Immunology Flashcards
1
Q
what are the 3 layers of defence our immune system has?
A
- physical barrier
- innate arm of immune response
- adaptive arm of immune response.
2
Q
what are some physical barriers of the immune system?
A
skin, nails, epithelial, mucosal layers.
3
Q
what are lysozymes in saliva most effective against?
A
most effective against gram +ve bacteria
4
Q
how do lysozymes preform their function in the oral cavity?
A
they cleave the chemical bonds between sugars on the peptidoglycan layer of bacteria, enabling other microbial agents to destroy the lipid bilayer around bacteria.
5
Q
how do antimicrobial peptides preform their function in the oral cavity?
A
attack the exposed lipid bilayer around bacteria.
6
Q
what are some antimicrobial peptides found in the oral cavity?
A
- Defensins
- Cathelicidins
- Histatins
7
Q
what is the purpose of defensins in the oral cavity?
A
several can insert into the lipid bilayer of bacteria, creating a pore - allowing the content to leak out.
8
Q
what is the purpose of cathelicidins in the oral cavity?
A
cause membrane disruption.
9
Q
what type of cathelicidins are found in humans?
A
LL-37
10
Q
what is the purpose of histatins in the oral cavity?
A
fight fungal pathogens
11
Q
what produces histatins?
A
salivary glands.
12
Q
what kind of receptors are found on innate arm response cells?
A
genome encoded receptors.
13
Q
which arm of the immune system has lasting protection?
A
adaptive responce.
14
Q
what is the purpose of the innate arm?
A
provide initial defence, limiting pathogen proliferation and spread.
15
Q
How long does it take the adaptive arm to start?
A
up to 4 days.
16
Q
why do the cells of the adaptive arm have a vast range of receptors? and what does this mean?
A
- as the receptors are not genome encoded so receptor recognition improves.
17
Q
why does the adaptive arm need to be more potent?
A
to control more virulent pathogens,
18
Q
why does the adaptive arm take longer?
A
because it has to be started by the innate response. And it takes time to raise population of cell specific for pathogen.
19
Q
what is the complement system?
A
plasma that ‘complemented’ the killing of bacteria by phagocytes.
20
Q
what are the functions of complement?
A
- facilitate recognition of bacteria by phagocytes.
- directly lyse bacteria.
21
Q
what is the classic pathways that the complement system can be activated?
A
when C1 interacts with a pathogen surface or binds to antibodies bound to the surface. has C1q (recognition component) and C1r+C1s (proteases) - these 3 form C1 complex.
22
Q
what is the alternative pathways that the complement system can be activated?
A
C3 undergoes spontaneous hydrolysis - forming a complex with factor D,P,B producing C3bBb complex (C3 convertase)
23
Q
what is the lectin pathways that the complement system can be activated?
A
lectin like molecules do the recognition and ficoline bind carbs on pathogen surface leading to C3 convertase.
24
Q
what do all compliment pathways generate?
A
C3 convertase.
25
what is the purpose of C3 convertase?
cleaves C3 - leaving C3b bound to microbial surface and releasing C3a.
The C3b then starts the release of C5a.
26
How do C3a and C5a aid in the immune response?
they recruit phagocytic cells to the site of infection and promote inflammation,
27
what is the purpose of compliment leaving C3b on the surface of the pathogen?
phagocytes with receptors for C3b with come and engolf + then destroy the pathogen.
28
what does completion of the complement cascade lead to?
formation of a membrane-attack complex (MAC) - which disrupts cell membrane and causes cell lysis.
29
what is a zymogen?
an inactive form of an enzyme, usually protease, that must be modified in some way (eg cleaved in a particular site) to become active.
30
where are immune effector cells derived from?
common pluripoten progenitor cell types in bone marrow
31
after a stem cell divides in the bone marrow, the daughter cells can either differentiate or divide - what happens if they differentiate?
they mature. This then restricts their potential and they lose the ability to self renew.
32
after a stem cell divides in the bone marrow, the daughter cells can either differentiate or divide - what happens if they divide?
they continue being a stem cell.
33
where do the adaptive effector cells come from?
a lymphoid and myeliod path in the bone marrow.
34
where do the innate effector cells come from?
a lymphoid and myeliod path in the bone marrow.
35
what are the adaptive effector cells?
- B cells
- Plasma cells
- T cells
- Activated T cells.
36
what are the lymphoid innate effector cells?
Natural Killer Cells and Activated Natural killer cells.
37
what are the myeliod innate effector cells?
