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TRANSMISSION OF PATHOGENS Infective agents can be transmitted from one host to another by: A VECTOR A carrying vector eg rats & fleas An injecting vector eg mosquito – malaria direct contact Droplet infection in air breathed or sneezed out Sexual contact Contaminated food or water Injecting with infected needle & syringe Transmission of Disease Diseases can be transmitted in three broadly different ways: Contact transmission Vehicle transmission Airborne droplet transmission Contact with contaminated blood Insects carrying disease Direct contact with skin Vector transmission Contact with contaminated food Vector Transmission Many pathogens have more than one host. An intermediate host may transmit the pathogen to its primary host. Bites from a variety of animals can introduce pathogens. Fleas Rodents Mosquitoes Carried on many animals, they are responsible for the spread of numerous bacterial diseases, including bubonic plague. Hantaviruses are carried by rodents. Infection occurs when humans come in contact with rodent droppings. Anopheles gambiae, a tropical mosquito, is one of the vectors for the malarial parasite. Ticks Fruit bat Foxes The deer tick transmits Lyme disease from wild mammals to humans. Hendra viruses are transmitted in the droppings of fruit bats. Rabies is transmitted in bites from infected foxes and other mammals (e.g. dogs). Contact Transmission Pathogens may be spread by contact with other infected humans or animals. Droplet Transmission Indirect Contact Direct Contact Mucus droplets carrying disease are discharged into the air. Includes touching contaminated objects. Direct transmission of an agent by physical contact between its source and a potential host. Examples: coughing Examples: Examples: sneezing eating utensils touching laughing drinking cups kissing talking bedding sexual intercourse toys money used syringes Vehicle Transmission Disease may be transmitted through a medium such as blood, water, food, or air. Waterborne Diseases Food-borne Diseases Blood-borne Diseases Usually associated with regions with poor sanitation, especially where fecal material enters the water supply. Hepatitis B and meningococcal disease can be spread by sharing drinking bottles. Occur when food is insufficiently cooked, poorly stored, or prepared in an unsanitary environment. Blood-borne diseases are transmitted when body fluids from at least two animals (one of them infected) are mixed. Examples: Typhoid fever, cholera and hepatitis B Examples: Bacterial food poisoning, e.g. salmonellosis and hydatids Examples: most viral pathogens (including HIV, hepatitis) Bacteria and Disease Lactobacillus bacteria are part of the normal flora found on healthy humans Of the many species of bacteria that exist in the world, relatively few are Photo: CDC/Dr Mike Miller. pathogenic. Most bacteria form part of the normal microflora found on healthy humans. Cell nucleus Bacteria infect a host in Human vaginal epithelial cell order to exploit the food potential of the host’s body tissues. The fact that this exploitation causes disease is not in the interest of the bacteria; a healthy host is better than a sick one. The Body’s Defenses If microorganisms never encountered resistance from our defenses, we would be constantly ill and would eventually die of various diseases. Nonspecific Defense Mechanisms Specific Defense Mechanisms 1st line of defense 2nd line of defense 3rd line of defense Intact skin Phagocytic white blood cells Specialized lymphocytes (B-cells and T-cells) Inflammation and fever Antibodies Mucous membranes and their secretions Antimicrobial substances Non specific defences These defences do not differentiate between any disease causing agents. They stop all things from entering the body. First line of Defence: • Enzymes in mucus, tears, gut • Skin • Sweat (contains acid) • Ciliated epithelium • Histamines Eyes Tears wash out pathogens and also contain an enzyme that can kill bacteria. Nose Mucus traps pathogens which are then swallowed or blown out in coughs and sneezes. Skin The outer layer of skin is dead and difficult for pathogens to grow on or penetrate. Cuts allow pathogens to gain entry to the body. Reproductive system Slightly acid conditions in the vagina and urethra help to stop the growth of pathogens. Mouth Friendly bacteria help to prevent the growth of harmful pathogens. Saliva cleans and removes bacteria. Lungs Mucus in the lungs traps bacteria and fungal spores. Tiny hairs, called cilia, move the mucus to the back of the throat where it is swallowed. Stomach Acid helps to sterilise the food. Large intestine Friendly bacteria help to stop the growth of harmful pathogens. Faeces contains over 30% live bacteria. Second line of Defence THE NON-SPECIFIC IMMUNE RESPONSE Defence against disease nd (2 Line) Cell-mediated defences involving phagocytic cells appear to have been present