Immunology and Infection 2 Flashcards
Why is immune regulation required and if it fails what are the three outcomes
Avoid excessive lymphocyte activation and tissue damage during protective response against infections
prevent reactions against self antigens (tolerance)
1) autoimmunity
2) Allergy
3) Hypercytokinemia and Sepsis
What is the definition of autoimmunity and give examples of diseases that come from this
immune response against self antigen
immune mediated inflammatory diseases can be systemic or organ specific
Rheumtoid arthritis, Irritable Bowel Disease, Multiple Sclerosis, Lupus
can target self antigens or microbial antigens (crohns disease)
Explain the underlying causes of autoimmune diseases
Failure of control mechanisms as well as causative factors such as susceptibility genes and environmental influences
aut
What is allergy
Harmful immune response to non infectious antigen that causes tissue damage
mediated by IgE and mast cells or T cells (type IV)
What is hypercytokinemia and Sepsis
too much immune response, positive feedback as causes more damage and bigger response
triggered by pathogens entering iron compartment (sepsis) or failure to regulate to correct level (hpercytokinemia)
What are the three phases of cell mediated immunity
INDUCTION- dendritic cell collects infected material and displays on MHCII, moves into lymph nose and presents to T-cells , T cell that matches is activated and clonal expands
EFFECTOR- the effector T cells then return to the site of infection and kill antigen
MEMORY- Effector pool contracts to memory pool shutting down immune response - this is SELF LIMITATION as removed the antigen source and can shut down
What signals are required to stimulate a T cell
antigen recognition
co stimulation
cytokine release
What are the outcomes of an immune response
Resolution- no tissue damage, back to normal, macrophages phagocytose the debris
Repair- heal with scar tissue and regenerate through fibroblasts and collagen synthesis
chronic inflammation- active inflammation attempts to repair damage
What is tolerance and what two types of tolerance is there
unresponsiveness to an antigen once lymphocytes have been exposed to it
before T or B cell enter circulation- central tolerance - destroys self reactive T or B cells
before can enter circulation, need to be deleted here before cause a response as self-reactive ones are made from generation of immune repertoire
destroy any self reactive T or B cells which do enter the circulation - peripheral tolerance
Describe B and T cell selection
B cell- if immature B cells in bone marrow encounter antigen in a form which can crosslink their IgM then it triggers apoptosis
T CELL- in thymus need to select ones that can bind to self MHS, don’t want it to bind too strongly (negative selection as dangerous), if binds weakly but doesn’t trigger immune response then positive selection
How do T cells meet antigen in the thymus
The transcription fact AIRE (autoimmune regulator) it allows the thymus expression of genes that are expressed in peripheral tissues.
problems with this causes multi organ immunity
What happens after a B cell meets antigen
B cell receptor is a surface bound antibody
After antigen exposure, naive B cells are activated by T cells and become perifollicular B cells which can become
1) antibody production by becoming a plasma cell
2) Memory by becoming a Memory B cell
3) Affinity maturation- it recognises antigen and changes shape to bind
What is it called when B cells can change specificity after leaving the bone marrow
Somatic hyper mutation - normally improves antibody quality but can alter outcome if meets self antigen during infection
What are the mechanisms of peripheral tolerance
Anergy- naive T cell sees MHC without appropriate costimulatory protein so becomes anergia, less likely to be stimulated. sees antigen but no stimulation
Ignorance- concentration of antigen too low of a concentration won’t trigger T receptor, places like eye brain (immunologically privileged sites) and compartmentalised places. no antigen and no co stimulation
Antigen Induced Cell Death (AICD)- Activated T cell to express the death ligand Fas ligand (CD95 ligand, FasL) . antigen + FasL
Regulation- T cells exposed to the cytokine TGF-beta can differentiate into “induced” T regulatory cells (Tregs) in the peripheral tissues.
