Immune System

An immune system is a system of biological structures and processes within an organism that protects against disease. Immunology is a science that examines the structure and function of the immune system. Louis Pasteur is the father of Immunology. Because the human body provides an ideal environment for many microbes, they try to pass your skin barrier and enter. Your immune system is a body wide network of cells, tissues, and organs that has evolved to defend you against such "foreign" invasions. The proper targets of your immune system are infectious organisms-bacteria such as these streptococci; fungi; parasites, including these wormlike microbes that cause malaria; and viruses.

 Antibodies are immune system-related proteins called immunoglobulins. Each antibody consists of four polypeptides two heavy chains and two light chains joined to form a "Y" shaped molecule. The unique variable region allows an antibody to recognize its matching antigen An antibody, also known as an immunoglobulin, is a large Y-shaped protein produced by B-cells that is used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, called an antigen. Each tip of the "Y" of an antibody contains a paratope (a structure analogous to a lock) that is specific for one particular epitope (similarly analogous to a key) on an antigen, allowing these two structures to bind together with precision. Using this binding mechanism, an antibody can tag a microbe or an infected cell for attack by other parts of the immune system, or can neutralize its target directly (for example, by blocking a part of a microbe that is essential for its invasion and survival). The production of antibodies is the main function of the humoral immune system.

Antibody

Antigen
Antigens: substances foreign to the host which stimulate antibody production by B lymphocytes An antigen is any substance that causes the immune system to produce antibodies against it. The substance may be from the environment or formed within the body. The immune system will kill or neutralize any antigen that is recognized as a foreign and potentially harmful invader.

Epitope, or antigenic determinant, is a small, specific portion of an antigen recognized by the immune system such as antibodies. A single antigen usually has several different epitopes. The region on an antibody which recognizes the epitope is called a paratope. Antibodies fit precisely and bind to specific epitopes.

Discrimination of self from non-self The success of the immune system depends on its ability to discriminate between foreign (nonself) and host (self) cells. Survival requires both the ability to mount a destructive immune response against nonself and the inability to mount a destructive response against self.

Markers of Self
Epithelial cell Muscle cell

Nerve cell

Leukocyte

At the heart of the immune response is the ability to distinguish between self and non-self. Every cell in your body carries the same set of distinctive surface proteins that distinguish you as self. Normally your immune cells do not attack your own body tissues, which all carry the same pattern of self-markers; rather, your immune system coexists peaceably with your other body cells in a state known as selftolerance. This set of unique markers on human cells is called the major histocompatibility complex (MHC) proteins.

Markers of Non-self
Bacteria SARS virus

Non-self leukocyte Non-self nerve cell

Epitope Antigen

Antigen = any non-self substance Virus Bacteria Non-self cell (foreign cell) Epitope = The distinctive markers on antigens that trigger an immune response

Markers of Self
At the heart of the immune response is the ability to distinguish between "self" and "non-self." Every cell in your body carries the same set of distinctive surface proteins that distinguish you as "self." Normally your immune cells do not attack your own body tissues, which all carry the same pattern of self-markers; rather, your immune system coexists peaceably with your other body cells in a state known as selftolerance. This set of unique markers on human cells is called the major histocompatibility complex (MHC). There are two classes: MHC Class I proteins, which are on all cells, and MHC Class II proteins, which are only on certain specialized cells.

Markers of Non-Self
Any non-self substance capable of triggering an immune response is known as an antigen. An antigen can be a whole nonself cell, a bacterium, a virus, an MHC marker protein or even a portion of a protein from a foreign organism. The distinctive markers on antigens that trigger an immune response are called epitopes. When tissues or cells from another individual enter your body carrying such antigenic non-self epitopes, your immune cells react. This explains why transplanted tissues may be rejected as foreign and why antibodies will bind to them.

