Immunology Flashcards
what are the 3 main functions of the immune system?
eliminate danger
without harming the body
remember the threat to respond more efficiently next time
what is the main purpose of the immune system?
eliminate a threat to our bodies health
what type of threat is usually eliminated by the immune system?
infection by a pathogen
define pathogen
a microorganism which causes disease to the host
what are the four main types of infectious microorganism?
bacteria
viruses
fungi
parasites
what are commensals?
non-harmful bacteria that live within or on the bodies of humans and animals
how do commensals protect us from pathogens?
using up lots of nutrients so there are fewer available for the bad bacteria to live off
What effect do products produced by commensal bacteria have on us?
good effect or none
does our immune system usually attack commensal microbes?
no
what do immune cells defend us from as well as infection?
cancer cells
what is the difference between a cancer cell and a normal body cell?
a cancer cell is a normal body cell that has accidentally acquired DNA mutations that make it go wrong
how does the immune system know to kill cancer cells if they are formed from self-cells?
as it is not functioning normally the immune system is able to recognise mistakes and kill it
what must the immune system do in order to eliminate threats?
use defences which could harm our own body
what must the immune system not do?
attack normal body tissues
what is immune recognition?
the ability of the immune system to distinguish self from non-self
what happens if immune response goes wrong and attacks normal body cells?
we get autoimmune disease
why are cancer cells treated as non-self?
they are not behaving normally and are dangerous to the body if not destroyed
what is immune effector function?
the ability to deal with infection and if possible eliminate it without harming our body in the process
why do we get symptoms of illness when we get an infection?
because it takes time for the immune system to recognise, respond and fight off the pathogen
what actually makes us unwell during an infection?
the toxic actions of the pathogen
what happens if we see the same immune threat twice?
the second time the immune system responds faster so it kills the threat before we get symptoms
define immune memory
the ability of the immune system to remember antigens from pathogens and mount and immune response of greater magnitude and with faster kinetics upon re-encounter of the same antigens
what are the 2 arms of the immune system?
innate and adaptive
which arm of the immune system is the first line of defence against pathogens?
innate immune system
what are the 2 functions of the innate immune system?
rapidly respond to slow down pathogenic threats
recruit adaptive immune cells
define innate immune system
a mixture of cells and barriers which act within minutes to slow down or limit microbial invasion and disease causing processes
is the innate immune system specific?
no
what is the more specific arm of the immune system?
adaptive
what is the adaptive immune system made up of?
cells and the antibodies produced by B lymphocytes
what are the cells of the adaptive immune system?
T cells and B lymphocytes
what are the functions of the adaptive immune system?
mount a highly specific defecnce against pathogens
rememeber the threat in case it is encountered again
define adaptive immune system
an immune response mediated by T and B lymphocytes which is highly specific to the pathogen that induced it and elimiminates disease-causing processes alongside the innate immune system
what allows lymphocytes to exert specialised functions tailored to specific pathogens?
they take longer to respond than innate immune cells but they are more specific
what cells stay in the body for a long time and are able to respond quicker upon re-encounter of the pathogen?
memory lymphocytes
do innate immune cells behave like memory lymphocytes?
no
what is one of the key differences between innate and adaptive immune responses?
their anatomical location
where are all immune cells made?
in the bone marrow
what cells are all immune cells formed from?
pluripotent haematopoetic stem cells
where do innate immune cells reside?
the peripheral tissues
where do adaptive immune cells reside?
at the central lymphoid tissues, the spleen and lymph nodes
where do B lymphocytes mature?
in the bone marrow
where do B lymphocytes travel to once mature?
the spleen and lymph nodes
where do T lymphocytes mature?
in the thymus
where do T lymphocytes travel to once mature?
the spleen and lymph nodes
what happens to B and T lymphocytes one in the spleen and lymph nodes?
they wait to be activated
what happens when infection is encountered in the body?
innate immunity kicks in and repsonds straight away, it sends portions of the pathogen to central lymphoid tissues for analysis by adaptive immune cells. It also kills the pathogen (tries!!)
where can immune cells enter the spleen and lymph nodes?
via the blood and lymphatic vessels
what happens when the pathogen is shown to the T and B lymphocytes by the innate immune system?
they become activated and mobilise to the infected tissue in order to join the immune defence
what is the importance of re-circulation of innate and adaptive immune cells from the infected tissues to the spleen and lymph nodes and back again?