“Induced” T regulatory cells have similar effector functions as natural T regulatory cells, but they are produced in the periphery rather than in the thymus. They block activation, or inhibit effector function of T cells and other cels
What is the phenotype of Treg cells and their mechanisms of action
CD4, high IL2 receptor, FoxP3 transcription factor
Secrete immunosuppressive cytokines TGFbeta, IL-10,IL-35, inactivation dendritic cells or responding lymphocytes
Mutation in FoxP3 results in what
mutation in FoxP3 transcription factor leads to severe IPEX syndrome, because FoxP3 turns T cells into Tregs so if it leads to improper development of Tregs then autoimmune disorders
What does IL-10 do
LIMITS IMMUNE RESPONSE pleiotropic- multi functional acts on many cells to block proinflammatory cytokine synthesis like TNF, IL-6, IL-8, IFNgamma down regulates macrophage function mimics virals making similar proteins
stops severe inflammation and decreases risk of autoimmune disorders by limiting response
What are the types of Tregs
Natural Tregs (nTregs)- develop in thymus recognise self antigen during T cell regulation and reside in peripheral tissues to prevent reactions against cells Indicible Tregs (iTregs) develop from mature CD4 T cells that are exposed to antigen in periphery
Difference between cytokine and chemokine
Cytokines programme immune response, can be inflammatory or antiinflammatory depending on the responses needs. IFNgamma, IL-2, IL-10. T cells make cytokines to activate B cells to switch Ig class and make different antibodies
chemokine drive movement around body
What are the main types of CD4 T helper cells and how do they work
TH1 cells used when pathogens are taken in by macrophages, broken down and presented
TH2 cells used when its receptor mediated endocytosis
they produce cytokines which will cross regulate to shut down other t helper cells response and produce more of the cytokine needed
Difference between T and B cell antigen stimulation, co stimulation and cytokine
T cells are activated by detecting MHC. Co stimulates by expressing CD40L to activate B cells and CD28 to be activated itself. IL-21 nd other cytokines activates response in T cell
B cells are activated by soluble antigen.Co stimulated by expressing CD40 to be activated by T cells and expressed B7 to be activate T cells
Describe Type 1 hypersensitivity reactions
‘immediate’
re exposure to an antigen called an allergen
asthma, allergic rhinitis, atopic dermatitis
People with allergies make IgE in response to common mutlivalent environmental antigens (allergens) instead of only making it in response to parasitic infections and venoms.
can use skin prick tests - wheal and flare
After IgE is made, TH2 CD4 cells and B cell helper follicular CD4 T cells which produce IL-4 and IL13 switch B cells to make antigen specific IgE. IgE rapidly binds to mast cells and basophils via the FcER1 receptor so isn’t found in circulation.
When allergen meets cell bound IgE there is rapid cross linking and degranulation so more TH2 differentiation and recruitment of other cells. Histamines released from degranulation cause capillaries to dilate and leak
How does anaphylactic shock occur
Instead f antigen meeting IgM lymphocyte and it switching to produce IgG, TH2 CD4 cells are activated to make IgE. IgE binds on mast cells and basophils via the FcER1 receptor to cause degranulations and release fo histamines.
Histamine dilates blood vessels, increases blood flow to surface and movement of fluid out blood stream (oedema)
constriction of airways, contract of smooth muscle
urticaria- red rash
effect depends on where allergen enters so if inhaled, mucosal mast cells, if in nasal passages then oedema in epithelial lining of nose which is allergic rhinitis aka hay fever
if allergen ingested then intestinal mucosal mast cells cause vomiting and diarrhoea
food ,insect bites, medication
What can be used to treat anaphylaxis shock
Adrenaline should be given as the dilation of blood vessels causes oedema and rashes but also blood pressure drops which can lead to shock. can cause breathing difficulties from lung constriction or cramps/ nausea from intestine
Antihistamines can be given and anti inflammatory corticosteroids
oxygen, bronchodilators
may feel faint from blood pressure drop so monitor to check for recovery
Describe Type II Hypersensitivity
antibody mediated cytotoxic hypersensitivity
IgG or IgM antibody destroys cells by binding to SURFACE BOUND antigens
mismatched blood transfusion, haemolytic disease of newborn, graves disease
can be exposure to foreign antigen or self antigen.