early in the evolution of animals. Most organisms are able to distinguish self from not self. Recognising SELF The bodies immune system has the ability to recognise ‘self’ from ‘non-self’. This is possible because all our cells have specific protein markers on their surface called ANTIGENS. Genes on chromosome number 6, called the Major Histocompatibility Complex (MHC), code for the production of these self MHC antigens Distinguishing Self The human immune system achieves self-recognition through the major histocompatibility complex Location of genes on chromosome 6 for producing the HLA antigens Class I HLA Class II HLA (MHC). The MHC is a cluster of tightly linked genes on chromosome 6 in humans. These genes code for protein molecules (MHC antigens) which are attached to the surface of body cells. HLA surface proteins (antigens) provide a chemical signature that allows the immune system to recognize the body’s own cells MHC The MHC antigens are used by the immune system to recognize its own and foreign material. Class I MHC antigens are located on the surface of virtually all human cells. Class II MHC antigens are restricted to macrophages and B-lymphocytes Second Line of Defence:(Internal) These include: Once a foreign material enters the body the second line of defense comes into play. ‘Phagocytes’ & ‘Lymphocytes’ which are White blood cells Proteins called Antibodies which destroy pathogens ‘Complement system’ which is large blood proteins that destroy bacteria ‘Interferon’ (proteins) which are produced by virus infected cells and interfere with viral reproduction Inflammation Blood Cells White Blood Cells Phagocytes *Neutrophil *Macrophages Lymphocytes Phagocytes Produced throughout life by the bone marrow. Scavengers – remove dead cells and microorganisms. Phagocytes are white blood cells that ingest microbes and digest them by phagocytosis. The Action of Phagocytes Detection Phagocyte detects microbes by the chemicals they give off (chemotaxis), and the microbes stick to its surface. Microbes Nucleus Ingestion The phagocyte wraps around the microbe, engulfing it and forming a vesicle. Phagosome Lysosome Phagosome forms A phagosome (phagocytic vesicle) is formed, enclosing the microbes in a membrane. Fusion with lysosome Phagosome fuses with a lysosome (containing powerful enzymes that can digest the microbe). Digestion The microbes are broken down by enzymes into their chemical constituents. Discharge Indigestible material is discharged from the phagocyte. Phagocytosis Neutrophils 60% of WBCs ‘Patrol tissues’ as they squeeze out of the capillaries. Large numbers are released during infections Short lived – die after digesting bacteria Dead neutrophils make up a large proportion of puss. Monocytes Monocytes and neutrophils share the same stem cell. (Monocytes are to macrophages what Bruce Wayne is to Batman.) They are produced by the marrow, circulate for five to eight days, and then enter the tissues where they are mysteriously transformed into macrophages. Here they serve as the welcome wagon for any outside invaders and are capable of "processing" foreign antigens and "presenting" them to the immunocompetent lymphocytes. They are also capable of the more brutal activity of phagocytosis Eosinophils Eosinophils respond to chemotaxis, substances released by bacteria and components of the complement system and can perform phagocytosis. They are often seen at the site of invasive parasitic infestations and allergic (immediate hypersensitivity) responses. Individuals with chronic allergic conditions (such as atopic rhinitis or extrinsic asthma) typically have elevated circulating eosinophil count. Lymphocytes When activated by whatever means, lymphocytes can become very large. Although such cells are classically associated with viral infection, they may also be seen in bacterial and other infections and in allergic conditions. Platelets Platelets are small fragments of cells found in blood and their main function is involved in the blood clotting process. Macrophages Larger than neutrophils. Found in the organs, not the blood. Made in bone marrow as monocytes, called macrophages once they reach organs. Long lived Initiate immune responses as they display antigens from the pathogens to the lymphocytes. Defensive molecules Cytokines are an important group of signalling molecules that coordinate many aspects of our immune responses. They are small glycoproteins released by body cells as a means of communication with the immune system. Cytokines indicate the presence of damage or a potentially dangerous invader. Interferons are a class of cytokines. They are produced by most virus-infected cells during viral invasion and are also secreted by activated T cells. Their production and secretion is triggered by the presence of double-stranded RNA, which does not occur in uninfected cells. Interferons are very active in interfering with virus replication