makes a bridge between the innate and adaptive immune systems
describe the life of an immune cell
haematopoetic stem cell differentiates into immature/naïve immune cell in the bone marrow which then ‘lives’ in home tissue. it is activated if it comes into contact with a pathogen and so preforms effector function. One this has happened it becomes a memory cell, switches off or dies
what happens if an immune cell never meets an antigen?
it remains naive
where are immune cells made?
in the bone marrow
define haematopoetic precursor cells
stem cells which are capable of differentiating into red (oxygen carrying) and white (immune) cells
why do we always need a new supply of new immune cells in the bone marrow?
immune cells can be used up or die
why is there always a population of immune cells available?
the haematopoetic precursor self renews
when may immune cells be activated?
at any point in the person/animals life when they meet their specific pathogen
describe the timeline of an immune response
infection, innate immunity, innate and adaptive immunity, elimination of pathogen, healing, immune memory
when does innate immunity occur?
0-5 days after meeting the pathogen
when does innate and adaptive immunity occur?
5 days- weeks after meeting pathogen depending on the severity ofinfection
within what time frame does elimination of pathogen occur?
weeks after meeting pathogen
how long does immune memory last?
months-years, potentially entire life
are immune responses to different pathogens the same?
no - immune responses to different pathogens are varied and helped by different specialised cell types
what do cytokines do?
help immune cells to communicate and tell each other what type of pathogen they are facing and what responses are needed
define cytokines
small secreted proteins released by immune cells, which allow them to interact and communicate
what do interferons do?
induce cells to resist viral replication
what are interlukins?
cytokines produced by WBC which have many different functions
what are chemokines?
cytokines that tell immune cells where to go
what must happen to innate and adaptive immune cells before they can start work?
they must be activated
what does it mean when innate and adaptive immune cells are activated?
they detect the presence of something not self and switch on
what do innate and adaptive immune cells respond to in order to be activated?
different receptors
what receptors does the innate immune system respond to?
protein recognition receptors (PRRs)
FC receptors
what receptors does the adaptive immune system respond to?
T and B cell receptors
what do pattern recognition receptors do?
bind PAMPs and DAMPs
what do FC receptors do?
bind antibodies
what do T and B cell receptors do?
bind antigen epitopes presented on MHC on the surface of antigen presenting cells
What are PRRs?
pattern recognition receptors which bind general bits/building blocks of cells called PAMPs and DAMPs
what are PAMPs?
pathogen associated molecular patterns that are fragments of pathogen capable of ligating PRRs on innate immune cells
what are DAMPs?
damage associated molecular patterns that are fragments of damaged self-cells capable of ligating PRRs on innate immune cells
give an example of a PAMP
bacterial flagella
give an example of a DAMP
HMGB-1, attached to DNA but released when cells die
do PAMPs and DAMPs give detailed information about the pathogen?
no - the innate immune response is very general
what other receptors do innate immune cells have on their surface?
receptors for antibodies
what are Fc receptors?
antibody receptors on the surface of immune cells
what is the effect of antibody receptors on the innate immune system?
triggers/encourages it to keep working
what are antibodies?
proteins secreted by B cells of the adaptive immune system which bind antigens to mediate pathogen destruction and to enhance the innate immune response
through what cells does the adaptive immune system respond?
T and B cell receptors
what do T and B cell receptors bind to?
epitopes
what are epitopes?
a short peptide sequence which is part of an antigenic protein
define antigen
a protein which is capable of initiating an immune response
why does the adaptive immune system get much more information than the innate immune system about the nature of an infectious threat?
because epitopes are so specific
how many epitopes are located on each lymphocyte?