self antigen results in disease through these mechanisms:
anti receptor activity- blocking or activating its function - FUNCTIONAL LOSS
antibody dependent cell- mediated cytotoxicity ADCC- antibody antigen complexes bound to Fc receptors of IgM or IgG cause lysis - CELLULAR DESTRUCTION
activation of complement cascade- antibody recognised by complement, forms MAC membrane and cell death due to loss of osmotic integrity. results in inflammation, opsonisation, recruitment and activation of immune cells- DAMAGE TO TISSUES
Describe Type III Hypersensitivity
immune complex driven disease
immune complex and non cell bound antibody and antigen complexes which the immune system normally clear. I not cleared are deposited in blood vessel walls and tissue which causes inflammation and tissue damage, fever, rashes, joint pain.
rheumatoid arthritis, lupus, multiple sclerosis
in lupus develop IgGs against DNA so immune complexes are persistent
can also be from forming antigens like anti-serum for snake bites will help but can’t use again
Describe Type IV Hypersensitivity
Delayed type, T cell mediated
need sensitisation where antigen presented to naive T cell by antigen presenting cells to make a memory cell
on second exposure as memory T cells are slower than antigen there’s an inflammation response 2-3 days later (infiltration of monocytes and lymphocytes) e.g contact dermatitis (with poison ivy)
drives TH1 response, reexposure memory cells make cytokines activate macrophages = swelling and oedema
Tuberculin skin test measures previous exposure
What is S.aureus and what are the two groups of S.aureus causing diseases
gram positive bacterium that lives harmlessly in most, an opportunistic pathogen
LOCALISED pyogenic (pus producing) diseases causes tissue destruction due to hydrolytic enzymes and cytotoxins
diseases mediated by toxins that function as super antigens, SYSTEMIC
Properties of S.aureus and its immune evasion mechanisms
grow aerobically and anaerobically at many temperatures and even high salt concentrations
polysaccharide capsule to stop phagocytosis
cell surface proteins (protein A and clumping factor protein) so bacteria can bind to host tissues
Catalase that protects staphylococci from peroxides that neutrophils and macrophages produce
Coagulase converts fibrinogen to insoluble fibrin to form clots and protect S aureus from phagocytosis
hydrolytic enzymes: lipases, nuelases, hylauronidasem to cause tissue destruction
cytotoxins (alpha beta gamma leukocidin) that lyse erythrocytes neutrophils, macrophages and other host cells
toxins:
1) enterotoxins - heat stable and acid resistant toxins responsible for food poisoning
2) exfoliative toxins A and B on the superficial layer of skin to peel off (scalded skin syndrome)
3) toxic shock syndrome toxin is a heat and protease resistant toxin
What is the cause of S.aureus infections
infections in community and hospital, easily spread person to prison through direct contact or exposure to contaminated bed linens, clothing and other surfaces
antibiotic resistant strains are in hospital and community
List some S.aureus pyrogenic and toxin-mediated diseases
PYOGENIC: (usually end in tis)
Impetigo: skin infection pus filled on reddened ertythramatous tissue
Wound infections: pus at site of trauma
Pneumonia: abscess in lung
Septic arthritis: swollen reddened infected joint
TOXIN-MEDIATED:
food poisoning: food contaminated with heat stable enterotoxin is rated causes severe vomiting, diarrhoea and stomach cramps after 2-4 hours
Scalded skin syndrome: bacteria in a localised infection produces a toxin that spreads in circulation so skin blisters and peels off- young children only
toxic shock syndrome- bacteria in a localised infection produce a toxin that affects other organs causes fever, hypotension and a rash.
What is the treatment, prevention and control of S.aureus
Infections managed by incision and drainage
antibiotics for systemic infections
trimethoprim-sulphametoxazole, clindamycin, or doxycycline as oral therapy
treat symptoms of food poisoning and identify course
cleanse wounds and wash hands, cover exposed sin
What are the innate immune cells
Neutrophils, `Eosinophils, Basophils, Dendritic Cells, Macrophages
What are neutrophils and what do they do
Most abundant leukocyte, recruited to infection site, detect microbes and kill them, ‘simple’ immune cells
neutrophils must be balanced to prevent infection and inflammation damage
Neutrophils adhere to the endothelial cells roll and transmigrate across, chemotaxis causes them towards complement components and bacterial proteins, there they meet pathogen and are activated so they can perform effector functions. They phagocytose antimicrobial molecules, degranulate to target antimicrobial molecules, they also undergo opsonisation which is where antibodies bind to surface of bacteria by recognising antigens , results in deposition of complement and neutrophils and others phagocytes can detect, causes inflammation
What is opsonisation
Opsonization is the molecular mechanism whereby molecules, microbes, or apoptotic cells are chemically modified to have stronger interactions with cell surface receptors on phagocytes and antibodies.
