Immunology Flashcards
1
Q
MHC class II molecules usually present peptides of what origin?
A
Exogenous
2
Q
Why can MHC class II molecules not bind to peptide in the ER?
A
A protein called the invariant chain in the MHC peptide-binding groove blocks peptides from binding
3
Q
Where are MHC class I and II molecules assembled?
A
Endoplasmic reticulum
4
Q
When is the invariant chain (protein blocking the MHC peptide-binding groove) degraded?
A
Following fusion with the endocytotic vesicle containing antigen
5
Q
What’s involved in antigen processing for MHC class I and II?
A
MHC class I: proteasome MHC class II: proteases within endocytic vesicle
6
Q
Where do MHC class I and II associate with its peptide fragment?
A
MHC class I: Within the ER MHC class II: Within endosomal vesicles
7
Q
MHC class I molecules usually present peptides of what origin?
A
Endogenous (microbial or self)
8
Q
Where are peptides produced from extracellular antigens/ pathogens?
A
Within enodcytic vesicle
9
Q
Where are peptides produced from viruses or intracytosolic bacteria?
A
Within cytosol
10
Q
What is sequence of class I antigen processing?
A
Endogenous antigen is degraded in cytosol by proteasome Peptides are translocated into the ER Peptides associate with MHC class I molecules within ER Peptide:MHC complexes move to cell surface
11
Q
What is sequence of class II antigen processing?
A
Exogenous antigen is taken up into cell via endocytic vesicles Antigen is degraded in endocytic vesicle by proteases (cathepsin L & S) MHC class II produced in ER transported in vesicle to & fuses with endosome Peptides associate with MHC class II molecules as invariant chain is degraded Peptide:MHC complexes move to cell surface
12
Q
What’s a CTL?
A
cytotoxic T lymphocyte
13
Q
Recognition of virally infected cells by CD8 killer T cells is dependent on what?
A
MHC class I
14
Q
What does CD8 bind to and what is CD8 expressed on?
A
CD8 binds to MCH class I CD8 expressed on cytotoxic T cells
15
Q
What does CD4 bind to and what is CD4 expressed on?
A
CD4 bind to MHC class II CD4 expressed on T helper cells
16
Q
What are Kupffer cells?
A
Phagocytic cell in liver that lines hepatic sinusoids
17
Q
How may extracellular antigens be presented by MHC class I molecules? And give an example
A
Cross presentation
e.g. Hepatitis C
18
Q
Why would CD4 T cells be expected to be generated in Hepatitis C? And why is this not the case?
A
Hepatitis C does not infect kupffer cells (macrophage-like cells of liver) - only infects hepatocytes Kupffer cells therefore acquire viral hepatitis C proteins by phagocytosis/ endocytosis of dying hepatocytes = pathway for MHC class II presentation generating CD4 T cells However cross presentation occurs and CD8 T cells are produced instead
19
Q
What is a dendritic cell?
What the difference between an immature and mature/ activated dendritic cell?
A
Dendritic cell: professional antigen presenting cell derived from bone marrow
Immature dendritic cell: take up and process antigens but cannot stimulate T cells
Mature dendritic cell: able to stimulate T cells, present in secondary lymphoid tissue
20
Q
Why are live attenuated vaccines the best way to achieve a cytotoxic T lymphocyte (CTL) response?
A
Only live viruses have capacity to replicate intracellularly Can be presented by MHC class I to CD8 T cells (which are cytotoxic T lymphocytes)
21
Q
What is the human leukocyte antigen (HLA) system?
A
Group of genes that encode cell surface antigen-presenting proteins
22
Q
Which HLA genes encode for MHC class I ?
A
HLA A, B and C
23
Q
Which HLA genes encode for MHC class II ?
A
HLA DP, DQ and DR
24
Q
Which cells are MHC class II molecules found on?
A
Immune cells e.g. dendritic cells, B cells, macrophages
25
Which cells are MHC class I molecules found on?
All nucleated cells
26
Name 3 professional antigen presenting cells
Conventional dendritic cells
B cells
Macrophages
27
What are the differences in structure between MHC class I and II molecules?
Class I: only 1 chain crosses the membrane, made of alpha 1, 2, 3 and beta 2 microglobulin domains
Class II: both/ 2 chains cross the membrane, made of alpha 1, 2 and beta 1, 2 domains
28
What do dendritic cells have that increase the chance of the antigen presented on its surface to come into contact with the antigen-specific T cell?
Dendrites that sweep large volumes of space
29
How do viruses prevent being killed by CTL/ cytotoxic T lymphocytes (express CD8)?
