Host Responses to Microbial Infection Flashcards
1
Q
Definition
the second branch of immunological tolerance, after central tolerance. It takes place in the immune periphery (after T and B cells egress from primary lymphoid organs). Its main purpose is to ensure that self-reactive T and B cells which escaped central tolerance do not cause autoimmune disease.
A
Peripheral tolerance
2
Q
The _________ is a multimolecular cytoplasmic protease
A
The proteosome is a multimolecular cytoplasmic protease
3
Q
Triggering PRR can lead to Type ___ interferon production
A
Triggering PRR can lead to Type I interferon production
4
Q
Define
Scavenger receptors
A
receptors on macrophages and other cells that bind to numerous ligands, such as bacterial cell-wall components, and remove them from the blood
5
Q
What is the name of the region of the MHC that the peptide sits?
A
Peptide-binding cleft
6
Q
What are B-cell receptors composed of?
A
2 identical heavy chains and 2 identical light chains
7
Q
Definition
one of three complement pathways that opsonize and kill pathogens. The pathway is triggered when the C3b protein directly binds a microbe
A
Alternative pathway
8
Q
Which cells can display cross presentation? Why does it occur?
A
Only occurs in some highly specialised dendritic cell populations and it is thought to be criticaclly important in initiating CD8 T cell responses
9
Q
What type of cells can Type I interferons activate?
A
NK cells
Dendritic cells
10
Q
Definition
T cell with CD8 receptor that recognizes antigens on the surface of a virus-infected cell and binds to the infected cell and kill it
A
CD8+ T-cell
11
Q
What are the two types of lymphocytes?
A
T-cells
B-cells
12
Q
What is the main Nod-like receptor that recognises bacterial and viral DNA and RNA?
A
NLRP3
13
Q
What does triggering PRR do to T cell immunity?
A
- Increases MHC expression and promotes antigen presentation
- Increases costimulation
- Promotes cytokine production
14
Q
Where are adaptive immune responses initiated?
A
Initiated by dendritic cells in the secondary lymphoid organs (nodes and spleen)
15
Q
Concerning B cell responses:
Select one:
a. IFNg drives switching to some subclasses of IgG
b. The isotype first secreted by B cells is high affinity IgM
c. All B cell responses require T cell help
d. Cytokine secretion by T cells is sufficient to drive isotype switching
A
Concerning B cell responses:
Select one:
a. IFNg drives switching to some subclasses of IgG
b. The isotype first secreted by B cells is high affinity IgM
c. All B cell responses require T cell help
d. Cytokine secretion by T cells is sufficient to drive isotype switching
16
Q
True or False:
Antigen receptors are not germline encoded
A
True
17
Q
Define
Alternative pathway
A
one of three complement pathways that opsonize and kill pathogens. The pathway is triggered when the C3b protein directly binds a microbe
18
Q
Which protein families are PRRs encoded by?
A
Toll-like receptors (TLR)
Lectins
Scavenger receptors
NOD-like receptors
RIG-like helicases
19
Q
What do CD4 cells differentiate into?
A
Thelper cells
20
Q
Definition
conserved molecular structures produced by microorganisms and recognized as foreign by the receptors of the innate immune system
A
Pathogen associated molecular patterns (PAMPs)
21
Q
How are peptides displayed on MHC I?
A
- Cellular proteins are degraded in the cytoplasm by the proteasome
- Peptides are pumped into the endoplasmic reticulum by TAP, where the bind to class I MHC
- Class I MHC/peptide is then transported to the cell surface
22
Q
Define
Chemokines
A
a family of small cytokines, or signaling proteins secreted by cells. Their name is derived from their ability to induce directed chemotaxis in nearby responsive cells
23
Q
Define
Ubiquitin
A
a compound found in living cells which plays a role in the degradation of defective and superfluous proteins. It is a single-chain polypeptide
24
Q
What does IL-12 do in the inflammatory response?
A
Activates NK cells
Induces the differentiation of CD4 T cells into Thelper cells
25
What are the three types of antigen presenting cells?
Dendritic cell
Macrophage
B lymphocyte
26
# Definition
a heterogeneous group of immune cells that mediate the cellular immune response by processing and presenting antigens for recognition by certain lymphocytes such as T cells
Antigen presenting cells (APC)
27
# Definition
A substance that is produced by a predecessor protein or in response to the presence of foreign material in the body and that triggers or participates in a complement reaction
Complement
28
# Define
Mannose binding lectin
a lectin that is instrumental in innate immunity as an opsonin and via the lectin pathway
29
# Definition
a biochemical process in the blood that helps or 'complements' cells of the immune system to eliminate invading pathogens
Complement cascade
30
# Definition
a colourless cell which circulates in the blood and body fluids and is involved in counteracting foreign substances and disease; a white (blood) cell. There are several types, all amoeboid cells with a nucleus, including lymphocytes, granulocytes, and monocytes
Leukocytes
31
Which complement(s) are responsible for opsonisation and phagocytosis?
