Immunology Flashcards
1
Q
What does the inmate immune system do?
A
This stops the proliferation of pathogens and kick starts the inmate immune system.
2
Q
What does the active immune system do?
A
Irradiates pathogens and creates a positive feedback loop to the inmate immune system
3
Q
How do epithelial cells create a barrier?
A
They create biochemical barriers like mucus etc and they also mechanicals seeps away these trapped bacteria.
4
Q
What is the microflora?
A
Barrier of bacteria that live on out surface membranes causing no harm but inhibit pathogenic bacteria.
5
Q
What is lysosome most effective against and how does it work?
A
Gram positive
Cleaves bonds between the sugars in peptidoglycan:
N-acetylglucosamine
N-acetylmuramic acid
6
Q
What are antimocrobrial peptides (3 forms)?
A
Defensin
Cathelicidins
Histatins
7
Q
What is a zymogen?
A
Inactive form of an enzyme usually needs proteolytic cleavage to become active
8
Q
Defensins?
A
Amphipathic Meaning they have hydrophilic and hydrophobic portions allowing them to insert into exposed lipid membranes forming a pore.
9
Q
Cathelicidins?
A
Amphipathic cause membrane disruption (LL-37)
10
Q
Histatins?
A
Produced by parotid gland, they are histadine (type of amino acid) rich and have antifungal properties.
11
Q
Which is faster the innate or adaptive?
A
Innate (mins hours)
Adaptive (days/weeks)
12
Q
How does the inmate arm recognise pathogens?
A
They recognise common foreign structures, it’s not pathogen specific.
This is encoded in the DNA
13
Q
How does the adaptive recognise pathogens?
A
Random generation of recognition improving the recognition. These receptors are not encoded in DNA but memory cells are formed for years
14
Q
When did the adaptive immune system form?
A
In the agnathans recent in evolutionary terms
15
Q
How is the compliment system so rapid?
A
Lots of zymogens are already made and in the blood and just need to be cleaved in a reaction cascade amplifying the response
16
Q
What are the three compliment system activation pathways?
A
Lectin pathway
Classical pathway
Alternative pathway
17
Q
What is the classical pathway
A
C1 complex interacts with pathogen surface and leads to the generation of C3 convertase activity which converts C3 into 2 products
18
Q
What is the alternative pathway?
A
C3 undergoes spontaneous hydrologists leading to the deposition of C3 convertase onto a cells surface.
19
Q
What is the lectin pathway?
A
Mannose binding lectin bonds to pathogen surface creating cascade leading to C3 convetase activity.
20
Q
What do all the compliment pathways do?
A
Activate C3 convertase, which cleaves C3 leaving C3b bound to microbe surface and releasing C3a
21
Q
What do C3a and C3B do
A
Mediate the release of C5a and C5b from the cutting of C5
22
Q
What do C3a and C5a do?
A
the recruit phagocytise cells at infection sites and promote swelling
23
Q
What does C3b do?
A
It is bound to the pathogen surface and it causes pathogens with a C3b receptor to engulf and destroy the pathogen
24
Q
What does C5b do?
A
Forms a complex with C6, C7, C8 which recruits lots of C9 molecules which join together and punch a hole in the cell membrane causing it to be lysed. MAC (membrane attack complex)
MAC also stands for macrophage depending on context
25
Lysosomes are more effective at gram positive because?
Gram posative don’t have an extra lipid layer meaning in gram positive the peptidoglycan layer is more accessible
26
Where do all immune cells come from?
Hamatapoetic bone marrow cells because immune cells are in the blood
(Pluripotent)
27
What do luckocytes mean?
All of the white blood cells
28
What cells make up the adaptive immune system?
T cells and B cells and there derivatives
29
What cells are part of the innate immune system?
```
NK cells
Dendritic Cells
Granulocytes
Macrophages
Mast cells
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30
Where are macrophages found what do they do (monocytes->macrophage)?
Immature monocytes circulate in the blood macrophages are found in sub mucosal layers
They have a long life span and are phagocytic (kill infected/dead cells and clear debris)
Present antigen to T cells and induce immune cells
31
What do granulocytes (specifically neutrophils) do?
They are in the blood and move to infection sites. They are phagocytic bactericidal numerous and have a short life span. Contain lots of vesicles with deadly enzymes.
