C3.2 Defense Against Disease PDF

C3.2 DEFENSE AGAINST DISEASE Interaction and Interdependence Guiding Questions How do body systems recognize pathogens and fight infections? What factors influence the incidence of disease in populations Learning Objectives Pathogens as the cause of infectious diseases Skin...

C3.2 DEFENSE AGAINST DISEASE Interaction and Interdependence Guiding Questions How do body systems recognize pathogens and fight infections? What factors influence the incidence of disease in populations Learning Objectives Pathogens as the cause of infectious diseases Skin and mucous membranes as a primary defense Sealing of cuts in skin by blood clotting Differences between the innate immune system and the adaptive immune system Infection control by phagocytes Lymphocytes as cells in the adaptive immune system that cooperate to produce antibodies Antigens as recognition molecules that trigger antibody production Activation of B-lymphocytes by helper T-lymphocytes Multiplication of activated B-lymphocytes to form clones of antibody-secreting plasma cells Immunity as a consequence of retaining memory cells Learning Objectives Transmission of HIV in body fluids Infection of lymphocytes by HIV with AIDS as a consequence Antibiotics as chemicals that block processes occurring in bacteria but not in eukaryotic cells Evolution of resistance to several antibiotics in strains of pathogenic bacteria Zoonoses as infectious diseases that can transfer from other species to humans Vaccines and immunization Herd immunity and the prevention of epidemics Evaluation of data related to the COVID-19 pandemic Pathogenesis A pathogen is an agent that causes disease – either a microorganism (bacteria, protist, fungi or parasite), virus or prion A disease is any condition that disturbs the normal functioning of the body (i.e. the body can no longer maintain homeostasis) An illness is a deterioration in the normal state of health of an organism (a disease may cause an illness) Pathogens are generally species-specific in that their capacity to cause disease (pathogenesis) is limited to a particular species Polio, syphilis, measles and gonorrhoea are examples of diseases caused by pathogens that specifically affect human hosts Pathogens Zoonoses Certain pathogens may cross the species barrier and be able to infect and cause disease in a range of hosts Diseases from animals that can be transmitted to humans are called zoonotic diseases (or zoonoses) Examples of zoonotic diseases include rabies (dogs), certain strains of influenza (ex. bird flu) and the bubonic plague (rats)  Transmission of infectious diseases can occur via a number of distinct Disease mechanisms: Transmission Direct contact – the transfer of pathogens via physical association or the exchange of body fluids Contamination – ingestion of pathogens growing on, or in, edible food sources Airborne – certain pathogens can be transferred in the air via coughing and sneezing Vectors – intermediary organisms that transfer pathogens without developing disease symptoms themselves Lines of The immune system can be divided into three basic lines of defense against pathogenic infection: Defense The first line of defense against infection are the surface barriers that prevent the entry of pathogens into the body The second line of defense are the non-specific phagocytes and other internal mechanisms that comprise innate immunity The third line of defense are the specific lymphocytes that produce antibodies as part of the adaptive immune response First Line of Both the skin and mucous Defense membranes release chemical secretions which restrict the growth of microbes on their surfaces If pathogens cannot enter the host body, they cannot disrupt normal physiological functions and cause disease Surface Barriers The first line of defense against infectious disease are the surface barriers that prevent the entry of pathogens into the body These surface barriers include both the intact skin and mucous membranes Surface Barriers Mucous Membranes Protects internal structures ( externally Skin accessible cavities and tubes – such as the trachea, esophagus and urethra) Protects external structures when Consists of a thin region of living intact (outer body areas) surface cells that release fluids to Consists of a dry, thick and tough wash away pathogens (mucus, saliva, region composed predominantly of tears, etc.) dead surface cells Contains biochemical defence agents Contains biochemical defense (secretions contain lysozyme which agents (sebaceous glands secrete can destroy cell walls and cause cell chemicals and enzymes which lysis) inhibit microbial growth on skin) Mucous membranes may be ciliated to The skin also secretes lactic acid and aid in the removal of pathogens (along fatty acids to lower the pH (skin pH with physical actions such as coughing is roughly ~ 5.6 – 6.4 depending on / sneezing) body region)  Blood Clots Clotting Clotting (hemostasis) is the mechanism by which broken blood vessels are repaired when damaged Clotting functions to prevent blood loss from the body and limit pathogenic access to the bloodstream when the skin is broken There are two key components of a blood clot – platelets and insoluble fibrin strands Platelets undergo a structural change when activated to form a sticky plug at the damaged region (primary hemostasis) Fibrin strands form an insoluble mesh of