Immunity and How Vaccines Work Tralee Cork · 2016-11-15 · Physical barriers Cellular responses...
Transcript of Immunity and How Vaccines Work Tralee Cork · 2016-11-15 · Physical barriers Cellular responses...
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Immunity and How Vaccines Work
Kevin ConnollyKevin Connolly
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Learning Characteristics
• Active: “let’s try it out and see how it works”• Active: let s try it out and see how it works
R fl ti “l t’ thi k it th h fi t”• Reflective: “let’s think it through first”
l l b b d• Visual: learn best by seeing pictures, diagrams, or demonstrations
• Verbal: learn best by written or spoken words
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Definitions
Antibody: immunoglobulin produced mainly by plasma cells; identifies and neutralises pathogens
Antigen: substance that can provoke an immuneresponse
Clone: group of identical decendents
Epitope: the specific piece of the antigen to which an antibody binds.
Humoral: relating to fluids
Innate: present from birth
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DefinitionsDefinitions
• Immunity: resistance to pathogens and their toxic effects (immunis ‐ exempt, protected)
• Immune system ‐ cells, tissues, and molecules that mediate resistance to infections
• Immunology ‐ study of structure and function of the immune system
• Immunity resistance of a host to pathogens and their toxic• Immunity ‐ resistance of a host to pathogens and their toxic effects
• Immune response ‐ coordinated response to introduction p pof foreign substances; mediated by cells and molecules of the immune system
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Role of Immune SystemRole of Immune System
• Defense against microbes• Defense against the gro th of t mor cells• Defense against the growth of tumor cells
• kills tumor cells
• Homeostasis• Homeostasis• destruction of abnormal or dead cells (e.g. dead blood cells, Ag‐Ab complex)
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Immune System Overview
•Hematopoietic •Vasculature•Lymphatic
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Immune SystemImmune System
1. Organs2. Cells2. Cells3. Molecules
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Innate ImmunityInnate Immunity
• Relies on already formed components• Response within minutes to limit the infection• Non‐specific
• same molecules / cells respond to a range of pathogens
• No memory ft t d• same response after repeated exposure
• Does not lead to clonal expansion
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Immune System Organs
• Tonsils and adenoids• Thymus• Lymph nodesy p• Spleen• Payer’s patchesPayer s patches• Appendix• Lymphatic vessels• Lymphatic vessels• Bone marrow
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Immune System Cells
• Lymphocytesl h• T‐lymphocytes
• B‐Lymphocytes, plasma cells • natural killer lymphocytes• natural killer lymphocytes
• Monocytes, Macrophage• Granulocytes• Granulocytes
• neutrophils • eosinophils p• basophils
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Immune SystemMoleculesImmune System Molecules
• Antibodies l• Complement
• CytokinesI t l ki• Interleukins
• Interferons• etc• etc
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Lymphoid System
Lymphoid organs: Sites where lymphocytes gather to encounter antigens
Skin, lymph nodes, spleen, thymus, tonsils, adenoidsGITGIT
Situated to allow for initiation of immune response from nearly any place in bodyresponse from nearly any place in body
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Inflammation
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Inflammation
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Physical barriers Cellular responses Humoral responses(proteins, etc.)
Innate Immunity
Skin
MucosaeCytokine production
Epithelial cells Complement
Cytokines
(p , )
Gastric acid, Gut motility,Mucus, Sebum
Physical featuresy p
reactive oxygen/nitrogenFluid secretion
Antigen-presenting cells
FeverMalaise
Kupffer cellsLangerhans Cells
Dendritic CellsMacrophages
PMNsMast Cells
Granulocytes
AdaptiveMast CellsEosinophils
Lymphocytes
Adaptive Immunity
NK cellsNK T cells
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Physical barriers Cellular responses Humoral responses(proteins, etc.)
Innate Immunity
Skin
MucosaeCytokine production
Epithelial cells Complement
Cytokines
(p , )
Gastric acid, Gut motility,Mucus, Sebum
Physical featuresy p
reactive oxygen/nitrogenFluid secretion
Antigen-presenting cells
FeverMalaise
Kupffer cellsLangerhans Cells
Dendritic CellsMacrophages
PMNsMast Cells
Granulocytes
AdaptiveMast CellsEosinophils
Lymphocytes
Adaptive Immunity
NK cellsNK T cells
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Adaptive Immune System
• Adaptive: responds to specific foreign substancessubstances
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Adaptive Immunity
Immune system adapts to previously unseen molecules
Induction by infection, vaccination
Immune system mounts response
Immune response must:
Recognise micro‐organism as foreign
Respond by producing specific antibodies lymphocytesRespond by producing specific antibodies, lymphocytes
Mediate elimination of organisms
Form memory
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Adaptive Immune System: Cells
Antigen Presenting Cells (APCs)Macrophages & B lymphocytesMacrophages & B lymphocytesIngest foreign materialPresent antigenic fragments on their cellPresent antigenic fragments on their cellFragments recognised by T‐cells.