1 they are specific for an epitope
what happens to lymphocytes when pathogens with their specific epitope are delivered by the innate immune system?
they begin to replicate
how can the delay between infection and adaptive immune response be explained?
massive cell multiplication of the lymphocyte with the specific epitope receptor must take place which takes time
why will multiple lymphocytes respond to a pathogen?
there are several antigens on each pathogen
when will T and B cells only recognise antigens and cause lymphocytes to divide?
after they have been chopped up into epitopes and presented by ‘antigen presenting cells’ APCs
what do innate immune cells respond to via pattern recognition receptors (PRRs)?
pathogen associated molecular patterns (PAMPs) and damage associated molecular proteins (DAMPs)
what do adaptive immune cells respond to via T and B cells?
epitopes presented on MHC by antigen presenting cells
where are cells of the innate immune system located?
around sites where infections commonly arise (e.g. lungs, GI tract)
why are there limited numbers of PAMPs and DAMPs?
they are common to many pathogens so there does not need to be a diverse range of cells
how quickly does the innate immune system respond to infection?
rapidly aided by it’s location and speed
what are the main components of the innate immune system?
cellular and non cellular
what are the 4 main non cellular components of the innate immune system?
physical barriers
chemical substances
microbiological
complement
what are the physical barriers of the innate immune system?
epithelial tight junctions
mucous or fluid flow
what are the chemical barriers of the innate immune system?
enzymes
acid
microbial peptides
what are the microbiological barriers of the innate immune system?
commensals
what are the complement barriers of the innate immune system?
a protein cascade which helps the immune system destroy pathogens
what are the cellular barriers of the innate immune system?
phagocytes
granulocytes
antigen presenting cells (APC)
how do epithelial cells joined by tight junctions defend against infection?
the body needs to be open in order for pathogens to enter. Epithelial cells at susceptible surfaces are joined by tight cell to cell connections that don’t allow pathogens through
how does mucous and fluid flow defend against infection?
mucous traps pathogens, cilia wave the mucous out of the body before pathogens can attach and divide. Flow of air, urine or ingesta keep pathogens moving through the body
how does low pH and acids defend against infection?
acidic conditions kill pathogens, stomach pH is 3.5 and omega 3 and 6 fatty acids on the skin protect against bacterial infection and enhance killing action of innate immune system
how do enzymes defend against infection?
directly kill pathogens or make them susceptible to other forms of killing (low pH)
what are antimicrobial peptides?
chemicals which are generally toxic to many different pathogens (bacteria/viruses and parasites)
how do commensals protect against infection?
occupy space in the body using nutrients and preventing harmful bacteria from establishing
how does a protein cascade prevent/fight infection?
presence of pathogen activates the first protein kicking of the cascade, the end of which leads to proteins which mark pathogens out for destruction and directly destroy pathogens by making a pore in the membrane
define commensals
non-harmful bacteria that live within or on the bodies of humans and animals
define competitive exclusion
the mechanism by which commensal micro-organisms defend against pathogens by competing for attachment sites and nutrients
what are the 4 main roles of innate immune cells?
phagocytosis
degranulation
antigen presentation
antibody dependent cellular cytotoxicity (ADCC)
what process assists phagocytosis and degranulation by dendritic cells?
opsonisation
what is phagocytosis?
the process of internalisation of large particles by phagocytic cells
what happens during phagocytosis?
matter is internalised via formation of membrane pockets called phagosomes. These form with lysosomes to digest pathogenic matter
what do lysosomes contain?
toxic acids, reactive organ species, antimicrobial peptide and enzymes
what is degranulation?
release of toxic granules to destroy a pathogen
what does the toxic contents of degranulation granules cause?
pathogen killing
what do basophils and eosinophils do during degranulation?
spit out granules in the immune system in response to pathogens
what do neutrophils do during degranulation?
have granules and destroy bacteria or virally infected self cells
what must happen before an innate cell will degenerate?
needs to be stimulated by engagement of Fc receptors on innate cell surface by antibody or inflammatory mediators such as histamine in the local environment
what do mast cell granules contain?
histamine which activates eosinophils to release own granules
when do allergies occur?
when eosinophils, basophils and mast cells mistakenly degranulate in response to an allergen
define allergen
a non-pathogenic molecule which should be ignored by the body but initiates an immune response instead
define opsonisation
the process by which molecules called opsonins stick to a pathogen and mark it out for degradation
what are the main opsonins?
antibodies
Fc receptors on innate cells binding to antibody stuck on the pathogen
complement receptors bind to a complement stuck on the pathogen
what is a complement?
a system of inflammatory proteins produced in the presence of a pathogenic threat
what does binding of opsonins to innate immune cells cause?
them to degranulate or phagocytose pathogens more effectively
what is antigen presentation?
processing and presentation of antigens to activate adaptive immune cells
what are dendritic cells?
innate immune cells which take in bits of pathogen, chop it up and present peptides (epitopes) from it to activate T and B cells
what is antibody dependent cellular cytoxicity (ADCC)?
specialised killing of virally infected or cancerous self cells by NK-cells, initiated by antibody Fc-receptor binding
how does ADCC differ from opsonisation?
self-cell rather than pathogen target
how do antibodies help destruction of virally infected or cancerous self cells?
notice self cells have gone wrong so stick to them, which marks the cells out as defective and needing to be destroyed. NK-cells bind via Fc-receptors to antibodies on the surface of the affected cell and activates NK-cells to degranulate and kill them
how is a dendritic cell activated?