fibres that trap blood cells at the site of damage (secondary hemostasis)  Components of a Blood Clot Coagulation Cascade The process by which blood clots are formed involves a complex set of reactions collectively called the coagulation cascade This cascade is stimulated by clotting factors released from damaged cells (extrinsic pathway) and platelets (intrinsic pathway) The coagulation cascade involves many intermediary steps, however the principal events are as follows: Clotting factors cause platelets to become sticky and adhere to the damaged region to form a solid plug These factors also initiate localized vasoconstriction to reduce blood flow through the damaged region Additionally, clotting factors trigger the conversion of the inactive prothrombin into the activated enzyme thrombin Thrombin in turn catalyzes the conversion of the soluble plasma protein fibrinogen into an insolube fibrous form called fibrin The fibrin strands form a mesh of fibres around the platelet plug and traps blood cells to form a temporary clot When the damaged region is completely repaired, an enzyme (plasmin) is activated to dissolve the Coagulation Cascade  Digging deeper (med school) Second Line of The second line of defense against infection are the non-specific cellular and molecular responses of the Defense innate immune system These defenses do not differentiate between different types of pathogen and respond the same way upon every infection Phagocytic leukocytes migrate to infection sites and engulf foreign bodies (dendritic cells then present antigens to lymphocytes) Inflammatory responses increase capillary permeability at infected sites, recruiting leukocytes but leading to localised swelling Antimicrobial proteins (such as cytokines and complement proteins) regulate immune activity within the body Fever increases body temperatures to activate heat- shock proteins and suppress microbial growth and propagation Phagocytes The second line of defense against infectious disease is the innate immune system, which is non-specific in its response A principle component of this line of defense are phagocytic white blood cells that engulf and digest foreign bodies Other components of the innate immune system include inflammation, fever and antimicrobial chemicals (complement proteins) The innate immune system has two key properties: It does not differentiate between different types of pathogens (non-specific) It responds to an infection the same way every time (non-adaptive) Phagocytes Phagocytosis is the process by which solid materials (such as pathogens) are ingested by a cell (cell ‘eating’ via endocytosis) Phagocytic leukocytes circulate in the blood and move into the body tissue (extravasation) in response to infection Damaged tissues release chemicals (ex. histamine) which draw white blood cells to the site of infection (via chemotaxis) Pathogens are engulfed when cellular extensions (pseudopodia) surround the pathogen and then fuse to form an internal vesicle The vesicle is then fused to a lysosome (forming a phagolysosome) and the pathogen is digested Pathogen fragments (antigens) may be presented on the surface of the phagocyte in order to stimulate the third line of defense Phagocytosis Inflammation Fever A fever is an abnormally high temperature associated with infection and is triggered by the release of prostaglandins Fever may help to combat infection by reducing the growth rate of microbes (via the inactivation of microbial enzymes) It may also increase metabolic activity in body cells and activate heat shock proteins to strengthen the immune response A fever occurs when activated leukocytes release pro- inflammatory chemicals called cytokines Cytokines stimulate the anterior hypothalamus to produce prostaglandins, which lead to an increase in body temperature Up to a certain point a fever may be beneficial, but beyond a tolerable limit it can cause damage to the body’s own enzymes Third Line of The final line of defense against infection are the lymphocytes that produce Defense antibodies to specific antigenic fragments Each B cell produces a specific antibody, and the body has millions of different B cells capable of detecting distinct antigens Helper T cells regulate B cell activation, ensuring that antibodies are only mass- produced at the appropriate times Both B and T cells will differentiate to form memory cells after activation, conferring long-term immunity to a particular pathogen Self vs Non-Self The immune system has the capacity to distinguish between body cells (‘self’) and foreign materials (‘non-self’) It will react to the presence of foreign materials with an immune response that eliminates the intruding material from the body All nucleated cells of the body possess unique and distinctive surface molecules that identify it as self These self markers are called major histocompatibility complex molecules (MHC class I) and function as identification tags The immune system will not normally react to cells bearing these genetically determined markers (self-tolerance) Self vs Non-Self Any substance that is recognized as foreign and is capable of triggering an immune response is called an antigen (non self) Antigens are recognized by lymphocytes which bind to and detect the characteristic shape of an exposed portion (epitope) Lymphocytes trigger antibody production (adaptive immunity) which specifically bind