Immunology Flashcards
1
Q
what are the 3 main functions of the immune system?
A
eliminate danger
without harming the body
remember the threat to respond more efficiently next time
2
Q
what is the main purpose of the immune system?
A
eliminate a threat to our bodies health
3
Q
what type of threat is usually eliminated by the immune system?
A
infection by a pathogen
4
Q
define pathogen
A
a microorganism which causes disease to the host
5
Q
what are the four main types of infectious microorganism?
A
bacteria
viruses
fungi
parasites
6
Q
what are commensals?
A
non-harmful bacteria that live within or on the bodies of humans and animals
7
Q
how do commensals protect us from pathogens?
A
using up lots of nutrients so there are fewer available for the bad bacteria to live off
8
Q
What effect do products produced by commensal bacteria have on us?
A
good effect or none
9
Q
does our immune system usually attack commensal microbes?
A
no
10
Q
what do immune cells defend us from as well as infection?
A
cancer cells
11
Q
what is the difference between a cancer cell and a normal body cell?
A
a cancer cell is a normal body cell that has accidentally acquired DNA mutations that make it go wrong
12
Q
how does the immune system know to kill cancer cells if they are formed from self-cells?
A
as it is not functioning normally the immune system is able to recognise mistakes and kill it
13
Q
what must the immune system do in order to eliminate threats?
A
use defences which could harm our own body
14
Q
what must the immune system not do?
A
attack normal body tissues
15
Q
what is immune recognition?
A
the ability of the immune system to distinguish self from non-self
16
Q
what happens if immune response goes wrong and attacks normal body cells?
A
we get autoimmune disease
17
Q
why are cancer cells treated as non-self?
A
they are not behaving normally and are dangerous to the body if not destroyed
18
Q
what is immune effector function?
A
the ability to deal with infection and if possible eliminate it without harming our body in the process
19
Q
why do we get symptoms of illness when we get an infection?
A
because it takes time for the immune system to recognise, respond and fight off the pathogen
20
Q
what actually makes us unwell during an infection?
A
the toxic actions of the pathogen
21
Q
what happens if we see the same immune threat twice?
A
the second time the immune system responds faster so it kills the threat before we get symptoms
22
Q
define immune memory
A
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
23
Q
what are the 2 arms of the immune system?
A
innate and adaptive
24
Q
which arm of the immune system is the first line of defence against pathogens?
A
innate immune system
25
what are the 2 functions of the innate immune system?
rapidly respond to slow down pathogenic threats
| recruit adaptive immune cells
26
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
27
is the innate immune system specific?
no
28
what is the more specific arm of the immune system?
adaptive
29
what is the adaptive immune system made up of?
cells and the antibodies produced by B lymphocytes
30
what are the cells of the adaptive immune system?
T cells and B lymphocytes
31
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
32
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
33
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
34
what cells stay in the body for a long time and are able to respond quicker upon re-encounter of the pathogen?
memory lymphocytes
35
do innate immune cells behave like memory lymphocytes?
no
36
what is one of the key differences between innate and adaptive immune responses?
their anatomical location
37
where are all immune cells made?
in the bone marrow
38
what cells are all immune cells formed from?
pluripotent haematopoetic stem cells
39
where do innate immune cells reside?
the peripheral tissues
40
where do adaptive immune cells reside?
at the central lymphoid tissues, the spleen and lymph nodes
41
where do B lymphocytes mature?
in the bone marrow
42
where do B lymphocytes travel to once mature?
the spleen and lymph nodes
43
where do T lymphocytes mature?
in the thymus
44
where do T lymphocytes travel to once mature?
the spleen and lymph nodes
45
what happens to B and T lymphocytes one in the spleen and lymph nodes?
they wait to be activated
46
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!!)
47
where can immune cells enter the spleen and lymph nodes?
via the blood and lymphatic vessels
48
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
49
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
50
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
51
what happens if an immune cell never meets an antigen?
it remains naive
52
where are immune cells made?
in the bone marrow
53
define haematopoetic precursor cells
stem cells which are capable of differentiating into red (oxygen carrying) and white (immune) cells
54
why do we always need a new supply of new immune cells in the bone marrow?
immune cells can be used up or die
55
why is there always a population of immune cells available?
the haematopoetic precursor self renews
56
when may immune cells be activated?
at any point in the person/animals life when they meet their specific pathogen
57
describe the timeline of an immune response
infection, innate immunity, innate and adaptive immunity, elimination of pathogen, healing, immune memory
58
when does innate immunity occur?
