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LO 1 Presented byCU MEDICAL EDUCATION SOCIETYSBA DAY SERIES CASE 9EXPLAIN THE GENERAL PRINCIPLES OF VIROLOGY INCLUDING THE NATURE OF VIRUSES, HOW THEY CAUSE DISEASE AND HOW WE CAN CONTROL THEM A REGISTERED NURSE PRESENTS TO OCCUPATIONAL HEALTH HAVING SUSTAINED A NEEDLESTICK INJURY. IT IS ELICITED THAT SHE IS IS UP-TO- DATE WITH ALL HER VACCINATIONS. AGAINST WHICH OF THE FOLLOWING VIRUSES MAY ‘POST-EXPOSURE’ PROPHYLAXIS BE GIVEN? A Hep B B EBV C Hep C D HIV HepA E A REGISTERED NURSE PRESENTS TO OCCUPATIONAL HEALTH HAVING SUSTAINED A NEEDLESTICK INJURY. IT IS ELICITED THAT SHE IS IS UP-TO- DATE WITH ALL HER VACCINATIONS. AGAINST WHICH OF THE FOLLOWING VIRUSES MAY ‘POST-EXPOSURE’ PROPHYLAXIS BE GIVEN? A Hep B B EBV C Hep C D HIV HepA EA Registered Nurse presents to occupational health having sustained a Needlestick injury. It is elicited that she is is up-to-date with all her vaccinations. Against which of the following viruses may ‘Post-exposure’ prophylaxis be given? • Bloodborne infection as it’s a Needlestick injury Hep C, Hep B and HIV • Vaccinations – schedule (covered later) Excludes Hep B • Post-exposure prophylaxis – which have vaccinations? Excludes Hep C (no vaccine) Describe transmission by contact and ingestion,body surfaces (H1) Classify which viruses infect mainly via the oral route or by direct contact (H1) Classify which viruses infect mainly via the bloodborne route.(H1) Horizontal Transmitted between individuals of the same generation Vertical Transmitted between individuals of different generations Classify which viruses infect mainly via the oral route or by direct contact (H1) Classify which viruses infect mainly via the bloodborne route.(H1) Waterborne Foodborne Bloodborne Fetal Direct contact HepA Hep B HIV Hep C Hep D Hep E HSV CMV VZV HIV MOMOUTH WITH A PEN TORCH AND SEES SPOTS ON HIS MUCOUS MEMBRANES SHOWNO HIS BELOW: WHICH OF THE FOLLOWING BEST DESCRIBES THE STRUCTURE OF THE CAUSATIVE AGENT? A Single-stranded +ve sense DNA surrounded by lipid bilayer B Single-stranded +ve sense DNA surrounded by the capsid. C Double stranded +ve sense DNA surrounded by a capsid Single stranded –ve sense RNA surrounded by a lipid bilayer D Double-stranded –ve sense RNA surrounded by a capsid E MOMOUTH WITH A PEN TORCH AND SEES SPOTS ON HIS MUCOUS MEMBRANES SHOWNO HIS BELOW: WHICH OF THE FOLLOWING BEST DESCRIBES THE STRUCTURE OF THE CAUSATIVE AGENT? A Single-stranded +ve sense DNA surrounded by lipid bilayer B Single-stranded +ve sense DNA surrounded by the capsid. C Double stranded +ve sense DNA surrounded by a capsid Single stranded –ve sense RNA surrounded by a lipid bilayer D Double-stranded –ve sense RNA surrounded by a capsid EDescribe the properties of herpes,small round viruses (SRV), enteroviruses and paramyxovirus Discuss how these viruses overcome immune responses and how they spread and persist in target cells/organs. Describe the properties of some major bloodborne pathogens:human immunodeficiency virus (HIV),hepatitis B virus (HBV),and hepatitis C virus (HCV). Koplik spots Koplik spots are little white spots found on mucous membranes and are indicative of Measles infection Describe the properties of some major bloodborne pathogens:human immunodeficiency virus (HIV),hepatitis B virus (HBV),and hepatitis C virus (HCV). Describe the properties of herpes,small round viruses (SRV), enteroviruses and paramyxovirus (H1) • Ribosomes make proteins • Ribosomes ONLY read mRNA RNA protein • +ve RNA is mRNA • In DNA the positive strand is the RNA protein functional proteins code • So negative strand is the template for the functional protein DNA RNA protein DNA RNA protein Hepatitis C Enterovirus +ve sense Non- RNA enveloped Nororvirus (SRV) HIV Single strand Single strand Lipid Non-enveloped +ve RNA Capsid membrane Single strand Capsid 2x strand RNA Capsid +ve RNA Lipid bilayer Capsid RNA is +ve Hepatitis B Lipid envelope Herpes virus Paramyxovirus Capsid Double strand DNA Single strand DNA Double strand -ve sense RNA Capsid Lipid bilayer Lipid bilayer Capsid envelope ELLA RETURNS FROM A BACKPACKING TRIP IN HER GAP YEAR AND PRESENTS TO THE A&E A FEW WEEKS LATER HAVING DEVELOPED A HEMORRHAGIC FEVER, SWOLLEN ANKLES AND FEET, SHORTNESS OF BREATH WHICH SHE DESCRIBES AS FEELING LIKE A ‘PILLOW OVER HER FACE’. WHICH OF THE FOLLOWTHE DISEASE RESPONSIBLE FOR HER PRESENTATION?ASURE AGAINST A Mosquito nets B Pre-exposureVaccination C Covering areas of standing water Using mouse and rat traps D Preventing aerosol re-entry E ELLA RETURNS FROM A BACKPACKING TRIP IN HER GAP YEAR AND PRESENTS TO THE A&E A FEW WEEKS LATER HAVING DEVELOPED A HEMORRHAGIC FEVER, SWOLLEN ANKLES AND FEET, SHORTNESS OF BREATH WHICH SHE DESCRIBES AS FEELING LIKE A ‘PILLOW OVER HER FACE’. WHICH OF THE FOLLOWTHE DISEASE RESPONSIBLE FOR HER PRESENTATION?ASURE AGAINST A Mosquito nets B Pre-exposureVaccination C Covering areas of standing water Using mouse and rat traps D Preventing aerosol re-entry EElla returns from a backpacking trip in her gap year and presents to theA&E a few weeks later having developed a hemorrhagic fever,swollen ankles and feet,shortness of breath which she describes as feeling like a‘pillow over her face’. Which of the following would be the best exposure prophylaxis measure against the disease responsible for her presentation? • Hemorrhagic fever,swollen ankles/feet,Pillow over face – Hantavirus • Exposure prophylaxis –Vector is mouse/rat droppingsVector borne viruses/ animal vectors (H1) Describe transmission by animal hosts,the concept of zoonosis,host range. Describe vector-dependent disease transmission Explain the interaction between virus and animal host and how specific virus infections can be eradicated by vector Describe the properties of some major animal-transmitted pathogens:dengue virus,yellow fever,and hantaviruses. Zoonosis Occurs when a disease is transferred from animals to humans.E.g.,Ebola transferred via bats in 2013 in Uganda Vector Organism that’s transmits disease from one animal or plant to another.E.g., Mosquito is a vector for transmission of malaria to humans Hantavirus Dengue Y ellow virus virus Genetic material Single strand –ve RNA Single strand +ve RNA Single strand +ve RNA Vector Mouse & Rat droppings Mosquitos Mosquitos Vaccine? No No 17D vaccine symptoms Hemorrhagic fever,renal symptoms, ‘Breakbone fever’, Breathlessness‘like a pillow’ rashes headache, High temp.Jaundice, internal bleeding hemorrhagic fever MRS. SPRIG IS A 46-YEAR-OLD, WITH A HISTORY OF ILLICIT IV DRUG USE. FOR THE LAST 6 MONTHS SHE HAS EXPERIENCED CHRONIC FATIGUE AND UPPER RIGHT QUADRANT PAIN. HER GP REFERS TAKES A BLOOD SAMPLE FOR SEROLOGICAL TESTING. IT IS DISCOVERED SHE HAS A CHRONIC ACTIVE HEP B INFECTION. WHICH OF THE FOLLOWING DESCRIBED THE SEROLOGY HER HEP B INFECTION? A B C D E MRS. SPRIG IS A 46-YEAR-OLD, WITH A HISTORY OF ILLICIT IV DRUG USE. FOR THE LAST 6 MONTHS SHE HAS EXPERIENCED CHRONIC FATIGUE AND UPPER RIGHT QUADRANT PAIN. HER GP REFERS TAKES A BLOOD SAMPLE FOR SEROLOGICAL TESTING. IT IS DISCOVERED SHE HAS A CHRONIC ACTIVE HEP B INFECTION. WHICH OF THE FOLLOWING DESCRIBED THE SEROLOGY HER HEP B INFECTION? A B C D EAcute chronic: • Means it’s Chronic ANDActive • Chronic means not cured so any with negative forAnti- HBsAg,but +ve for HBsAg • Active means that its HBeAg is active so will be +ve andAnti-HBeAg should be negative • We should see HBcAg present and maybeAnti-HBcAgRecapYear 1 – Hepatitis B serology HbsAg HBcAg HBeAg DNA EnzymeHBsAg/Anti-HBsAG HBcAg/Anti-HBcAg HBeAg/Anti-HBeAg . • We don’t measure the • Peaks when patient actual core protein is most ill • HBeAg indicates onlyAb virus is actively replicating • Indicates • When HBcAg is recent/chronic present IgM it represents acute infection • If there is reaction to infection. antibodies against • Anti-bodies against it,then there is low • When HBcAg IgG is infectivity it indicate curative present