C3b
32
# Definition
A protein that transports a peptide from the cytoplasm into the lumen of the endoplasmic reticulum
TAP
33
What determines the specificity of MHC molecules?
The amino acids in MHC that contact the peptides determine precisely which peptide an MHC molecule can present
34
Which complement protein is the most potent?
C5a
35
# Definition
a type of cascade reaction in the complement system, similar in structure to the classical complement pathway, in that, after activation, it proceeds through the action of C4 and C2 to produce activated complement proteins further down the cascade
Lectin pathway
36
How many different PRRs does a single innate immune cell express?
Many
37
Which region of the MHC does alleleic variation occur?
Peptide-binding region
38
# Definition
the process of eliminating any developing T or B lymphocytes that are reactive to self. Through elimination of autoreactive lymphocytes, tolerance ensures that the immune system does not attack self peptides
Central tolerance
39
What happens in the Alternative pathway?
C3 is activated and binds directly to the pathogen surface (via a chemical reaction) - non-specific
40
# Define
TAP
A protein that transports a peptide from the cytoplasm into the lumen of the endoplasmic reticulum
41
# Define
Leukocytes
a colourless cell which circulates in the blood and body fluids and is involved in counteracting foreign substances and disease; a white (blood) cell. There are several types, all amoeboid cells with a nucleus, including lymphocytes, granulocytes, and monocytes
42
# Definition
the process by which T cells and B cells randomly assemble different gene segments – known as variable, diversity and joining genes – in order to generate unique receptors (known as antigen receptors) that can collectively recognize many different types of molecule
VDJ recombination
43
What are the adhesion molecules that allow leukocytes to stably ashere?
Integrins
44
# Define
Pathogen associated molecular patterns (PAMPs)
conserved molecular structures produced by microorganisms and recognized as foreign by the receptors of the innate immune system
45
# Definition
one of two primary classes of major histocompatibility complex (MHC) molecules and are found on the cell surface of all nucleated cells in the bodies of jawed vertebrates. They also occur on platelets, but not on red blood cells.
MHC I
46
# Definition
any of a number of substances, such as interferon, interleukin, and growth factors, which are secreted by certain cells of the immune system and have an effect on other cells
Cytokines
47
What are the two major types of MHC?
Class I
Class II
48
# Define
CD8+ T-cell
T cell with CD8 receptor that recognizes antigens on the surface of a virus-infected cell and binds to the infected cell and kill it
49
True or False:
MHC is expressed co-dominantly
True
50
# Definition
an interleukin that is naturally produced by dendritic cells, macrophages, neutrophils, and human B-lymphoblastoid cells (NC-37) in response to antigenic stimulation
IL12
51
# Define
IL6
an interleukin that acts as both a pro-inflammatory cytokine and an anti-inflammatory myokine
52
What are the first blood cell to arrive at the site of infection?
Neutrophils
53
What are the key features of the adaptive immune system?
Specificity
* Immunity to a particular antigen due to:
* Specific antigen receptors on T and B cells
* Specificity of antibody molecules and effector T cells
Diversity
* Extremely large number of lymphocyte clones, each with a particular antigen specificity
* At least 109 distinct antigenic determinants can be recognised
Discrimination between self and non-self
* Normally immune receptors are to foreign antigens and not to self antigens
* Self-tolerance is established during development of the immune system
Memory
* Primary and secondary immune responses
* Secondary immune response is always greater in magnitude
Self-regulation
* Immune responses are self-limiting
* Antigen cleared from the system
* Lymphocyte lifespan
* Feedback mechanisms
54
What does activation of PRR lead to in innate immune cells?
* Inflammatory response
* Type I interferon production
* The oxidative burst
55
The T-cell receptor recognised peptide antigen presented by what?
MHC
56
# Definition
One of a group of related proteins made by leukocytes (white blood cells) and other cells in the body. Made mainly by macrophages, and helps the lymphocytes fight infections.
IL-1β
57
MHC I tends to display *intracellular/extracellular* peptides
MHC I tends to display **intracellular** peptides
58
What are the 2 major types of T lymphocyte?
CD4+ T-cells
CD8+ T-cells
59
True or False:
MHC is the same in everyone
False
MHC is highly polymorphic
60
How are peptides displayed on MHC II?
* Extracellular proteins are endocytosed/phagocytosed
* Proteins are degraded by the lysosome
* MHC class II is generated in the ER, in association with the invariant chain MIIC vesicle
* MHC vesicles fuse with endo/lysosomes, peptides are loaded onto Class II in MIIC vesicles
* MHC II/peptide is exported to the cell surface
61
How many alleles of classical MHC class II molecules does an activated human dendritic cell typically express?
Select one:
a. 4: HLA-A, HLA-B, HLA-C, HLA-D
b. 6: 2 alleles of HLA-DP, 2 alleles of HLA-DQ, 2 alleles of HLA-DR
c. 3: HLA-DP, HLA-DQ, HLA-DR.
d. 1: HLA-class II
How many alleles of classical MHC class II molecules does an activated human dendritic cell typically express?