Body Defenses: Overview

Physical barriers: skin & epithelial linings & cilia Chemical: acids, mucous & lysozymes Immune defenses internal Innate, non-specific, immediate response (min/hrs) Acquired attack a specific pathogen (antigen) Steps in Immune defense Detect invader/foreign cells Communicate alarm & recruit immune cells Suppress or destroy invader

Blood
Blood is 55% liquid (plasma) and 45% cellular Cellular component of blood:
Red blood cells = carry oxygen White blood cells = immune system Platelets = clot blood

Stem Cell

All blood cells arise from a

pluri-potent stem cell found in bone marrow

Blood cells

Red Blood cells White blood cells (immune cells) Platelets

Cells of the innate immune response

All white blood cells (WBC) are known as leukocytes. White blood cells or leukocytes, are cells of the immune system involved in defending the body against both infectious disease and foreign materials. Five different and diverse types of leukocytes exist, but they are all produced and derived from a multipotent cell in the bone marrow known as a hematopoietic stem cell. They live for about 3 to 4 days in the average human body. Leukocytes are found throughout the body, including the blood and lymphatic system. White blood cells are often characterized as granulocytes or agranulocytes: Granulocytes (polymorphonuclear leukocytes): These granules are membrane-bound enzymes that act primarily in the digestion of endocytosed particles. There are three types of granulocytes: neutrophils, basophils, and eosinophils, which are named according to their staining properties. Neutrophils engulf bacteria upon contact and send out warning signals. Eosinophils deal with parasitic infections, while basophils are responsible for allergic response (releasing histamine). Neutrophils are mainly in charge of defending us from bacteria and fungus. Agranulocytes (mononuclear leukocytes): leukocytes characterized by the apparent absence of granules in their cytoplasm. Although the name implies a lack of granules these cells do contain non-specific azurophilic granules, which are lysosomes. The cells include lymphocytes, monocytes, and macrophages. Lymphocytes are common in the lymphatic system. There are three types: B cells, T cells and natural killer cells. Monocytes turn into macrophages in body tissues and gobble up foreign invaders. (Phagocytosis). If the number of leukocytes is higher than normal, the condition is called leukemia. If the number of leukocytes is lower, the condition is called leukopenia.

Inflammation
Inflammation- Cells that have been infected produce chemical called histamine. This chemical causes the blood capillaries to dilate (get wider) and become more porous. As a result the area swells, gets red, becomes warm, and is painful. This results in more white blood cells coming to the area to fight the infection. If the inflammation happens over the whole body we get a fever. The fever is the bodys way to combat bacteria and viruses. The higher temperature inhibits the pathogen from reproducing.

Inflammation

Diabetic foot ulcer

Phagocytic Cells Macrophages, Neutrophils, Eosinophils, Monocytes.

When WBCs are released from the bone marrow into the peripheral blood. Leukocytes fight infection through a process known as phagocytosis. During phagocytosis, the leukocytes surround and destroy foreign organisms. White blood cells also produce, transport, and distribute antibodies as part of the body's immune response. Mechanisms of phagocytic cells i) The phagocyte adheres to the microbe by recognizing the carbohydrates on the membrane. ii) Cytoplamsic arms surround it. iii) Lysomes kill & digest it.

 Neutrophil granulocytes are the most abundant type of white blood cells in mammals and form an essential part of the innate immune system.

Nonspecific Defenses, Phagocytes

Remove cellular debris and respond to invasion by foreign pathogens
Monocyte-macrophage system Fixed and free Microphages Neutrophils and eosinophils Move by diapedesis Exhibit chemotaxis

Nonspecific Defenses, Immunological surveillance

Constant monitoring of normal tissue by NK cells NK cells
Recognize cell surface markers on foreign cells Destroy cells with foreign antigens