represents state long term infection or curedHistory of Hep B History of Hep B Vaccination Active chronic Acute Hep BDiscuss how these viruses overcome immune responses and how they spread and persist in target cells/organs VIRAL LATENCY • Virus lies dormant in host cells –The genome is maintainedW/out any lytic action e.g.,no viral budding • Evades immune detection by remaining in non-dividing cells and not producing any viral protein (can be integrated into host chromosome) EBV – Bone Marrow CMV – Monocytes & Marrow HSV – Spinal nerves &Trigeminal SSCHOOL VACCINATIONS. SHE ASKS THE DOCTOR WHY HER DAUGHTERRE- CAN’T HAVE VACCINATIONS AGAINST THE COMMON COLD. WHICH OF THE FOLLOWING IS THE PHENOMENA IS RESPONSIBLE FOR THIS? A Antigenic Shift B Antibody Re-enhancement C Somatic Hypermutation D Antigenic Drift E VDJ Sequence Rearrangement SSCHOOL VACCINATIONS. SHE ASKS THE DOCTOR WHY HER DAUGHTERRE- CAN’T HAVE VACCINATIONS AGAINST THE COMMON COLD. WHICH OF THE FOLLOWING IS THE PHENOMENA IS RESPONSIBLE FOR THIS? A Antigenic Shift B Antibody Re-enhancement C Somatic Hypermutation D Antigenic Drift E VDJ Sequence RearrangementDescribe the consequences of the phenomenon of antibody enhancement for the development of a dengue vaccine Antigenic Drift Antigenic Shift Epidemic Pandemic• When infected with Dengue the bodies innate and adaptive immune systems fight the infection • They create antibodies against the virus (or can artificially by a vaccine) • Next time the same person is reinfected the antibodies against them will aid the virus infecting the bodies cellsOUTLINE THE PRIMARY AND SECONDARY RESPONSE TO ANTIGEN MRS. SANDS PRESENTS TO THE GP WITH HER NEWBORN BABY AND DESCRIBES HIM AS HAVING SHORTNESS OF BREATH, SALTY SKIN AND BOWEL MOVEMENTS THAT ARE LARGE AND GREASY LOOKING. HE IS REFERRED FOR GENETIC TESTING AND IT SHOWS HE HAS DELETION ON CHROMOSOME 7. WHICH PHYSICAL BARRIER TO INFECTION IS MOST LIKELY TO BE COMPROMISED IN THIS BABY? A Skin B Tears C Mucocilliary clearance D Microbiota E Tears MRS. SANDS PRESENTS TO THE GP WITH HER NEWBORN BABY AND DESCRIBES HIM AS HAVING SHORTNESS OF BREATH, SALTY SKIN AND BOWEL MOVEMENTS THAT ARE LARGE AND GREASY LOOKING. HE IS REFERRED FOR GENETIC TESTING AND IT SHOWS HE HAS DELETION ON CHROMOSOME 7. WHICH PHYSICAL BARRIER TO INFECTION IS MOST LIKELY TO BE COMPROMISED IN THIS BABY? A Skin B Tears C Mucocilliary clearance D Microbiota E TearsMrs.Sands presents to the GP with her newborn baby and describes him as having shortness of breath,salty skin and bowel movements that are large and greasy looking.He is referred for genetic testing and it shows he has deletion on chromosome 7. Which physical barrier to infection is most likely to be compromised in this baby? • Symptoms and deletion indicative of Cystic fibrosis • Cystic fibrosis have problems with producing thin mucous due to lack of CFTR channel protein (see picture) • Therefore,the mucous in ciliary escalator will be affected,so that’s your answer • Cystic fibrosis patients often have recurrent chest infections because of this• Explain how the immune response protects against infection and functions in distinct phases Innate immunity has 2 stages: Immediate and Induced Immediate is Induced is all all the the cellular mechanical components barriers detects PAMPS via PRR’s Adaptive immunity is triggered by dendritic cells and involvedT and B cells with aim of producing high affinity antibodies A 66-YEAR-OLD CAUCASIAN MALE PRESENTS FOR A ROUTINE COLONOSCOPY, AS PART OF THE BOWEL SCREENING WALES PROGRAMME. A POLYP IS FOUND IN THE TRANSVERSE COLON AND ON HISTOLOGICAL EVALUATION IS FOUND TO BE CANCEROUS. UPON EXAMINATION, IT IS FOUND THAT THESE CANCEROUS CELLS HAVE DECREASED MHC CLASS I EXPRESSION ON THEIR SURFACE. WHICH IMMUNE SYSTEM CELL IS MOST CAPABLE OF KILLING THESE TUMOUR CELLS? A Macrophages B B-Lymphocytes CytotoxicT cells (CD8+) C Natural Killer Cells D HelperT cells (CD4+) E A 66-YEAR-OLD CAUCASIAN MALE PRESENTS FOR A ROUTINE COLONOSCOPY, AS PART OF THE BOWEL SCREENING WALES PROGRAMME. A POLYP IS FOUND IN THE TRANSVERSE COLON AND ON HISTOLOGICAL EVALUATION IS FOUND TO BE CANCEROUS. UPON EXAMINATION, IT IS FOUND THAT THESE CANCEROUS CELLS HAVE DECREASED MHC CLASS I EXPRESSION ON THEIR SURFACE. WHICH IMMUNE SYSTEM CELL IS MOST CAPABLE OF KILLING THESE TUMOUR CELLS? A Macrophages B B-Lymphocytes CytotoxicT cells (CD8+) C Natural Killer Cells D HelperT cells (CD4+) EB cells bind and present antigens to T cells via MHC class 2 receptors and have no direct acting "killing effects" Macrophages phagocytose cells upon opsonization with complement or by Fc receptors after specific opsonization by antibodies. Only Professional antigen presenting cells may activate these cells via MHC class 2 Cytotoxic T-cells, or CD8 T-cells, carry out their killing function when they recognize a specific antigen: MHC I complex on target cells. The Natural Killer cells have both inhibitory and activating receptors on their surface, the balance of these decides the action. Due to the lack of MHC class 1 this is the only other immune cell in the answer set that may target the Cancer Explain that the TCR recognises a complex of processed antigen bound to major histocompatibility complex (MHC) I and II receptors What are MHC’s? Where are MHC’s? Where areTCR’s? Major histocompatibility complexes , MHC 1 is found on all nucleated cells they enable the host to detect foreign On CD8+ and CD4+ cells,when antigens,by presenting them toT cell MHC 2 is found on the‘professional the MHC andTCR combine they receptors on CD4 or CD8 cells. antigen presenting cells’:B cells activate theT cells macrophages,cDc’s MHC 1 processing MHC class 1 is combined with antigen that been processed in the cytoplasm directly via a proteosome MHC 2 processing and will be a peptide that’s displayed to CD8+ MHC class 2 will be endosomal processed in a phagolysosome and then presented to CD4+ cells A 29-YEAR-OLD RHESUS POSITIVE LADY P3 G2 ATTENDS THE DELIVERY SUITE. HER CHILD IS JAUNDICED WHEN BORN AND THE MIDWIFE EXPLAINS THAT IT IS DUE TO HER BABY BEING RHESUS NEGATIVE. WHICH IMMUNOGLOBULIN PRODUCED BY THE MOTHER IS MOST LIKELY RESPONSIBLE FOR HER BABY’S IMMEDIATE PRESENTATION? A IgA B IgD C IgE D IgG E IgM A 29-YEAR-OLD RHESUS POSITIVE LADY P3 G2 ATTENDS THE DELIVERY SUITE. HER CHILD IS JAUNDICED WHEN BORN AND THE MIDWIFE EXPLAINS THAT IT IS DUE TO HER BABY BEING RHESUS NEGATIVE. WHICH IMMUNOGLOBULIN PRODUCED BY THE MOTHER IS MOST LIKELY RESPONSIBLE FOR HER BABY’S IMMEDIATE PRESENTATION? A IgA B IgD C IgE D IgG E IgMExplain why secondary (memory) immune responses differ from primary immune responses Primary response Secondary response Naive B andT cell respond Memory B cells respond Lag phase 4-7 days Lag phase 1-4 days Antibody peak at 7-10 days Antibody peak at 3-5 days IgM primarily produced IgG primarily produced Ab’s high affinity for antigens Ab’s low affinity for antigens A STUDENT AT UNIVERSITY RESIDENCES HAS CONTRACTED INFLUENZA TYPE A. THEY DESCRIBE FEELING FATIGUED, ANOREXIC AND HAVE ACHY MUSCLES. WHICH OF THE FOLLOWING IS MOST LIKELY RESPONSIBLE FOR THE STUDENTS SYMPTOMS? A IF-Type 1 B IF-Type 2 C IL-2 D IL-6 E IL-1 A STUDENT AT UNIVERSITY RESIDENCES HAS CONTRACTED INFLUENZA TYPE A. THEY DESCRIBE FEELING FATIGUED, ANOREXIC AND HAVE ACHY MUSCLES. WHICH OF THE FOLLOWING IS MOST LIKELY RESPONSIBLE FOR THE STUDENTS SYMPTOMS? A IF-Type 1 B IF-Type 2 C IL-2 D IL-6 E IL-1Explain importance of interferons in defending against viral infection (H2) Trigger‘antiviral state‘ in cells via the JAK/Stat pathway Induces apoptosis virally infected cells The collective actions causes a‘cellular firebreak’ Recruits immune cells like NK cells Interferons are also responsible for symptoms such as:malaise sleepiness, myalgia & loss of appetite NATURAL KILLER CELLS ARE IMPORTANT IN OUR BODIES DEFENSE AGAINST VIRUSES. WHICH OF THE FOLLOWING BEST FITS THE TLR’S CARRIED BY THESE CELLS? A TLR-3 B TLR-9 C