- Granulocytes
- Mast cells
- Macrophages
38
what is the function of a macrophage in the innate immune response?
- 1st responders .
- phagocytosis.
- remove dead cells and debris.
- draw in other immune cells
- present antigen from phagocyte on its surface for T cells.
(killers nad whistle blowers)
39
What are granulocytes?
polymorphonuclear leukocytes, (neutrophils)
40
what is the function of neutrophils in the innate immune response?
- Phagocytic
- Bactericidal
(many killer soldiers)
41
what is pus?
dead neutrophils
42
where are neutrophils located?
in the blood.
43
where are macrophages located? (mature and immature)
mature = most tissues in submucosal layers.
immature = in blood.
44
what is the function of dendritic cells in the innate immune response?
phagocytosis. - to then present the antigen to the adaptive arm - activating the adaptive arm.
(transporter)
45
what is the function of Natural killer cells in the innate immune response?
release cytotoxic granules. These can damage host cells .
| they look for cells that are infected with a virus or a tumour.
46
where are dendritic cells located? (mature and immature)
immature = under surface epithelial and in solid organs.
| Once they phogolose a pathogen they move to the lymph nodes and mature.
47
where are natural killer cells located?
blood.
48
what cells can phagocytose?
- macrophages
- neutrophils
- Dendritic cells.
49
what are the receptors that are found on phagocytic cells that start an immune response?
- Fc receptors.
- complement receptors. (recognise C3b)
- Pattern recognition Receptors (PRR)
50
what are PAMPS?
Pathogen associated molecular patterns that are found on pathogens.
51
what are the 3 types of PAMPS?
- Lectin Like
- Scavenger receptors
- Toll like receptors.
52
what are the stages of phagocytosis?
- bacterial binds to receptor on cell surface
- endocytosis (engolfing) of the bacterial into the cell
- this created a membrane bond vesicle in the cell. (phagosome)
- lysosomes fuse with the phagosome forming the phagolysosome - they inject toxic material breaking and killing it.
53
what is the function of toll like receptors?
to recognises a distinct set of PAMP not found in vertebrates.
54
why are toll like receptors important?
in preventing fungal infections.
55
how do phagocytes prevent bacterial growth and kill some?
pH is very low.
56
what are the antimicrobial mechanisms of phagocytes?
- pH very low
- Respiritory burst (cause cells stimulated to produce lots of toxic o2 species and toxic nitrogen species which damage the engulfed microbes.
- Phagocytes stimulated to reases anti-microbial peptides (cathelicidin)
- produce decretive enzymes (lyzsozyme)
57
what is a cytokine?
a small protein that affects the behaviour of other cells.
58
what is chemokine?
small chemoattractant protein that draws cells to where they are needed.
59
during the immune response what cells initiate inflammation?
macrophages and complement.
60
when macrophages engulf the bacterial what is triggered to be released?
cytokine (eg IL-1 and chemokine)
61
what makes the blood vessels in the infected areas more permeable and why?
- cytokines.
- they make it more permeable meaning that neutrophils can come out more easily. It also allows more plasma to leave the blood. (increasing complement proteins for clotting factors and phagocytosis)
62
what are the purposes of cytokines in the innate immune response?
- make blood vessels more leaky
| - tell neutrophils where they need to go.
63
what cells initiate the adaptive immune response?
dendritic cells.
64
what is the difference between PAMPS and specific antigen?
specific antigens are only for one receptors where as PAMPs are for many.
65
what happens to B and T cells once they mature?
have their own unique specificity for antigen.
66
where do B cells mature?
in the bone marrow
67
where do T cells mature?
in the Thymus
68
why only once a cell with a specific antigen for the infected pathogen does it undergo colonal expansion?
because there isn't enough room in the blood for every single possible cell with a unique antigen for everything.
69
what are left behind when the infection is cleared and why do the other cells die?
Memory cells. The other die to allow for enough room for other cells to fight a different infection.
70
what mechanism allows us to fight infection within the limited space we have in the blood?
constant colonal expansion and retraction periods so there isn't loads of these cells in the blood system at one time.
71
what is a problem with receptors in B/T cells being randomly generated?
we make some that are self reactive.
72
where are self reactive cell receptor cells removed?
either in the bone marrow or in the thymus.
73
what are the 2 cells that B cells can differentiate into?
- effector cells that can produce the antigen
| - memory cells.
74
what are the 2 cells that T cells can differentiate into?
- effector cells
| - memory cells.
75
what do B cells mature into?
Plasma cells.