This is the mechanism of identifying invading particles (antigens) by the use of specific components called opsonins.
The opsonins act as markers or tags that allow recognition by the immune system of the body.
An opsonin is any molecule that enhances phagocytosis by marking an antigen for an immune response or marking dead cells for recycling.
The purpose of opsonization is to make the antigens palatable to the antibody or the phagocytic cells.
How does S.aureus evade antibodies
1) S.aureus capsule hides antigens: capsule means innate and adaptive immune components can’t detect
2) protein A (SpA binds to IgG Fc region- it expresses protein A and binds antibodies fc region not Fab which prevents opsonisation and therefore neutrophils cannot detect. Sbi does same thing
3) S.aureus SSL10 binds IgG to inhibit detection- SSL10 is a protein that’s secreted to bind to Fc region of IgG so can’t be detected. Sak does same thing
What are some antibody evasion strategies that S.aureus doesn’t use
1) proteases cleave antibodies so they can’t function (group B streptococcus)
2) Antigenic variation, they switch to a different surface structure so they can’t recognise (N-gonorrhoea)
What is complement opsonisation and how does it work
Proteins that react to opsonise pathogens or kill them by forming MAC (membrane attack complex)
In all 3 ways Initiation leads to a C3 convertase being made (C4bC2b or C3bBb), these converses can make C3b, when C3b and factor B work together it makes C5 convertase (C3bBbC3b). this degrades into C5 + C5a +C5b. C5b is deposited onto microbial surface to recruit C6,7,8,9 which form MAC
How does S.aureus stop complement opsonisation
1) S.aureus Efb binds C3d in C3 causing a conformational change preventing binding of factor B to C3 and C3dg binding to CR2
2) SCiN binds to C3bBb (the C3 in alternate pathway), causeless C3b being produces so less deposited onto S.aureus surface so it can’t be detected, less 3b so reduced signal for other cells to come, and as C3b isn’t made as much C5 convertase can’t be made so no MAC formed. Efb can also do this
3) SSL7 stops C5 being converted to C5a and C5b so MAC can’t be formed
Other complement evasion strategies S.aureus doesn’t use
Proteases cleave complement components. S.pyogenes (SpeB) degraded C3 to become non functional
Acquired host derived complement regulations : fH degrades C3b, C4BP which has Fi degrades C2a from C3 convertase (C4b2a)
How do neutrophils detect bacteria
Through receptors they detect microbes, microbial products or self proteins
Pathogen recognition receptors directly detect microbes or microbial products, TLR detects microbial structures, CLEC receptors detect microbial carbohydrates, FPR receptors detect formulated peptides
They also indirectly detect bacteria as microbes can become opsonised by antibody which the fc receptors detect or complement which neutrophils complement receptors detect
How does S.aureus inhibit chemotaxis and activation
Reduces amount of neutrophils that arrive to infection site
Neutrophils have C5aReceptors to detect C5a and FPR1 to detect fMLP (formulated peptides)
CHIPS binds to these neutrophil receptors so agonists can’t bind this means that neutrophils do not migrate to sites
How does S.aureus inhibit phagocytosis once microbes have already been opsonised
FLIPr blocks Fc gamma receptors which neutrophils need to detect opsonised microbes, this means that antibodies can’t interact and can’t detect IgG opsonised bacteria . This reduces antibody mediated phagocytes
SSL5 does the same but blocks Fc alpha receptor so IgA that binds to surface can’t be recognised
How does S.aureus kill neutrophils
toxin expression, bind and cause lysis or bind to active receptor to inhibit
4 methods of bacterial immune evasion
Bind inhibitory receptors : neutrophil can’t function
inhibit antimicrobial effect: s.aureus makes SPIN to combat what degranulation releases)
manipulate intracellular signalling
modify bacterial surface
Difference between acute and chronic allergic reactions
at lymphocyte activation instead of IgM to IgG becomes IgE
Acute: allergen specific IgE is rebound to FceR1 receptor on mast cells, the allergen meets and causes cross linking and degranulation
Chronic: recruitment and activation of allergen specific T cells and others via mast cell derived mediators like histamines