PRRs bind to PAMPs and DAMPs
what is the function of dendritic cells?
combat viruses and bacteria
specialise in antigen presentation to activate T cells
release cytokines to tune the correct type of immune response
how are macrophages activated?
PRRs bind to PAMPs and DAMPs
Fc receptors bind antibodies
what is the function of macrophages?
combat extracellular bacteria
efficient at phagocytosis
antigen presentation to activate lymphocytes
cytokine release
how are neutrophils activated?
Fc receptors bind antibody (IgG)
what is the function of neutrophils?
‘first responder’ to site of inflammation
combat virus, parasites and both intra and extra cellular bacteria
phagocytosis
degranulation
how are eosinophils activated?
Fc receptors to bind antibody (IgE)
what responses are eosinophils most involved with?
anti-parasite responses
inappropriate responses can cause allergy/asthma
degranulation
how are mast cells activated?
Fc receptors to bind antibody (IgE)
what is the function of mast cells?
anti-parasite responses
inappropriate responses can cause allergy/asthma
degranulation containing histamine to enhance the innate response
how are basophils activated?
Fc receptors to bind antibody (IgE)
what is the function of basophils?
degranulation
how are NK (natural killer) cells activated?
NK receptor
Fc receptors (ADCC)
lack of MHC-I (shows that a cell is damaged e.g. cancerous)
what is the function of NK cells?
anti-viral and anti-tumor responses (responds to self cell gone wrong)
degranulation triggered via ADCC
Where do adaptive immune cells reside?
in lymphoid tissues so they have to mobilise to the sight of infection
what sort of recognition does the adaptive immune system use?
sequence specific
What does each T and B cell have that is unique?
receptor with responds to an epitope (part of the antigen)
what is the antigen that a T and B cell receptor binds to called?
cognate antigen
what are the only lymphocytes that are activated in an immune response?
only those with receptors that recognise the pathogenic threat
define antigen
protein which is capable of initiating an immune response
what are the pieces of antigen presented to lymphocytes by?
antigen presenting cells
define epitope
a short peptide sequence making up the processed part of an antigen that can bind to lymphocyte receptors
what are B cell and T cell receptors more specific than?
pattern recognition generators expressed on innate immune cells
when does the adaptive immune response kick in?
about 5 days after the innate immune response
why is the length of time taken for the adaptive immune system to work needed?
because of the location of the cells and specificity of response
where must adaptive immune cells travel to the site of infection from?
spleen and lymph nodes
why do adaptive immune cells take time to multiply?
as they are highly specific there is only 1 or 2 that can respond to a specific pathogen, once they are presented with the epitope they then must vastly replicate in order to have enough cells to pass off the infection
what cells is the adaptive immune system composed of?
B and T lymphocytes
what are the 2 main functions of B lymphocytes?
produce antibodies during the immune response
memory B cells remain in the body for a long time and will divide and produce antibodies if the pathogen comes back
what are plasma cells?
activated B cells which produce antibodies
define antibodies
secreted proteins which facilitate immune neutralisation of pathogens by binding to antigens expressed on the pathogen or it’s products
how are antibodies found in the body?
secreted by B cells
stuck on the surface of a B cell
what is the function of antibodies produced by B cells?
neutralisation of pathogens
what do antibodies on the surface of B cells do?
activate B cells
what are antibodies on the surface of B cells known as?
the B cell receptor
what shape proteins are antibodies?
Y
what are antibodies made up of?
two heavy chains and two light chains stuck together
what are antibodies also known as?
immunoglobulins
what do the ends of the heavy and light chains from?
antigen binding region
what is the antigen binding region known as?
variable region
why are there a vast number of different variable regions?
to bind to all the different possible epitopes
what happens if the epitope shape doesn’t match the antibody binding site (variable region)?
it wont fit
what part of the heavy and light chains of the antibodies forms the constant region?
backbone
what does the constant region of an antibody provide to the variable regions?
scaffold for the variable regions to sit on
how many constant region chains of antibodies are there?