in cells. Complement system The complement system is a very complex group of 20 serum proteins which is activated in a cascade fashion. Three different pathways involved in complement activation. The first recognizes antigen-antibody complexes, the second spontaneously activates on contact with pathogenic cell surfaces, the third recognizes mannose sugars, which tend to appear only on pathogenic cell surfaces. A cascade of protein activity follows complement activation; this cascade can result in a variety of effects including phagocytosis of the pathogen, destruction of the pathogen by formation and activation of the membrane attack complex, and inflammation. The organs of your immune system are positioned throughout your body. They 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. Bone marrow, the soft tissue in the hollow center of bones, is the ultimate source of all blood cells, including the immune cells. The thymus is an organ that lies behind the breastbone; lymphocytes known as T lymphocytes, or just T cells, mature there. The spleen is a flattened organ at the upper left of the abdomen. Like the lymph nodes, the spleen contains specialized compartments where immune cells gather and confront antigens. The Third Line of Defense Specific resistance is a third line of defense. It forms the immune response and targets The 2nd line of defense specific pathogens. The 3rd line of defense Specialized cells of the immune B cell: Antibody production system, called lymphocytes Lymphocytes are: T cell: Cell-mediated immunity B-cells: produce specific proteins called antibodies, which are produced against specific antigens. T-cells: target pathogens directly. Lymphocyte (SEM) Specific Immunity This is the third line of defense and has the ability to remember a previously encountered organisms so as to attack them. This includes: Immune responses ‘Specificity’: that is they act on certain foreign objects ‘Memory’: this is where the system remembers the foreign object. Plant immunity To defend against parasites plants use encapsulation, a vast array of chemical defences including antibiotics, enzymes and hormones that disrupt the function of parasites. They also allow rapid death of tissue under attack. Immune system of mammals The immune response of mammals involves: Humoral immunity – antibodies are released by B cells Cell mediated immunity - active destruction by T cells SPECIFIC IMMUNITY Two main groups of LYMPHOCYTES are involved in specific immunity. All lymphocytes are made in the bone marrow. Some mature in the bone marrow to become B cells others leave early to mature in the Thymus, they become T cells. Specific Immunity This is the third line of defense and has the ability to remember a previously encountered organisms so as to attack them. This includes: • Immune responses • ‘Specificity’: that is they act on certain foreign objects • ‘Memory’: this is where the system remembers the foreign object. White blood cells (leukocytes) Are a diverse group of blood cells, all are Manufactured in the bone marrow Possess a nucleus Play a role in response to pathogens and/or foreign material Capable of independent movement Many have a role in non-specific defences. Lymphocytes are important in specific defences. Handout Short lived and broken down once infection is resolved. Live for many years making small amounts of antibody. Lymphocytes Produce antibodies B-cells mature in bone marrow then concentrate in lymph nodes and spleen T-cells mature in thymus B and T cells mature then circulate in the blood and lymph Circulation ensures they come into contact with pathogens and each other Humoral immune response Humoral means in the body fluids (blood and extracellular) B cells are lymphocytes that produce large quantities of antibodies when stimulated by particular antigens. This is the humoral immune response. B cells are made in the bone marrow and spleen. B cells have immunoglobulins (a protein that identify antigens) on their surface. Each B cell identifies one kind of antigen only. When B cells identify an antigen, it replicates rapidly to produce large numbers of special cells called PLASMA cells. Humoral Immunity Other B-cells recognize different antigens Surface antigen The humoral response begins when a foreign protein (antigen) activates a particular B-cell. The particular B-cells multiply, to form many plasma cells. Plasma cells make antibodies specifically designed to attack and kill the identified pathogen. Some B-cells differentiate into long lived memory cells. These memory cells will rapidly produce antibodies if the same pathogen enters the body again. Recognition B-cell Pathogen Plasma cells Second Exposure Antibodies Original B-cell B-cells (also called B-lymphocytes) originate B–Cells and mature in the bone marrow of the long bones (e.g. the femur). They migrate from the bone marrow to the lymphatic organs. B-cells defend against: Bacteria