Chapter six The Immune System Dr Sanaa Tork

Chapter six: The Immune System Dr. Sanaa Tork

In this chapter you will learn about : 1. What Is the Immune System and what does It do? The immune system is the body's defense against infectious organisms and other invaders. 2. The immune system is made up of a network of cells, tissues, and organs that work together to protect the body. 3. Distinguish between internal defense mechanisms of invertebrates and vertebrates 4. Distinguish between specific and nonspecific immune responses 5. The cells that are part of this defense system are white blood cells, or leukocytes. 6. Leukocytes are produced or stored in many locations throughout the body, including the thymus, spleen, and bone marrow. For this reason, they are called the lymphoid organs. There also clumps of lymphoid tissue throughout the body, primarily in the form of lymph nodes, that house the leukocytes. The leukocytes circulate through the body between the organs and nodes by means of the lymphatic vessels. Dr. Sanaa Tork

7. Two basic types of leukocytes combine to seek out and destroy the organisms or substances that cause disease. The phagocytes: are cells that chew up invading organisms. The most common type is the neutrophils which primarily fight bacteria. The lymphocytes: are cells that allow the body to remember and recognize previous invaders. 8. There are two kinds of lymphocytes: the B lymphocytes and the T lymphocytes. Lymphocytes start out in the bone marrow and either stay there and mature into B cells, or they leave for the thymus gland, where they mature into T cells. 9. B lymphocytes and T lymphocytes have separate jobs to do: B lymphocytes are like the body's military intelligence system, seeking out their targets and sending defenses to lock onto them. T cells are like the soldiers, destroying the invaders that the intelligence system has identified. 10. Explain the meaning of antigen (a foreign substance that invades the body and can detect by several types of cells work together to recognize and respond to it. These cells trigger the B lymphocytes to produce antibodies) 11. Antibodies are specialized proteins that lock onto specific antigens. 12. Compare active and passive immune system Dr. Sanaa Tork

13. Disorders of the immune system can be broken down into four main categories: immunodeficiency disorders (primary or acquired) , autoimmune disorders (in which the body's own immune system attacks its own tissue as foreign matter), allergic disorders (in which the immune system overreacts in response to an antigen), cancers of the immune system Dr. Sanaa Tork

Immunity Pathogens -Bactria -Virus -Parasite -Fungi Transplantation Foreign invaders (Non-self) Vaccination Immunity The ability of organism to resist infection by any forgein invaders (non-self) The Immune System Is an interacting set of specialized cells and proteins designed to identify and destroy foreign invaders and abnormal substances befor they can damage the body. Function of immune system: Defends body against foreign invaders Can distinguish between self (normal component of the body) and non-self (foreign component) Dr. Sanaa Tork

Immune system divided into: Non-specific immune System (innate or natural) Specific immune System (adaptive or acquired) innate Immune system Acquired Immune system There is immediate maximal response There is a lag time between exposure and maximal response Non-specific Exposure results in no immunologic memory Exposure results in immunologic memory Dr. Sanaa Tork

Innate defense against infection • All animals have some form of innate immunity (first line of defense) • Innate immune response are defenses that act the same whether or not an invader has been encountered. 1. Invertebrate immune system: Invertebrates rely on the innate immunity for example: ØInsects : a)have an exoskeleton, which is a dry barrier that keeps out of bacteria and viruses. b)Pathogens that breach that external defense confront a set of internal defense like: low p. H and secretion of lysozyme (digest cell wall of many bacteria) c)Circulating insect immune cells are capable of phagocytosis, engulfing and destroying foreign invaders d)Insects innate immune system also includes recognition proteins that bind to molecules found only on the outside of the bacteria, fungi and other pathogens e)Recognition of the invading microbes triggers the production of antimicrobial peptides that bring about the destruction of the invaders. 2 - Vertebrate immune system In vertebrates, innate immune system coexists with the more recently evolved system of acquired immune system Dr. Sanaa Tork