Lymphocytes are the type of white blood cell responsible for acquired immunity. Lymphocytes enable the body to remember antigens and to distinguish self from nonself (foreign). Lymphocytes circulate in the bloodstream and lymphatic system and move into tissues as needed. Lymphocytes may be T cells or B cells. T Cells: T cells are produced in the thymus. There, they learn how to distinguish self from nonself. Only the T cells that ignore self antigen molecules are allowed to mature and leave the thymus. Mature T cells are stored in secondary lymphoid organs (lymph nodes, spleen, tonsils, appendix, and Peyer's patches in the small intestine). These cells circulate in the bloodstream and the lymphatic system. After they first encounter a foreign or abnormal cell, they are activated and search for those particular cells. There are different types of T cells: T cells are a key component in the cell-mediated response, the specific immune response that utilizes T cells to neutralize cells that have been infected with viruses and certain bacteria. There are three types of T cells: cytotoxic, helper, and suppressor T cells. Cytotoxic (Killer) T cells destroy virus-infected cells in the cell-mediated immune response. Killer T cells may kill these cells by making holes in their cell membrane and injecting enzymes into the cells or by binding with certain sites on their surface called death receptors. This binding triggers reactions within the foreign or abnormal cell that lead to death. Helper T cells play a part in activating both the antibody and the cell-mediated immune responses. Suppressor T cells deactivate T cells and B cells when needed, and thus prevent the immune response from becoming too intense.

B Cells: B cells are formed in the bone marrow. B cells have particular sites (receptors) on their surface where antigens can attach. B cells (B lymphocytes) are a type of white blood cell that gives rise to antibodies. The B-cell response to antigens has two stages: Primary immune response: When B cells first encounter an antigen, the antigen attaches to a receptor, stimulating the B cells. Some B cells change into memory cells, which remember that specific antigen, and others change into plasma cells. Helper T cells help B cells in this process. Plasma cells produce antibodies that are specific to the antigen that stimulated their production. After the first encounter with an antigen, production of enough of the specific antibody takes several days. Thus, the primary immune response is slow. Secondary immune response: But thereafter, whenever B cells encounter the antigen again, memory B cells very rapidly recognize the antigen, multiply, change into plasma cells, and produce antibodies. This response is quick and very effective. Null cells They are lymphocytes with cytotoxic properties. They are intermediate between T and B cells.

Organs of the Immune System

The organs concerned with immune reactions are called lymphoid organs because they are home to lymphocytes--the white blood cells that are key operatives of the immune system. Within these organs, the lymphocytes grow, develop, and are deployed. The lymphoid organs and the lymphoid cells constitute the lymphoid system. The lymphoid organs are of two types. 1. Primary lymphoid organs Bone marrow, Thymus. The B lymphocytes are formed in the bone marrow and T lymphocytes formed in the thymus. The mature, non functional lymphocytes migrate through the blood or lymph and accumulate in the secondary lymphoid organs. 2. Secondary lymphoid organs Spleen, lymph node, tonsils etc. In the secondary lymphoid organs, the lymphocytes are made functional. Here these cells are exposed to antigenic stimulus and become functional by producing specific antibodies or by producing sensitized cells.

Lymphatic System
The organs of your immune system are connected with one another and with other organs of the body by a network of lymphatic vessels. 1. Lymphatic vessels closely parallels the bodys veins and arteries - Lymphatic vessels carry lymph, a clear fluid that bathes the bodys tissues - Cells/fluids are exchanged between blood and lymphatic vessels, enabling the lymphatic system to monitor the body for invading microbes. 2. Lymph nodes contain high levels of immune cells

Immunity
Immunity is defined as resistance to infection. Immunity is broadly classified into two types, namely innate immunity and acquired immunity. There are 2 type of immunity:1.Innate immunity/natural immunity (Non specific) - Natural defense mechanism. (Resistance that a person has from the time of birth). 2. Acquired/Adaptive immunity (Specific) :- Resistance developed by man during his life. (Specific component of immunity is the ones that adapt themselves to the new disease and generate immunity against that specific pathogen). Acquired immunity - Two types of Acquired immunity. 1. Active Immunity - This is when immunity is induced by antigens in the host body itself. 2. Passive Immunity - This is when antibodies from an immune host is transferred to the host body. Active immunity - Two types of Active immunity. 1. Natural active immunity - derive from infection. e.g: Life time immunity following chicken pox. 2. Artificial active immunity due to immunization. eg: BCG, Measles etc. Passive Immunity - Two types of Passive immunity. 1. Natural Passive Immunity - derive from maternal. 2. Artificial Passive Immunity because of antibody transfer. eg: Anti tetanus serum is used for the treatment of tetanus.