and viruses outside the cell Toxins produced by bacteria (free antigens) Each B-cell can produce antibodies against only one specific antigen. A mature B-cell may carry as many as 100 000 antibody molecules embedded in its surface membrane. B-cell (B-lymphocyte) B -Lymphocytes There are approx 10 million different Blymphocytes, each of which make a different antibody. The huge variety is caused by genes coding for antibodies changing slightly during development. There are a small group of clones of each type of B-lymphocyte B -Lymphocytes At the clone stage antibodies do not leave the Bcells. The antibodies are embedded in the plasma membrane of the cell and are called antibody receptors. When the receptors in the membrane recognise an antigen on the surface of the pathogen the B-cell divides rapidly. The antigens are presented to the B-cells by macrophages B–Cell Differentiation B-cells differentiate into two kinds of cells: Memory cells Memory cell When these cells encounter the same antigen again (even years or decades after the initial infection), they rapidly differentiate into antibody-producing plasma cells. Plasma cells These cells secrete antibodies against antigens. Each plasma cell lives for only Antibody a few days, but can produce about 2000 antibody molecules per second. Plasma cell B -Lymphocytes B -Lymphocytes Some activated B cells become PLASMA CELLS these produce lots of antibodies, < 1000/sec The antibodies travel to the blood, lymph, lining of gut and lungs. The number of plasma cells goes down after a few weeks Antibodies stay in the blood longer but eventually their numbers go down too. B -Lymphocytes Some activated B cells become MEMORY CELLS. Memory cells divide rapidly as soon as the antigen is reintroduced. There are many more memory cells than there were clone cells. When the pathogen/infection infects again it is destroyed before any symptoms show. How B-cells work… Pathogen (e.g. bacteria, virus) Macrophage B-cells Each recognise a different antigen. The correct one develops into… Macrophage Phagocytoses pathogen and displays antigens on surface Plasma cells Clones of the correct B-cell, which produce antibodies 1st meeting a pathogen, this process takes 10-14 days Memory B cell= subesquent meetings, takes about 5 days Antibodies Also known as immunoglobulins Globular glycoproteins The heavy and light chains are polypeptides The chains are held together by disulphide bridges Each antibody has 2 identical antigen binding sites – variable regions. The order of amino acids in the variable region determines the shape of the binding site Antibodies Antibodies are specific proteins produced by lymphocytes that react with particular antigen molecules Antigen – substance capable of binding with antibody Antibody – specific protein which binds with antigen How Antibodies work Some act as labels to identify antigens for phagocytes Some work as antitoxins i.e. they block toxins for e.g. those causing diphtheria and tetanus Some attach to bacterial flagella making them less active and easier for phagocytes to engulf Some cause agglutination (clumping together) of bacteria making them less likely to spread Antigens and Antibodies Molecular model Antibodies recognize and bind to antigens. Symboli c model Antibody Antibodies are highly specific and can help destroy antigens. Each antibody has at least two sites that can bind to an One of the two binding sites on the antibody antigen. Antigen Antibody Structure Most of an antibody molecule is made up of constant regions which are the same for all antibodies of the same class. Hinge region connecting the light and heavy chains. This allows the two chains to open and close (like a clothes peg). Heavy chain (long) Light chain (short) Variable regions form the antigen-binding sites. Each antibody can bind two antigen molecules. Antibody The antigen-binding sites between antibodies of different types. Antigen: Most antigens are proteins or large polysaccharides and are often parts of invading microbes. Examples: cell walls, flagella, bacterial toxins, viral proteins and other microbial surfaces. Type Number of antigen binding sites Site of action Functions IgG 2 Blood Increase Tissue fluid CAN CROSS PLACENTA macrophage activity Antitoxins Agglutination Blood Agglutination IgM 10 Tissue fluid IgA 2 or 4 Secretions (saliva, tears, small intestine, vaginal, prostate, nasal, breast milk) Stop bacteria adhering to host cells Prevents bacteria forming colonies on mucous membranes IgE 2 Tissues Activate mast cells HISTAMINE Worm response Blood group Antigens present on the red blood cells A Contains anti-B antibodies, but no antibodies that would antigen A B Antibodies present in the plasma antigen B AB antigens A and B O Neither antigen A nor B attack its own antigen A Contains anti-A antibodies, but no antibodies that would attack its own antigen B Contains neither anti-A or anti-B antibodies