TLR-3 & TLR-8 D TLR-7 &TLR-9 E TLR-7 & TLR-8 NATURAL KILLER CELLS ARE IMPORTANT IN OUR BODIES DEFENSE AGAINST VIRUSES. WHICH OF THE FOLLOWING BEST FITS THE TLR’S CARRIED BY THESE CELLS? A TLR-3 B TLR-9 C TLR-3 & TLR-8 D TLR-7 &TLR-9 E TLR-7 & TLR-8Recognise that NK cells provide an early defence against viral infections Located in the blood,and some in peripheral tissues Can bring about direct lysis of cells virally infected CarriesTLR-3 &TLR-8,these are endosomal receptors – most viruses infect intracellularly They have 3 methods of inducing cell death:production of cytokines,the secretion of cytolytic granules,and the use of death receptor-mediated cytolysis OUTLINE THE ROLE OF T LYMPHOCYTES IN RELATION TO ANTIGEN EXPOSURE ACROSS THE LIFE COURSE WHICH STATEMENT CORRECTLY IDENTIFIES THE FEATURES OF DENDRITIC CELLS? A Conventional dendritic cells are found in lymph/blood and aid in the production of interferon 1 to fight viral pathogens B All dendritic cells (both plasmacytoid and conventional cells) contain the MHC class 1 receptor. Some have MHC class 2 but not all. C Plasmacytoid dendritic cells are found in peripheral tissue and contain highTLR which aids in the production of interferons in response to a virus. D Conventional dendritic cells (cDCs) are sentinel cells found in peripheral tissue.In reaction to a pathogen,they migrate to the nearest lymph node for presentation to CD4 and CD8T cells. E Plasmacytoid dendritic cells contain both MHC class 2 and MHC class 1 receptors. Conventional dendritic cells contain only MHC class 2 receptor on the cell surface membrane, WHICH STATEMENT CORRECTLY IDENTIFIES THE FEATURES OF DENDRITIC CELLS? A Conventional dendritic cells are found in lymph/blood and aid in the production of interferon 1 to fight viral pathogens B All dendritic cells (both plasmacytoid and conventional cells) contain the MHC class 1 receptor. Some have MHC class 2 but not all. C Plasmacytoid dendritic cells are found in peripheral tissue and contain highTLR which aids in the production of interferons in response to a virus. D Conventional dendritic cells (cDCs) are sentinel cells found in peripheral tissue.In reaction to a pathogen,they migrate to the nearest lymph node for presentation to CD4 and CD8T cells. E Plasmacytoid dendritic cells contain both MHC class 2 and MHC class 1 receptors. Conventional dendritic cells contain only MHC class 2 receptor on the cell surface membrane, CONVENTIONAL VS PLASMACYTOID DENDRITIC CELL • Plasmacytoid dendritic cells • Found in lymph/blood (when virus spills into blood) • Contains highTLR (toll-like receptors) – can produce large amounts of interferons (creates anti-viral state) • How are interferons released? 1. PAMPs recognized by PRR e.g.,TLR/RLR 2. Any infected cells can release alpha/beta interferons 3. Create anti-viral state + activate NK cells if interferons cannot clear infection. Conventional dendritic cells • Found in peripheral tissue – type of sentinel cells (APCs – cDCs,macrophages,mast cells). • Drains to nearest lymph node to present antigen on MHC II toT cells • Contains both MHC I and MHC II receptors • Contains B7 + CCR7 receptors WHICH STATEMENT CORRECTLY IDENTIFIES THE ROLES OF TOLL-LIKE RECEPTORS ON THE RELEASE OF INTERFERONS? A TLR 1,2,4,and 6 are found on endosomes intracellularly.TLR 3,7,8 ,and 9 are found on cells surface membranes.They are activated by interferons to produce the anti-viral state. B TLR 3,7,8,and 9:intracellularTLR that responds to foreign nucleic acids (ds/ss RNA).They activate IRF (interferon releasing factor) to mass produce interferons for an anti-viral state. C IntracellularTLR 7/8 is activated by double stranded RNA viruses e.g.,rotavirus.The consequent release of alpha/beta interferons create the anti-viral state. D Only conventional dendritic cells containTLR which can produce an interferon response on their surfaces, E In response to a viral pathogen, alpha/beta interferons activateTLR to create an anti-viral state. WHICH STATEMENT CORRECTLY IDENTIFIES THE ROLES OF TOLL-LIKE RECEPTORS AND THE RELEASE OF INTERFERONS? A TLR 1,2,4,and 6 are found on endosomes intracellularly.TLR 3,7,8 ,and 9 are found on cells surface membranes.They are activated by interferons to produce the anti-viral state. B TLR 3,7,8,and 9:intracellularTLR that responds to foreign nucleic acids (ds/ss RNA).They activate IRF (interferon releasing factor) to mass produce interferons for an anti-viral state. C IntracellularTLR 7/8 is activated by double stranded RNA viruses e.g.,rotavirus.The consequent release of alpha/beta interferons create the anti-viral state. D Only conventional dendritic cells containTLR which can produce an interferon response on their surfaces, E In response to a viral pathogen, alpha/beta interferons activateTLR to create an anti-viral state. INTERFERON ACTIVATION BY TOLL-LIKE RECEPTORS • What are the types of interferons? Overview of innate response to virus: 1. Virus invades cell – entry + replication • Type 1 • Alpha – infected leukocytes 2. Identified by sentinel cells (macrophages, cDCs,mast cells) via PRR (TLR detect PAMPs) • Beta – fibroblasts 3. Release interferons 4. NK activation to identify abnormal MHC I and • Binds to IFN receptor and stimulate ISG (previous slide) kill infected cells. • Type 2 5. If that does not clear virus – adaptive immunity next! • Gamma – activatedT cells + NK cells INTERFERON ACTIVATION BY TOLL-LIKE RECEPTORS • Types ofToll-like receptors: PRR (e.g.,TLR) recognise • CSM:1,2,4,and 6 PAMPs/DAMPs • Endosomes:3 (ds RNA),.7/8 (SS rna).9 (cPg RICH DNA) • How are interferons released? 1. Virus activatesTLR (ss/ds) 2. Cell produces IRF (Interferon Releasing Factor) 3. Nucleus – IFN mRNA production 4. IFN binds to receptors on cells 5. Activates ISG (interferon stimulated genes) – suppress viral entry/replication AFTER MIGRATION, THE CONVENTIONAL DENDRITIC CELLS ACTIVATES CD4 AND CD8 EXPRESSING T CELLS. WHICH STATEMENT RELATNG THIS PROCESS IS INCORRECT? A IL-2 is released as the third signal inT cell activation,It binds to the IL-2 receptor on the same T cell. B CD4+ cells are activated by MHC I (HLA-DP,HLA-DQ,and HLA-DR) C T cell receptors recognize not only the antigen but also the type of MHC molecule it is presented on. D CD4 coreceptor is found onT helper cells whereas CD8 coreceptors are found on cytotoxicT cells. E Second signal (costimulation) via B7 ligand onAPC (CD80) and CD28 onT cell.Costimulation increases activity. AFTER MIGRATION, THE CONVENTIONAL DENDRITIC CELLS ACTIVATES CD4 AND CD8 EXPRESSING T CELLS. WHICH STATEMENT RELATNG THIS PROCESS IS INCORRECT? A IL-2 is released as the third signal inT cell activation,It binds to the IL-2 receptor on the same T cell. B CD4+ cells are activated by MHC I (HLA-DP,HLA-DQ,and HLA-DR) C T cell receptors recognize not only the antigen but also the type of MHC molecule it is presented on. D CD4 coreceptor is found onT helper cells whereas CD8 coreceptors are found on cytotoxicT cells. E Second signal (costimulation) via B7 ligand onAPC (CD80) and CD28 onT cell.Costimulation increases activity. T CELL ACTIVATION: NAIVE TO EFFECTOR CELLS Im m s u no u p pr - T helper cells CytotoxicT cells in h ess iv a b it T e d r Contains CD4 coreceptor Contains CD8 coreceptor ctiv a ce l u g s tio n ! CD4 binds to MHC II CD8 binds to MHC I • HLA-DP • HLA-A • HLA-GQ • HLA-B • HLA-DR • HLA-C TCR binds to antigen TCR binds to antigen Costimulation Costimulation 1. First signal: MHC toTCR 2. Second signal (costimulation):prevents anergy (lack of immune response) • B7 (APC) binds to CD28 (T cells) 3. Third signal (autocrine/paracrine signalling )– signal for production of interleukins byT cell.IL-2 is produced which binds to the receptor on the same cell and different cells = proliferation.ARMY OF WHICH STATEMENT CORRECTLY IDENTIFIES THE MAIN SOURCES OF EACH INTERLEUKIN? A IL-5:TH2 cells IL-3:Macrophages B IL-5:Macrophages IL-6:TH2 cells C IL-1:macrophages