```
Viruses down regulate MHC class I molecules on infected cells
So not recognised by CD8 on CTL
```
30
If infected cells do not present MHC molecules on their surface, how are they disposed of?
Killed by natural killer cells
If there were MHC molecules on the cell, they would bind to inhibitory receptors on NK cells preventing them from killing the cell
31
1) What 2 things are required for activation of a naïve T cell?
2) Why is signal 1 alone not enough to activate T cells?
1) Antigen-specific signal
(T cell receptor and its co-receptor CD8/ 4 recognise the peptide:MHC class I/ II complex on the dendritic cell surface)
Co-stimulatory signal
(T-cell co-stimulatory receptor CD28 binds to the B7 co-stimulatory molecule expressed on the dendritic cell)
T cell receptor, CD8/4 and CD28 receptor on naive T cell
peptide:MHC complex and B7 molecule on dendritic cell
2) MHC groove is always filled with peptide e.g. from self proteins sometimes, so should insufficient to activate T cell
32
Once a CD8 T cell is activated, what trigger is required for it to kill cells?
```
Triggered by MHC class I presented on cell
(No need for co-stimulatory signal once activated)
```
33
Which cell is extremely efficient at stimulating naive T cells and why?
Dendritic cells - they express a high level of B7
34
How do natural killer cells and cytotoxic T cells kill target cells?
Release perforin and granzymes
| Causing apoptosis
35
What is the role of Fas within cytotoxic T cell action?
CTLs express Fas ligands on their surface
Which binds to Fas molecule on target cell membrane
Activating caspases = apoptosis
36
Which cells do naive CD4 T cells become which are most relevant to viral infection? What do they do and produce?
TH1 cells
Exit lymph node, go to site of infection and activate macrophages
Release IL-2 and IFN gamma
37
Which T cells remain within lymph nodes?
Follicular helper T cells
38
What is linked recognition?
B and T cells can interact as they recognise the same antigen
39
What type of MHC molecule do B cells express?
MHC class II
40
How do B cells presenting viral peptides on their MHC II molecules bind to helper T cells?
CD40 on B cells bind to CD40 ligand on TH cell
| Peptide:MHC II complex binds to T cell receptor
41
What sort of epitopes can B cells recognise?
| compared to T cells
Protein/ carbohydrate/ lipid/ nucleic acid
| T cells only recognise peptide epitopes
42
How do B cells undergo antibody isotype change to increase antibody affinity?
Class switching
| Somatic hyper-mutation
43
What type of viruses are the majority that infect humans?
RNA viruses
44
Name 3 sentinel cells
Macrophages
Dendritic cells
Natural killer cells
45
What are the molecular tripwires of the innate immune system?
Pattern recognition receptors
46
What do pattern recognition receptors (PRRs) recognise?
Pathogen-associated molecular patterns (PAMPs)
47
How are PRRs effective at detective viral infection?
Viral nucleic acids detected in cytosol - viruses use host's machinery for transcription, translation and replication
48
Name 2 important cytoplasmic pattern recognition receptors (PRRs)
RIG-1 like receptor
| MDA-5
49
What do RIG-1 like receptors (RLRs) bind to?
Unusual RNA: double stranded or mRNA without a cap on 5' end
This binding causes RLR to bind to MAVS (mitochondrial protein)
50
What does RLR binding to MAVS essentially cause?
Type I interferon expression
51
What do toll like receptors (TLRs) do?
Sense microbial products inside and outside human cells
52
Which toll like receptors (TLRs) are present on endosomes?
3, 7, 8 and 9
53
Which toll like receptors (TLRs) are present on plasma membranes?
1, 2, 4 and 5
54
Name 3 pyogenic (cause fever) cytokines
IL-6
IL-1beta
TNF-aplha
55
How long does immediate innate immunity last?
0-4 hours
56
Which defences are involved in immediate innate immunity?
Recognition and elimination by preformed soluble and resident effector molecules
Complement system
57
How long does induced innate immunity last?
4 hours to 4 days
58
Which defences are involved in induced innate immunity?
Recruitment of additional innate effector cells
| Inflammation, fever, acute response
59
Which TLRs respond to RNA viruses?
TLR 3, 7 and 8
60
Which TLRs respond to DNA viruses?
TLR 9
61
What recognises viruses at plasma membranes and endosomes?
Pattern recognition receptors (PRR)
62
Which toll-like receptors recognise viral glycoproteins?
TLR 1, 2 and 4
63
TLR signals lead to transcription of what?