In mammals: innate immune System (natural) consists of: A- Anatomic Barriers (skin and mucous membrane) B- Cellular response - Phagocytosis (phagocytes): Ingestion and destruction of foreign particles by microphages and macrophages (type of white blood cells - Complement system - NK (natural killer) (another types of WBC, are not phagocytes, they attack cancer cells and virus –infected cells by releasing chemicals that promote programmed cell death) -mast cells - inflammatory reaction C- Soluble factors include proteins that either attack microbes directly or impede their reproduction. like interferons which are proteins produced by virus-infected cells that help other cells to resist viruses (stimulating the production of antiviral proteins that block viral reproduction)

A-The first lines of defense (Anatomical barriers ): The natural barriers 1 - the skin 2 - mucous membranes That protect organ system open to the external environment such as the digestive, respiratory, reproductive system and urinary system Dr. Sanaa Tork

Component Functions Skin and mucous membranes – mechanical factors Intact skin Mucous membranes Forms a physical barrier to the entrance of microbes. Inhibit the entrance of many microbes, but not as effective as intact skin. Mucus Traps microbes in respiratory and digestive tracts. Hairs (nostril hairs) Filter incoming air from microbes and dust in nose. Cilia (on cells lining the respiratory tract) Tear ducts Saliva Epiglottis Urine Together with mucus, trap and remove microbes and dust from upper respiratory tract. Tears dilute and wash away irritating substances and microbes. Washes microbes from surfaces of teeth and mucous membranes of mouth. Prevents microbes and dust from entering trachea. Washes microbes from urethra. Skin and mucous membranes – chemical factors Gastric juice Acid p. H of skin Unsaturated fatty acids Defensins (low molecular weight proteins) Surfactants Lysozyme and phospholipase Destroys bacteria and most toxins in stomach. Discourages growth of many microbes. Antibacterial substance in sebum (sweat). found in the lung and gastrointestinal tract have antimicrobial activity. in the lung (substances that promote phagocytosis of particles by phagocytic cells). found in tears, saliva and nasal secretions can breakdown the cell wall of bacteria and destabilize bacterial membranes (Antimicrobial substance) Skin and mucous membranes – biological factors The normal flora On the skin and in the gastrointestinal tract can prevent the colonization of pathogenic bacteria by secreting toxic substances or by competing with Dr. Sanaa Tork pathogenic bacteria for nutrients or attachment to cell surfaces.

2. Second line of defense (Cellular barrirs) • Microbes that breach a mammal’s external barriers are confronted by innate defense cells (second line of defense or cellular response). • These are classified as white blood cells (Phagocytes). • They are found in the interstitial fluid as well as blood vessels 1. Phagocytes: • They are produced throughout life by the bone marrow. They are stored there before being distributed around the body in the blood. • Neutrophils are a kind of phagocyte and form about 60% of the white cells in the blood. They travel throughout the body often leaving the blood by squeezing through the walls of capillaries to the tissues. During an infection they are releases in large numbers from their stores but they are short-lived cells. • Macrophages are also phagocytes but are larger than neutrophils and tend to be found in organs, such as the lungs, liver, spleen, kidney and lymph-nodes and through the interstitial fluid rather than remaining in the blood. they leave the bone marrow and travel in the blood as monocytes, which develop into macrophages once they leave the blood and settle in the organs, removing any foreign matter found there (eating any bacteria and virus infected cells they encounter).

• Macrophages are long-lived cells and play a crucial role initiating immune responses since they do not destroy pathogens completely, but cut them up to display antigens that can be recognized by lymphocytes. • Conclusion Macrophages : very large white cells that can move around body, or remain in certain tissues. Long lived, act as scavengers • • ingest bacteria, viruses, dead cells, dust most circulate in the blood, lymph and extracellular fluid they are attracted to the site of infection by chemicals given off by dying cells after ingesting a foreign invader, they “wear” pieces of it called antigens on their cell membrane receptors – this tells other types of immune system cells what to look for Dr. Sanaa Tork