5
what does each different constant region chain of antibodies determine?
how the immune system responds to the pathogen
what is the constant region chain named by?
the greek letter which matches the antibody isotype
what are the 5 different antibody isotypes?
IgM IgG IgA IgE IgD
what is the IgM constant chain formed from?
Mu
what is the function of IgM?
first antibody produced after antigen invasion
general, transient defence until B cell switches to a more appropriate antibody for the pathogen
what is the structure of IgM?
forms a pentamer (5 IgM joined together)
what is the IgG constant chain formed from?
gamma
what is the function of IgG?
the best antibody for opsinisation and neutralisation
attacks pathogens such as viruses and intracellular bacteria
what is the structure of IgG?
monomer
what is the IgA constant chain formed from?
alpha
what is the function of IgA?
immunity at mucosal surfaces (e.g resp or GI tract)
what is the structure of IgA?
a monomer in tissue fluid and blood a dimer (2 IgA joined) in mucosal secretions
what is the constant chain of IgE formed from?
eta
what is the function of IgE?
induces mast cell and basophil degranulation in response to parasites
involved in allergy response
what is the structure of IgE?
monomer
what is the IgD constant chain formed from?
delta
what is the function of IgD?
unknown
where is IgD found?
naive B cells before activation
what structure is IgD?
monomer
where are B cells activated?
lymph nodes
spleen
where are lymph nodes found?
junctions between lymphatic vessels
what do lymphatic vessels do?
collect fluid and cells from tissues and deliver to the lymph nodes
what are the 2 main parts of the lymph node?
cortex and medulla
where do B cells go in the spleen once they meet their specific antigen?
areas of the cortex known as germinal centres
what happens to B cells in germinal centres?
under go intense proliferation to generate clone B cells which respond to the same antigen
what do CD4+T helper cells do to aid B cell proliferation?
localise to paracortical areas where they produce chemicals which assist proliferation
what is found in the white pulp of the spleen?
lymphocytes, germinal centres and nearby areas for CD4+T helper cells
how is the spleen supplied with innate immune cells bearing antigens?
blood supply rather than lymphatic vessels
what is the role of the red pulp of the spleen?
collection and disposal of old RBC
what happens when an epitope is shown to a B cell by an antigen presenting cell?
ligates the IgM B cell receptor binding site and triggers B cell activation
What happens to B cells after activation?
divide at germinal centres and the become either antibody producing cells or memory B cells
what is a plasma cell?
antibody excreting effector B cell
What isotype is found in the blood during early immune response?
IgM
when does isotype switching occur?
after the B cell is stimulated by an antigen
define isotype switching
the rearrangement of genes which code for antibody proteins, to achieve the production of a different class of antibody
how does the B cell undergo isotype switching?
after studying the protein the cell decides to make a different antibody for the pathogen
it rearranges the isotype DNA template to produce a different constant protein region
where do T cells originate from?
like B cells, the bone marrow from the common haematopoetic precursor
where do T cells mature?
the thymus
what cells are deleted during thymic development of T cells?
those T cells which have receptors specific for antigens expressed on normal body self-cells
what is a positive effect of having no self-reactive cells within the body?
T cells cannot attack the body
define immune tolerance
the process by which immune cells prevent attack of self tissues
what is tolerance during T cell development known as?
central tolerance
why is tolerance during T cell development known as central tolerance?
happens in the thymus
where do mature T cells go once leaving the thymus?
to spleen and lymph nodes to be activated by engagement of their T cell receptor
what family do T cell receptors belong to?
immunoglobulins
how many chains do T cell receptors have?
2
what are the names of the two T cell receptor chains?
alpha and beta
what are the main sections found on a T cell receptor?
variable binding region and a constant backbone (similar to antibodies)
how many constant regions are found in T cell receptors?
one
what must happen in order for the T cell to become activated?
the T cell receptor must bind to the cognate antigen presented by the antigen presenting cells (e.g. dendritic cells)
what are the names of the co-receptors expressed by mature T cells?