what is the effect of Type I reactions
mast cell sin connective tissue (under skin) and in epithelial mucosa (lung and intestine)
Histamine causes vasodilation which increases blood flow and causes oedema in connective tissues. Uriticaria- raised red rash,
In epithelial mucosa constriction of airways if reached bronchioles, if inhaled nasally then oedema in epithelial lining of nose along with mucus secretion. Also causes contraction of small muscle in intestine if allergen ingested
What are viruses
Infectious, obligate intracellular parasites
DNA or RNA
uses host cell machinery to make its proteins and viral components
can be non-enveloped or enveloped within a capsid
What are the basics of how DNA bases are replicated
genome is in positive sense (complimentary) 5’ ATG-CCG etc
RNA is in negative sense 3‘UAC-GCC etc
mRNA uses negative sense to return to complimentary 5’ AUG-CCG
this is what is used to make the proteins
positive sense RNA virus consists of viral mRNA that can be directly translated into proteins whereas negative sense RNA virus consists of viral RNA that is complementary to the viral mRNA.
How does the genome of a virus affect how it replicates
RNA VIRAL GENOMES- use own polymerase, lacks proof reading so high mutation rate, limited in size as RNA is unstable, complex coding strategies to make lots of proteins
DNA VIRAL GENOMES- large lots of room for accessory genes to modify hosts immune response
SEGMENTED GENOMES- easy form of recombination of two different viruses called reassortment, difficult to package
How viruses use the host cell to replicate steps
1) attaches to surface onto glycoprotein virus receptor
2) once inside, capsid comes off exposing viral genome, can be transcribed into mRNA if its RNA to make early regulatory proteins or replicated if DNA to RNA then mRNA to make late structural proteins- does his by using cells ribosomes and either its own polymerase or the cells. proteins then assemble, form new viruses and leave
Describe the replication cycle of HIV-1
HIV’s gp120 spike protein binds to CD4 on T cells bringing it closer to CCR5 and CXCR4
membranes fuse and HIV RNA, reverse transcriptase, integrate and viral proteins enter the cell
Reverse transcriptase makes DNA
DNA integrates into host DNA
viral RNA is used as genomic RNA and made into proteins, these proteins move to cell surface forming more virus
Describe the replication cycle of Influenza
Binds to sugars on cell surface (glycoproteins and glycolipids),
taken in via endocytosis inside lipid endosome. (like vesicle)
viral particle fuses its envelope with eadosomal lipids to release its genomic sequence (negative sense RNA),
RNA enters nucleus and RNA polymerase II makes it into mRNA so the host cell ribosomes can make proteins, RNA polymerase II also makes new genomes. The genomes and proteins made leave as newly formed virus particles
What is the difference between the replication process of HIV and influenza virus
HIV contains positive sense RNA which means a RNA polymerase isn’t required just a reverse transcriptase to turn it into DNA
Influenza contains negative sense RNA which means it needs the cells RNA polymerase to turn it into mRNA before it can be used
What is the cytopathic effect
Virus lysing the cell- the slides In lab will will show cell membranes becoming rounder, detached and then clumped.
cells that have been infected leave a plaque which appears as a clear hole
How can you measure how many virus particles are in a preparation
PLAQUE ASSAY
make dilutions and put onto monolayers, count the plaques that form
What is syncytia
Viruses with surface proteins often fuse together at neutral pH, fuse cells instead of a plaque
How cn a virus be detected and diagnosed
PCR- amplifies viral DNA, if RNA have to convert: detects viral genome
IFA, ELISA- raise antibodies with stain to detect presence of a viral protein: detects viral antigen
EM, HA detects virus particles
serology- detecting antibodies to virus (a time after first infection)
What antiviral drug has high specificity, how does it work
ACYCLOVIR
is a chain terminator as has a nucleoside that looks like guanosine, this modified nucleoside is incorporated into DNA and as it has no OH it stops a phosphodiester bond forming so the chain is terminated .
