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2 Health & Disease (Immunity)
•Immune response, antigen, & antibody – definitions •Primary defences; Phagocytes & phagocytosis •Structure of antibodies & mode of action T and B lymphocytes •Cell signalling & memory cells •Primary and secondary immune response •Active. Passive, natural, and artificial immunity •Vaccination in the control of disease •Influenza – antigenic shift – challenges •Sources of medicines – microorganisms and plants – biodiversity
Many pathogens cannot cause disease due to non-specific barriers (physical, chemical) and cellular defences, that prevent them from entering the body. If they do enter, the immune system (the specific immune response) can prevent them from spreading through the body Body has three lines of defence against pathogens:
Barriers preventing entry - non-specific
Physical Skin – physical barrier (keratinised) impermeable Mucociliary escalator – airways (mucus and cilia) Reflexes - sneezing; coughing; blinking Sebum – antibacterial fatty acids (acidic) – pH 5.4 Tears – lysozyme – destroys bacterial cell wall HCl acid – gastric juice; lactic acid - vagina
Non-specific responses Inflammatory response –phagocytes and chemicals Phagocytosis – phagocytes (+ intracellular chemicals) Blood clotting (haemostasis) Specific response (specific for pathogen or toxin) Immune response – active and passive immunity T and B cells (lymphocytes – WBC’s)
Non-specific (innate / natural)
Response is always of similar magnitude Does not discriminate No memory of encountered Ag (foreign agent)
Specific (adaptive / acquired) Specific for particular initiating Ag Adaptive – mechanism of eradication dependent on nature of Ag (bloodborne – by antibodies; intracellular – e.g. viruses – by specific effector cells) Eradicate Ag rapidly and effectively Immunological memory to future infection – to prevent re-infection
If innate is breached – adaptive immune system responds
1st Line of defence Skin Dry; composed of dead cells containing keratin (protein) – keratin cannot be digested easily – protective barrier to pathogens; outer layer of cells are shed taking bacteria with them. Microbes can only penetrate when surface is broken; shedding of skin Sebum (sebaceous glands) contains long chain fatty acids – lowers pH (acidic- pH 5.4) – inhibits growth of microorganisms and viruses Sweat (sweat glands) – contains lysozyme – digests cell wall of bacteria Tears – lysozyme and washing action Gut Saliva – lysozyme; amylase HCL acid in stomach – destroys ingested bacteria Mechanical flushing – due to movement of contents and fibre
Respiratory tract Mucus (goblet cells) – traps particle and microorganisms Cilia – sweeps mucus towards throat
Urinary/Reproductive tract Semen (male) – spermine – antibacterial Vagina – mucus membrane - acidic (lactic acid) Urethra – acidic (due to acidic urine); washing action of urine
2nd Line of Defence Non specific responses Inflammatory response Phagocytosis Blood clotting Phagocytosis flow chart Phagocytes – originate from bone marrow / foetal liver •Pathogen recognised as foreign – pathogen is antigenic. HCl. chemotaxis •Pathogen attached to phagocyte by antibody and surface receptors •Engulfed by phagocyte by endocytosis – invagination of plasma cell membrane to form a phagosome (a membrane bound vesicle containing the pathogen) •Lysosomes (containing lysins & hydrolytic enzymes) fuse to phagosome •Release of H2O2. free radicals into phagosome •Digest pathogen – harmless products removed (egested / excreted) or used by phagocyte •Phagocyte also displays antigenic components on external surface of plasma cell 5 membrane (antigen presentation) to start immune response .
Any agent (foreign) to which an Ab can bind Antibody Immunoglobulin (proteins) produced in response to antigen during the immune response Agglutinate (clump) pathogens (antigens) – for easier phagocytosis Coat pathogen – to attract other chemicals (termed complement proteins). IgA Fulfil a specific role within days after encountering Ag Hb – long term evolution to fulfill role 6 .3rd Line of Defence – Immune Response (Specific) Immune Response Body’s reaction to a foreign antigen or pathogen Antigen Substances capable of eliciting the immune response (production of antibodies – which are usually proteins – termed immunoglobulins). that destroy the pathogen Neutralize toxins Five classes – IgA. IgE. IgD. IgM.
come from other source No exposure to Ag Immediate protection Short-term protection No memory cells produced Natural Infection Artificial Vaccination Natural Transfer of maternal Ab’s to foetus/baby via milk or through placenta Artificial Administration of pre-formed Ab’s •Tetanus injection •Rabies injections •Anti-venom Ab’s 7 .Immunity Active Exposure to Ag Ag (pathogen) invades body Lag phase before protection develops Long-term protection Memory cells produced Passive Ab mediated No immune response – Ab’s not made .
act nat. pas art.art. act art. act nat . pas 8 .