CD4 and CD8
what is expressed alongside T cell receptor on the T cell to help it bind strongly to the antigen?
either CD4 or CD8 (never together)
do CD4+T cells and CD8+T cells have different functions?
yes
where does T cell activation occur?
at the spleen and lymph nodes
what does T cell activation require?
3 signals
what are the 3 signals required for T cell activation?
binding of T cell receptors to epitopes of antigens presented on the surface of antigen presenting cells
co-stimulation through CD80/86 and CD28
cytokines which tell the T cell about the most appropriate response
how are epitopes of antigens presented on antigen presenting cells?
by MHC (major histocompatibility complex) molecules on the surface of antigen presenting cells
what are MHC (major histocompatibility complex) molecules?
glycoproteins that are expressed on the surface of cells and which display peptide antigens
what are the types of MHC that can be expressed by antigen presenting cells?
MHC class 1 (MHC-1) MHC class 2 (MHC-2)
where is antigen presented on MHC-1 from?
within the cell
how are antigens presented on MHC-1 receptors on the outside of the cell?
antigen sticks to MHC-1 in the endoplasmic reticulum and is then taken to the surface
where is antigen presented on MHC-2 from?
outside the cell
how are antigens presented on MHC-2 receptors from outside the cell?
antigen sticks to MHC-2 in endocytotic vesicles and is taken to the surface
what are the most efficient antigen presenting cells?
dendritic cells
what other cells can act as antigen presenting cells?
B cells and macrophages
what MHC do CD4+T cells recognise?
antigen on MHC-2
what type of pathogen are CD4+T activated to combat?
extracellular pathogens
how do CD4+T combat extracellular proteins?
offering helpful signals and cytokines to innate cells and B cells
what do CD8+T cells recognise?
antigen on MHC-1
what are CD8+T activated to do?
combat intracellular pathogens such as viruses and cancer
how do CD8+T combat intracellular pathogens?
finding affected self-cells and killing them
what is the key point of co-stimulation through CD80/86?
helps the T cell to ensure the antigen presented by dendritic cells is definitely dangerous
what could T cell activation without a genuine pathogenic threat lead to?
destruction of normal body cells and autoimmunity
what do PAMPs and DAMPs in the environment cause when there is pathogen present?
activation of dendritic cells which upregulate co-stimulatory receptors (CD80/86)
what is the name of the co-stimulatory receptors that are upregulated by dendritic cells?
CD80/86
what does CD80/86 bind to?
CD28 on T cells
what does the binding of CD80/86 to CD28 on T cells do?
Tells T cell that there is a genuine threat and it should be activated
what will activation of a T cell without CD80/86 cause?
no ligation of CD28 which will cause T cells to switch off and become tolerant
what is tolerance due to lack of signals (CD80/86) at activation a form of?
peripheral tolerance
define peripheral immune tolerance
immune tolerance that develops outside the thymus
when do antigen presenting cells produce cytokines?
during T cell activation
what is the cytokine required for the T cell to start dividing and making clones.
IL-2
what are the broad roles of cytokines?
tell the T cell which kind of pathogen it is responding to
if a strong signal 1, 2 and 3 is present what will happen?
the T cell will be successfully activated
what is the function of CD8T cells?
kill compromised self cells
what cells is MHC-2 expressed on?
professional antigen presenting immune cells
what cells is MHC-1 expressed on?
all body cells (e.g. epithelium and stroma)
what type of molecule is presented on all cell surfaces by MHC-1?
peptide
what do the peptides presented on cell surfaces by MHC-1 show?
that they are either functioning normally or that cells are infected and have become cancerous
what will a healthy self cell present on MHC-1?
self-antigens and so be ignored by the immune system
where does CD8+ T cell activation occur?
the lymph node
what is CD8+ T cell activation also known as?
priming
how many times will CD8+ T cells encounter MHC-1 in their life?
twice
what is happening during the first exposure of CD8+ T cells to MHC-1?
activation
what happens during priming of CD8+ T cells in the lymph node?
a naive CD8+ T cell sees epitopes of viral peptides presented on MHC-1 by dendritic cells
what does interaction of a naive CD8+ T cell with its antigen for the first time trigger?
activation and proliferation of CD8+ T cell
what happens if the CD8+ T cell receptor is specific for the epitope presented?
will bind and receive signal 1
what happens with CD8+ T cells to cause killing at the tissues?