76
what is the function of plasma cells?
can release their receptors and bind to a specific antigen alone.
77
what are Immunoglobulins?
B cells
78
what do T cells mature into?
activated T cells.
79
when can a T cell bind to antigen?
once it has been shown to it through the antigen having already have binded with MHC
80
what is an epitope?
a site on an antigen that is recognised by specific lymphocyte receptors.
81
Are B cell epitopes most likely to be continuous or discontinuous?
discontinuous
82
Are T cell epitopes most likely to be continuous or discontinuous?
continuous
83
what is mean by a multivalent antigen?
contains many epitopes.
84
what is the basic structure of immunoglobulin?
- Y shaped
- 4 polypeptides bonded together
- 2 light chains
- 2 heavy chains.
85
what bond holds together the 4 polypeptides of immunoglobulin?
disulphide bond,
86
what are the unctions of immunoglobulin?
- recognise and bind antigen
- the elicit effector functions, recruiting additional immune molecules or cells to destroy pathogens following antigen binding.
87
what is affinity?
the strength of binding of one molecule to another at a single site, eg the binding of a monovalent Fab fragment of antibody to a monovalent antigen.
88
what is avidity?
the sum total of the strength of binding of 2 molecules or cells to one another at multiple sites.
89
what is papain?
a protiase
90
what are the effects of papain on an antibody (immunoglobulin)?
- cleaves the antibody molecule. leaving 2x Fab fragments and FC fragment.
91
Once a immunoglobulin have been cleaved by papain what does the Fc fragment bind to?
cell receptors.
92
what does Fab stand for?
Fragment antigen binding.
93
what is pepsin?
a protiase
94
what are the effects of pepsin on an antibody (immunoglobulin)?
- cleaves at a different site when compaired to papain. this results in a F(ab')2 fragment and many peptide frgaments.
95
how many binding sites will a F(ab')2 fragment have?
2 - as pepsin doesn't cleave them away from each other.
96
regarding affinity and avidity: what is the same and what is different for Fab and F(ab)2 fragments?
affinity is the same (they both still bond to the antigen the same)
avidity is different. (they dont have the same number of binding sites, Fab only has one now, F(ab)2 has 2 binding sites.)
97
What bond is stronger to an antigen, Fab or F(ab)2?
F(ab)2 as it has 2 binding sites so the avidity is twice as strong.
98
what are the 2 types of light chains found in humans?
kappa and lambda
99
How many light chain immunoglobulin folds are in IgG?
2
100
How many heavy chain immunoglobulin folds are in IgG?
4
101
what causes changes in antigen binding specificity of immunoglobulin?
changes in amino acid sequence at the hypervariable regions which alter the CDRs.
102
how are antigen and antibodies binded non-covalently?
- electrostatic forces
- hydrogen bonds
- hydrophobic forces
- van der waals forces.
103
what can disrupted antigen and antibody binding?
- high salt concentration
- extreme pH
- detergents
- high concentration of purified epitope
104
what is the function of different Ig classes determined by?
the heavy chain Fc region.
105
what are the functions of the different Ig classes?
- neutralisation
- opsonisation
- activation of the complement
- TRIM 21 activation.
106
what is meant by Ig neutralisation?
antibodies bind to pathogen and toxins, preventing binding to the cellular receptors that pathogens use to gain entry to the cell.
107
what is meant by Ig opsonisation?
coating of pathogen with antibody phagocytes recognise the Fc region and triggers phagocytosis.
108
what is TRIM 21 ?
a receptor within a cell that detect the invaded antibody and recruits proteasome to degrade it.
109
what are the primary/ central lymphoid organs?
inside the Thymus or bone marrow.
110
what are the secondary/ peripheral lymphoid organs?
- adenoids
- tonsils
- lymph nodes
- spleen
- appendix
- peyers patches.
111
what is mean by some T and B cells are nieve?
they havent come across any antigen yet.
112
how are the variable regions of Ig gene encoded?
gene segments.
113
How is there diversity in Ig?
- Germline diversity (multiple choice for each gene segment)
| - Combinatorial diversity (segments randomly selected and together in different combinations)
114
what are the 2 types of segments that encode for the light chain variable regions?
- variable
| - joining.
115
what are the 3 types of segments that encode for the heavy chain variable regions?
- variable
- joining
- diversity
116
What does the control of recombination always ensure (within the Ig chains) is joined together?
that variable segment is always joined to a joining segment (or in heavy chains that variable is always connected to diveristy)
so always a 23 space joins a 12 space.