placental transfer) or artificial (administered) No exposure to Ag No immune response – Ab’s not made -come from other source Immediate protection .high concentration of Ab immediately after injection and then falls Short-term protection No memory cells produced Advantages Immediate protection Ag / toxin neutralized / inhibited Few or no symptoms Secondary response (2o) Immunological memory – memory cells produced in clonal expansion in primary response – remain in blood / lymph Rapid response + larger production of Ab in 2o than 1o 9 . increased cytoplasm) Ab synthesis & release from plasma cells Passive Immunity Ab mediated – Natural (via milk.Active Immunity Exposure to Ag Natural (infection) or artificial (administered) Involves memory Long -lived Lag phase in primary (1o) response Ag presentation (phagocyte) Clonal selection & expansion (mitosis) Involvement of T helper cells (release of cytokines) B cell differentiation and growth into plasma cells (large cells.
White blood cells (Leucocytes) 1% RBC’s 45% Defence against .parasites 10 .
Cytokines Cytokines stimulate B cells to divide and differentiate into plasma cells and memory cells Secrete cytokines 11 .
less time to produce same number of plasma cells –hence. Infection (Ag) 2. increased affinity of Ab for Ag. This is due to the presence of memory cells (made during the primary response) – no need for antigen presentation and clonal selection 12 Long-lived. a greater [Ab] compared to 1o response. Lag phase 3 4 5 6 Antibodies produced Antibody level rises to combat infection Ag dealt with Ab level declines – short lived Secondary Response After the primary response.Antibody Concentration – Primary and Secondary Response Primary Response 1. Ab’s do not stay in blood – the level declines If the body is infected by the same Ag a second time Ab’s must be made again Re-infection causes much more rapid and a stronger immune response – concentration of Ab’s rises sooner.reaches a higher concentration – more plasma cells than in 1o response – more cells to respond to Ag. basis of vaccination .
Primary – establishes immunological memory 13 .
protein (antibody synthesis B cells Humoral response Has Ag receptors – carries Ab (receptor) on surface Complimentary to only one Ag Clonal selection Each B cell – molecules of single type of Ab on outer surface of plasma membrane Selection and activation of appropriate B lymphocyte / B cell and T lymphocyte by APC’s (macrophages) Clonal expansion T cells divide by mitosis to form a clone (clonal expansion) .Lag phase – antigen presentation (by macrophage /phagocyte).and secrete signal molecules termed cytokines (lymphokines) which stimulate the selected B cells to divide by mitosis to form a clone (clonal expansion) B cells specialise / differentiate to form larger Ab secreting plasma cells Ab’s are specific / complementary to Agnitiating the response B cells and T cells also differentiate into memory cells – long lived / remain in circulation – provide immunological memory to provide a secondary response on subsequent exposure to the same Ag. B cell activation. formation of plasma cells. clonal selection (T + B lymphocytes). produces larger 14 amount of Ab . 2o response is more rapid and stronger. production of cytokines. clonal expansion.
Phagocyte (has enzymes) Partial digestion of Ag Ag still whole Antigen presenting cell (antigen presentation) Clonal selection – receptors On T cell membrane – complementary to Ag Clonal expansion (T cells) – divide by mitosis Clonal expansion (B cells) Remain in body to produce a rapid and stronger 2o response on exposure to the same Ag – 15 divide to make Ab producing plasma cells – .
Clonal Selection Ag selects B Cell with right Shape of recepror Clonal Expansion Divide by mitosis To form a clone of Plasma cells and a Clone of memory cells 16 .
adding carbohydrate (to make glycoprteins) More space for organelles Ab (protein) made by ribosomes (RER). ATP required (mitochondria) 18 .increase in protein (antibody) synthesis. transport More ribosomes. more mitochondria (ATP for synthesis and secretion) More Golgi apparatus – for secretory vesicles.B cell Smaller Origin – bone marrow + foetal liver cells Development – bone marrow + foetal liver Low nucleus to cytoplasm ratio – nucleus larger relative to cytoplasm Plasma cell Larger Derived from B cell Large nucleus to cytoplasm ratio – nucleus smaller relative to cytoplasm Develops extensive RER .
ensures specificity for a particular Ag Specific shape – complementary to Ag – “Lock and Key” Bind with a specific Ag Hinge region – allows spatial flexibility to branches of the Y shaped variable region of the Ab Allows for binding to more than one Ag Constant region (Fc) Related to class of Ab 19 Enables Ab to bind to receptors and attach to cells – e. different shapes antigen binding sites .g.An antibody molecule Produced by B lymphocytes Large globular proteins – Y shaped 4 polypeptide chains (held together by S-S (disulphide) bonds Ag binding site (Fab) Variable region – varies from one Ab to another – due to variable amino acid sequence (primary structure) – different 3o and 4o structures. Phagocytes / mast cells .