Given in unphosphorylated form only active inside cells that have the virus as they will have a thymidine kinase to phosphorylate acyclovir monophosphate to acyclovir triphosphate
has higher affinity for viral DNA polymerase than most
Things only resistant if thymidine kinase isn’t there
What is another antiviral drug that is an analogue of adenosine
Remdesivir
chain termination as twists shape of growing molecule
What are the antivirals targeting influenza and how do they work
Target unique and essential genes or function of the virus, is effective for many strains, easy to administer and few side effects
1)Amanditines: cyclic, bulky, active against Influenza A, targets M2 ion channel which sits next to haemagglutinin and neuraminidase : amanditines sit in M2 channel and stop H+ ions from moving in which means the proton concentration won’t build up inside and it won’t break down the proteins surrounding it: the virus is locked within the endosome
Mutations such as S31N in M2 channel makes it resistant so most H3N2 and H5N1 are resistant
2)Oseltamivir (tamiflu), Zanamivir(relenza), Sialic Acid: the crystal structure of neuraminidase allows it to be targeted. silica acid adds a hydroxyl to the active site of neurominadase, Zanamivir adds a guanidine and oseltamivir adds a hydrophobic group. Neuraminidase cleaves sialic acid from the surfaces of cells to allow the virus to be released inside, the inhibitor prevents the virus getting into the cell and its stuck
What caused oseltamivir resistance
histamine become tyrosine at position 274
What is baloxavir
targets PA endonuclease
How is HIV treated and what is this medications target
antiretroviral drugs
co receptor antagonists to stop attachment
fusion inhibitors to stop fusion
reverse transcriptase inhibitor or non-nucleoside reverse transcriptase inhibitor to stop reverse transcription
stop integration
protease inhibitors to bloc maturation
What is the future for antiviral therapies to help resistance
therapies that target host
combinations of drugs with different targets
broad acting antivirals
delivery suitable for population
justifiable use
What is HTLV-1
Human T cell Leukaemia Type 1
transmitted from mother to infant, sexual contact and blood
causes slowly progressive weakness and spacticty of one or both legs
HTLV1 is a single stranded enveloped RNA virus (ssRNA)
attaches to surface proteins to enter CD4+ T cells, ssRNA released into host celll cytosol, reverse transcribed by reverse transcriptase to make ssDNA. this is converted to dsDNA which enters the nucleus and integrates into host genome, the viral genome can now replicate
number of infected T-cells correlates with severity and likelihood of transmitting virus
Oncogenesis of infected cell due to Tax protein which targets IL-2 receptor causing mass proliferation of T cells
How is HTLV-1 diagnosed through the western blot method and what will the result be
Western blot method : blood taken and tested for HTLV-1 antibodies. different viral proteins will migrate at lengths paces on gel- smaller go faster. proteins transferred to membrane and viral proteins stick to membrane, are then immobilised - incubated with primary antibody which will bind to protein of interest, then washed away so unbound antibody is moves. then incubation with a secondary antibody (linked to an enzyme) which will bind to the primary antibody. Then when incubate the enzyme will convert and create a band
If infected with HTLV1 will have the synthetic peptide MTA-1, viral core proteins: p53, p24, p19 and recombinant glycoprotein gd21
How is HTLV-1 diagnosed through the PCR chain reaction
Step 1: denaturation, denature for one minute at 84 degrees to have one strand
Step 2: annealing, cooled to 54 degrees, forward and reverse primers are added, the primers re designed to amplify the HTLV-1 tax gene
Step 3: extension, for 2 minutes at 72 degrees dNTPPS are added as well as DNA polymerase to fill in the gaps, need a reaction buffer too
How is the sample obtained for PCR
Take blood, isolate peripheral blood mononuclear cells (lymphocytes and monocytes), then isolate the DNA
How does gel electrophoresis work
DNA is separated by size by applying a current
the DNA is negatively charged and migrates to the positive anode, smaller particles move further
a DNA stain is used so bands can be seen
a DNA loading dye is used to increase weight of sample so it sinks to bottom of DNA wells and can indicate how far migrated
a DNA marker/ladder is useful to estimate PCR fragment size
What is Quantitative real time PCR (qRT-PCR)
provide info on amount of viral DNA in a sample, helps to predict the severity of disease and transmission likelihood
two methods
TaqMan method: There are two probes on the gene : Flurophore and Quencher, Polymerisation and Strand Displacement occurs and this growth separates the probes (probe cleavage. This means that when tested the flurophore will be coloured/ luminescent instead of the quencher absorbing it if its in close proximity. This shows the completion of polymerisation as the chain has grown bigger.