Phases of phagocytosis: 1. Chemotaxis and adherence of microbe to phagocyte: when pathogens invade the body and cause an infection, some of the cells under attack respond by releasing chemicals such as histamine. These with any chemicals released by the pathogens themselves, attract passin phagocytes to the site. The phagocytes destroy the pathogens by phagocytosis. 2. Attachments and uptake (Ingestion of microbes by phagocyte): The phagocytes move towards the pathogens, which may be clustered together and covered in antibodies. This further stimulates the phagocytes to attack them. This is because phagocytes have receptor proteins on their surfaces that recognize antibody molecules and attach to them. 3. Digestion: formation of phagosome, fusion of phagosome with lysosyme to form phagolysosome, digestion of the ingested microbes and the formation of residual body. 4. After ingesting a foreign invader, they “wear” pieces of it called antigens (antigenic determinant) on their cell membrane receptors (Major Histocompatibility Complex (MHC)– in this case it named Antigen Presenting Cell (APC) this tells other types of immune system cells what to look for Dr. Sanaa Tork

Dr. Sanaa Tork

2. Second line of innate defence cont. Complement: • • • Complement is not a cell but a group of proteins set of about 30 different kinds of proteins that circulate in an inactive form in the blood These proteins can act together (in complement) with other defense mechanisms made in the liver Activated by infection: Substances on the surfaces of many microbes trigger a cascade of steps that activate the complement system, leading to the lyses (bursting) of the invaders, activated complements: – help to recruit phagocytes to site of inflammation and activate them – bind to receptors on phagocytes, helping to remove agent of infection – form pores in the invader or infected cell’s membrane (like the NKs do) – activate mast cells to release histamine and other factors – Certain complement proteins also help trigger the inflammatory responses Dr. Sanaa Tork

Dr. Sanaa Tork

Natural killer cells (NK cells) • instead of attacking the invaders, they attack the body’s own cells that have become infected by viruses • they also attack potential cancer cells, often before they form tumors • they bind to cells using an antibody “bridge”, then kill it by secreting a chemical (perforin) that makes holes in the cell membrane of the target cell. With enough holes, the cell will die, because water rushing inside the cell will induce osmotic swelling, and an influx of calcium may trigger apoptosis. Dr. Sanaa Tork

Mast cells • found in tissues (connective tissues and mucous membranes) like the skin, near blood vessels. • are activated after antigen binds to a specific type of antibody called Ig. E that is attached to receptors on the mast cell. • activated mast cells release substances that contribute to inflammation, such as histamine. • mast cells are important in allergic responses but are also part of the innate immune response, helping to protect from infection. Soluble factors • Interferon is a protein produced by virus-infected cells that inhibits the synthesis of viral proteins, leading to decreased viral replication. It also can cause apoptosis of virus-infected cells. Acute phase proteins – proteins in the plasma that increase during infection and inflammation – can be used diagnostically to give an indication of acute inflammation – An example of an acute phase protein is C-reactive protein, which fixes complement.

INNATE IMMUNE SYSTEM Cellular response 1 - Inflammatory response: 1 - Is a major component of our innate immune system 2 - any damage to tissue, whether caused by microorganisms or by physical injury triggers this response 3 - the injury area become red, worm and swollen this reaction is inflammation Inflammation The damage cells release chemical alarm signals such as histamine, which is a vasodilator. This causes localised swelling, redness, heat, pain. Can also cause high temperature, brings white cells to the area of infection The major results of inflammatory response are : 1 - to disinfect and clean injury area 2 - also helps prevent the spread of infection to surrounding tissues 3 - Clotting proteins present in blood plasma pass into the interstitial fluid during inflammation, along with platelets form local clots that help seal off the infected region and allow healing to begin.

Events that make up the inflammatory response in case where a pin has broken the skin, allowing infection by bacteria: 1 - the damage cells soon release chemical alarm signals like histamine and prostaglandin 2 - the chemicals spark the mobilization of various defenses, histamine and prostaglandin induces neighboring blood vessels to dilate and become leakier. Blood flow to the damage area increases and blood plasma pass out of the leaky vessels into the interstitial fluid of the affected tissues. Other chemicals (some of complement system) attract phagocyte to the affected area. The phagocytes squeeze between the cells of the blood vessels wall. The local increase in blood flow, fluid and cells produces the redness, heat, and swelling characteristic of inflammation. 3 - the phagocytes engulf bacteria and the remains of damage body cells, many blood cells die in the process, their remains are also engulfed and digested. The pus that often accumulates at the site of an infection consists mainly of dead white cells and fluid that has leaked from the capillaries during the inflammatory response. 4 - the inflammatory response may be localized or widespread (systemic), some bacteria or protozoans get into the blood or release toxins that carried throughout the body in the bloodstream. Another response to systemic infection is fever, an abnormally high body temperature. Dr. Sanaa Tork