0-5 days after meeting the pathogen
59
when does innate and adaptive immunity occur?
5 days- weeks after meeting pathogen depending on the severity ofinfection
60
within what time frame does elimination of pathogen occur?
weeks after meeting pathogen
61
how long does immune memory last?
months-years, potentially entire life
62
are immune responses to different pathogens the same?
no - immune responses to different pathogens are varied and helped by different specialised cell types
63
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
64
define cytokines
small secreted proteins released by immune cells, which allow them to interact and communicate
65
what do interferons do?
induce cells to resist viral replication
66
what are interlukins?
cytokines produced by WBC which have many different functions
67
what are chemokines?
cytokines that tell immune cells where to go
68
what must happen to innate and adaptive immune cells before they can start work?
they must be activated
69
what does it mean when innate and adaptive immune cells are activated?
they detect the presence of something not self and switch on
70
what do innate and adaptive immune cells respond to in order to be activated?
different receptors
71
what receptors does the innate immune system respond to?
protein recognition receptors (PRRs)
| FC receptors
72
what receptors does the adaptive immune system respond to?
T and B cell receptors
73
what do pattern recognition receptors do?
bind PAMPs and DAMPs
74
what do FC receptors do?
bind antibodies
75
what do T and B cell receptors do?
bind antigen epitopes presented on MHC on the surface of antigen presenting cells
76
What are PRRs?
pattern recognition receptors which bind general bits/building blocks of cells called PAMPs and DAMPs
77
what are PAMPs?
pathogen associated molecular patterns that are fragments of pathogen capable of ligating PRRs on innate immune cells
78
what are DAMPs?
damage associated molecular patterns that are fragments of damaged self-cells capable of ligating PRRs on innate immune cells
79
give an example of a PAMP
bacterial flagella
80
give an example of a DAMP
HMGB-1, attached to DNA but released when cells die
81
do PAMPs and DAMPs give detailed information about the pathogen?
no - the innate immune response is very general
82
what other receptors do innate immune cells have on their surface?
receptors for antibodies
83
what are Fc receptors?
antibody receptors on the surface of immune cells
84
what is the effect of antibody receptors on the innate immune system?
triggers/encourages it to keep working
85
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
86
through what cells does the adaptive immune system respond?
T and B cell receptors
87
what do T and B cell receptors bind to?
epitopes
88
what are epitopes?
a short peptide sequence which is part of an antigenic protein
89
define antigen
a protein which is capable of initiating an immune response
90
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
91
how many epitopes are located on each lymphocyte?
1 they are specific for an epitope
92
what happens to lymphocytes when pathogens with their specific epitope are delivered by the innate immune system?
they begin to replicate
93
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
94
why will multiple lymphocytes respond to a pathogen?
there are several antigens on each pathogen
95
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
96
what do innate immune cells respond to via pattern recognition receptors (PRRs)?
pathogen associated molecular patterns (PAMPs) and damage associated molecular proteins (DAMPs)
97
what do adaptive immune cells respond to via T and B cells?
epitopes presented on MHC by antigen presenting cells
98
where are cells of the innate immune system located?
around sites where infections commonly arise (e.g. lungs, GI tract)
99
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
100
how quickly does the innate immune system respond to infection?
rapidly aided by it's location and speed
101
what are the main components of the innate immune system?
cellular and non cellular
102
what are the 4 main non cellular components of the innate immune system?
physical barriers
chemical substances
microbiological
complement
103
what are the physical barriers of the innate immune system?
epithelial tight junctions
| mucous or fluid flow
104
what are the chemical barriers of the innate immune system?
enzymes
acid
microbial peptides
105
what are the microbiological barriers of the innate immune system?
commensals
106
what are the complement barriers of the innate immune system?
a protein cascade which helps the immune system destroy pathogens
107
what are the cellular barriers of the innate immune system?
phagocytes
granulocytes
antigen presenting cells (APC)
108
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
109
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
110
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
111
how do enzymes defend against infection?
directly kill pathogens or make them susceptible to other forms of killing (low pH)
112
what are antimicrobial peptides?
chemicals which are generally toxic to many different pathogens (bacteria/viruses and parasites)
113
how do commensals protect against infection?
occupy space in the body using nutrients and preventing harmful bacteria from establishing
114
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
115
define commensals
non-harmful bacteria that live within or on the bodies of humans and animals
116
define competitive exclusion
the mechanism by which commensal micro-organisms defend against pathogens by competing for attachment sites and nutrients
117
what are the 4 main roles of innate immune cells?