Puss is mainly neutrophils
32
What are dendritic cells?
They are immature under surface epithelium in organs. When they take up antigen they move to lymph nodes and mature. Here they digest antigen and present it to adaptive immune cells and kick start active immune system.
33
What are natural killer cells (NK)?
In the blood move to tumours and infection sites. That are lymphocytes but are considered part of the inmate arm. They release toxic material extra cellulary killing pathogens and our own cells that are mutated.
34
What are opsonins?
Flags pinned on things suggesting it needs to be digested in phagocytosis
35
What are pattern recognition receptors (PRRs)?
These recognise pathogen associated molecular patterns
36
What are Fc receptors?
They recognise antibody molecule (self molecules) saying this needs to be engulfed.
37
What are the 3 pattern recognition receptors? What do they do?
Lectin like detectin 1
Scavenger receptors
Toll like receptors
They recognise particular structures (broad range)
38
How does phagocytosis work?
Compliment receptor 1 recognised C3b and then this binds to the receptor. Endocytosis of the bacterium forming a membrane bound vesicle which fuses withy lysosome forming phagolysosome
39
What are toll like receptors (TLRs)?
There are 10 human one and the each recognise a specific characteristic. Not all are expressed in cell surface some intracellulary which help detect viral infection. They trigger expression of antimocrobrial peptides and cytokines.
40
How do macrophages kill bacteria?
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Acid
Toxic oxygen derived products
Toxic nitrogen oxides
Peptides
Lysosome
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41
How do neutrophils destroy bacteria?
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Acid
Toxic oxygen products
Nitric oxide
Defensins
Lysosomes
Lactoferrin (binds iron ions)
```
42
What is a cytokine?
A small protein that affects the behaviour of other types of cell (only if the cell has the correct receptor).
43
What is a chemokine?
A small protein that stimulates the migration and activation of cells
44
What releases cytokines and chemokines? What do they do at infection site?
Macrophages
Change blood vessel permeability And diameter (increase) allowing neutrophils and plasma to exit.
Additionally it can clot micro vessels to stop infection spreading
45
What is colonal expansion and deletion?
T and B cell binds to antigen and then multiples then once pathogen removes they delete and produce memory cells
46
How do we ensure that antigen cells aren’t created that attack self cells?
When developing in the bone marrow of the bind to a cell here then they die via apoptosis because they know it’s a self cell
47
What do B cells mature into
Plasma cells and memory cells
48
What is the T cell receptor and how is it different to the B cell receptor?
B cell is antigen bound to surface T cell is a more specific receptor and will only bind to the antigen if it is coupled with a major histocompatability complex
49
What is an epitope?
(Antigenic determinant) this is the actual part of the antigen that binds to the antibody
50
What is a continuous/linear epitope?
Fragment of polypeptide chain one amino acid after another
51
What is a conformational/discontinuous epitope?
Binds to amino acids at different points in the protein
52
What epitopes do B cells recognise?
Surface antigens
53
What do T cells recognise
Epitopes buries writhing antigen structure presented by MHC molecule
54
What is a multivalent antigen?
Has more than one epitope
55
How many pollypeptides is an antibody made from?
Heavy chains and light chains 2 of each so 4 chains in total held together by 4 disulpide bonds.
56
What regions does and anybody have?
Variable and constant regions
57
What drains does a light chain have?
1 variable and 1 constant
58
What regions does a heavy chain have?
1 variable and 3 constant
59
What is affinity?
Strength of binding of one molecule to another
60
What is avidity
The sum total strength of two molecules binding at multiple sites
61
What does papain digestion produce?
2 Fab fragments and an Fc fragment
62
What does pepsin digestion produce?
One F(ab)2 fragment and peptide fragments
63
What are the two different types of antibody light chain in humans?
```
K and (upside down Y)
Any particular antibody will have one or the other of these chains in its structure
Ratio 2:1 K:Y
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64
What are the different sub types of heavy chains and what do they create (classes of antibody)
IgG IgA IgM IgD IgE
65
What is the immunoglobulin fold?
This is a loop on the heavy and light chains
Light - 2
Heavy - 3
They are made of 2 anti parallel beta pleated sheets held together by a disulphides bond. The b strand is linked by flexible loops allowing strands to change direction
66
what is a complementary determine region?