Dr. Sanaa Tork

The release of histamine and prostaglandin causes local vessel dilation resulting in: • increased capillary permeability • increased blood flow more WBCs to site redness and warmth • phagocytes move out of vessels into intracellular fluid (ICF) • edema (swelling) due to fluids seeping from capillaries Fevers have both positive and negative effects on infection and body functions POSITIVE (moderate fever) • indicate a reaction to infection • stimulate phagocytosis and hasten tissue repair • slow bacterial growth – increases body temperature beyond the tolerance of some bacteria – decreases blood iron levels (Lactoferrin and Transferrin) NEGATIVE • extreme heat enzyme denaturation and interruption of normal biochemical reactions > 39° C (103°F) is dangerous > 41°C (105°F) could be fatal and requires medical attention, leading to a condition called septic shock which characterized by very high fever and low blood pressure

Immune system Acquired immune system Innate immune system Humoral (antibody mediated) Cellular (Cell mediated) immune response B-lymphocytes T-lymphocytes 1 st line of defense Skin Mucous membrane Dr. Sanaa Tork 2 nd line of defense Inflammation Phagocytosis Complement Interferons Natural killers

The acquired immune system 1. When the innate immune response fails to ward off a pathogen, the acquired immune response provides a second line of defenses. 2. Acquired immunity found only on vertebrates, is a set of defenses that are activated only after exposure to pathogens. 3. Once activated , the acquired immune response provides a strong defense against pathogens that is highly specific (acts against one infectious agent but not another) 4. Acquired immune response has a remarkable memory (it can remember antigen it has encountered before and react against them) 5. Can amplify certain innate responses such as inflammation and the complement system 6. acquired immunity is usually obtained by natural exposure to antigens but it can also be achieved by vaccination (vaccine is composed of a harmless variant or part of a diseasecausing microbe such as an inactived bacterial toxin, a dead or weakened microbe, or a pieces of a microbe) 7. Vaccination also known as immunization, because vaccine stimulates the immune system to mount specific defense against this harmless antigen, if it is exposed to the actual microbe, our immune system will respond quickly and effectively 8. For this reason the widespread of vaccination of children has virtually eliminated some viral diseases such as polio, smallpox and measles.

Induced Immunity (acquired immune response) Passive immunity Active immunity 1. An individual is given antibodies by another (received of premade antibodies) 2. Short-term resistance (weeks- 6 months) Production of a person’s own antibodies. Long lasting Natural Active Artificial Active When pathogen enters body in the normal way, we make antibodies • Vaccination – usually contains a safe antigen from the pathogen. • Person makes antibodies without becoming ill 3. Passive immunity is temporary because the recipient’s immune system is not stimulated by antigen Natural Passive Artificial Passive • Fetus obtains • Gamma globulin antibodies from its injection mother’s bloodstream. • extremely fast, but short • Baby receives lived antibodies in breast milk • (e. g. snake venom, which controlled by injecting the victim with antivenin) Dr. Sanaa Tork

• Antigens (antibody generating) – foreign molecules that stimulate an acquired immune response which responds with an increase in the number cells that either attack the invader directly or produce immune proteins called antibody • Most antigens are proteins or large polysaccharides on the surface of foreign invaders such as protein coat molecules of viruses, parts of the capsules and cell walls of bacteria and ; macromolecules on the surface cells of other kinds of organisms such as protozoan and parasitic worms or antigenic molecules on blood cells or tissue cells from other individuals or found dissolved in body fluids like bacterial toxins and bee venom. • Antibodies (immunoglogulins) – proteins found in the blood plasma that attached to one particular kind of antigen and helps counter its effects It produced by lymphocytes in response to antigens • Antibody usually recognizes and binds to a small surface-exposed region of an antigen that binds to antigen-binding site of antibody called antigenic determinant or epitope • Paratope or antigen-binding site: a specific region on the antibody molecule, recognize an antigenic determinant by the fact that the binding site and antigenic determinant have complementary shapes (like lock and key)