phagocytosis
degranulation
antigen presentation
antibody dependent cellular cytotoxicity (ADCC)
118
what process assists phagocytosis and degranulation by dendritic cells?
opsonisation
119
what is phagocytosis?
the process of internalisation of large particles by phagocytic cells
120
what happens during phagocytosis?
matter is internalised via formation of membrane pockets called phagosomes. These form with lysosomes to digest pathogenic matter
121
what do lysosomes contain?
toxic acids, reactive organ species, antimicrobial peptide and enzymes
122
what is degranulation?
release of toxic granules to destroy a pathogen
123
what does the toxic contents of degranulation granules cause?
pathogen killing
124
what do basophils and eosinophils do during degranulation?
spit out granules in the immune system in response to pathogens
125
what do neutrophils do during degranulation?
have granules and destroy bacteria or virally infected self cells
126
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
127
what do mast cell granules contain?
histamine which activates eosinophils to release own granules
128
when do allergies occur?
when eosinophils, basophils and mast cells mistakenly degranulate in response to an allergen
129
define allergen
a non-pathogenic molecule which should be ignored by the body but initiates an immune response instead
130
define opsonisation
the process by which molecules called opsonins stick to a pathogen and mark it out for degradation
131
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
132
what is a complement?
a system of inflammatory proteins produced in the presence of a pathogenic threat
133
what does binding of opsonins to innate immune cells cause?
them to degranulate or phagocytose pathogens more effectively
134
what is antigen presentation?
processing and presentation of antigens to activate adaptive immune cells
135
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
136
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
137
how does ADCC differ from opsonisation?
self-cell rather than pathogen target
138
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
139
how is a dendritic cell activated?
PRRs bind to PAMPs and DAMPs
140
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
141
how are macrophages activated?
PRRs bind to PAMPs and DAMPs
| Fc receptors bind antibodies
142
what is the function of macrophages?
combat extracellular bacteria
efficient at phagocytosis
antigen presentation to activate lymphocytes
cytokine release
143
how are neutrophils activated?
Fc receptors bind antibody (IgG)
144
what is the function of neutrophils?
'first responder' to site of inflammation
combat virus, parasites and both intra and extra cellular bacteria
phagocytosis
degranulation
145
how are eosinophils activated?
Fc receptors to bind antibody (IgE)
146
what responses are eosinophils most involved with?
anti-parasite responses
inappropriate responses can cause allergy/asthma
degranulation
147
how are mast cells activated?
Fc receptors to bind antibody (IgE)
148
what is the function of mast cells?
anti-parasite responses
inappropriate responses can cause allergy/asthma
degranulation containing histamine to enhance the innate response
149
how are basophils activated?
Fc receptors to bind antibody (IgE)
150
what is the function of basophils?
degranulation
151
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)
152
what is the function of NK cells?
anti-viral and anti-tumor responses (responds to self cell gone wrong)
degranulation triggered via ADCC
153
Where do adaptive immune cells reside?
in lymphoid tissues so they have to mobilise to the sight of infection
154
what sort of recognition does the adaptive immune system use?
sequence specific
155
What does each T and B cell have that is unique?
receptor with responds to an epitope (part of the antigen)
156
what is the antigen that a T and B cell receptor binds to called?
cognate antigen
157
what are the only lymphocytes that are activated in an immune response?
only those with receptors that recognise the pathogenic threat
158
define antigen
protein which is capable of initiating an immune response
159
what are the pieces of antigen presented to lymphocytes by?
antigen presenting cells
160
define epitope
a short peptide sequence making up the processed part of an antigen that can bind to lymphocyte receptors
161
what are B cell and T cell receptors more specific than?
pattern recognition generators expressed on innate immune cells
162
when does the adaptive immune response kick in?
about 5 days after the innate immune response
163
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
164
where must adaptive immune cells travel to the site of infection from?
spleen and lymph nodes
165
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
166
what cells is the adaptive immune system composed of?
B and T lymphocytes
167
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
168
what are plasma cells?
activated B cells which produce antibodies
169
define antibodies
secreted proteins which facilitate immune neutralisation of pathogens by binding to antigens expressed on the pathogen or it's products
170
how are antibodies found in the body?
secreted by B cells
| stuck on the surface of a B cell
171
what is the function of antibodies produced by B cells?
neutralisation of pathogens
172
what do antibodies on the surface of B cells do?
activate B cells
173
what are antibodies on the surface of B cells known as?
the B cell receptor
174
what shape proteins are antibodies?
