such as ascaris, hook worm. It cannot cross placenta and does not activate complement. Its concentration in serum is very low but rises in allergy and helminth infections.IgD: It occurs in B – cell surface.ROLE OF LYMPHOID TISSUE IN ACQUIRED IMMUNITYAcquired immunity is the product of body’s lymphoid tissue. There are two types of lymphoid tissue. a- Central lymphoid tissue b- Peripheral lymphoid tissueCENTRAL LYMPHOID TISSUE: Thymus, bone marrowThese are the tissues in which primitive lymphoid cells in the fetus are developed and get maturation.PERIPHERAL LYMPHOID TISSUE: Lymph node Spleen Tonsils Gut associated lymphoid tissue Peripheral bloodThese are the tissues in which mature lymphocytes reside and respond to antigenic stimuli.CELLS OF THE IMMUNE SYSTEM:LYMPHOCYTES: are cells derived from lymphoid stem cells in the bone marrow and develop in the fetallife. Lymphocytes may be classified on the basis of their site of development in the fetus. a- T lymphocytes: develop in thymus of the fetus. Then in adult life in bone marrow. b- B lymphocytes: develop in fetal liver or bone marrow.
T-LYMPHOCYTES:They arise from the stem cells in the bone marrow. They are immature and are taken to the thymus formaturation during fetal life. About 80-90% of peripheral blood lymphocytes are T-lymphocytes. MatureT lymphocytes circulate in the blood and pass to peripheral lymphoid tissue. e.g. a- Paracortical areas of lymph nodes b- Periarteriolar lymphoid sheath in the white pulp of spleen.After stimulation or activation by specific antigen, T lymphocytes transform into large actively dividingcells known as transformed T- lymphocytes, which then divide to produce effector cells. These effectorT-lymphocytes are also called sensitized, cytotoxic or killer T-cells.T lymphocytes can’t be activated by free antigens. They are activated by processed antigens presentedto them by macrophages, dendritic and Langerhan’s cells.T CELL SURFACE MOLECULES: T Cell Receptor (TCR): binds to Antigen presented by macrophages and Langerhan’s cells. CD3 molecular complex: they don’t bind to antigens but transduct signals to T cells after it has bound to antigen. (CD = Cell Differentiation) CD4 molecules: are expressed on 60% of mature CD3 + T cells. During antigen presentation they bind to class II MHC molecules on antigen presenting cells. CD8 molecules: are expressed on 30% of mature CD3 + T cells. (So CD4/CD8 ratio is 2:1)During antigen presentation they bind to class I MHC molecules on antigen presenting cells.TYPES OF T LYMPHOCYTES: 1- Helper T cell (CD4+) subdivided into a- Helper inducer T cells b- Helper suppressor T cells 2- Suppressor T cells (CD8+) 3- Cytotoxic/Killer T cells (CD8+)FUNCTIONS OF T LYMHOCYTES:Cellular immune reaction: They are responsible for cell mediated immunity e.g. against foreignhistocompatibility antigens, virus infected cells and some tumor cells.Regulatory function: They control the T & B cell mediated response through: 1- T-helper cells which help in the production of T & B cells. 2- T-suppressor cells which suppress T & B cell function.
B LYMPHOCYTES:They also arise from the stem cells in the bone marrow and are taken to some unknown part of the bodypossibly the fetal liver, bone marrow, GIT mucosa for maturation. Mature B-lymphocytes are taken tothe peripheral lymphoid tissue e.g. lymph node (lymphoid follicles in superficial cortex),spleen(lymphoid follicles in white pulp) and Peyer’s patches of GIT. About 10-20% of peripheral bloodlymphocytes are B- cells.FUNCTIONS OF B LYMPHOCYTES:After stimulation by an antigen B cells differentiate into plasma cells that secrete immunoglobulins(antibodies).Specific antigenic stimulation B lymphocytes lymphoblast plasmoblast plasma cells specificantibodies directed against the antigen that caused antibody formationNONPOLYMORPHIC MOLECULES ON B – LYMPHOCYTES: CD17 & CD20 are two non-polymorphicmolecules present on B cell surface. They are of practical value in classification of lymphoid molecules.(CD = Cell Differentiation)MACROPHAGES: are the large, mononuclear highly phagocytic cells, occurring in the walls of bloodvessels (adventitial cells) and in loose connective tissue (histocytes). They are usually fix but whenstimulated by inflammation they become mobile.FUNCTIONS OF MACROPHAGES: They present antigens to immunocompetent T cells. (they process and present antigens to CD$ + T cells which recognize antigen by binding to class II MHC molecules on macrophages. Note: T cells can’t recognize free unprocessed antigen) In addition to phagocytosis, macrophages also produce cytokines/monokines:interleukin – 1 (IL- 1) which promotes the differentiation of both T &B lymphocytes and TNF-α(Tissue Necroting Factor) is also produced which is a pro-inflammatory. Macrophages produce CytokinesIL-1enhanced activity of helper T cells Macrophages produce TNF inflammatory response i.e., swelling, redness, pain and edema They lyse tumor cells by secreting toxic metabolites and proteolytic enzymes thus play a role in immunosurveillance. They act as powerful effector cells in certain forms of cell-mediated immunity, such as the delayed hypersensitivity reactions (type IV).NATURAL KILLER CELLS: are large granular lymphocytes because they contain azurophilic cytoplasmicgranules. They are peripheral blood lymphocytes (10-15%). They differ from T and B cell function and
are also larger than B&T cells. They are lymphocytes in nature but do not pass through thymus formaturation. NK cells are devoid of cell surface immunoglobulins. They do not have immunologicalmemory and don’t have T cell receptors. NK cells have a basic role in innate immunity and areconsidered to provide first line of defense against tumors and virus infections.Surface molecules on NK cells are CD2 CD16 (Fc receptor for IgG) CD56FUNCTIONS OF NK CELLS:THEY are capable of lysing a variety of tumor cells, virus-infected cells, and fungi without priorsensitization hence called natural killer cells. NK cells destroy tumor cells by secreting cytotoxins similarto T lymphocytes.NK cells have Fc receptors for IgG, so they can lyse IgG- coated target cells. (ADCC: Antibody dependent,cell mediated cytotoxicity).INTERFERONS: ϒ – interferons are produced by NK cells that activate macrophages.NK cells ϒ – interferonsMacrophage activationWhereas, α andβinterferones are produced by virus infected cells that activate NK cells.Virus in fected cells α,βinterferonsNK cell activationDENDRITIC AND LANGERHAN’S CELLS:Dendritic cells are found in lymphoid tissue whereas,Langerhan’s cells are located in epidermis. Theyhave: 1- Dendritic cytoplasmic processes 2- Class II MHC molecules on surfaceFUNCTIONS:These cells themselves are poorly phagocytic in nature. They process and present antigens to CD4 + Tcells which recognize antigen by binding to class II MHC molecules on dendritic and Langerhan’s cells.Further see: difference between innate and acquired immunity, between passive and active immunity,between T and B lymphocytes etc.