an activated CD8+ T cell sees epitopes of viral peptides presented on MHC-1 by infected target cells
describe how an activated CD8+ T cell performs it’s effector function
activated CD8+ T cell binds to epitope MHC on the target cell
T cell only requires signal 1 (T cell receptor engagement by epitope) to activate as it is not naive
CD8+ T cells kill by releasing toxic granules at the target cell
once one cell is hit the CD8+ T cells leave to go onto the next
what does engagement of T cell receptor of a previously activated T cell trigger?
killing rather than activation and proliferation
what do the toxic granules released by CD8+ T cells contain?
perforin and granzyme
what is the function of perforin?
pore forming - makes holes in target cell membrane
what is the function of granzyme?
protein which causes apoptosis when it enters the cell through the pore created by perforin
what is the function of CD4+ T cells?
coordinate the immune response
what are CD4+ T cells often known as?
T helper cells
when are cytokines released?
by innate immune cells at the beginning of the immune response, dendritic cells then carry on producing cytokines when they travel to the lymph node and present pathogenic epitopes
when does CD4+ T cell priming occur?
when their T cell receptor sees it’s specific epitope presented on MHC-2 by dendritic cells at the lymph node
what are CD4+ cells known as before they are activated?
Th0 cells
what signals do CD4+ T cells receive during activation?
signal 1,2 and 3 from dendritic cells
what do signals 1, 2 and 3 involve during activation of T cells?
1 - TCR engagement
2 - co-stimulation through CD80/86
3 - cytokines
what do signal 3 cytokines tell the Th0 cell?
about the type of immune response required by different pathogens
what do cytokines cause in Th0 cells?
them to differentiate into a specialised T helper phenotype
what are the 4 main T helper cell phenotypes?
T helper 1 cells (Th1)
T helper 2 cells (Th2)
T helper 17 cells (Th17)
Treg
what is the role of T helper 1 cells (Th1)?
help with responses to intracellular pathogens
what is the role of T helper 2 cells (Th2)?
help with responses to extracellular pathogens
what is the role of T helper 17 cells (Th17)?
help with fungi and bacteria that Th2 cannot manage
what are Tregs?
a group of T lymphocytes which help to reduce or switch off immune responses when they are no longer needed, or when they are mistakenly directed at healthy cells
what are Tregs a component of?
peripheral immune tolerance
what happens to CD4+ T cells after priming?
divide to form a clone
what happens once CD4+ T cells go elsewhere to produce more cytokines?
support B cells at the germinal centre and tell them what antibody class to produce support effector cells at the tissue and tell them to kill more effectively
what do CD4+ T cells do once the pathogen has gone?
produce regulatory cytokines to switch off the immune response
what is the role of IL-2?
makes T cells proliferate
what is the role of IFN-gamma?
helps the Th1 immune response (involves killing of viruses and cancer)
what is the role of IL-4?
helps Th2 responses (allergy and parasite infection)
what is the role of IL-10 and TGF-beta?
produced by regulatory immune cells to switch off the immune response
what is the role of chemokines?
circulate all around the body telling immune cells which tissue to go to (show where pathogen is)
what cytokines induce Th1?
IFN-gamma
what cytokines induce Th2?
IL-4
what cytokines induce Th17?
TGF-beta and IL-6
what cytokines induce Tregs?
TGf-beta and IL-10
what cytokines does Th1 produce?
IL-2 (T cell proliferation)
IFN-gamma (support immune effector functions)
what cytokines does Th2 produce?
IL-4 (B cell division and switch to IgE in germinal centre)
IL-5 (B cell division and switch to IgA in germinal centre)
what cytokines does Th17 produce?
IL-17
what cytokines does Tregs produce?
IL-10, TGf-beta, IL-35
what cells are involved in Th1 immune responses?
innate - neutrophils, macrophages and NK cells
adaptive - CD8+ T cells
what cells are involved in Th2 immune responses?
innate - neutrophils, eosinophils, basophils and macrophages
adaptive - B cells
define immune memory
the ability of the immune system to remember antigens from pathogens and mount an immune response of greater magnitude with faster kinetics upon re-encounter of the same antigens
what does vaccination involve?
showing a piece of the pathogen, or dead or inactivated pathogen, to the immune system in order to generate a primary immune response and an associated memory response
what part of vaccination stops you from getting symptoms when exposed to the pathogen again?
immune memory response generated by the vaccine
what processes prevent our immune system from attacking healthy self tissues?
immune tolerance
what are the 2 types of immune tolerance?
central tolerance
peripheral tolerance
when does central tolerance occur?
during T cell development in the thymus
what happens in central tolerance during T cell development?