Type I interferons alpha and beta
64
What can interferon response factors (IRFs) initiate once phosphorylated and entered the nucleus?
Initiate mRNA synthesis
65
Which cells are capable of producing Type I interferons alpha and beta?
Nearly all cells
66
What are 3 actions of interferon response?
Induce resistance to viral replication in all cells
Increase expression of ligands for receptors in NK cells
Activate NK cells to kill virus-infected cells
67
Why can naive T cells only be activated by professional antigen presenting cells?
Because only professional APCs have B7 for co-stimulatory signal
68
How does CMV (cytomegalovirus) try to block peptide entry to ER?
Inhibits peptide loading
69
How does TLR (toll like receptor) triggering relate to activation of naïve CD8 T cells?
TLR triggering leads to up regulation of co-stimulatory ligands B7 on dendritic cells
70
What if the T and B cell interacting recognise different epitopes of the viral particle?
As long as both epitopes are from the SAME COMPLEX this is fine
71
In hepatitis B infection, what order are the antibodies produced?
Core before surface
72
How can immunity against hepatitis B by vaccination be distinguished from by natural infection?
Natural infection: core antibodies present as well as surface
Vaccination only contains surface antigens so only surface antibodies present in blood afterwards
73
How can chronic hepatitis B infection be differentiated from acute?
Acute: IgM
Chronic: IgG
(core antibodies present in blood in both)
74
What are the 4 possibilities with the following serology results:
HBsAg - negative
anti-HBs - negative
anti-HBc - positive
Resolved infection - most common
False-positive anti-HBc
Low level chronic infection
Resolving acute infection
75
Where are the primary lymphoid tissues and what do they do?
Bone marrow and thymus
| Lymphocyte development and maturation occurs here
76
Where are the secondary lymphoid tissues and what do they do?
Lymph nodes, spleen and mucosal-associated lymphoid tissue
| Acquired immune responses initiated here
77
Why vaccinate asplenics and people with sickle cells disease and severe coeliac disease with pneumococcal conjugate vaccine?
sickle cells disease = functional asplenia
severe coeliac disease damages the spleen
asplenia = decreased clearance of encapsulated bacteria (e.g. Hib, E. coli, salmonella, pneumococcus, neisseria meningitidus) from bloodstream
APC migrate to spleen via bloodstream as no lymphatic supply - secondary lymphoid tissue
78
Which TLRs recognise single stranded viral RNA?
7 and 8
79
Which TLRs recognise double stranded viral RNA?
3
80
Which immunoglobulins are present in milk and can cross the placenta?
Milk - IgA
| Placenta - IgG
81
Explain generally how pattern recognition receptors (PRRs) work within the innate response
PRR detect PAMPs
Activates IRFs
that are phosphorylated and enter the nucleus
to cause interferon synthesis
Interferons binds to interferon receptors
Triggering transcription of hundreds of interferon stimulated genes (ISG)
82
What do interferon stimulated genes (ISGs) do?
Suppress:
Viral entry
Viral replication
Alter cellular metabolism to generate anti-viral state
83
What increases proteasome and macrophage efficiency?
IFN gamma
| released by NK cells
84
What is the primary role of conventional dendritic cells?
Activation of naïve T cells
85
What is the primary role of plasmacytoid dendritic cells?
Production of interferons upon virus exposure
86
What do plasmacytoid dendritic cells express high levels of and what does this allow?
TLR 7 and 9
| Detection of viral infection
87
What can be given for hep B and C viral infections?
Recombinant interferon a
88
Which cytokines activate natural killer cells?
Interferon alpha and beta
IL-12
TNF-alpha
89
What are the 3 waves of defence against viral infection?
1st: cytokines (IFN-alpha and beta, TNF-alpha ans IL-12)
2nd: natural killer cells
3rd: T-cells
90
When are cytokines/ NK cells/ T cells produced and when do their numbers peak during viral infection?
Cytokines until day 5, peak at day 2
Natural killer cells until day 6, peak at day 3
T-cells from day 2, peak at day 7
91
Why do subcutaneous and intramuscular injections produce good immune responses?
Both areas well served with conventional dendritic cells
| subcut more likely to trigger side effects
92
Why does injecting into the buttocks not produce a good immune response?
Adipose tissue poorly vascularised and poorly served by DCs
93
How do conventional dendritic cells transport antigens from infection site to the secondary lymphoid tissue?