Paratope • An antigen usually has several different determinants, so different antibodies can bind to the same antigen • The immune system’s ability to defend against an enormous variety of antigens depends on a process known as clonal selection: (one particular antigen interacts only with the tiny fraction of lymphocytes bearing receptors specific to that antigen, once activated by the antigen, these few selected cell proliferate, forming a clone (genetically identical population) of thousands of cells all specific for the stimulating antigen) this antigen-driven cloning of lymphocytes- clonal selection is the vital step in the acquired immune response against infection

• Steps of clonal selection 1 - The first time an antigen enters the body and is swept into the lymph node 2 - antigenic determinants on its surface bind to the few B cells that have complementary receptors 3 -the selected cell is activated , grow, divided and differentiates into two distinct types of cells (memory cell and plasma cell (effector cell)) 4 - each plasma cell secrets antibody molecules (as many as 2000 copies of its antibody per second) each plasma cell require large amounts of endoplasmic reticulum, the secreted antibodies circulate in the blood and lymphatic fluid, contributing to the humoral immune response. Each effector cell lasts only 4 -5 days before dying off Dr. Sanaa Tork

• Two groups of cells produced by the activated B cells: 1. Plasma cell which are highly effective and combating infection, it lasts only 4 -5 days (short lived) 2. Memory cell which differ from effector cells in both appearance and function, it lasts for decades in the lymph nodes, activated by a second exposure to the antigen These steps show the primary immune response this phase occurs when lymphocytes are exposed to an antigen for the first time. When the produced memory cells activated by the second exposure to the same antigen, they initiate the secondary immune response, this response is faster and stronger than the first, the selected memory cells multiply quickly, producing a large second clone of lymphocytes, produces very high levels of antibodies than the first response, effector cells are often more effective against antigen than those produced during the primary response Dr. Sanaa Tork

Antibody Molecules 1. Antibodies are the weapons of the humoral immune response 2. Each antibody molecule is made of four peptide chains, two identical heavy chains (give the molecule its Y shape) and two identical light chains, each light chain bounded to one of the heavy chain, at the fork of the Y bonds the two heavy chains 3. Each of the four chains of the molecule has a c (constant) region and a V (variant) region. At the tip of each arm of the Y, a pair of V regions forms an antigen-binding site (a region of a molecule responsible for the antibody’s recognition and binding function) 4. A huge variety in the three-dimensional shapes of the binding sites of different antibody molecules arises from a similarly large variety in the amino acid sequences in the V regions. This structural variety account for the diversity of lymphocytes and given the humoral immune system the ability to react to any kind of antigen. Region binds to Complement Region binds to Macrophage

• • • The tail of the antibody molecule, formed by the constant regions of the heavy chains, helps mediate the disposal of the bound antigen. Antibodies with different kinds of heavy chains C regions are grouped into different classes. Human and other mammals have five major classes of antibodies called : Ig. A, Ig. D, Ig. E, Ig. G, Ig. M Antibodies inactive antigen by: 1. agglutination of microbes : makes pathogens clump together, enfances phagocytosis. 2. Neutralization (antitoxins) neutralize the toxins produced by bacteria, blocks viral binding sites, coats bacteria. 3. Activation of complement system (leads to cell lysis) digests the bacterial membrane, killing the bacterium 4. opsonisation (precipitation of dissolved antigens) coats the pathogen in protein that identifies them as foreign cells Dr. Sanaa Tork

Lymphocytes: • Lymphocytes are white blood cells, smaller than phagocytes. They have a large nucleus that fills most of the cell. , like all blood cells, lymphocytes originate from stem cells before birth in bone marrow, there are two types of lymphocyte 1. B lymphocytes (B cells) continue developing in the bone marrow until they are mature and then spread throughout the body concentrating in lymph nodes and the spleen. 2. T lymphocytes ( T cells ) leave the bone marrow and collect in the thymus where they mature. Only mature lymphocytes can carry out immune responses. Both types of lymphocytes are responsible for the acquired immune system Dr. Sanaa Tork