These are regions ( 3 in heavy and 3 in the light) 12 total. They are located at the tip of the Fab fragment in the loop and combine from the heavy and light chain to make he antigen binding site
67
Where is the antigen binding site
N terminal domains of heavy and light chains
68
What alter antigen antibody binding affinity?
Salt concentration
Detergents
pH
Epitope concentration
69
What is neutralisation?
They block the antibody from interacting with cells and our body
Opsonisation= coating pathogen with antibody
Phagocytes recognise Fc region triggering phagocytosis
70
What does trim 21 do?
This is and Intracellular receptor that detects anyibody that will be bound to a virus that the recruits proteozome to digest the virus
71
What is the estimated number of antibodies we can make?
4 x 10 to the 11
72
What is germline diversity?
This is the idea that there are multiple choices for each gene
73
What is combinational diversity
That the segments are randomly selected and brought together in different combinations
74
What gene fragments are the heavy and light chains made of?
Variable joining constant - light
| Variable diversity joining and constant - heavy
75
How is the light chain rearranged?
L and J brought together by somatic recombination in DNA.
| The VJ is only brought to the C segment in splicing of the mRNA.
76
How is the heavy chain rearranged?
Somatic recombination 1 D and J brought together
Somatic recombination 2 the V and DJ segment brought together.
Then after splicing the VDJ is brought to the C.
77
What is a leader sequence
This guides the protein to where it needs to be for example presentation or secretion
78
What is the 12 23 rule
Recombinant signal sequences have a heptomer and nonomer seperated by 12 or 23 base pairs. Genes will only combine of one has the 12 and the other has the 23 RSS. So it’s like complimentary pairing.
The number of base pairs corresponds to turns in the DNA helix
79
What are p nucleotides
Nucleotides that are already in the sequence
80
What are n nucleotides
Ew ones that are added by TDT
81
What is the problem with junctions diversity
Lots of cutting and joining and adding of nucleotides this can cause lots of problems like frameshift if it’s not done in multiples of 3
82
What are primary immunodeficiency
Fault in enzyme used in antibody production.
83
What is allelic exclusion
This is the process where the regulation DNA rearrangement is controlled selecting different alleles if a non functional protein is produced
84
Explain the steps in allelic exclusion
1. DJ rearrangement
2 V-DJ rearrangement on chromosome 1 if unsuccessful then in chromosome 2 if unsuccessful again cell dies. Successful heavy chain expressed in cell surface.
3. Heavy chain on cell surface causes recombinase (RAG) enzymes expression switch off to stop heavy chain rearrangement and creates survival signal.
4. Rearranging of the Kappa gene on first chromosome. Then second chromosome. Lander light chain on chromosome one. Then chromosome 2. If successful RAG 1&2 switched off. If not cell dies.
85
In pre B cells we create self reactive molecules what happens to these?
If the Pre B cells bind to host cell at multiple sites in the bone marrow then the B cell kills it’s self.
86
What happens if the immature B cell binds to little soluble host antigen.
Doesn’t die but become Anergic (unresponsive) so that it’s less dangerous
87
When and where are the different types of antibody produced
All antibody classes are produced by the same cell with the same specificities just a different antibody type as well as secreted and transmembrane forms
88
How is it decided if the antibody is hydrophilic or hydrophobic?
Alternative splicing if carboxy exons
Hydrophilic (secretory)
Hydrophobic (trans membrane domains)
89
IgM?
```
First made
Pentamer form increasing avidity
Present in blood but not tissues
Activated compliment strongly
Does not have hinge so less flexibility
```
90
IgD
Made first with IgM we don’t know what it does
91
IgG
Principle antibody in the blood and extra cellular fluids
It’s in our tissues
Activated compliment
It can be transported across placenta
92
IgE
Offers defence against multicellular parasites. It causes allergy by binding to mast cells causing sneezing vomiting etc
93
IgA
Very important in epithelial surfaces and in secretions
It’s monomeric or dimeric
It neutralises and can be secreted in breast milk
94
How does IgG cross the placental barrier
They bind to FcRn causes endocytosis and then exocytosis into the baby
95
How are B cells activated
T Independent antigens which activate B cells without help from T cells. it engages lots of B cell receptors.