Contains both anti-A and anti-B antibodies Clonal Selection Theory The clonal selection theory is the accepted model for how the immune system responds to infection and how certain types of B and T lymphocytes are selected for specific antigens invading the body. There are 4 parts: Each lymphocyte has a single type of receptor with a unique specificity. Receptor occupation is required for cell activation. The differentiated effector cells derived from an activated lymphocyte has receptors of identical specificity as the parental cell. Those lymphocytes bearing receptors for self molecules will be deleted early. Cell mediated immune response T cells are responsible for cell mediated immune responses. They act against virus infected cells, cancer cells and transplanted tissue T cells are formed in the thymus gland from precursor cells made in bone marrow T-cells originate from stem cells and mature after passing through the thymus gland. T-Cells They respond only to antigenic fragments that have been processed and presented bound to the MHC by infected cells or macrophages (phagocytic cells). T-cells defend against: Molecular Immunology Foundation, www.mifoundation.org Intracellular bacteria and viruses. Protozoa, fungi, flatworms, and roundworms. Cancerous cells and transplanted foreign tissue. T-cells attacking a cancer cell T-Cells T-cells can differentiate into four specialized types of cell: Helper T-cell Activates cytotoxic T cells and other helper T cells. Necessary for B-cell activation. Suppressor T-cell Regulates immune response by turning it off when no more antigen is present. T-cell for delayed hypersensitivity Causes inflammation in allergic reactions and rejection of tissue transplants. Cytotoxic (Killer) T-cell Destroys target cells on contact. Types of T cells 1. 2. T helper cells – acts with T cytotoxic cells (Killer T cells) to destroy fungi, virus infected cells, cancer cells and transplanted tissue Work with B plasma cells to create antibodies which inactive toxins bind to bacteria, causing clumping and promoting engulfment by phagocytes Cell Mediated Immunity Antigens, such as those produced by abnormal cells, are identified by and activate specific killer T-cells. Killer T-cells Antigen produced by abnormal cell Recognitio n Helper T-cell Note: HIV (the AIDS virus) disrupts the cellular immune system by destroying helper T-cells. The killer T-cells attach to and destroy the abnormal cell. Killer T-cells remain as memory cells to quickly attack any abnormal cells that reappear. With the assistance of helper T-cells the killer T-cells begin to multiply. T-Lymphocytes After activation the cell divides to form: T-helper cells – secrete CYTOKINES help B cells divide stimulate macrophages Cytotoxic T cells (killer T cells) Kill body cells displaying antigen Memory T cells remain in body 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 FUNCTIONING OF THE IMMUNE SYSTEM HUMORAL (ANTIBODY MEDIATED) IMMUNE RESPONSE CELL MEDIATED IMMUNE RESPONSE ANTIGEN (1ST EXPOSURE) ENGULFED BY MACROPHAGE FREE ANTIGENS DIRECTLY ACTIVATE ANTIGENS DISPLAYED BY INFECTED CELLS ACTIVATE BECOMES APC STIMULATES B CELLS STIMULATES STIMULATES MEMORY HELPER T CELLS GIVES RISE TO STIMULATES PLASMA CELLS HELPER T CELLS MEMORY B CELLS SECRETE ANTIBODIES STIMULATES ANTIGEN (2nd EXPOSURE) STIMULATES CYTOTOXIC T CELL GIVES RISE TO STIMULATES MEMORY T CELLS ACTIVE CYTOTOXIC T CELL Role of antigen receptors in the immune response • Both B cells and T cells carry customized receptor molecules that allow them to recognize and respond to their specific targets. • The B cell’s antigen-specific receptor that sits on its outer surface is also a sample of the antibody it is prepared to manufacture; this antibody-receptor recognizes antigen in its natural state. • The T cell’s receptor systems are more complex. T cells can recognize an antigen only after the antigen is processed and presented in combination with a special type of major histocompatibility complex (MHC) marker. • Killer T cells only recognize antigens in the grasp of Class I MHC markers, while helper T cells only recognize antigens in the grasp of Class II MHC markers. This complicated arrangement assures that T cells act only on precise targets and at close range. Role of cytokines in immune response • Cytokines are diverse and potent chemical messengers secreted by the cells of your immune system. They are the chief communication signals of your T cells. Cytokines include interleukins, growth factors, and interferons. • Lymphocytes, including both T cells and B cells, secrete cytokines. Cytokines are also secreted by monocytes and macrophages. Interferons are naturally occurring cytokines that may boost the immune system’s ability to recognize cancer as a foreign invader. • Binding to specific receptors on target cells, cytokines recruit many other cells and substances to the field of action. Cytokines encourage