Innate Immunity
Innate Immunity: All living organisms are naturally gifted with the resistance to certain infections from birth and this natural defense mechanism is known as innate immunity or natural immunity. It includes the general protective reactions of organisms against any invasion and not against any particular micro-organism, it is also known as non specific immunity. Organs Involved in Innate Immunity Eyes: tears wash away pathogens and have bacteriocidal enzymes. Skin: Difficult for a pathogen to penetrate, sweat creates high salt conditions, oil layer makes an inhospitable environment. Stomach: acid kills pathogens and sterilizes food. Nose: Mucus traps pathogens which are swallowed or blown out. Mouth: Natural microbiota prevents growth of opportunistic pathogens. Lungs: mucus lining of lungs traps pathogens and cilia move particles out to throat and it is swallowed. Large intestine: Natural microbiota prevents growth of opportunistic pathogens. Reproductive system: acid conditions and natural microbiota. Innate Immunity Influences Age Nutrition Endocrine functions: disorders including diabetes, hyperthyroidism, adrenal dysfunction and stress.

Adaptive or Acquired Immunity Acquired after birth Seen only in vertebrates Characteristic features are:
Diversity Specificity Self vs non-self Memory

Adaptive immunity. There are two types of adaptive immunity: humoral and cell-mediated. Humoral immunity is mediated by antibodies that are produced by B lymphocytes. It is the principal defense mechanism against extracellular microbes and their toxins, with secreted antibodies binding to microbes and toxins to assist in their elimination. Cell mediated immunity is mediated by T cells, with dendritic cells playing important roles in antigen presentation. T cells can function by various methods: (1) activating macrophages to kill phagocytosed microbes; (2) directly destroy infected cells; and (3) by releasing cytokines and alter the surrounding around them. Cytokines are cell signaling proteins that are produced in response to an antigen and function as chemical messengers for regulating the innate and adaptive immune systems.

Humoral (Antibody-mediated) immunity

The humoral immune response (HIR) is the aspect of immunity that is mediated by secreted antibodies produced in the cells of the B lymphocytes. B Cells (with co-stimulation) transform into plasma cells which secrete antibodies. Antigen can activate B cell in two ways:
direct binding provokes less vigorous response B cells process antigen (act as APC) and display processed antigen with MHC proteins
TH cells recognise processed antigen TH cells provide co-stimulation for B cell

Activated B cell
proliferates and differentiates
plasma cells secrete antibodies with same antigen binding properties as receptors memory B cells

Cell mediated immunity

When antigens are destroyed by cells without producing antibodies, the immunity is called cell mediated immunity. Cell-mediated immunity is an immune response that does not involve antibodies but rather involves the activation of macrophages, natural killer cells (NK), antigen-specific cytotoxic T-lymphocytes, and the release of various cytokines in response to an antigen. T cells must be activated Must have both surface antigen recognition and costimulation to activate T cell receptors recognise and bind to specific antigen presented with MHC complexes
T cell only activated if binds to antigen and receives costimulation
Co-stimulation provided by cytokines or membrane proteins

Need for co-stimulation prevents immune responses occurring accidentally

Recognition (binding to receptor) without costimulation results in anergy (prolonged state of inactivity) in both B and T cells

Once T cell co-stimulated it is activated

Proliferates Differentiates (forms more highly specialised cells)

Activation, proliferation and differentiation occurs in secondary lymphatic organs and tissues