TLR signalling
Causes CCR7 receptors to be expressed on DC
They bind to CCL21 (chemokine produced by lymphoid tissue)
So DC migrates to lymphoid tissue
Antigen presenting function also enhances
So activate naïve T cells in lymphoid tissue
94
How does CMV down regulate MHC class I?
Blocks peptide entry to ER
| Inhibiting peptide loading
95
Where are B cells stored?
Lymph node
| Migrate to bone marrow as plasma cells
96
What does Activation-Induced Cytidine Deaminase (AID) do?
Catalyses somatic hypermutation of Ig genes leading to affinity maturation of antibodies in B cells
Catalyses class switching of Ig constant regions leading to isotype-switching of antibodies
97
How is the complement system involved in immediate innate immune response?
Mannose-binding lectin is a PRR
98
How do the most pathogenic viruses prevent the body from entering an antiviral state?
Shut off interferon supply
99
When does the adaptive immune response take over? Which defences are involved in adaptive immunity?
```
From 4 days
Virus-reactive T and B Cells are
identified in draining lymph node,
proliferate and differentiate to
become effector cells
```
100
Which TLR do conventional dendritic cells express?
All but TLR 9
101
How does whooping cough infection prevent infected individuals from clearing their lungs leading to a cough?
Cytotoxin protein produced by B. Pertussis stops cilia from beating
102
What causes whooping cough?
Bordetella pertussis bacterium
103
What is the incubation period of whooping cough?
6-20 days
104
If the whole cell pertussis vaccine produces more efficient and longer lasting immunity than the acellular vaccine, why do we use the latter?
Whole cell vaccine is reactogenic (seizures, high fever and permanent brain damage (extremely rare)
105
When should mothers be injected with DTaP?
3rd trimester of each pregnancy
106
What is the incubation period for mumps?
15-24 days
107
How is mumps diagnosed?
Parotitis (90% of patients with symptomatic mumps have one or both swollen parotid glands) Anti-mumps specific IgM in the saliva 7 days after onset of parotid swelling
108
How are primary and secondary vaccine failures different?
Primary: no seroconversion after vaccination (no vaccine-specific antibody response)
Secondary: loss of immunity after seroconversion (memory waning).
109
What sort of diseases is herd immunity ineffective against?
Diseases that are not transmitted from person to person e.g. tetanus
110
What type of pathogen is Hib?
Facultatively anaerobic gram-negative bacterium (makes ATP by aerobic respiration if oxygen is available but capable of switching to anaerobic respiration if oxygen is unavailable)
111
Why is encapsulation a major cause of virulence?
Can prevent efficient complement fixation by the alternative pathway
Requires high affinity IgG to overcome encapsulation
112
What does Hib cause?
Pneumonia (not influenza)
Epiglottitis
Meningitis
113
How is Hib diagnosed?
Hib isolated from STERILE site (cerebrospinal fluid or blood)
as Hib is a commensal organism in the nasopharynx
114
What type of vaccine is Hib?
Conjugate
115
How do conjugate vaccines elicit a greater immune response?
Polysaccharides on their own elicit weak T-cell independent immune responses as only peptides stimulate TCR
Conjugate vaccines recognised by B and T cells
Ensures T cell help is made available
116
Which region of the MHC molecule does class switching affect?
Constant region of heavy chain
| does not change the VDJ region and the light chain so antigen specificity is maintained
117
Where is IgM found? Where is IgM produced?
Found circulating in blood and lymph
| Made principally by plasma cells resident in the lymph nodes, spleen and bone marrow
118
Which immunoglobulin is favoured for Hib immunity?
Hib is an encapsulated bacteria
| So IgG2 favoured as very effective at binding to the polysaccharide coats of encapsulated bacteria
119
What are examples of encapsulated bacteria?
```
Hib
E. Coli
Salmonella
Pneumococcus
Neisseria meningitidus
Klebsiella pneumoniae
```
120
Which HPV strains cause genital warts on the skin around the anus and vagina (low risk of cancer)?
HPV 6, 11
121
Which HPV strains cause cells in throat or cervix to undergo dysplasia making them more likely to become cancerous?
HPV 16, 18
122
What type of vaccines are diphtheria and tetanus?
Toxoid
123
What do IL-1 beta and TNF-alpha do?
Increase vascular permeability to allow effector cells to enter infected tissues
124
What does C reactive protein do?
Binds to pathogens
Acts as an opsonin
Triggering classical pathway of complement fixation in the absence of antibodies
125
What causes measles?
Morbillivirus of paramyxovirus family
126
What causes mumps?
Rubulavirus of paramyxovirus family
127
What causes rubella?
Rubivirus of togavirus family