S-S (covalent) bonds hold polypeptide chains (H & L) together 20 .
Mode of Action of Antibodies Neutralisation and agglutination -also promotes phagocytosis by the constant region attracting -phagocytes Immobilise pathogens (bind with flagellum) Destroy bacterial cell wall (lysis) 21 Stop spread .
Cell Signalling in Immune Response Communication between cells 23 .
Some Th cells become memory cells 24 .
Cell mediated immunity (CMI) 25 .
T cells Ag presentation by phagocytes Receptors on T cell surface complementary to Ag – specificity Clonal selection – Ag selects only those T cells with complementary receptors and activates them Clonal expansion . Tk cells on stimulation with Ag 26 . Tcyt.activated T cells divide by mitosis into a clone Th cells release cytokines (signalling chemicals) Stimulate B cells to divide by mitosis to form a clone of B lymphocytes (low nucleus to cytoplasm ratio) These differentiate into larger plasma cells (large nucleus to cytoplasm ratio) Secrete antibodies Tcyt – kill cells with intracellular parasites Tk – kill abnormal cells with markers for cancer Tsup – regulate immune response Memory T cells – able to differentiate rapidly into Th.
Flow chart to represent the immune response 27 .
Vaccination Types of Vaccines Live – live pathogens Dead – killed pathogens Attenuated – weakened pathogens Toxoids – toxins (made harmless) DNA Edible vaccines 28 .
mumps and rubella (MMR vaccine) and polio (oral) vaccine virus. to produce the dangerous. Live vaccines produce the best immunisation because they closely imitate the real thing. Immunity lasts for life. The immune system of normal healthy people quickly kills and eliminates them from the body. clinical disease – e. polio (injected form). Dead Microbes Cultures of the pathogenic microbial strains killed in such a way that they retain their ability to stimulate the body to produce an immunological response to the live form – e.g. 29 . The infection elicits a primary immune response that results in the production of memory cells. measles. anthrax and rabies vaccine. Vaccination .g the cowpox virus.consists of infecting a person with a living attenuated microbe which then produces a limited infection. disease-producing form of the injected microbe used in the vaccine. either naturally (through mutation) or by treatment in the laboratory.Vaccination Inducing a specific immune response to a pathogen artificially – Antigen injected or taken orally – not caught Living attenuated (“weak”) microbes Administration of microbes that have lost the ability. influenza Immunity lasts several years. The host is protected from infection (disease) by the virulent.
No whole organisms. living or dead are present in these vaccines – e.Vaccination using components of pathogens Vaccines consisting of substances isolated from the virulent strains. botulinum. polysaccharide from pathogenic Pneumococci.g. Haemophilus influenzae Toxoid vaccines Made by treating toxins (or poisons) produced by pathogens with heat or chemicals (e. DNA Vaccines Vaccines consisting of DNA fragments that can be transformed into host tissue. tetanus. 30 . such as polysaccharide material or proteins components.e. formalin) – destroys ability to cause illness . diphtheria. hepatitis A and B. The food is eaten by the "patient" and the cloned-antigen stimulates the immune system. Vaccinations by eating ( “edible” vaccines) Experiments are underway to deliver vaccines through common foods like potatoes and bananas.g. Once in the host tissue.g. Genes that make an antigen effective against a microbe are cloned into a common food. the DNA is transcribed and translated and the protein produced is seen by the specific immune system as foreign material and an immune response is induced.
make disease notifiable . travel restrictions.Artificial active immunity (Vaccination) Ag injected/taken orally (not caught) Vaccine Administration of Ag or attenuated/weakened/dead/similar pathogen to activate Immune system – causes immune response Engulfed by phagocytes Ag’s presented on cell surface membrane Selection/production of active Th cells (lymphocytes) T cells divide by mitosis to form a clone Some form memory cells Secrete cytokines (lymphokines) Activate B cells B cells divide by mitosis to form a clone Majority mature into antibody secreting plasma (effector) cells Some form memory cells – remain in body Allows a more rapid and stronger secondary response No symptoms of disease on vaccination Use of vaccines in eradication programmes Herd vaccination (vaccinate most/all of people) – stops infection spreading within population Ring vaccination – vaccinate all people around victim – contains spread within ring 31 – stops transmission Trace and isolate contacts.
factors Difficult to diagnose disease Not enough population vaccinated – need herd immunity Poor response to vaccine Migrants bringing disease into a community Length of time vaccine remains effective (boosters) Mutation of pathogen Severity of disease – affects decision to get vaccinated Concerns as to side-effects – people reluctant to be vaccinated The safety of medical procedures and agents always carry a degree of risk. usually a child. develops a severe.. often fatal. disease caused by the smallpox vaccine. that it will be "virulent" only for that individual. The live vaccines present the highest risk because it is always possible that a mutation may occur that reverts the avirulent strain to virulence or that a particular individual will be susceptible to the avirulent strain. Killed vaccines have had safety problems when the lethal treatment failed to kill 100% of the microbes.Vaccination – not effective in eradication of some diseases . i.e. So the killing treatments must balance. This has happened in the case of smallpox where an occasional person. . 32 . The problem is that if you over treat the microbe to be certain that all the organisms are dead you can destroy the immunising components and make the vaccine ineffective.