IL-2:TH2 cells D IL-3:T helper cells IL-1:T helper cells E IL-1:macrophages IL-2:TH1 cells WHICH STATEMENT CORRECTLY IDENTIFIES THE MAIN SOURCES OF EACH INTERLEUKIN? A IL-5:TH2 cells IL-3:Macrophages B IL-5:Macrophages IL-6:TH2 cells C IL-1:macrophages IL-2:TH2 cells D IL-3:T helper cells IL-1:T helper cells E IL-1:macrophages IL-2:TH1 cells WHAT IS THE MAIN SOURCE AND MAIN FUNCTION OF TNF – ALPHA? A Main source:TH2 cells Main function:stimulate B cell differentiation B Main source:TH2 cells Main function:stimulateT cell differentiation C Main source:TH1 cells Main function:B cell activation D Main source:macrophages Main function:neutrophil chemotaxis and induction of fever E Main source:macrophages Main function:stimulateT cell activation WHAT IS THE MAIN SOURCE AND MAIN FUNCTION OF TNF – ALPHA? A Main source:TH2 cells Main function:stimulate B cell differentiation B Main source:TH2 cells Main function:stimulateT cell differentiation C Main source:TH1 cells Main function:B cell activation D Main source:macrophages Main function:neutrophil chemotaxis and induction of fever E Main source:macrophages Main function:stimulateT cell activationMAIN SOURCES AND FUNCTIONS OF INTERLEUKINS What happens when the CD4+T helper cells are activated? They can form: Activated to form either: •TH1 (T helper cell 1) - viral/bacterial • Activated by IL-12 • Leave lymph nodes and release interferon-gamma (stimulates macrophages) •TH1f (T follicular cell) - viral/bacterial • Do not leave lymph node • Interact with B cells - class switching + clonal expansion •TH2 (T helper cell 2) - viral and bacterial • Activated by 1L-4 • Produce IL4+IL5 - stimulate clonal expansion •TH17 (T helper 17) - bacterial • Release 1L-7 • Stimulate neutrophil productionEXPLAIN THE DIFFERENTIATION OF B LYMPHOCYTES AND NATURE TO ANTIBODIES PRODUCED IN RELATION TO ANTIGEN EXPOSURE IDENTIFY THE CORRECT STATEMENT DESCRIBING MHC FORMATION? A MHC II:found in all nucleated cells.Proteins are phagocytosed into the cell to form a phagosome. B MHC II:viral proteins are present in the cytosol and not confined within a phagosome. MHC1:found in all nucleated cells.When the groove is empty,MHC I is found only in C endoplasmic reticulum.The virus is present in the cytosol and is broken down by proteosomes. D MHC I:viral proteins are confined within a phagosome and never make contact with the cytosol. E MHC II:presents endogenous antigens on cell surface membrane. IDENTIFY THE CORRECT STATEMENT DESCRIBING MHC FORMATION? A MHC II:found in all nucleated cells.Proteins are phagocytosed into the cell to form a phagosome. B MHC II:viral proteins are present in the cytosol and not confined within a phagosome. MHC1:found in all nucleated cells.When the groove is empty,MHC I is found only in C endoplasmic reticulum.The virus is present in the cytosol and is broken down by proteosomes. D MHC I:viral proteins are confined within a phagosome and never make contact with the cytosol. E MHC II:presents endogenous antigens on cell surface membrane. MHC I AND MHC II PROCESSING MHC I MHC II Endogenous antigens Exogenous antigens Antigen derived from inside the cell e.g.Antigen acquired from outside the cell normal self antigen or neoantigen e.g.extracellular bacteria (cancer) or viral antigens • Pathogenic proteins are broken • Phagocytosis:antigen taken inside down to small peptides by phagosome proteosomes • Phagosome and lyzosomes fuse = • Enters ER viaTAP transporter phagolysosome (hydrolases breaks • In ER,fills in the groove of‘empty’ down to peptides) MHC I • Fuse with endosomes containing MHC • Carried via endosome to cell surface II • Fills groove of MHC II and move to surface WHICH STATEMENT ABOUT B/T LYMPHOCYTE FORMATION/SELECTION SI CORRECT? A T lymphocytes mature in thymus.They must undergo positive and negative selection before migration to secondary lymphoid tissue. B B lymphocytes mature in bone marrow,They must undergo positive and negative selection before migration to secondary lymphoid tissue. C B andT lymphocytes both are produced and mature in the bone marrow before migration to lymphoid tissue D After migration to lymphoid tissue,B lymphocytes mature in the bone marrow. E After migration to lymphoid tissue,T lymphocytes mature in the thymus. WHICH STATEMENT ABOUT B/T LYMPHOCYTE FORMATION/SELECTION SI CORRECT? A T lymphocytes mature in thymus.They must undergo positive and negative selection before migration to secondary lymphoid tissue. B B lymphocytes mature in bone marrow,They must undergo positive and negative selection before migration to secondary lymphoid tissue. C B andT lymphocytes both are produced and mature in the bone marrow before migration to lymphoid tissue D After migration to lymphoid tissue,B lymphocytes mature in the bone marrow. E After migration to lymphoid tissue,T lymphocytes mature in the thymus. LYMPHOCYTE FORMATION AND SELECTION • Both B andT T lymphocytes • Positive selection – keep lymphocytes are ones that bind to foreign produced in the antigen and destroy ones bone marrow. that do not. • B lymphocytes • Negative selection – mature in bone destroy ones that bind to marrow self antigen and keep ones • T lymphocytes that do not (self- mature inThymus tolerance). • Summary:must bind to foreign antigen and must not bind to self antigen HOW DO CD4+ (TH1F) STIMULATE B CELLS IN LYMPH NODES? A BCR binds to MHC I complex.CD40 binds to CD40L. B BCR binds to MHC II complex.B7 binds to CD28 for costimulation. C TCR binds to MHC II complex.CD40 binds to CD40L.Releases cytokines to induce somatic hypermutation and class switching. D TCR binds to MHC I complex.B7 binds to CD28 for costimulation. E BCR binds toTCR.B7 binds to CD28. HOW DO CD4+ (TH1F) STIMULATE B CELLS IN LYMPH NODES? A BCR binds to MHC I complex.CD40 binds to CD40L. B BCR binds to MHC II complex.B7 binds to CD28 for costimulation. C TCR binds to MHC II complex.CD40 binds to CD40L.Releases cytokines to induce somatic hypermutation and class switching. D TCR binds to MHC I complex.B7 binds to CD28 for costimulation. E BCR binds toTCR.B7 binds to CD28. CLONAL SELECTION • Naïve B cells are covered in BCR (membrane found of immunoglobulins) • BCR binds and engulfs antigens • Displayed on MHC II molecule (APC) toTCR ofTH2 cells • TH2 cells release cytokines that induce B cell proliferation to make clones – they synthesise + secrete antibodies with same recognition as BCR initially had to the antigen • Costimulation via CD40-CD40L interaction WHICH STATEMENT CORRECTLY IDENTIFIES THE STRUCTURE AND FUNCTION OF IMMUNOGLOBULINS? A IgG (monomer):found in lymph and blood B IgA (dimer):activates basophils and mast cells IgM (pentamer):involved in allergic reactions e.g.type 1 hypersensitivity C D IgE (monomer):most abundant in the body E IgG (monomer):can pass through placenta. WHICH STATEMENT CORRECTLY IDENTIFIES THE STRUCTURE AND FUNCTION OF IMMUNOGLOBULINS? A IgG (monomer):found in lymph and blood B IgA (dimer):activates basophils and mast cells IgM (pentamer):involved in allergic reactions e.g.type 1 hypersensitivity C D IgE (monomer):most abundant in the body E IgG (monomer):can pass through placenta.