Y
175
what are antibodies made up of?
two heavy chains and two light chains stuck together
176
what are antibodies also known as?
immunoglobulins
177
what do the ends of the heavy and light chains from?
antigen binding region
178
what is the antigen binding region known as?
variable region
179
why are there a vast number of different variable regions?
to bind to all the different possible epitopes
180
what happens if the epitope shape doesn't match the antibody binding site (variable region)?
it wont fit
181
what part of the heavy and light chains of the antibodies forms the constant region?
backbone
182
what does the constant region of an antibody provide to the variable regions?
scaffold for the variable regions to sit on
183
how many constant region chains of antibodies are there?
5
184
what does each different constant region chain of antibodies determine?
how the immune system responds to the pathogen
185
what is the constant region chain named by?
the greek letter which matches the antibody isotype
186
what are the 5 different antibody isotypes?
```
IgM
IgG
IgA
IgE
IgD
```
187
what is the IgM constant chain formed from?
Mu
188
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
189
what is the structure of IgM?
forms a pentamer (5 IgM joined together)
190
what is the IgG constant chain formed from?
gamma
191
what is the function of IgG?
the best antibody for opsinisation and neutralisation
| attacks pathogens such as viruses and intracellular bacteria
192
what is the structure of IgG?
monomer
193
what is the IgA constant chain formed from?
alpha
194
what is the function of IgA?
immunity at mucosal surfaces (e.g resp or GI tract)
195
what is the structure of IgA?
```
a monomer in tissue fluid and blood
a dimer (2 IgA joined) in mucosal secretions
```
196
what is the constant chain of IgE formed from?
eta
197
what is the function of IgE?
induces mast cell and basophil degranulation in response to parasites
involved in allergy response
198
what is the structure of IgE?
monomer
199
what is the IgD constant chain formed from?
delta
200
what is the function of IgD?
unknown
201
where is IgD found?
naive B cells before activation
202
what structure is IgD?
monomer
203
where are B cells activated?
lymph nodes
| spleen
204
where are lymph nodes found?
junctions between lymphatic vessels
205
what do lymphatic vessels do?
collect fluid and cells from tissues and deliver to the lymph nodes
206
what are the 2 main parts of the lymph node?
cortex and medulla
207
where do B cells go in the spleen once they meet their specific antigen?
areas of the cortex known as germinal centres
208
what happens to B cells in germinal centres?
under go intense proliferation to generate clone B cells which respond to the same antigen
209
what do CD4+T helper cells do to aid B cell proliferation?
localise to paracortical areas where they produce chemicals which assist proliferation
210
what is found in the white pulp of the spleen?
lymphocytes, germinal centres and nearby areas for CD4+T helper cells
211
how is the spleen supplied with innate immune cells bearing antigens?
blood supply rather than lymphatic vessels
212
what is the role of the red pulp of the spleen?
collection and disposal of old RBC
213
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
214
What happens to B cells after activation?
divide at germinal centres and the become either antibody producing cells or memory B cells
215
what is a plasma cell?
antibody excreting effector B cell
216
What isotype is found in the blood during early immune response?
IgM
217
when does isotype switching occur?
after the B cell is stimulated by an antigen
218
define isotype switching
the rearrangement of genes which code for antibody proteins, to achieve the production of a different class of antibody
219
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
220
where do T cells originate from?
like B cells, the bone marrow from the common haematopoetic precursor
221
where do T cells mature?
the thymus
222
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
223
what is a positive effect of having no self-reactive cells within the body?
T cells cannot attack the body
224
define immune tolerance
the process by which immune cells prevent attack of self tissues
225
what is tolerance during T cell development known as?
central tolerance
226
why is tolerance during T cell development known as central tolerance?
happens in the thymus
227
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
228
what family do T cell receptors belong to?
immunoglobulins
229
how many chains do T cell receptors have?
2
230
what are the names of the two T cell receptor chains?
alpha and beta
231
what are the main sections found on a T cell receptor?
variable binding region and a constant backbone (similar to antibodies)
232
how many constant regions are found in T cell receptors?
one
233
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)
234
what are the names of the co-receptors expressed by mature T cells?
CD4 and CD8
235
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)
236
do CD4+T cells and CD8+T cells have different functions?
yes
237
where does T cell activation occur?
at the spleen and lymph nodes
238
what does T cell activation require?