to epitopes via complementary paratopes Antigenic determinants include: Surface markers present on foreign bodies in the blood and tissue – including bacterial, fungal, viral and parasitic markers The self markers of cells from a different organism (this is why transplantation often results in graft rejection) Even proteins from food may be rejected unless they are first broken down into component parts by the digestive system Application: Blood Types Different organisms have distinct self markers which prevent transplantation of tissues (unless a very close genetic match) Red blood cells are not nucleated and hence do not possess the same distinctive and unique self markers as all other body cells This means that red blood cells can be transferred between individuals without automatically causing immune rejection However, red blood cells do possess basic antigenic markers which limit the capacity for transfusion (the ABO blood system) Red blood cells may possess surface glycoproteins (A and B antigens) either independently (A or B) or in combination (AB) Alternatively, red blood cells may possess neither surface glycoprotein (denoted as O) Application: Blood Types Lymphocytes The third line of defense against infectious disease is the adaptive immune system, which is specific in its response It can differentiate between particular pathogens and target a response that is specific to a given pathogen It can respond rapidly upon re-exposure to a specific pathogen, preventing symptoms from developing (immunological memory) The adaptive immune system is coordinated by lymphocytes (a class of leukocyte) and results in the production of antibodies B lymphocytes (B cells) are antibody-producing cells that recognize and target a particular pathogen fragment (antigen) Helper T lymphocytes (TH cells) are regulator cells that release chemicals (cytokines) to activate specific B lymphocytes Adaptive Immune System When phagocytic leukocytes engulf a pathogen, some will present the digested fragments (antigens) on their surface These antigen-presenting cells (dendritic cells) migrate to the lymph nodes and activate specific helper T lymphocytes The helper T cells then release cytokines to activate the particular B cell capable of producing antibodies specific to the antigen The activated B cell will divide and differentiate to form short-lived plasma cells that produce high amounts of specific antibody Antibodies will target their specific antigen, enhancing the capacity of the immune system to recognize and destroy the pathogen A small proportion of activated B cell (and activated TH cell) will develop into memory cells to provide long-lasting immunity Adaptive Immune System Antibodies Antigen: An antigen is a substance that the body recognizes as foreign and that will elicit an immune response Antibody: An antibody is a protein produced by B lymphocytes (and plasma cells) that is specific to a given antigen Antibodies are made of 4 polypeptide chains that are joined together by disulphide bonds to form Y-shaped molecules The ends of the arms are where the antigen binds – these areas are called the variable regions and differ between antibodies The rest of the molecule is constant across all antibodies and serves as a recognition site for the immune system (opsonization) Each type of antibody recognizes a unique antigen, making antigen-antibody interactions specific (like enzymes and substrates) Antigen-Antibody Specificity Antibodies Collectively, the action of antibodies enhance the immune system by aiding the detection and removal of pathogens by the phagocytic leukocytes of the innate immune system (macrophages) The constant region of antibodies can be recognized by macrophages, improving pathogen identification (opsonization) The macrophages can now engulf and eliminate pathogens more efficiently, reducing disease symptoms Antibodies Immunity The adaptive immune system relies on the clonal expansion of plasma cells to produce sufficiently large numbers of antibodies This means there is a delay between the initial exposure to a pathogen and the production of large quantities of antibodies If pathogens can reproduce rapidly during this delay period, they can impede normal body functioning and cause disease Immunological Memory Memory cells are produced to prevent this delay in subsequent exposures and hence prevent disease symptoms developing When a B lymphocyte is activated and divides to form plasma cells, a small proportion will differentiate into memory cells Memory cells are long living and will survive in the body for many years, producing low levels of circulating antibodies If a second infection with the same pathogen occurs, memory cells will react more vigorously to produce antibodies faster As antibodies are produced faster, the pathogen cannot reproduce in sufficient amounts to cause disease symptoms Hence, because pathogen exposure no longer causes the disease to occur, the individual is said to be immune Immunologica l memory HIV Infection The Human Immunodeficiency Virus (HIV) is a retrovirus that infects helper T cells, disabling the body’s adaptive immune system It causes a variety of symptoms and infections collectively classed as Acquired Immuno-Deficiency Syndrome (AIDS) Effects of HIV HIV specifically targets the helper T lymphocytes which regulate the adaptive immune system Following infection, the virus