T dependant antigens used with T cells providing 2 signals.
1. Signal 1 antigen binding inter globulin in BCR causing antigen digestion and then the antigen is presented
2. Then the complimentary helper T cell will bind then the T cell will release cytokines (interleukins) and CD40 to the B cell causing B cell proliferation
96
What is linked recognition
The B cell presents and the T cell binds to different epitopes of the same antigen so they are physically associated
97
What is a cognate T cell
A T cell that is primed for the same antigen (deferent epitope)
98
Where do the B cells go (primary focus)?
The lymphnode via blood stream to encounter antigen in the follicle and then gets the complimentary T cell to help to male a little bit of antibody quickly in the first 5 days.
99
What is the germinal centre reaction?
Goes on for 3-4 weeks post infection where stromal cells secrete chemokines causing B cells to stay put.
Point mutations occult in Ig V regions increasing affinity of these different B cells with variable affinity for the same antigen. They all compete to bind the antigen provided by follicular dendritic cells.
100
What is somatic hypermututation
Triggered by AID enzymes (activation induced cytosine deaminaze) when DNA is transcribed AID swaps C for u (base) causing DNA repair to correct this alteration and this is less accurate because not always the correct base is put back. This increases affinity so the best most effective B cells become memory cells. Hence why secondary response is better.
101
What is class switching?
This is the same antibody is produced in different classes. The HC VDJ region is combined wit any HC C region. Transcription or C exams opens DNA allowing AID to repair recombination machinery
102
What’s a hybridoma
Immortal cell line
103
How are monoclonal antibodies produced?
Immortal cell and B cell fused to produce immortal B cell, best B cell made to produce loads of antibody
104
What is the ELISA test
Identifies specific protein and it’s concentration
105
SDS/PAGE/western blotting/immunoblotting
Identifies specific protein estimates it’s molecular size and quantity
106
Immunohistochemistry/immunocytochemistry
Research and diagnostic technique
107
Flow cytometry and FACS
Detects expression of molecules by cells in suspension allowing identification of different cell types in different samples
108
Where do T cells mature
Thymus
109
Where do T cells circulate
Thymus blood lymph node then blood agaiN
| T cell primes if it finds it’s antigen
110
What is a T cell receptor
Like and antibody but not an antibody similar to a Fab fragment with only one binding site
That can only bind to antigen when it is processed and combined with an MHC complex
111
What is CD3
This complexes with the T cell receptor and senses when a T cell receptor has bound to antigen and tells this to the rest of the cell
112
What is CD8
Found in cytotoxic T cells
| Goes MHC1
113
What is CD4
```
Found in helper T cells ramp up macrophage activity and kill resistant bacteria
Pairs MHC class 2
```
114
How are TCR genes rearranged
Rag proteins perform V(D)J somatic recombination guided by 12/23 rule and have hypervariable regions
115
What is the structure of a T cell receptor
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Antigen binding site
Constant region
Variable region
Cytoplasmic tail
Carbohydrate
```
116
What is the MHC complex majour histocompatibility complex
Transmembrane glycoproteins
Variation in MHC lead to transplant graft rejection
I travel Lylas and extracellular antigen is presented with tissue type matching
117
What’s a the similarities and differences between MHC 1 and 2
Class 1
Binds and presents Intracellular antigen
Carried out by all cells but not red blood cells
Healthy host proteins won’t cause a response
Viruses within cell are non self am will cause response
Mutated tumour antigens won’t be recognised as self
Class 2
Binds extracellular antigen
Carried out by professional antigen presenting cells
Bacteria or products infested elicit response
118
What is the difference in structure of the MHC classes
Class 1 has microglobulin and has only 8-10 binding residues
Class 2 has 13 residues
119
How is class 1 antigen processed
1 viral protein cooped to peptides by enzymes
2 TAP transporter transport fragments across membrane
3class 1 MHC is being produced at the same time that large and small chains of the MHC molecule come together
4 the antigen binding groove binds to the small peptides viral or self
5 the Golgi apparatus then exports this to be presented for inspection of T cells