• IgM (pentamer) • IgA (dimer) • IgD,IgE,IgG (monomer) • IgG –Abundant. pass through placenta • IgA – mucus membranes.Pass through breastmilk. • IgM – blood + lymph.First to be made in infection. • IgE – allergic reactions.Type 1 hypersensitivity reaction with mast cell priming, • IgD – activate basophils + mast cells WHICH STATEMENT CORRECTLY DESCRIBES SOMATIC HYPERMUTATION AND CLASS SWITCHING? A Class switching refers to changes that occur in the genes coding for the constant regions.It causes the change from IgM to IgG/IgA/IgE B Class switching refers to point mutations in genes coding for the variable regions.Higher affinity antibodies multiply. C Somatic hypermutation refers to changes that occur in the genes coding for the constant regions.It causes the change of immunoglobins. D Somatic hypermutation refers to point mutations in genes coding for the variable regions.High affinity antibodies multiply. E Somatic hypermutation refers to changes in genes coding for the disulfide bridge present on immunoglobins WHICH STATEMENT CORRECTLY DESCRIBES SOMATIC HYPERMUTATION AND CLASS SWITCHING? A Class switching refers to changes that occur in the genes coding for the constant regions.It causes the change from IgM to IgG/IgA/IgE B Class switching refers to point mutations in genes coding for the variable regions.Higher affinity antibodies multiply. C Somatic hypermutation refers to changes that occur in the genes coding for the constant regions.It causes the change of immunoglobins. D Somatic hypermutation refers to point mutations in genes coding for the variable regions.High affinity antibodies multiply. E Somatic hypermutation refers to changes in genes coding for the disulfide bridge present on immunoglobins SOMATIC HYPERMUTATION AND CLASS SWITCHING • Somatic hypermutation – point mutations in genes coding for the variable regions: • Winners – higher affinity antibodies can compete for antigens (clonal expansion) • Losers – lower affinity antibodies cannot compete for antigens (apoptosis) • Class switching – changes occur in genes coding for constant regions • IgM changes to higher affinity IgG/IgA/IgE • B cell encounters pathogen,binds to BCR,release IgM • T follicular cells – causes B cell somatic hypermutation + class switching = IgG (higher affinity)EXPLAIN THE IMMUNE RESPONSE TO VACCINATIONS AND HOW VACCINATIONS WORK TO PROVIDE PROTECTION TO THE INDIVIDUAL AND THE COMMUNITY. TEENAGERS AT A SECONDARY SCHOOL ARE BEING OFFERED THE GARDASIL VACCINE AGAINST HPV. WHICH STRAINS OF HPV DOES THE VACCINE PROTECT AGAINST? A 7,11,16,18 B 6,11,16,18 C 6, 11, 16, 21 D 6, 17,33, 32 E 6, 17, 52, 58 TEENAGERS AT A SECONDARY SCHOOL ARE BEING OFFERED THE GARDASIL VACCINE AGAINST HPV. WHICH STRAINS OF HPV DOES THE VACCINE PROTECT AGAINST? A 7,11,16,18 B 6,11,16,18 C 6,11,16,21 D 6,17,33,32 E 6,17,52,58 HPV VACCINE • Offered to girls and boys,aged 12-13,as part of the NHSVaccination programme. • Helps to protect against cervical cancers (16 and 18) and genital warts (6,11) • The newer Gardasil 9 vaccine which is being introduced will provide protection against types: 6,11,16,18,31,33,45,52 and 58. • 31,33,45,52,58 are also associated with increased cancer risk. A 12-YEAR-OLD CHILD PRESENTS TO THEIR GP WITH A TWO-WEEK HISTORY OF COLD-LIKE SYMPTOMS AND, IN THE PAST TWO DAYS, HAS DEVELOPED A CHARACTERISTIC ‘WHOOPING’ COUGH. THE VACCINATION AGAINST THE CAUSATIVE ORGANISM IS CLASSIFIED AS WHICH TYPE? A Toxoid B Live-attenuated C Conjugate D Inactivated E Recominant A 12-YEAR-OLD CHILD PRESENTS TO THEIR GP WITH A TWO WEEK HISTORY OF COLD-LIKE SYMPTOMS AND, IN THE PAST TWO DAYS, HAS DEVELOPED A CHARACTERISTIC ‘WHOOPING’ COUGH. THE VACCINATION AGAINST THE CAUSATIVE ORGANISM IS CLASSED AS WHICH TYPE? A Toxoid B Live-attenuated C Conjugate D Inactivated E Recominant VACCINE TYPES • Live-attenuated contain weakened,whole pathogens/viruses Rotavirus,MMR,yellow fever • Inactivated contain‘dead’ whole pathogens/viruses Polio (IPV),influenza,rabies • Recombinant protein HepB,HPV,MenB • Toxoid contain inactivated toxins Diphtheria,tetanus,pertussis • Conjugate Hib,MenC,PCV,MenACWY A PRE-SCHOOL CHILD, AGED 3, ATTENDS THE VACCINATION CLINIC FOR THEIR 4- IN1 BOOSTER. THIS INCLUDES VACCINATION AGAINST TETANUS. THE RECOGNITION OF TETANUS TOXOID PROTEINS BY CD4+ CELLS PRIMARILY STIMULATES PRODUCTION OF WHICH TYPE OF IMMUNOGLOBULIN? A IgM B IgE C IgG D IgD E IgA A PRE-SCHOOL CHILD, AGED 3, ATTENDS THE VACCINATION CLINIC FOR THEIR 4- IN1 BOOSTER. THIS INCLUDES VACCINATION AGAINST TETANUS. THE RECOGNITION OF TETANUS TOXOID PROTEINS BY CD4 CELLS PRIMARILY STIMULATES PRODUCTION WHICH TYPE OF IMMUNOGLOBULIN? A IgM B IgE C IgG D IgD E IgA IMMUNOGLOBULINS • The tetanus toxoid protein is processed and presented by MHC class II receptors on cDCs to CD4T cells. • This eventually stimulates a strong IgG response. • IgG antibodies are able to neutralise the bacterial tetanus toxins. • IgG is the most abundant antibody in the blood. YOU ARE A GP. MORGAN, A FIRST-TIME FATHER, HAS BEEN READING ABOUT THE ‘6-IN1’ DTAP/IPV/HIB/HEPB VACCINE, OFFERED TO INFANTS AT 8 WEEKS. HE COMES INTO THE PRACTICE TO ASK YOU WHY THIS VACCINATION CONTAINS ALUMINIUM SALTS. USING YOUR KNOWLEDGE ABOUT THE CONCEPT OF VACCINE ADJUVANTS WHAT WOULD YOU TELL MORGAN? A To minimise the number of doses required. B To inactivate the ‘live’ components of the vaccine, making it safer. To ensure that the vaccine can be stored for long periods of time, without the need for C refrigeration. D To enhance the immune response to the vaccination by retaining antigens at injection site, extending their presence within the blood. E Because it is a by-product of the vaccines production which is difficult to remove without impacting the efficacy of the vaccine. YOU ARE A GP. MORGAN, A FIRST-TIME FATHER, HAS BEEN READING ABOUT THE ‘6-IN1’ DTAP/IPV/HIB/HEPB VACCINE, OFFERED TO INFANTS AT 8 WEEKS. HE COMES INTO THE PRACTICE TO ASK YOU WHY THIS VACCINATION CONTAINS ALUMINIUM SALTS. USING YOUR KNOWLEDGE ABOUT THE CONCEPT OF VACCINE ADJUVANTS WHAT WOULD YOU TELL MORGAN? A To minimise the number of doses required. B To inactivate the ‘live’ components of the vaccine, making it safer. To ensure that the vaccine can be stored for long periods of time, without the need for C refrigeration. D To enhance the immune response to the vaccination by retaining antigens at injection site, extending their presence within the blood. E Because it is a by-product of the vaccines production which is difficult to remove without impacting the efficacy of the vaccine. ADJUVANTS • Added to the vaccine to enhance the strength and quality of the immune response stimulated by that vaccine. • The‘depot’ effect – the absorption of antigens onto adjuvant molecules, prolongs their presence at the injection site,allowing them time to stimulate a more effective immune response • ‘Danger Hypothesis’ – adjuvants create a pro-inflammatory environment which promotes recruitment of innate immune cells and subsequently dendritic cells which activate the adaptive immune response. A 48-YEAR-OLD HEALTHCARE PROFESSIONAL IS FOUND TO HAVE CONTRACTED HEPATITIS B FOLLOWING A NEEDLE-STICK INJURY AT WORK. THEY ARE VERY SHOCKED BECAUSE THEY STATE THAT THEY HAD RECEIVED THEIR VACCINATIONS AVACCINE FAILURE COULD EXPLAIN HOW THIS COULD HAVE OCCURRED?IMARY A Waning antibody levels B Incorrect storage of the vaccine C Age-related decline in immunological function D Obesity-related immunosuppression ‘Non-responder’ HLA phenotype E A 48-YEAR-OLD HEALTHCARE PROFESSIONAL IS FOUND TO HAVE CONTRACTED HEPATITIS B FOLLOWING A NEEDLE-STICK INJURY AT WORK. THEY ARE VERY SHOCKED BECAUSE THEY STATE THAT THEY HAD RECEIVED THEIR VACCINATIONS AVACCINE FAILURE COULD EXPLAIN HOW THIS COULD HAVE OCCURRED?IMARY A Waning antibody levels B Incorrect storage of the vaccine C Age-related decline in immunological function D Obesity-related immunosuppression ‘Non-responder’ HLA phenotype E VACCINE FAILURE Definition:occurrence of disease in individual who has been vaccinated against it. • Primary vaccine failure – individual fails to make an initial immune response to the vaccine • Secondary vaccine failure – individual makes initial immune response but this protection wanes over time. • Primary vaccine failure can occur due to vaccine-related factors or host- related factors. IMMUNE RESPONSE GENES • The Major Histocompatibility Complex or the Human LeukocyteAntigen Complex is located on chromosome 6. • This complex of genes codes for MHC class I and MHC class II molecules which present antigenic peptides toT cells. • HLA genes are highly polymorphic.This means that the HLA allele frequency within the human population is highly varied. • Polymorphism occurs in domains responsible for epitope binding. • Genetic