cell growth, promote cell activation, direct cellular traffic, and destroy target cells-including cancer cells. • When cytokines attract specific cell types to an area, they are called chemokines. These are released at the site of injury or infection and call other immune cells to the region to help repair damage and defend against infection. Immunity to Infection Immunity is the acquired ability to defend against infection by disease-causing organisms. The adaptive immune system is responsible for immunity. Vaccines The word vaccination comes from vacca, which is Latin for cow. Edward Jenner could be considered the “father of vaccination” as he developed a method of protecting people from smallpox. He noticed that milkmaids who had previously been infected with cowpox (similar disease but milder) did not catch smallpox. In 1796, Jenner deliberately infected a small boy with material from a cowpox pustule, then six weeks later infected the boy with material from a smallpox pustule. The boy survived! Our current understanding of pathogens indicates that Jenner got lucky – not all dangerous diseases have a less pathogenic equivalent as was the case with smallpox and cowpox. Types of Vaccine There are four main types of vaccinations: Live attenuated vaccines Killed vaccines Toxoid vaccines Component vaccines Many vaccines contain adjuvants. This is a general term given to any substance that when mixed with an injected immunogen will increase the immune response. Examples of adjuvants include aluminium hydroxide and aluminium phosphate. Live attenuated vaccines Contain bacteria or viruses that have been altered so they can't cause disease. Usually created from the naturally occurring germ itself. The germs used in these vaccines still can infect people, but they rarely cause serious disease. Viruses are weakened (or attenuated) by growing them over and over again in a laboratory under nourishing conditions called cell culture. The process of growing a virus repeatedly-also known as passing--serves to lessen the disease-causing ability of the virus. Vaccines are made from viruses whose disease-causing ability has deteriorated from multiple passages. Examples of live attenuated vaccines include: Measles vaccine (as found in the MMR vaccine) Mumps vaccine (MMR vaccine) Rubella (German measles) vaccine ( MMR vaccine) Oral polio vaccine (OPV) Varicella (chickenpox) vaccine Killed vaccines Contain killed bacteria or inactivated viruses. Inactivated (killed) vaccines cannot cause an infection, but they still can stimulate a protective immune response. Viruses are inactivated with chemicals such as formaldehyde. Examples of inactivated (killed) vaccines: Inactivated polio vaccine (IPV), which is the injected form of the polio vaccine Inactivated influenza vaccine Toxoid vaccines Contain toxins (or poisons) produced by the germ that have been made harmless. Toxoid vaccines are made by treating toxins (or poisons) produced by germs with heat or chemicals, such as formalin, to destroy their ability to cause illness. Even though toxoids do not cause disease, they stimulate the body to produce protective immunity just like the germs' natural toxins. Examples of toxoid vaccines: Diphtheria toxoid vaccine (may be given alone or as one of the components in the DTP, DTaP, or dT vaccines) Tetanus toxoid vaccine (may be given alone or as part of DTP, DTaP, or dT) Component vaccines Contain parts of the whole bacteria or viruses. These vaccines cannot cause disease as they contain only parts of the viruses or bacteria, but they can stimulate the body to produce an immune response that protects against infection with the whole germ. Component vaccines have become more common with the advent of gene technology, as the antigenic proteins can be identified and cloned then expressed in a laboratory to provide material for vaccination. Examples of component vaccines: Haemophilus influenzae type b (Hib) vaccine Hepatitis B (Hep B) vaccine Hepatitis A (Hep A) vaccine Pneumoccocal conjugate vaccine How do diseases evade the immune response? Pathogens that infect the human body have evolved a number of different techniques for avoiding the immune response. These include: Antigenic variation Antigenic mimicry Evading macrophage digestion Hiding in cells Immune suppression Disarming antibodies Avoiding the immune response Antigenic variation Some species of protozoan parasites evade immune response by shedding their antigens upon entering the host. Others (e.g. trypanosomes and malarial parasites) can change the surface antigens that they express so that the specific immune system needs to make a new antibody to respond to the infection. This is known as antigenic variation. Antigenic mimicry This involves alteration of the pathogen’s surface so that the immune system does not recognise the pathogen as “non-self”. Blood flukes can hijack blood group antigens from host red blood cells