3 signals
239
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
240
how are epitopes of antigens presented on antigen presenting cells?
by MHC (major histocompatibility complex) molecules on the surface of antigen presenting cells
241
what are MHC (major histocompatibility complex) molecules?
glycoproteins that are expressed on the surface of cells and which display peptide antigens
242
what are the types of MHC that can be expressed by antigen presenting cells?
```
MHC class 1 (MHC-1)
MHC class 2 (MHC-2)
```
243
where is antigen presented on MHC-1 from?
within the cell
244
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
245
where is antigen presented on MHC-2 from?
outside the cell
246
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
247
what are the most efficient antigen presenting cells?
dendritic cells
248
what other cells can act as antigen presenting cells?
B cells and macrophages
249
what MHC do CD4+T cells recognise?
antigen on MHC-2
250
what type of pathogen are CD4+T activated to combat?
extracellular pathogens
251
how do CD4+T combat extracellular proteins?
offering helpful signals and cytokines to innate cells and B cells
252
what do CD8+T cells recognise?
antigen on MHC-1
253
what are CD8+T activated to do?
combat intracellular pathogens such as viruses and cancer
254
how do CD8+T combat intracellular pathogens?
finding affected self-cells and killing them
255
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
256
what could T cell activation without a genuine pathogenic threat lead to?
destruction of normal body cells and autoimmunity
257
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)
258
what is the name of the co-stimulatory receptors that are upregulated by dendritic cells?
CD80/86
259
what does CD80/86 bind to?
CD28 on T cells
260
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
261
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
262
what is tolerance due to lack of signals (CD80/86) at activation a form of?
peripheral tolerance
263
define peripheral immune tolerance
immune tolerance that develops outside the thymus
264
when do antigen presenting cells produce cytokines?
during T cell activation
265
what is the cytokine required for the T cell to start dividing and making clones.
IL-2
266
what are the broad roles of cytokines?
tell the T cell which kind of pathogen it is responding to
267
if a strong signal 1, 2 and 3 is present what will happen?
the T cell will be successfully activated
268
what is the function of CD8T cells?
kill compromised self cells
269
what cells is MHC-2 expressed on?
professional antigen presenting immune cells
270
what cells is MHC-1 expressed on?
all body cells (e.g. epithelium and stroma)
271
what type of molecule is presented on all cell surfaces by MHC-1?
peptide
272
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
273
what will a healthy self cell present on MHC-1?
self-antigens and so be ignored by the immune system
274
where does CD8+ T cell activation occur?
the lymph node
275
what is CD8+ T cell activation also known as?
priming
276
how many times will CD8+ T cells encounter MHC-1 in their life?
twice
277
what is happening during the first exposure of CD8+ T cells to MHC-1?
activation
278
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
279
what does interaction of a naive CD8+ T cell with its antigen for the first time trigger?
activation and proliferation of CD8+ T cell
280
what happens if the CD8+ T cell receptor is specific for the epitope presented?
will bind and receive signal 1
281
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
282
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
283
what does engagement of T cell receptor of a previously activated T cell trigger?
killing rather than activation and proliferation
284
what do the toxic granules released by CD8+ T cells contain?
perforin and granzyme
285
what is the function of perforin?
pore forming - makes holes in target cell membrane
286
what is the function of granzyme?
protein which causes apoptosis when it enters the cell through the pore created by perforin
287
what is the function of CD4+ T cells?
coordinate the immune response
288
what are CD4+ T cells often known as?
T helper cells
289
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
290
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
291
what are CD4+ cells known as before they are activated?
Th0 cells
292
what signals do CD4+ T cells receive during activation?
signal 1,2 and 3 from dendritic cells
293
what do signals 1, 2 and 3 involve during activation of T cells?