During the maturation process : • many different types of B and T lymphocyte develop, Perhaps many millions, certain genes in the lymphocyte cell are turn on , this leads the cell to synthesize molecules of specific protein, incorporated into the plasma membrane. The molecules are antigen receptors, capable of binding one specific type of antigen, each type is specialized to respond to one antigen, giving the immune system as a whole the ability to respond to almost any type of pathogen that enters the body. • Each T and B cells has about 100 000 antigen receptors on a single cell and all the receptors on a single cell are identical- they all recognize the same antigen • In case of B cells , the receptors are almost identical to the particular antibody that the B cell will secrete. • When mature, both B and T cells circulate between the blood and the lymph. This ensures that they are distributed throughout the body so that they come into contact with any pathogens and with each other. • Acquired immune responses depend on B and T cells interacting with each other to give an effective defense. • When a B and T cell within a lymphatic organ first confronts the specific antigen it is programmed to recognize, it differentiates further and becomes a fully mature component of the immune system. Dr. Sanaa Tork

Two types of acquired immune response: 1 - The humoral immune response: - involves the secretion of antibodies by B cell into the blood and lymph, - the humoral defense defends primary against bacteria and viruses present in body fluids - this defense can be passively transferred by injecting blood plasma (containing antibodies) from an immune individual into a non immune individual 2 - The cell- mediated immune response: - produced by T cells - this defensive system results from the action of defensive cells rather than the defensive proteins of the humoral response -certain T cells attack body cells that are infected with bacteria or viruses, others function indirectly by promoting phagocytosis by other blood cells and by stimulating B cells to produce antibodies Thus T cells play a part in both the cell- mediated and humoral immune response Dr. Sanaa Tork

• Briefly, some Tcells (TH) coordinate the immune response, stimulating B cells to divide and then secrete antibodies into the blood; these antibodies destroy the antigenic pathogens. Other Tcells (NK) seek out and kill any of the body’s own cells that are infected with pathogens. To do this they must make direct contact with infected cells. Dr. Sanaa Tork

T helper cells stimulate humoral and cell-mediated immune responses • • • Helper T cells interact with others white blood cells –including macrophages, B cells, and other types of immune cells-that function as antigen –presenting cells. All the cell mediate immune response and much of the humoral immune response depend on the precise interaction of antigen-presenting cells and helper T cells. The interaction activate other cells of the immune system The antigen presenting cells presents a foreign antigen to helper T cell. The ability of a helper T cell to recognize a unique self-nonself complex on an antigen – presenting cell depends on the receptors embedded in the T cell’s plasma membrane. T cell receptor actually has two binding sites: one for antigen and one self protein. The two binding sites enable T cell receptor to recognize the overall shape of a self-nonself complex on an antigen –presenting cell. The immune response is highly specific because the receptors on each helper T cell can bind only one kind of self – nonself complex on an antigen-presenting cell. The binding of T cell receptor to self –nonself complex activates the helper T cell Other kinds of the signals can enhance this activation such as interleukin-1 which diffuse to the T helper cell and stimulate it. Activated helper T cell promote the immune response in several ways, being the secretion of addational stimulatory proteins such as: interleukin-2 which make T helper grow and divide, producing both memory cells and qdditional active helper T cells. It also activate B cells , thus stimulating the humoral immune response, and stimulates the activity of cytotoxic T cells Dr. Sanaa Tork

B-lymphocytes • • The antibody- producing B-cells of the humoral response make up one arm of the acquired immune response network Humoral defense system identifies and helps destroy invaders that are in our blood, lymph or interstitial fluid (outside our body cell) B cell respond to free antigens present on the surface of the body fluids, T cells respond only to antigens present on the surface of the body’s own cells B lymphocytes make antibodies = immunoglobulins 1000 s of different B cells, each recognises a different antigen on the surface of a macrophage. Each antigen stimulates production of a single specific antibody B cells (along with T cells) come in contact with antigen. They are stimulated (by T cells) to produce many clones, plasma cells, which make antibodies. Memory B cells – faster, more sensitive reaction = secondary response Dr. Sanaa Tork

How B-cells work… Pathogen (e. g. bacteria, virus) Macrophage B-cells Each recognise a different antigen. The correct one develops into… Plasma cells Clones of the correct B-cell, which produce antibodies Macrophage Phagocytoses pathogen and displays antigens on surface Dr. Sanaa Tork 1 st meeting a pathogen, this process takes 10 -14 days Memory B cell= subesquent meetings, takes about 5 days