and incorporate them onto their outer surface so that the immune system does not respond to the infection. Avoiding the immune response Evading macrophage digestion Macrophages have an important role in the immune system as they phagocytosis and destroy foreign material. Some microbes (e.g. Leishmania) are able to avoid enzymatic breakdown by lysosomes and can remain and grow inside the macrophage – this means they are able to avoid the immune system. Some bacteria can avoid phagocytosis by releasing an enzyme that destroys the component of complement that attracts phagocytes. Other bacteria can kill phagocytes by releasing a membrane-damaging toxin Hiding in cells Bacteria such as heliobacter can invade the epithelial lining of the intestine to multiply and divide, then transfer into neighbouring cells without entering the extracellular space where they would be vulnerable to detection. Avoiding the immune response Immune suppression Most parasites are able to disrupt the immune system of their host to some extent. HIV is an example of this. It selectively destroys T helper cells, therefore disabling the host immune system. Disarming antibodies Bacteria such as Staphylococcus aureus have receptors on their surface that disrupt the normal function of the host’s antibodies. These receptors bind to the constant region (the stem) rather than the normal antigen binding sites. This prevents normal signalling between antibodies and other parts of the immune system such as complement activation or initiating phagocytosis of a bound antigen. Invader antigens are everywhere! What does it need to get by? Skin! neutrophils Monoctyes (macrophages) Invader dies! T - Helper lymphs B lymphs Plasma B cells Memory B cells Antibodies!! Invader dies!! More T - Helper lymphs! Cytotoxic T lymphs Invader dies!! Immunity We have natural or innate resistance to certain illnesses including most diseases of other animal species. Immunity involves a specific defense response by the host to invasion by foreign organisms or substances: Active immunity develops Acquired immunity is the protection after exposure to that develops against specific microorganisms or foreign microbes or substances foreign substances. Passive immunity is acquired when antibodies are transferred from one person to another. Naturally Acquired Immunity Naturally Acquired Passive Active Antibodies pass from the mother to the fetus via the placenta during pregnancy or to her infant through her milk. The infant's body does not produce any antibodies of its own. Antigens enter the body naturally, as when: • Microbes cause the person to catch the disease. • There is a sub-clinical infection (one that produces no evident symptoms). The body produces specialized lymphocytes and antibodies. Artificially Acquired Immunity Artificially Acquired Active Passive Antigens (weakened or dead microbes or their fragments) are introduced in vaccines. Preformed antibodies in an immune serum are introduced into the body by injection (e.g. anti-venom used to treat snake bites). The body does not produce any antibodies The body produces specialized lymphocytes and antibodies. . Induced Immunity Active immunity Production of a person’s own antibodies. Long lasting Natural Active Artificial Active When pathogen Vaccination – usually enters body in the contains a safe antigen normal way, we from the pathogen. make antibodies Person makes antibodies without becoming ill Edward Jenner Passive immunity An individual is given antibodies by another Short-term resistance (weeks- 6months) Natural Passive Baby in utero (placenta) Breast-fed babies Artificial Passive Gamma globulin injection Extremely fast, but short lived (e.g. snake venom) Active and Passive Immunity Active immunity Lymphocytes are activated by antigens on the surface of pathogens Natural active immunity - acquired due to infection Artificial active immunity – vaccination Takes time for enough B and T cells to be produced to mount an effective response. Active and Passive Immunity Passive immunity B and T cells are not activated and plasma cells have not produced antibodies. The antigen doesn’t have to be encountered for the body to make the antibodies. Antibodies appear immediately in blood but protection is only temporary. Active and Passive Immunity Artificial passive immunity Used when a very rapid immune response is needed e.g. after infection with tetanus. Human antibodies are injected. In the case of tetanus these are antitoxin antibodies. Antibodies come from blood donors who have recently had the tetanus vaccination. Only provides short term protection as abs destroyed by phagocytes in spleen and liver. Active and Passive Immunity Natural passive immunity A mother’s antibodies pass across the placenta to the foetus and remain for several months. Colostrum (the first breast milk) contains lots of IgA which remain on surface of the baby’s gut wall and pass into blood