1 - TCR engagement
2 - co-stimulation through CD80/86
3 - cytokines
294
what do signal 3 cytokines tell the Th0 cell?
about the type of immune response required by different pathogens
295
what do cytokines cause in Th0 cells?
them to differentiate into a specialised T helper phenotype
296
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
297
what is the role of T helper 1 cells (Th1)?
help with responses to intracellular pathogens
298
what is the role of T helper 2 cells (Th2)?
help with responses to extracellular pathogens
299
what is the role of T helper 17 cells (Th17)?
help with fungi and bacteria that Th2 cannot manage
300
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
301
what are Tregs a component of?
peripheral immune tolerance
302
what happens to CD4+ T cells after priming?
divide to form a clone
303
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
```
304
what do CD4+ T cells do once the pathogen has gone?
produce regulatory cytokines to switch off the immune response
305
what is the role of IL-2?
makes T cells proliferate
306
what is the role of IFN-gamma?
helps the Th1 immune response (involves killing of viruses and cancer)
307
what is the role of IL-4?
helps Th2 responses (allergy and parasite infection)
308
what is the role of IL-10 and TGF-beta?
produced by regulatory immune cells to switch off the immune response
309
what is the role of chemokines?
circulate all around the body telling immune cells which tissue to go to (show where pathogen is)
310
what cytokines induce Th1?
IFN-gamma
311
what cytokines induce Th2?
IL-4
312
what cytokines induce Th17?
TGF-beta and IL-6
313
what cytokines induce Tregs?
TGf-beta and IL-10
314
what cytokines does Th1 produce?
IL-2 (T cell proliferation)
| IFN-gamma (support immune effector functions)
315
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)
316
what cytokines does Th17 produce?
IL-17
317
what cytokines does Tregs produce?
IL-10, TGf-beta, IL-35
318
what cells are involved in Th1 immune responses?
innate - neutrophils, macrophages and NK cells
| adaptive - CD8+ T cells
319
what cells are involved in Th2 immune responses?
innate - neutrophils, eosinophils, basophils and macrophages
| adaptive - B cells
320
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
321
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
322
what part of vaccination stops you from getting symptoms when exposed to the pathogen again?
immune memory response generated by the vaccine
323
what processes prevent our immune system from attacking healthy self tissues?
immune tolerance
324
what are the 2 types of immune tolerance?
central tolerance
| peripheral tolerance
325
when does central tolerance occur?
during T cell development in the thymus
326
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
327
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
328
what is peripheral tolerance?
immune tolerance that occurs in peripheral body tissues outside the thalamus
329
when do peripheral tolerance mechanisms occur?
during the T cells lifetime not during development
330
what are the main mechanisms of peripheral tolerance?
```
lack of signal 2 and 3 during T cell activation
regulatory cells (Tregs)
```
331
what type of cells are allowed to leave the thymus during central tolerance?
non self-reactive T cells and weakly self-reactive T cells
332
why are weakly reactive self cells useful?
help in destruction of infected self cells
333
what conditions must be met for a weakly self-reactive self cell to activate?
strong signal 2 and 3 from dendritic cells
334
under what conditions will dendritic cells provide strong signal 2 and 3?
detection of PAMPs and DAMPs
335
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.
336
where are Tregs produced?
some in the thymus, others differentiate from CD4+Th0 cells
337
what do Tregs do?
produce cytokines (e.g. IL-10 and TGF-beta) to switch off immune responses
338
when do autoimmune diseases occur?
when immune tolerance is broken
339
define autoimmune disease
clinical syndromes caused by a break in immune tolerance permitting immune responses directed at healthy self-tissues
340
give 4 examples of autoimmune disease
type 1 diabetes
multiple sclerosis
immune mediated polyarthritis (IMPA)
auto-immune uveitis
341
what normal immune response is an autoimmune response similar to?
Th-1 anti-viral response
342
define hypersensitivity reactions
group of excessive immune responses to (usually harmless) molecules
343
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
344
what are hypersensitivity types 1-3 driven by?
antibodies
345
what cells is hypersensitivity type 4 driven by?
driven by T cells
346
what can type 1 hypersensitivity be likened to?
an inappropriate Th2 response
347
define allergen
a harmless molecule which should be ignored by the immune system but which initiates a allergic immune response in some individuals
348
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
349
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
350
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
351
when does anaphylaxis occur?
when the animal has a systemic allergic reaction
352
what are the most common clinical signs of anaphylaxis?
itching, hives, swollen face, excessive salivation, vomiting, diarrhoea, difficulty breathing and cyanosis
353
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
354
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.
355
what happens during type 4 hypersensitivity?
CD4T cell produce cytokines that activate macrophages. CD8T cells direct killing granules at healthy self cells
356
what is a clinical example of immediate (type 1) hypersensitivity?
seasonal allergies/ flea allergic dermatitis
357
what is a clinical example of antibody mediated (type 2) hypersensitivity?
blood transfusion reaction (antibodies against donor cells)
358
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'
359
what is a clinical example of delayed (type 4) hypersensitivity?
contact sensitivity