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Antigen Presenting Cell
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Innate and Adaptive Immunity Work Together
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Adaptive Immunity: active and passive
Active Immunity Passive Immunity
Natural Clinical sub-clinical via breast milkNatural Clinical, sub-clinical infection
via breast milk, placenta
Artificial Vaccination: Immune serum, immune cellsLive, non-live immune cells
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Cell mediated Immune ResponseCell‐mediated Immune Response
Primary response • Production of specific clones of effector T cells and memory
lclones• Develops in several days • Does not limit the infection
Secondary response • more pronounced, faster • more effective at limiting the infection
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Generation of Immune ResponseGeneration of Immune Response
~ 4‐7 days to generate primary immune response
d d h• IgM produced then IgG • After ~3 weeks primary response turned off• Ab producing cells memory B cells formed• Ab‐producing cells, memory B cells formed• Memory B cells secrete Ab when same agent
encountered again • This is secondary immune response• Memory lasts weeks / years
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Adaptive System: T Cells
Sorted in the ThymusManage the immune responseEliminate microbes that survive within
phagocytes or other infected cellsphagocytes or other infected cellsProduce memory cells
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T lymphocytesT lymphocytes
Two types
• Helper T‐ lymphocytes (THL)‐activate phagocytes to kill microbes‐activate phagocytes to kill microbes‐activate B cell
• Cytotoxic T‐lymphocyte (CTL)‐destroy infected cells containing microbes
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Functions of TH CellsH
Orchestrate immune responsep• Recognize antigen presented by APC• Cytokines are deliveredC t ki ti t APC t d t ti• Cytokines activate APC to destroy antigen
Activate B cellActivate B cellIf TH cell encounters B cell bearing antigen
• TH cell produces cytokinesH p y• Cytokines activate B cell• B cell proliferates
D i f ti f B ll• Drives formation of B memory cells
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Cell‐mediated Immune Response
1. T‐cell • recognizes antigen on
macrophagemacrophage • identifies molecules on
cell surfaces 2. T‐cell goes into effector stage
that can kill infected cellsl1
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Slide 32
l1 Is this sentence right?Suzi Lyons, 20/03/2006
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Adaptive System: B CellsAdaptive System: B Cells
• Eliminate extra‐cellular microbes and their toxinsEliminate extra cellular microbes and their toxins• Are APCs and Ab‐producing cells
Antigen binds to B‐cell receptors Antigen ingested by B‐cellAntigen ingested by B cellB cell presents antigen to T‐cellB cell produces antibodyB cell produces antibody
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Humoral (B cell) Immune Response
1. B lymphocytes recognize specific antigensspecific antigens
• proliferate and differentiate into Ab‐secreting plasma cellscells
2. Abs bind to specific Ags on microbes; destroy microbes
3. Some B lymphocytes evolve into memory cells
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Recirculating B cells pass throughlymphoid organs
B cells inbloodT cell area
B cell area
Efferentlymphy p
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Recirculating B cells are trapped by foreign antigens in lymphoid organs
B cells leave blood & enter lymph node via
high endothelial venulesB cells high endothelial venulesB cellsproliferaterapidly
Antigen entersnode in afferent
lymphatic
YY
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
YGERMINAL CENTRE
Germinal centrereleases B cellsh diff iGERMINAL CENTRE
Transient structure ofIntense proliferation
that differentiateinto plasma cells
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Summary (1)Summary (1)
Innate immunity • relies on mechanisms already existing before microbe infects
hosthost • is the first line of defense • has no memory for subsequent exposure• relies on non specific mechanisms
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Summary (2)Summary (2)
Adaptive immunity • develops following entry of microbe• develops following entry of microbe • comes into action after innate immunity fails to get rid of
microbe• has memory to deal with subsequent exposure• happens through specific cells
• T cells (cell mediated)T cells (cell mediated) • B cells (antibody mediated)
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Summary (3)Summary (3)
P i iPrimary immune response • short lasting• smaller in magnitude
Secondary immune response • longer in duration• longer in duration • larger in magnitude • develope ‘memory cells’ following primary response
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IgM IgG sequential responseIgM – IgG sequential responseAnamnestic response
titer
response
Antib
ody
t
IgG
A
IgM
Time
First stimulusSecond stimulus
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Summary of Adaptive Immune Response
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What is a Vaccine?What is a Vaccine?
• Biological preparation that improves immunity to a particular disease
• Contains antigen(s) that resembles a pathogeng ( ) p g
• Stimulates immune system to recognise antigen as foreign,
d d " b "destroy it, and "remember" it
• Pathogens later encountered cause memory response
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Types of vaccines
LiveAttenuated Inactivated
Toxoids Cellular fraction vaccines
Recombinant vaccinesAttenuated
vaccinesInactivated vaccines
•BCG •Typhoid •Diphtheria •Meningococcal pol saccharide
•Hepatitis B accine•Typhoid
oral•Oral polioY ll
•Cholera•Pertussis•Plague
•Tetanus polysaccharide vaccine•Pneumococcal polysaccharide
vaccine
•Yellow fever•Measles•Mumps
•Rabies•IPV•Influenza
polysaccharide vaccine•Hepatitis B polypeptide
•Mumps•Rubella•IntranasalInfluenza
•Japanese encephalitis
vaccine
Influenza
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Live attenuated pathogensLive attenuated pathogensMMR, BCG, Cholera
Inactivated pathogensp gIPV, Pertussis
Subunit / Peptide components HepB (Hepatitis B surface antigen)Influenza (purified HA & NA antigens)
Conjugate (polysaccharides joined to protein carrier))HiB , PCV, MenB, C, ACWY
ToxoidsDiphtheria, tetanus
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Pros and Cons of Different Types of Vaccines
Live attenuated pros: better immune responsecons: reversion ‐ oral polio
infection in immunodeficientless stable
Inactivated pros: may be safer; more stable than livecons: weaker immune response; boosters
contaminants
Molecular components pros: no living pathogen presentMolecular components pros: no living pathogen presentvery stablefewer side effects
cons: fewer epitopescons: fewer epitopesweaker immune response
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Innate Control of Vaccine Immunogenicity
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Reported Cases of VPDs, Europep , p
Available from: http://apps.who.int/immunization_monitoring/globalsummary [cited 28 November 2014].
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How Vaccines WorkHow Vaccines Work
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BP Primary and Memory Response and Antibody ResponseResponse