117
why is you more likely to find pseudogenes (mutations that cannot produce functional proteins) in Ig?
because there is less pressure on them to get it correct evolutionary
118
what proteins cleave DNA?
RAG proteins.
119
what are the 3 ways in which Ig can get diversity?
- Germline (different gene segments available)
- Combinatorial (different combo of gene segments and different heavy/light chains)
- Junctional (adding /removing nucleotides)
120
what are some genetic disorder that affect the immune system?
- severe combined immunodeficencies
- deficiencies in antibody production
- phagocytic disorders
- complement deficiencies
121
what does allelic exclusion regulate?
- rearrangement of Ig.
| - make sure B cells have only 1 specific antigen receptor.
122
what is a problem with the way in which we generate Ig diversity?
it generates some self reactive B cells.
123
How do we prevent B cells that are self reactive to leave the primary lymphoid organ?
cause cell death though B cell receptor clustering.
124
what is B cell receptor clustering?
where many receptors on the B cell attach to the self cell receptors - the self cells send a strong message to B cell and it undergoes colonial deletion.
125
what is IgM good for?
- Strong activator of the complement system
| - good at controlling infection in blood stream
126
what is a limitation of IgM?
not as flexible as other Ig due to having no hinge.
127
what is IgG good at?
- diffuses into tissues well
- good activator of complement
- preform neutralisation and optimisation.
- transported across placenta to protect the baby.
128
where is IgG the principle antibody?
in the blood/ extracellular fluid.
129
what is IgE good at?
- defence against multicellular parasites
- functions in allergy
- binds mast cells which have induce pathogen expulsion by coughing, sneezingm vomiting.
130
where is IgA a principal antibody?
in secretions. (saliva)
131
what is IgA good at?
- good at neutralisation
| - transports across epithelium.
132
how does IgG trigger engulfment of a phagocyte?
binds to the phagocyte FcRs.
133
How does IgG cross the placental?
binds to neonatal FCR and gives passive maternal derived protection to newborns.
134
what Ig can be found in breast milk?
IgA and IgG.
135
where does B cell activation occur?
in the secondary lymphoid organs.
136
what is different about a T-independent antigen?
can activate B cells alone 0 without T cell help.
137
How do the T-dependant antigens activate the B cells?
- B cell receptor binds to antigen, B cell engulfs the antibody/antigen complex. Digest it via MHC molecule. Which is them placed on the surface of the B cell- showing it to T cells.
- T helper cell activates the 2nd signal by putting cytokines into the B cell and connects the T and B cell via a CD40/CD40L to the MHC molecule.
138
what is linked recognition?
where T cells must respond to the same antigen as the b Cell.
139
what do B cells after they have been activated differentiate into?
memory cells and plasma cells.
140
what do plasma cells produce?
antibodies. (Immunoglobulin)
141
how long can a germinal centre reaction last post infection?
3-4 weeks after
142
where do activated B cells go to proliferate?
germinal centre.
143
what is somatic hypermutation? and why does it occur when B cells proliferate?
where the cells reproducing have a high rate of mutation.
| This is because B cells express an enzyme (AID) which attacks the DNA of our Ig genes.
144
what does AID do to your Ig genes?
AID swaps some of the bases as Ig is being transcribed. This causes mutations .
145
what are the effects of bases swaps in Ig due to AID?
- can improve the function of B cells
| - Can reduce the function of B cells.
146
How is the secondary response better that the primary response in the adaptive immune response?
due to mulations with Ig due to AID in B cell cell activation and proliferation making B cells better at phagocytosis. So this means that 'un-mutated' B cells are less competitive and die. Leaving behind highly efficient B cells.
147
what is Affinity maturation?
Improving of the B cells via mutations during the Ig production by AID
148
Where can Ig switch class?
in the germinal centre
149
what does Ig need in order to switch class?
AID
150
what are the results of mAb?
cells combining the characteristics of producing antigen specific antibody with ability to grow in culture with unlimited lifespan.
151
what are some immunological techniques for research etc?
- ELISA
- SDS/ western blotting / immunoblotting
- Immunohistochemistry / Immunocytochemistry
- Flow cytometry and FACs
152
where do T cells develop their specific antigen receptors?
Thymus.
153
once a T cell has found an antigen and undergoes proliferation, what does it differentiate into?
effector cells (memory T cells)
154
what type of family is the T cell receptor part of?
Ig family - but it isnt an Ig
155
what is the structure of a T cell receptor?
2 polypeptide chains - alpha and beta.