Smallpox Stable pathogen – does not mutate – one type of Ag Live vaccive – more effective (c.Successful Vaccine – e. freeze-dried. heat stable Infected people easy to identify and cooperative Easy to administer. no booster needed (only one inoculation) No other reservoir of infection – only human host Funds Volunteers /spotters used to find new cases 33 . cheap. 100%) Easy to produce.e. high availability Easy storage. reusable needle.
and they can be seriously harmed or even killed as a result.Also it is difficult to detect the one live organism present in a 1. The UK is one of the safest countries in the world when it comes to communicable diseases. Diseases are always present and they do not recognise borders. Some people will react violently to these substances. usually in an allergic reaction. or the person you sit by on the bus may be a recent immigrant or traveller coming from another country that is carrying a disease the UK is "free" of. The use of chemical components of pathogens also carries some risks. Everyone who drives or is driven on the highways is in far more danger of harm than they are being vaccinated.000 liters of treated material. We are so intimately connected with the rest of the world today that diseases can appear from anywhere. but we probably are not the safest. The DPT vaccine combination has caused such reactions Modern vaccines are about as safe as anything in this dangerous world. The strawberries or lettuce you just purchased at the supermarket yesterday may have come from a country with far less sanitation than we practice. yet one live organism is sufficient to produce a lethal infection. Think about it! 34 . In these cases your only real protection is vaccination.
Treatment of Influenza – Challenges – use of science to inform decision making Influenza (flu) virus – Capable of mutation Changes antigenic structure – change in glycoprotein structure -antigenic shift Vaccine against one strain not effective against another strain of the influenza virus Need to develop new vaccines each year for prophylaxis Surface proteins (neuraminidase + haemagglutinin) act as antigens Antigens change structure regularly – forming new strains of the virus Memory cells from infection from previous strain do not recognize new strains (antigens) WHO + CDC monitor emergence of new strains and collect samples New vaccines developed (in chicken eggs) against the new strains– one chosen that is most effective against the recently circulating strain Authorities implement a programme of vaccination Bacteria – mutate .g.antibiotic resistance (e. MRSA). ineffective vaccines 35 .
different antigens – due to mutation / variation More than one stage of life cycle (within human). different stages have different Ag’s Need a different vaccine for each strain / stage Parasite concealed in cells – RBCs and hepatocytes Parasite only exposed in circulation for short time 36 .Malaria – vaccines Loss of immunity on leaving a malarial area No repeat infections – no further exposure to Ag – no booster Lose immunological memory – limited life for memory cells – reduced number of memory cells No secondary response No effective malarial vaccine Different strains / species of Plasmodium.
g. cows Enzymes – pancreatic – for CF – from animals Aspirin – analgesic / antiinflammatory .bark of willow tree Tamoxifen – anticancer – Pacific Yew tree Cinnamon – antidiabetic Star anise – Tamiflu – antiviral – from shikimic acid Only a limited number of organisms investigated so far – numerous others exist – to be investigated Need to protect above sources of drugs by protecting the species and maintaining biodiversity Species may die and become extinct before being studied Organisms already studied could provide additional substances for use as drugs due to development of powerful new techniques for identifying. animals. microorganisms (bacteria) . Streptomycin – antibiotic in TB – from bacteria Penicillin – antibacterial – from Penicillium (fungus) Quinine – antimalarial – Cinchona tree Insulin (hormone) – antidiabetic – pigs. and fungi – e. and testing compounds. purifying.Sources of Medicines Many drugs obtained from or made from natural substances found in plants. Use of bacteria in genetic engineering 37 .
Passive immunization is provided in the following circumstances: When people cannot synthesize antibody. immunodeficiency disorders Rabied immune globulin Tetanus immune globulin Antivenom antibodies (spiders. jellyfish Preparation Inject Ag (toxin) into animal – produces antibodies – antibodies harvested – must conform to WHO standards prior to use 40 . ticks. scorpions. caterpillars. snakes. Boyulinum antitoxin Diphtheria antitoxin Immune globulin (poled human antibodies) – prophylaxis. When people have been exposed to a disease that they are not immune to or that is likely to cause complications When people have a disease and the effects of the toxin must be ameliorated.
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