If the protein is host then it will be ignored this is the internal antigen thus it can only be viral presented
120
What is the MHC 2 activation pathway
Bacteria destroyed via phagocytosis
Endsomes chop antigen Into 10 amino acid length fragments
MHC 2 being created
To stop MHC 2 binding intracellular antigen the invariant chain is carriages with very high affinity for the MHC2 thus outcompete gets any other molecule
The class 2 MHC is in vesicle which fuses with another vesicle containing endosomes to destroy inveriant chain to clip molecules
This vesicle then fuses again with a extracellular peptide contain vesicle and a DM protein containing vesicle the DM binds CLIp and the MHC2 binds the extracellular protein
This is presented in macrophage membrane
Helper cell recognised this and created lymphokines causing good immuglobin supply
121
How are T cells primed
Naive T cells are make way to lymph node to T cell area. If there is no interaction it will exit and move to another lymph node
If it does then it will proliferate and undergo more maturation
T cells express interleukin 2 receptors (autochrine stimulatuon)
122
What are the 3 types of antigen presenting cells
Dendritic cells taking antigen from anywhere
Macrophages engulf and kill harbour pathogen and present
B cells
123
What do cytotoxic T lymphocytes do
Respond to MHC1
Forms immunoglobulin synapse sends cytotoxic granules toward cell
Forms a pore within membrane and granzyme B and others cause apoptosis
Same way NK cells kill
124
What’s positive selection and negative selection
Positive is survive signal
| Negative is suicide signal
125
What is a hypersensitivity reaction
Exaggerated reaction (not normal)
126
What’s a type 1 hypersensitivity reaction
Mediated by IgE
Soluble antigen picked up by dendritic cells priming an immune response
IgE bonds to mast cells via Fc region
Re exposure causes mast cell to degranulate releasing antihistamine
It’s immediate
127
What’s type 2 hypersensitivity reaction
Mediated by IgG cell specific can result in the activation of compliment phagocytic of NK cells
If the antigen is a cell surface receptor IgG will interrupt this by blocking it
128
What is type 3 hypersensitivity reaction
This is also mediated by IgG
It binds to soluble antigen to form complexes
Serum sickness is a type 2 hypersensitivity reaction this forms rash driver 7-10 days after antigen exposure
129
What’s a type 4 hypersensitivity reaction
This is a delayed type reaction
Mediated by effector T cells and cytotoxic T cells
Allergens are highly reactive molecules that bind to and alter host proteins
2 stages sensitisation and elicitation
130
What is an autoimmune disease
A disease in which the pathology is caused by and adaptive response to self antigens
It can occur when tissue damage exceeds repair
They can be systemic or organ specific
131
What factors lead to an autoimmune diseases
Genetic susceptibility
Tolerance breakdown
Infection/ environmental exposures
132
Give an example of a site specific autoimmune disease
| Systemic autoimmune disease
Type 1 diabetics
| Arthritis
133
What type is diabetes
What type is arthritis
What type is heart valve scarring
4
3
2
134
What is he difference between HIV 1&2
1 causes most AIDS
| 2 is and endemic in west Africa
135
What is the structure of HIV
2 copies of RNA
Gp120 surface protein I fects cells with CD4
numerous copies of viral enzymes required for initial infection
The genome can be read in 3 reading frames
Long polypeptides cleaved to make multiple functional proteins
136
How is the virus replicated
```
Gp120 binds CD4
RNA converted to cDNA by viral enzymes
cDNA interstates into human genome by integrase
Viral genes made by host
Multiple viruses made
```
137
How does HIV kill CD4 positive cells
Direct killing by overwhelming
Apoptosis chance increased
Cytotoxic T cells will kill the jnfected cells
138
How does HIV escape elimination by the immune system
CD4 T cells are the ones that fight the infection
The antibodies produce do not bind well to intact virus particles of infected cells
HIV rapidly mutates
139
How do HIV drugs work/not work
The only work in combination because soon HIV mutates to resist one drug hence a combination needs to be taken
Post exposure prophylaxis reverse transcriptase inhibitors viral protease inhibitors
Fusion and entry inhibitors
140
What is the HIV and saliva problem
There is some in saline probably from GCF
HIV is rarely transmissible by saliva
Saliva contain anti HIV factors as well
Mucins and leukocyte protiase inhibitor produces by saliva stops HIV access