predisposition to vaccine failure. USEFUL RESOURCES • https://assets.publishing.service.gov.uk/government/uploads/system/uploads/atta chment_data/file/949797/Greenbook_chapter_1_Jan21.pdf - Immune system and how vaccines work • https://academic.oup.com/occmed/article/57/8/552/1474357 - types of vaccine and how they are made • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4962729/ - article on reasons for vaccine failure • https://www.karger.com/Article/FullText/106559 lots of detail on role of genetic variation in response to vaccines OUTLINE THE PUBLIC HEALTH PRINCIPLES OF IMMUNIZATION AND SURVEILLANCE OF INFECTIOUS DISEASES NEL IS PREPARING TO TRAVEL TO THAILAND. HER TRAVEL INSURANCE COMPANY HAVE RECOMMENDED THAT SHE RECEIVE A TETANUS BOOSTER. WHAT IS THE AIM OF THE TETANUS VACCINATION PROGRAMME WORLDWIDE? A Eradication of disease B Containment of disease C Protection of the vulnerable D Protection of healthcare resources in developing countries E Elimination of disease NEL IS PREPARING TO TRAVEL TO THAILAND. HER TRAVEL INSURANCE COMPANY HAVE RECOMMENDED THAT SHE RECEIVE A TETANUS BOOSTER. WHAT IS THE AIM OF THE TETANUS VACCINATION PROGRAMME WORLDWIDE? A Eradication of disease B Containment of disease C Protection of the vulnerable D Protection of healthcare resources in developing countries E Elimination of disease OBJECTIVES OF IMMUNISATION PROGRAMMES • General objectives: - Prevent serious diseases or complications - Protect individuals and communities - Control outbreaks of disease (protection of health resources) • Specific objectives: - Containment - Elimination - Eradication MR AND MRS CLIFFORD ARE HOLIDAYING IN PERU. 4 DAYS INTO THEIR TROPICAL SOUTH AMERICAN TRIP, MR CLIFFORD DEVELOPS A HIGH FEVER, SEVERE HEADACHE, AND EXTREME FATIGUE. AFTER A WEEK MR CLIFFORD FEELS BETTER AND ENJOYS THE LAST WEEK OF HIS HOLIDAY. ONCE BACK IN THE UK, MRS CLIFFORD NOTICES MR CLIFFORD HAS BECOME JAUNDICE. VACCINATION AGAINST WHICH DISEASE COULD HAVE PROTECTED MR CLIFFORD? A Typhoid B Dengue fever C Hep B D Rabies Yellow fever E MR AND MRS CLIFFORD ARE HOLIDAYING IN PERU. 4 DAYS INTO THEIR TROPICAL SOUTH AMERICAN TRIP, MR CLIFFORD DEVELOPS A HIGH FEVER, SEVERE HEADACHE, AND EXTREME FATIGUE. AFTER A WEEK MR CLIFFORD FEELS BETTER AND ENJOYS THE LAST WEEK OF HIS HOLIDAY. ONCE BACK IN THE UK, MRS CLIFFORD NOTICES MR CLIFFORD HAS BECOME JAUNDICE. VACCINATION AGAINST WHICH DISEASE COULD HAVE PROTECTED MR CLIFFORD? A Typhoid B Dengue fever C Hep B D Rabies Yellow fever E ADULT IMMUNISATION • Older people (65+) - Influenza yearly - Shingles (70+) - PPV • Pregnancy - Influenza - Pertussis (from 16 weeks gestation)ADULT IMMUNISATION TRAVEL IMMUNISATION • Polio • Typhoid • HepA • Cholera • Hep B • Japanese encephalitis • Rabies • Tick- borne encephalitis • TB • Yellow fever A 7-MONTH PREGNANT WOMAN COMES INTO THE VACCINATION CENTRE TO RECEIVE HER COVID-19 BOOSTER. 3 DAYS AGO, SHE RECEIVED HER FLU VACCINATION. UPON QUESTIONING BY THE VACCINATOR, SHE EXPERIENCED SOME TENDERNESS AROUND SITE OF ADMINISTRATION AFTER HER LAST DOSE, AS WELL AS EXPERIENCING SOME DIARRHOEA. A FEW DAYS LATER, SHE DEVELOPED A PAINFUL, RED, SWOLLEN LEFT LEG. WHICH OF THE FOLLOWING IS AN ABSOLUTE CONTRAINDICATION TO HER RECEIVING THE COVID-19 VACCINATION? A Recent flu vaccine B History of painful,red,swollen leg C History of tenderness around site of administration D Pregnancy History of diarrhoea after vaccination E A 7-MONTH PREGNANT WOMAN COMES INTO THE VACCINATION CENTRE TO RECEIVE HER COVID-19 BOOSTER. 3 DAYS AGO, SHE RECEIVED HER FLU VACCINATION. UPON QUESTIONING BY THE VACCINATOR, SHE EXPERIENCED SOME TENDERNESS AROUND SITE OF ADMINISTRATION AFTER HER LAST DOSE, AS WELL AS EXPERIENCING SOME DIARRHOEA. A FEW DAYS LATER, SHE DEVELOPED A PAINFUL, RED, SWOLLEN LEFT LEG. WHICH OF THE FOLLOWING IS AN ABSOLUTE CONTRAINDICATION TO HER RECEIVING THE COVID-19 VACCINATION? A Recent flu vaccine B History of painful,red,swollen leg C History of tenderness around site of administration D Pregnancy History of diarrhoea after vaccination E VACCINE SAFETY • Adverse reactions can be reported via theYellow Card Scheme which serves as an early warning scheme for vaccine-related safety concerns Contraindications:anaphylaxis/allergy to vaccine ingredients,history of thrombosis Cautions:acute illness,prior allergic reaction (hives,angioedema),myocarditis Adverse reactions:local reaction at injection site,systemic reactions (tiredness, headache,muscle ache,pyrexia) DATA COLLECTED THROUGH WHICH OF THE FOLLOWING METHODS IS COMMONLY USED FOR DISEASE SURVEILLANCE. A UK death register B Randomised clinical trials C Population surveys D Statutory disease notification E Pharmaceutical companies DATA COLLECTED THROUGH WHICH OF THE FOLLOWING METHODS IS COMMONLY USED FOR DISEASE SURVEILLANCE. A UK death register B Randomised clinical trials C Population surveys D Statutory disease notification E Pharmaceutical companies ROGER, A 76-YEAR-OLD PATIENT, HAS UNDERGONE A SPLENECTOMY DUE TO COMPLICATIONS OF HIS LYMPHOMA DIAGNOSIS. PRIOR TO HIS SURGERY, HE WAS UP TO DATE WITH ALL HIS ROUTINE VACCINATIONS. FOLLOWING THE SPLENECTOMY, WHICH VACCINE WILL HE NOW REQUIRE EVERY 5 YEARS? A MenB (meningococcal B) B MMR C Influenza D HPV E PPV (Pneumococcal) ROGER, A 76-YEAR-OLD PATIENT, HAS UNDERGONE A SPLENECTOMY DUE TO COMPLICATIONS OF HIS LYMPHOMA DIAGNOSIS. PRIOR TO HIS SURGERY, HE WAS UP TO DATE WITH ALL HIS ROUTINE VACCINATIONS. FOLLOWING THE SPLENECTOMY, WHICH VACCINE WILL HE NOW REQUIRE EVERY 5 YEARS? A MenB (meningococcal B) B MMR C Influenza D HPV E PPV (Pneumococcal) IMMUNISATION OF INDIVIDUALS WITH MEDICAL CONDITIONS • The spleen plays an important role in protecting against bacteraemia (infection of the bloodstream by bacteria) by encapsulated bacteria. • Resident macrophages within the spleen remove encapsulated bacteria from the bloodstream. • Marginal zone B cells,abundant in the spleen,are crucial for immune response to polysaccharide antigens (present on encapsulated bacteria).They produce anti-capsular antibodies. • It is crucial that asplenic patients receive vaccinations against encapsulated bacteria,including pneumococcal and meningococcal. ASPLENIC VACCINE SCHEDULE Older children (10+) and adults,regardless of previous vaccination,should receive: • One dose of PPV23 (booster to be given every 5 years) • One dose of MenB and MenACWY • An additional MenB vaccine dose 4 weeks later • Annual influenza vaccine DESCRIBE HOW THE CHILD VACCINATION PROGRAMME IS ORGANISED AND IMPLEMENTED WHY IS THE IMMUNISATION SCHEDULE IMPORTANT? • Protects individuals and the population from contracting particular diseases • Prevention of serious diseases • Control outbreaks of diseases • Try to eliminate and eradicate diseases UK IMMUNISATION SCHEDULE 6 IN 1 6 in 1 • Diphtheria – toxicoid • Tetanus – toxicoid • Pertussis – toxicoid • Polio (IPV) – whole-killed • Haemophilus influenzae type B (Hib) – conjugate • Hepatitis B (Hep B) – recombinant MEASLES • Incubation period: Treatments: • 10-14 days after infection • no specific treatments but condition usually • Communicable period: improves within 7 to 10 days. • cthespread the virus to others for about 8 days → starting 4 days before To ease the symptoms: • Transmission: • paracetamol or ibuprofen to reduce fever. • lives in the nose and throat mucus of an infected person → spreads to • plenty of fluids. others through coughing and sneezing • a humidifier to ease a cough and sore • breathing in contaminated air,touching and infected surface and then throat. touching eyes,nose or mouth → can become infected • vitaminA supplements. • Symptoms: • Fever Virology: • Dry cough • Morbillvirus • Runny nose • single stranded RNA that is non-segmented • Sore throat • Inflamed eyes (conjunctivitis) • Tiny white spots with bluish-white centers on a red background found spotse the mouth on the inner lining of the cheek — also called Koplik's • A skin rash made