undergoes a period of inactivity (clinical latency) during which infected helper T cells reproduce Eventually, the virus becomes active again and begins to spread, destroying the T lymphocytes in the process (lysogenic cycle) With a reduction in the number of helper T cells, antibodies are unable to be produced, resulting in a lowered immunity The body becomes susceptible to opportunistic infections, eventually resulting in death if the condition is not managed Progression of AIDS  HIV is transmitted through the exchange of body fluids (including unprotected sex, HIV blood transfusions, breastfeeding, etc.) The risk of exposure to HIV through sexual contact can be minimized by using latex Transmission protection (condoms) A small minority of people are immune to HIV infection (they lack the CD4+ receptor on TH cells that HIV requires for docking) HIV is a global issue, but is particularly prevalent in poorer nations with poor education and health systems Antibiotics Antibiotics are compounds that kill or inhibit the growth of microbes (specifically bacteria) by targeting prokaryotic metabolism Metabolic features that may be targeted by antibiotics include key enzymes, 70S ribosomes and components of the cell wall Because eukaryotic cells do not possess these features, antibiotics will target the pathogenic bacteria and not the infected host Antibiotics may either kill the invading bacteria (bactericidal) or suppress its potential to reproduce (bacteriostatic) Antibiotics Viruses do not possess a metabolism (they are not alive) and instead take over the cellular machinery of infected host cells As such, they cannot be treated with antibiotics and must instead be treated with specific antiviral agents Antiviral treatments target features specific to viruses (e.g. viral enzymes like reverse transcriptase or components of the capsid) Antibiotics Since the discovery of the first antibiotic in 1928, antibiotic compounds have been used to treat a variety of bacterial infections Antibiotics can be narrow spectrum (effective against specific bacteria) or broad spectrum (effective against many bacteria) Some strains of bacteria have evolved with genes that confer resistance to antibiotics and some strains have multiple resistance Genes may confer resistance by encoding traits that degrade the antibiotic, block its entry, increase its removal or alter the target Because bacteria reproduce at a rapid rate, resistant strains of bacteria can proliferate very quickly following the initial mutation Additionally, resistant strains can pass resistance genes to susceptible strains via bacterial conjugation (horizontal gene transfer) Antibiotic Resistance The prevalance of resistant bacterial strains is increasing rapidly with human populations due to a number of factors: Antibiotics are often over-prescribed (particularly broad-spectrum drugs) or misused (ex: given to treat a viral infection) Many antibiotics are freely available without a prescription and certain antibiotics are commonly included in livestock feed Multi-drug resistant bacteria are especially common in hospitals (ex. nosocomial infections) where antibiotic use is high An example of an antibiotic resistant strain of bacteria is Golden Staph (MRSA – Methicillin Resistant Staphylococcus aureus) Antibiotic Resistance  The first chemical compound found to have antibiotic properties was penicillin, which was Penicillin identified by Alexander Fleming in 1928 The discovery of penicillin was a fortuitous accident, resulting from the unintended contamination of a dish containing S. aureus A Penicillium mould began to grow on the plate and a halo of inhibited bacterial growth was observed around the mould Fleming concluded that the mould was releasing a substance (penicillin) that was killing the nearby bacteria Vaccination Vaccinations induce long-term immunity to specific pathogenic infections by stimulating the production of memory cells A vaccine is a weakened or attenuated form of the pathogen that contains antigens but is incapable of triggering disease The antigenic determinants in a vaccine may be conjugated to an adjuvant, which functions to boost the immune response The body responds to an injected vaccine by initiating a primary immune response, which results in memory cells being made When exposed to the actual pathogen, the memory cells trigger a more potent secondary immune response As a consequence of this more potent immune response, disease symptoms do not develop (individual is immune to pathogen) Vaccination The length of time a person is immune to infection following a vaccination depends on how long the memory cells survive for Memory cells may not survive a lifetime and individuals may subsequently require a booster shot to maintain immunity Herd Immunity Vaccinations programmes are implemented to reduce the outbreak of particular infectious diseases within populations An epidemic is a substantially increased occurrence of a particular infection within a given region A pandemic is an epidemic that has spread across a large geographical area (like a continent) Vaccination confers immunity to vaccinated individuals but also indirectly protects non-vaccinated individuals via herd immunity Herd immunity is when individuals who are not immune to a pathogen are protected from exposure by the large amounts of immune individuals within the community Herd Immunity