156
what is the bond between the chains on a T cell receptor ?
disulphide bond
157
How many binding sites does a T cell receptor have?
1.
158
what do T cell receptors bind to?
antigen presented within a complex with MHC ll
159
what are the other receptors on a T cell?
- CD3
- CD8
- CD4
160
what is the purpose of a CD3 on a T cell?
informs the inside of the cell that the receptor has bound to an antigen
161
what is the purpose of a CD4 on a T cell?
found on T helper cells - helps B cells join (how the B cells are activated)
162
what is the purpose of a CD8 on a T cell?
only found on cytotoxic T cells. Kills host cells that they detect are effective by a virus or will become a cancer cell.
163
How are T cell receptors generated?
- similaer process to Ig
| - uses RAG proteins to perform V(d)J somatic recombination.
164
where is the hypervariable regions on a T cell receptor?
where the antigen binding site is.
165
what is it that can lead to a transplant graft/organ rejection?
polymorphisms (many different genetic variations exist within a species) in MHC
166
how are their 2 type of MHCs?
intra and extra cellular antigen. MHC 1 is intracellualr.
| MHC ll is extracellular.
167
what does MHC l bind and present?
intracellular derived antigen
168
where can MHC l be found?
on the majority of cells (just not RBC)
169
what does MHC ll bind and present?
extracellular derived antigen.
170
what type of cells carry out MHC ll?
professional antigen presenting cells (APC)
171
on what cells is MCH l found?
all cells
172
on what cells is MHC ll found?
dendritic cells
B cells
Macrophages.
173
what receptor on a T cell does MHC l bind to?
CD8
174
what is the pathway of MHC l antigen?
- virus in cells, takes over protein making machinery, produces viral proteins
- infected cells creates viral+own proteins down to small peptides
- peptides taken to endoplasmic reticulum through TAP
- MHC (at the same time) is being synthesised on the ribosomes of the Rough Endoplasmic reticulum
- large+small chanins of MHC 1 come together to form MHC 1
- antigen binding grooves of MHC 1 bind to the incoming small peptides.normal cell transport mechanisms take place. (MHC 1 is inserted through the cell onto the membrane)
175
what is TAP and what is its purpose inside a cell?
TAP= specialised transporter channel
| It transports peptides into the endoplasmic reticulum.
176
What cells will recognise MHC 1 with viral proteins?
cytotoxic T cells
177
what receptor on a T cell does MHC ll bind to?
CD4
178
How does the formation of MHC ll onto the surface of the membrane differ from MHC l?
- once the MHC is being synthesised, the invariant chain (a small peptide) is produced to prevent MHC binding to intracellular antigens. This binds to the MHC ll.
- this complex passes through the golgi, where endosome containing enzymes degrade the invariant chain down into CLIP (a small residue).
- Vesicles containing peptides and MHC ll (with CLIP) fuse together
- another vesicle containing DM joins.
- DM out competes MHC ll for CLIP
- MHC now binds to extracellular antigens.
- MHC ll is then inserted through the cell onto the membrane.
179
what drives the proliferation of T cells?
IL- 2
180
what dells takes an antigen to the lymph nodes?
dendritic cells.
181
what cells produce IL-2? and why?
T cells - because it drives the proliferation of the T cells.
182
what cells are professional antigen presenting cells?
Dendritic cells.
Macrophages
B cells.
183
what are CTLs?
Cytoxoxic T lymphocytes
184
what is the purpose of Cytotoxic T Lymphocytes?
bind with complimentary antigen+MHC l on a cell surface and to polarises cytotoxic granules towards the target cell.
granules fuse with the membrane and create a pore in it. inducing apoptosis (self suicide)
185
How many cells can CTLs kill?
many. they have along life span.
186
what is the function of T helper 1 cells?
increase macrophage activity against intracellular bacteria.
187
what is the function of T helper 2 cells?
promote responses to parasite, helping B cells class switch to IgE.
188
what receptor on T cells does HIV bind to?
CD4.
189
why does HIV binding to CD4 receptors lead to immune collapse?
means that viruses can not be detected due to CD4 receptors not being able to bind to T helper cells.
190
where do immature T cells gain receptors?
immature T cells produced in the bone marrow relocate to the thymus where there is a re-arrangement of T cell receptors gene seguence and they then express TCRs.
191
what happens to immature T cells that fail to recognise MHC? what is this process called?
they die so never become mature.
| Positive selection
192
what % of precursor T cells are screened out and die before they mature>
98%