up of large,flat blotches that often flow into one another RUBELLA • Incubation: • 17 days with a range of 12 to 23 days Treatments: •no specific tretments → symptoms can be • Communicable period: managed with bed rest and medicines for fever • most contagious when the rash is erupting but they can be contagious such as paracetamol Virology: from 7 days before to 7 days after the rash appears • Transmission: •enveloped RNA virus •positive sense single-stranded RNA virus • direct or droplet contact from nasopharyngeal secretions •classified as a Rubivirus • Symptoms: • malaise • coryza or pharyngitis • arthrits • conjunctivitis • maculopapular rash • fever • athralgias → joint stiffness MUMPS • Incubation: • 12 to 25 days Treatments: •most children and adults recover from an • Communicable period: uncomplicated case within a few weeks • 2 days before to 5 days after parotitis onset •generally no longer contagious and can safely • Transmission: return to work or school about 5 days after the • direct contact with saliva or respiratory droplets of a person infected witappearance of signs and symptoms mumps • the risk of spreading the virus increases the longer and the closer the contact the person Virology: •mumps virus • Symptoms: •enveloped,single-stranded RNA virus in the • primary sighn is swollen salivary glands that cause the cheeks to puff out paramyoxvirus (parotitis) •related to parainfluenza and Newcastle disease • pain in the swollen salivary glands on one or both sides of your face viruses and antibodies to these viruses may • pain while chewing or swallowing cross-react with mumps virus • fever • headache • muscle aches • weakness and fatigue • loss of appetite OUTLINE THE KEY STAGES IN NORMAL CHILD DEVELOPMENT (0-5YRS) AND THE GENERAL PRINCIPLES OF DEVELOPMENTAL EXAMINATION MILESTONES • Developmental milestones are they grow,possible to pick up on • Gross motor medical conditions or developmental disorders when • Fine motor milestonesot meeting particular • Communication • Social skills • Vision GROSS MOTOR 3-6 6-9 months 9-18 0-3 months Sitting months months Rolling independently Cruising 2-3 Gain head and (15) years control reaching (9) Running for toys Crawls on Walking (30) (3) (6) hands and feet (18) 3 years – ride a tricycle 4 years – hop on 1 foot FINE MOTOR 12 3 years 4 years 5 years 6 Months months 18 24 4 Transfer 9 months months Builds Pours Use months objects months Start to Drinks Copies blocks and cuts fork Can hold hand to Inferior feed straight more than Can and pincer themselves from cup 6 copy spoon a toy and hand Begins to and uses lines or Turns more Self- shake it Palmar grip build with spoon circles book pages shapes toilet grasp bricks VISION MILESTONES 0-3 months Interested in 2 years lights 9 months Recognition of Briefly holds gaze Peek-a-boo faces in a photo Fixes on mother’s Interested in Inspects objects face pictures without touching them 6 months Follows adults 1 year or moving Enjoys picture objects across books midline Points to Interested in pictures human faces SOCIAL MILESTONES 9 months 0-3 months Proto- 2 years Recognises imperative Pretend play, mother,social pointing, possessive of toys, smile recognizes and responds to helps with dessing own name,puts 6 months Spontaneous arms out to be 1 year smile, held Proto- communication declarative with sounds, pointing holds bottle brieflyDESCRIBE HOW THE CHILD VACCINATION PROGRAMME IS ORGANISED AND IMPLEMENTED MR JONES PRESENTS TO THE GP WITH HIS 1 YEAR OLD DAUGHTER. HE APPEARS VERY ANXIOUS ABOUT HIS DAUGHTER RECEIVING HER MMR VACCINE. MOST OF ALL, HE WANTS TO KNOW WHY SHE HAS TO WAIT UNTIL SHE IS 3 YRS AND 4 MONTHS OLD FOR THE NEXT DOSE OF THE VACCINE. WHICH OF THE FOLLOWING WOULD BE THE BEST ANSWER TO THIS QUESTION? A It would cause the child to be infected with mumps,measles and rubella B The interferon response to the first vaccine would suppress replication of the second vaccine C It would cause the child to have an adverse reaction D The antibody response to the first vaccine would suppress replication of the second vaccine E It would prevent the formation of memory cells MR JONES PRESENTS TO THE GP WITH HIS 1 YEAR OLD DAUGHTER. HE APPEARS VERY ANXIOUS ABOUT HIS DAUGHTER RECEIVING HER MMR VACCINE. MOST OF ALL, HE WANTS TO KNOW WHY SHE HAS TO WAIT UNTIL SHE IS 3 YRS AND 4 MONTHS OLD FOR THE NEXT DOSE OF THE VACCINE. WHICH OF THE FOLLOWING WOULD BE THE BEST ANSWER TO THIS QUESTION? A It would cause the child to be infected with mumps,measles and rubella B The interferon response to the first vaccine would suppress replication of the second vaccine C It would cause the child to have an adverse reaction D The antibody response to the first vaccine would suppress replication of the second vaccine E It would prevent the formation of memory cells MMR VACCINE • Attenuated live virus vaccine • Protects against Mumps,Measles and Rubella • Given around 12 months old and second dose at 3 yrs 4 months • Can cause a mild fever and rash around 6 to 12 days after the vaccination which lasts around 2-3 days.This is due to stimulation of the immune response which triggers the usual physiological responses.Fever is caused by development of viraemia and the rash occurs due to perivascular and lymphocytic infiltration • Interferons are responsible for the anti-viral response A MOTHER PRESENTS TO HER GP WITH HER SON WHO IS 16 MONTHS OLD FOR HIS SCHEDULED IMMUNISATIONS. HE IS HAVING THE 6 IN 1 VACCINATION AND ONE OTHER. WHICH OF THE FOLLOWING DISEASES WILL THE OTHER VACCINATION HE RECEIVES PROTECT AGAINST? A Rotavirus B MMR C Pneumococcal D Meningococcal group B E Pertussis A MOTHER PRESENTS TO HER GP WITH HER SON WHO IS 16 MONTHS OLD FOR HIS SCHEDULED IMMUNISATIONS. HE IS HAVING THE 6 IN 1 VACCINATION AND ONE OTHER. WHICH OF THE FOLLOWING VIRUSES WILL THE OTHER VACCINATION HE RECEIVES PROTECT AGAINST? A Rotavirus B MMR C Pneumococcal D Meningococcal group B E Pertussis CHILDHOOD VACCINATION SCHEDULE • Rotavirus – 8 weeks,12 weeks • MMR – 12 months,3 years 4 months • Pneumococcal – 12 weeks,12 months • Meningitis B – 8 weeks,16 weeks • Pertussis – 8 weeks,12 weeks,16 weeks HOLLIE IS 8 WEEKS OLD AND IS DUE TO HAVE HER FIRST IMMUNISATIONS. HER MOTHER IS VERY ANXIOUS AND WANTS TO KNOW IF SHE CAN WAIT UNTIL HOLLIE IS OLDER BEFORE HAVING THESE VACCINES. THE GP EXPLAINS THAT THE ROTAVIRUS VACCINE IN PARTICULAR SHOULD BE ADMINISTERED BEFORE 15 WEEKS. WHICH OF THE FOLLOWING IS THE BEST EXPLANATION FOR WHY THIS IS THE CASE? A It will prevent intussusception from occurring B It is less likely that the side effect of intussusception will occur if the vaccines start before 15 weeks C The child is already immune to rotavirus by this age D The child will already have contracted rotavirus by this age and be immune Rotavirus only affects children under the age of 15 weeks E HOLLIE IS 8 WEEKS OLD AND IS DUE TO HAVE HER FIRST IMMUNISATIONS. HER MOTHER IS VERY ANXIOUS AND WANTS TO KNOW IF SHE CAN WAIT UNTIL HOLLIE IS OLDER BEFORE HAVING THESE VACCINES. THE GP EXPLAINS THAT THE ROTAVIRUS VACCINE IN PARTICULAR SHOULD BE ADMINISTERED BEFORE 15 WEEKS. WHICH OF THE FOLLOWING IS THE BEST EXPLANATION FOR WHY THIS IS THE CASE? A It will prevent intussusception from occurring B It is less likely that the side effect of intussusception will occur if the vaccines start before 15 weeks C The child is already immune to rotavirus by this age D The child will already have contracted rotavirus by this age and be immune Rotavirus only affects children under the age of 15 weeks E ROTAVIRUS • Cause of gastroenteritis in young babies • Commonly causes watery diarrhoea,vomiting and fever • Can be very serious • It is possible to contract rotavirus more than once, however it is likely to be milder • Intussusception – 1-6/100,000 babies vaccinated will be affected by the vaccine and develop intussusception where a part of the intestine slides into an adjacent part of the intestine JOSIE