What is a vaccine
something that stimulates the immune system without causing serious harm or side effects. the aim of immunisation is to provoke immunological memory to protect individuals against a particular pathogen if they later encounter it
What is the ideal vaccine
cheap, easy to administer, single dose, needle free, stable, life long protection
How do vaccines stop infection
1) prevention of entry : antibodies bind and opsonise or macrophages engulf pathogens
2) killing infected cells: CD8 cells kill infected cells, CD4 helps and activated B cells to make Ig
3) Boost immune response: antigens in vaccine recognised by CD4
What is R0 and what does R0 mean
R0 id yer basic reproduction number
if R0 is smaller than 1 then the infection will die out in the long run, I its larger then the infection will be able to spread to a population
How does vaccination impact R0 and how does this link to herd immunity
If vaccinated fewer people can become infected so if the infection only meets immune people it won’t spread so less than 1
This links to herd immunity because if people are immune then the susceptible people are indirectly protected as there are less infected
What is in a vaccine
Inactivated protein Recombinant protein live attenuated pathogen dead pathogen carbohydrate
What is an example of a vaccine that has inactivated protein in it
Tetanus toxoid
inactivated form of toxin, induces antibody, antibody blocks the toxin from binding to nerves
cheap and safe but needs good understanding of biology of infection as not all organisms encode toxins
toxins work by binding to cell surface receptors, endocytosing the toxin:receptor complex, the toxin dissociates to release an active chain which poisons the cell. Neutralising antibody blocks binding of toxin to receptor
What is an example of a vaccine that has recombinant protein in it
Hep B surface antigen (isolate gene from one, mass produce and isolate a single protein)
induces classic neutralising antibodies
pure and safe but expensive
protein structure is crick as when manufactured have to get perfusion shape
Why are conjugate vaccines needed, give an example
Bacteria often have a polysaccharide capsule, not good at inducing B cell response
S.pneumoniae
polysaccharide coat with an immunogenic carrier protein
protein enlists CD4 to help boost B cell response to polysaccharide or dendritic cell will engulf the `antigen and present of MHII, the Tfh will find matching B cell and boost B cell to Mae antibodies
improves immunogenicity, controls bacterial infection
costly, protein can interfere
Give an example of a dead pathogen vaccine
Influenza split vaccine
chemically killed pathogen, not just single antigen
induces antibody and T cell responses
ad: leaves antigenic contents in tact and in the right context of other antigens making it immunogenic. cheap and quick
dis: killing can alter antigen chemical structure, dirty, need to grow pathogen,
Give an example of a live attenuated vaccine
BCG
Pathogens attenuated, lose virulence factors so can’t infect
replicate in situ, trigger innate response and boost immune
Ad: strong immune response
dis: can evert to virulence, can infect immunocompromised, attenuation may lose antigens
What is an adjuvant
have signals that activate dendritic cells Tomoe to lymph node and present antigen to T cells
substance used in combination with a specific antigen that produced a more robust immune response than antigen alone
Why is there. need for new vaccines and what are the barriers
Ageing demographic
changing environment: new viruses and diseases
old disease still not fixed
antibody resistance
Barriers: scientific challenges, injection safety, development issues with time and cost, public expectation to be risk free
Why is HIV difficult to target
High variability virus, antibodies recognise specific parts, if mutates and doesn’t keep that part its now useless
classic immunity only recognises one serotype so vaccines need to cover all
How vaccines are approved and what needs to be considered
preclinical, phase 1 with a small amount then up to phase 3 with increasing numbers, FDA review for safety and effectiveness, phase 4
consider:aim, need, scheduling with other vaccines: children getting more and more, vailabilty, cost