T cells which have receptors specific for antigens expressed on normal, healthy self cells are identified, those that react strongly to self-tissues are deleted
what happens if there are no self reactive cells in the T cell repertoire?
none of our T cell responses will be directed at healthy self tissues
what is peripheral tolerance?
immune tolerance that occurs in peripheral body tissues outside the thalamus
when do peripheral tolerance mechanisms occur?
during the T cells lifetime not during development
what are the main mechanisms of peripheral tolerance?
lack of signal 2 and 3 during T cell activation regulatory cells (Tregs)
what type of cells are allowed to leave the thymus during central tolerance?
non self-reactive T cells and weakly self-reactive T cells
why are weakly reactive self cells useful?
help in destruction of infected self cells
what conditions must be met for a weakly self-reactive self cell to activate?
strong signal 2 and 3 from dendritic cells
under what conditions will dendritic cells provide strong signal 2 and 3?
detection of PAMPs and DAMPs
what is anergy?
T cell receptor binds to antigen presented on a dendritic cell (signal 1) without co-stimulation (signal 2) or stimulating cytokines (signal 3) the T cell then switches off instead of becoming activated.
where are Tregs produced?
some in the thymus, others differentiate from CD4+Th0 cells
what do Tregs do?
produce cytokines (e.g. IL-10 and TGF-beta) to switch off immune responses
when do autoimmune diseases occur?
when immune tolerance is broken
define autoimmune disease
clinical syndromes caused by a break in immune tolerance permitting immune responses directed at healthy self-tissues
give 4 examples of autoimmune disease
type 1 diabetes
multiple sclerosis
immune mediated polyarthritis (IMPA)
auto-immune uveitis
what normal immune response is an autoimmune response similar to?
Th-1 anti-viral response
define hypersensitivity reactions
group of excessive immune responses to (usually harmless) molecules
what are the 4 types of hypersensitivity reaction?
type 1: immediate hypersensitivity
type 2: antibody mediated hypersensitivity
type 3: antibody-antigen complex
type 4: delayed type hypersensitivity
what are hypersensitivity types 1-3 driven by?
antibodies
what cells is hypersensitivity type 4 driven by?
driven by T cells
what can type 1 hypersensitivity be likened to?
an inappropriate Th2 response
define allergen
a harmless molecule which should be ignored by the immune system but which initiates a allergic immune response in some individuals
why is the response mild the first time the body meets an allergen?
because B cell differentiation to plasma cells and class switching to produce IgE in response to the allergen is not yet efficient
what happens the second time a body meets an allergen?
memory B cells rapidly activate and produce large amounts of IgE, which produces an aggressive immune response
what causes the itching, mucous production and vasodilation associated with an allergic response?
mediators in granules produced by mast cells eosinophils and basophils act on different aspects of the tissues
when does anaphylaxis occur?
when the animal has a systemic allergic reaction
what are the most common clinical signs of anaphylaxis?
itching, hives, swollen face, excessive salivation, vomiting, diarrhoea, difficulty breathing and cyanosis
what happens during type 2 hypersensitivity?
free floating IgM and IgG antibodies bind to a tissue and cause recruitment and activation of neutrophils and macrophages
what happens during type 3 hypersensitivity?
IgM/IgG antibodies bind to circulating antigen and form immune complexes which circulate in the blood. Causes recruitment and activation of neutrophils and macrophages.
what happens during type 4 hypersensitivity?
CD4T cell produce cytokines that activate macrophages. CD8T cells direct killing granules at healthy self cells
what is a clinical example of immediate (type 1) hypersensitivity?
seasonal allergies/ flea allergic dermatitis
what is a clinical example of antibody mediated (type 2) hypersensitivity?
blood transfusion reaction (antibodies against donor cells)
what is a clinical example of antigen-antibody immune complex mediated (type 3) hypersensitivity?
complexes tend to get stuck in glomerulus, joints or small blood vessel walls. Causes things refurred to as ‘autoimmune disease’
what is a clinical example of delayed (type 4) hypersensitivity?
contact sensitivity