IS 7 YEARS OLD. HER PARENTS BRING HER TO THE GP AS SHE HAS BEEN COMPLAINING OF A HEADACHE AND RUNNY NOSE. HER TEMPERATURE IS 39.6 DEGREES CELSIUS. ON EXAMINATION, SHE HAS A MACULOPAPULAR RASH AND KOLPIK SPOTS. WHERE WOULD THESE SPOTS BE FOUND? A On the inside of the cheeks B On the tongue C On the tonsils D In the eyes E Around the earsJOSIE IS 7 YEARS OLD. HER PARENTS BRING HER TO THE GP AS SHE HAS BEEN COMPLAINING OF A HEADACHE AND RUNNY NOSE FOR A FEW DAYS. HER TEMPERATURE IS 39.6 DEGREES CELSIUS. ON EXAMINATION, SHE HAS A MACULOPAPULAR RASH (WHICH HAS DEVELOPED TODAY) AND KOLPIK SPOTS. WHERE WOULD THESE SPOTS BE FOUND? A On the inside of the cheeks B On the tongue C On the tonsils D In the eyes Around the ears E MEASLES • Symptoms : • High fever,cough,runny nose (coryza) and conjunctivitis. • The maculopapular rash appears around 3-5 days after the development of the first symptoms • Koplik spots are small white spots with a bluish- white centre found on the inside of the cheeksALFIE IS 6 YEARS OLD AND HAS COME TO THE GP WITH HIS MOTHER FOR HIS YEARLY VASAL FLU SPRAY. WHICH OF THE FOLLOWING WOULD EXPLAIN WHY THE GP REFUSED TO ADMINISTER THE SPRAY? A Alfie felt unwell for 3 days after the nasal flu spray last year B The GP noticed thatAlfie had a noticeable wheeze when breathing C Alfie has never had the nasal flu spray before D Alfie has a temperature of 37.6 E Alfie hasn’t had any other vaccines as part of the childhood immunisation programmeALFIE IS 6 YEARS OLD AND HAS COME TO THE GP WITH HIS MOTHER FOR HIS YEARLY VASAL FLU SPRAY. WHICH OF THE FOLLOWING WOULD EXPLAIN WHY THE GP REFUSED TO ADMINISTER THE SPRAY? A Alfie felt unwell for 3 days after the nasal flu spray last year B The GP noticed thatAlfie had a noticeable wheeze when breathing C Alfie has never had the nasal flu spray before D Alfie has a temperature of 37.6 E Alfie hasn’t had any other vaccines as part of the childhood immunisation programme CONTRAINDICATIONS TO THE NASAL FLU SPRAY • Impaired immune response Children receiving the nasal flu spray should avoid close • Active wheezing contact with people with weakened immune symptoms • Concomitant use with antiviral therapy for influenza for 2 weeks after vaccination. • Severe asthma • E.g.those undergoing chemotherapy or isolating in preparation for a transplant Side effects: • Most side effects are mild and do not last long,such as: • a runny or blocked nose • a headache • tiredness • loss of appetite OUTLINE THE KEY STAGES IN NORMAL CHILD DEVELOPMENT (0-5YRS) AND THE GENERAL PRINCIPLES OF DEVELOPMENTAL EXAMINATION JAMES IS 19 MONTHS OLD. HOWEVER, HIS MOTHER IS CONCERNED THAT HE IS NOT HITTING HIS DEVELOPMENTAL MILESTONES. WHICH OF THE FOLLOWING WOULD BE A RED FLAG FOR JAMES? A Being unable to walk B Being unable to jump C Being unable to make a tower of 6 building blocks D Being unable to join two ore more words to make a simple phrase E Not being potty/toilet trained JAMES IS 19 MONTHS OLD. HOWEVER, HIS MOTHER IS CONCERNED THAT HE IS NOT HITTING HIS DEVELOPMENTAL MILESTONES. WHICH OF THE FOLLOWING WOULD BE A RED FLAG FOR JAMES? A Being unable to walk B Being unable to jump C Being unable to make a tower of 6 building blocks D Being unable to join two ore more words to make a simple phrase E Not being potty/toilet trained DEVELOPMENTAL MILESTONES • Divided into 4 functional areas: • Gross motor • Vision and fine motor • Hearing, speech and language • Social, emotional and behavioural SUZIE WANTS TO KNOW AT WHAT AGE HER BABY SHOULD START SAYING SOME WORDS E.G. MAMA, DADA, JUICE ETC. WHICH OF THE FOLLOWING WOULD BE THE BEST ANSWER FOR SUZIE? A 1-2 years B 4-6 months C 7 -12 months D 10-16 months E 12-17 months SUZIE WANTS TO KNOW AT WHAT AGE HER BABY SHOULD START SAYING SOME WORDS E.G. MAMA, DADA, JUICE ETC. WHICH OF THE FOLLOWING WOULD BE THE BEST ANSWER FOR SUZIE? A 1-2 years B 4-6 months C 7 -12 months D 10-16 months E 12-17 months CHILD DEVELOPMENT: SPEECH • Speech Summary • 0-3 months – reacts to loud noises • 4-6 months – follows sounds with eyes,babbles,pays attention to music • 7months – 1 year – understands common words,juice up etc,one or two words mama dada dog etc • 1-2 years – knows a few parts of the body,acquires new words regularly,uses some two word questions ‘where kitty’.Puts two words together. • 2-3 years – uses sentences of 4 or more words • 4-5 years – understands most of what’s said at home,uses sentences that give many details • If there are any concerns the health visitor can give leaflets to the parents with various exercises to encourage speech development.If this doesn’t help they can be referred to speech and language therapy – SALT. DR JONES IS TESTING THE REFLEXES OF A 5 DAY OLD BABY. SHE STROKES THE CORNER OF THE BABY’S MOUTH AND THE BABY TURNS THEIR HEAD TOWARDS THE STROKING AND OPENS THEIR MOUTH. WHAT IS THE NAME OF THIS BIRTH REFLEX? A Grasp reflex B Stepping reflex C Supporting reflex D Moro reflex E Rooting reflex DR JONES IS TESTING THE REFLEXES OF A 5 DAY OLD BABY. SHE STROKES THE CORNER OF THE BABY’S MOUTH AND THE BABY TURNS THEIR HEAD TOWARDS THE STROKING AND OPENS THEIR MOUTH. WHAT IS THE NAME OF THIS BIRTH REFLEX? A Grasp reflex B Stepping reflex C Supporting reflex D Moro reflex E Rooting reflex BIRTH REFLEXES Perseverance of primitive reflexes may indicate a neurological issue https://youtu.be/b0CLcNtOOEQ WHICH OF THE FOLLOWING IS THE MOST IMPORTANT STEP WHEN EXAMINING A CHILD AND THEIR DEVELOPMENT? A Observe the child playing B Ask the child questions and note how they respond C Observe the child walking D Asking the parents about their child E Test the child’s reflexes WHICH OF THE FOLLOWING IS THE MOST IMPORTANT STEP WHEN EXAMINING A CHILD AND THEIR DEVELOPMENT? A Observe the child playing B Ask the child questions and note how they respond C Observe the child walking D Asking the parents about their child E Test the child’s reflexes CHILD DEVELOPMENT: GENERAL PRINCIPLES OF DEVELOPMENTAL EXAMINATION • Important to test the 4 functional areas • Always ask the parents about their child and the milestones they have already hit – are they developing at a similar rate to their older siblings/peer group? • Observing the child playing with toys/ walking around the room can be really helpful and will also make the child feel more comfortable – will be more receptive when you ask them to do specific things ON MADDIE’S GROWTH CHART THERE IS A SMALL DIP IN HER CHART AT AROUND 2 YEARS OF AGE? WHICH OF THE FOLLOWING IS THE MOST LIKELY EXPLANATION? A The child malnourished B There is a change in the way the child is measured at 2 years C The child is naturally short D The child has a chronic disease E The child was born prematurely ON MADDIE’S GROWTH CHART THERE IS A SMALL DIP IN HER CHART AT AROUND 2 YEARS OF AGE? WHICH OF THE FOLLOWING IS THE MOST LIKELY EXPLANATION? A The child malnourished B There is a change in the way the child is measured 2 years C The child is naturally short D The child has a chronic disease E The child was born prematurely GROWTH CHARTS • How are growth charts produced? Key factors in determining growth: •genetics • data obtained from a 'normal population' → described as healthy, •sex non- deprived breastfed children of mothers who did not smoke •first two years → nutrition aged 2 weeks- 4 years •over two years → hormones (groth hormones and • growth chart 0-4 years: thyroxine and sex hormones during puberty) • UK preterm and birth data from around 1990 • growth chart 2-18 years: • WHo growth standard for children aged 2-4 years • UK 1990 growth reference for children at birth and from 4-18 years • 0-4 age charts → step at 2 years of age • up until the age of 2 → children measured lying down → length measured • after 2 → measured standing up → spine compressed a little • data sets up to and after 4 are different → centiles do not match CORRECTED MEASUREMENT FOR PREMATURE BABIES Measurement taken at 14 weeks old -> born 8 weeks premature