T lymphocytes • • • Mature T cells have specific cell surface receptors called T cell receptors. T cells are activated when they encounter this antigen in contact with another host cell. Sometimes this is a macrophage that has engulfed a pathogen and cut it up to expose the pathogen's surface molecules or it may be a body cell that has been invaded by a pathogen and is similarly displaying the antigen on its plasma membrane as a kind of “signal”. Those T cells that have matching receptors respond to the antigen by dividing. • There are two main types of T cell: 1. T helper cells; 2. Killer T cells. when T helper cells are activated they release hormone – like cytokines that stimulate appropriate B cells to divide, develop into plasma cells and secrete antibodies. Some T helper cells secret cytokines that stimulate macrophges to carry out phagocytosis more vigorously. Killer T cells search the body for cells that have become invaded by pathogens and are displaying foreign antigens from the pathogens on their plasma membranes. Killer T cells recognise the antigens, attach themselves to the surface of infected cells and secrete toxic substances, killing the body cells and the pathogens inside. In addition to the helper cells and killer cells, memory T cells are produced which remain in the body and become active very quickly during the secondary response to antigens. Dr. Sanaa Tork

T-lymphocytes Mature in Thymus, which is most active just before and after birth. The thymus starts to shrink during puberty. Helper T-Cells • Recognise antigens on surface of leukocytes, especially macrophages • Enlagre and form a clone of T-helper cells • Secrete interferon and cytokines which stimulate B-cells and stimulate killer -cells • Can be infected by HIV Killer T-Cells Also called cytotoxic • Destroy abnormal body cells, e. g. virus infected or cancer cells • Stimulated by cytokines (THcells) • Release perforin, which forms pores in target cells. This allows water and ions in = lysis Suppressor T-Cells • Control the immune system when the antigen /pathogen has been destroyed • Only recently discovered so little is known about them Dr. Sanaa Tork Memory T-Cells • Can survive a long time and give lifelong immunity from infection • Can stimulate memory B-cells to produce antibodies • Can trigger production of killer T cells

Abnormal cell e. g cancer cell, infected cell Killer T-cell recognises antigen How T-cells work… X Antigen Clones of killer T-cell attach to antigen Normal cell X Killer T-cells release perforin pores X Helper T-cell stimulates correct killer T-cell to multiply Helper T-cell also stimulates B-cells to make antibodies Suppressor T-cells turn off immune response Abnormal cell gains water, swells and bursts Memory Tcells stay in circulation Dr. Sanaa Tork

Dr. Sanaa Tork

Duration of immunity Memory B-cells circulate for a long time. If the same pathogen infects the body again, these B-cells can produce large amounts of specific antibody very quickly. This is why you usually don’t suffer from the same infection twice. Memory T-cells survive a long time and trigger an immune response Immune disorders • Sometimes the body produces antibodies against its own tissues e. g. autoimmune diseases e. g. rhumatoid arthritis, Crohn’s disease, SCID (bubble boy disease), Asthma In Lupus, for example, B cells make antibodies against a wide range of self molecules such as histones and DNA released by the normal breakdown of body cells. Lupus is characterized by skin rashes, fever, arthritis and kidney mal-function In rheumatoid arthritis is another antibody-mediated autoimmune disease, it leads to damage and painful inflammation of the cartilage and bone of joints In multiple sclerosis, T cells react against the myelin sheath , peoples with MS has a number of serious neurological abnormalities • In Crohn disease, a chronic inflammation of the digestive tract, may be caused by an autoimmune reaction against normal flora that inhabit the intestinal tract. Dr. Sanaa Tork

Immune deficiency diseases: here immune deficient people lack one or more of the component of the immune system this makes them susceptible to frequent and recurrent infections. In rare congenital disease severe combined immunodeficiency (SCID) both T and B cells are inactive or absent, people with SCID are sensitive to even minor infection. • Allergies occur when the body reacts to antigens in our surrounding e. g. peanut • Antigens that cause allergies are called allergins • Tumours – in most cases the body recognises tumours as being bad, because they express abnormal molecules on the cell surface. However sometimes the body doesn’t notice and cancers can develop Dr. Sanaa Tork