Select one:
a. 4: HLA-A, HLA-B, HLA-C, HLA-D
**b. 6: 2 alleles of HLA-DP, 2 alleles of HLA-DQ, 2 alleles of HLA-DR**
c. 3: HLA-DP, HLA-DQ, HLA-DR.
d. 1: HLA-class II
62
# Define
Cytokines
any of a number of substances, such as interferon, interleukin, and growth factors, which are secreted by certain cells of the immune system and have an effect on other cells
63
# Define
B-cell
a lymphocyte not processed by the thymus gland, and responsible for producing antibodies
64
# Define
Lectin pathway
a type of cascade reaction in the complement system, similar in structure to the classical complement pathway, in that, after activation, it proceeds through the action of C4 and C2 to produce activated complement proteins further down the cascade
65
# Definition
adhesion molecules that allow leukocytes to stably adhere
Integrins
66
The adaptive immune system works via ______ selection
The adaptive immune system works via **clonal** selection
67
# Definition
A type of immune cell that is one of the first cell types to travel to the site of an infection
Neutrophil
68
# Definition
antigen-presenting cells(also known as accessory cells) of the mammalian immune system. Their main function is to process antigen material and present it on the cell surface to the T cells of the immune system. They act as messengers between the innate and the adaptive immune systems.
Dendritic cell
69
# Define
Mast cell
a cell filled with basophil granules, found in numbers in connective tissue and releasing histamine and other substances during inflammatory and allergic reactions.
70
# Definition
a lymphocyte of a type produced or processed by the thymus gland and actively participating in the immune response.
T-cell
71
# Definition
a cell signaling protein (cytokine) involved in systemic inflammation and is one of the cytokines that make up the acute phase reaction.
TNFα
72
What 3 signals from antigen presenting cells are needed by T-cells?
1. Antigen + MHC
2. Costimulation (CD80 and CD86)
3. Cytokines to differentiate T cells into effector cells
73
# Define
Complement
A substance that is produced by a predecessor protein or in response to the presence of foreign material in the body and that triggers or participates in a complement reaction
74
What happens in the Classical pathway?
C3 is activated by antibody (IgM and IgG) bound to antigen
75
How many receptor types does each lymphocyte have?
One
76
When is self-tolerance developed?
During development of the immune system
77
# Define
Integrins
adhesion molecules that allow leukocytes to stably adhere
78
# Definition
a class of proteins that play a key role in the innate immune system. They are single, membrane-spanning, non-catalytic receptors usually expressed on sentinel cells such as macrophages and dendritic cells, that recognize structurally conserved molecules derived from microbes
Toll-like receptors
79
What are the characteristics of activated/mature dendritic cells?
* Low phagocytosis
* High MHC II (high Ag presentation)
* High co-stimulation
80
What happens in the Lectin pathway?
C3 is activated by mannose binding lectin (a soluble recognition receptro found in serum) that binds to mannose residues found exclusively on surface glycoproteins of microbes
81
What are Type I interferons?
Cytokines with potent antiviral activity
82
Which parts of microbes can be recognised by Toll-like receptors?
Diacyl lipopeptides
Triacyl lipopeptides
Flagella
LPS
CpG DNA
ssRNA
dsRNA
83
Dendritic cells activated by _______ migrate from the periphery to \_\_\_\_\_\_\_\_\_
Dendritic cells activated by **PAMPs** migrate from the periphery to **draining lymph node**
84
What are the Type I interferons?
IFNα
IFNβ
85
What is required for an NK cell to kill another cell?
Activation of their activation receptor (stress ligand receptor)
No activation of their inhibitory receptor (indicates no MHC I present)
86
What does IL-1 do in the inflammatory response?
Activates vascular endothelium
Activates lympocytes
Local tissue destruction
Increased access of effector cells
Leads to fever
Leads to production of IL-6
87
# Define
Toll-like receptors
a class of proteins that play a key role in the innate immune system. They are single, membrane-spanning, non-catalytic receptors usually expressed on sentinel cells such as macrophages and dendritic cells, that recognize structurally conserved molecules derived from microbes
88
# Define
Macrophage
a large phagocytic cell found in stationary form in the tissues or as a mobile white blood cell, especially at sites of infection.
89
# Define
NOD-like receptors
a group of pattern recognition receptors that are expressed in the cell cytosol. They can sense molecules that are associated with infection (for example, bacterial peptidoglycans) and induce inflammatory immune responses that help clear the infection
90
What is TAP?
An ATP-dependent peptide pump that is embedded in the ER membrane an pumps peptides from the cytoplasm to the lumen of the ER
91
What are the two major branches of the immune syste?
Innate and adaptive
92
# Define
Lymphocytes
a form of small leucocyte (white blood cell) with a single round nucleus, occurring especially in the lymphatic system
93
What pro-inflammatory cytokines and chemokines are involved in the inflammatory response?
Cytokines: IL-1, IL-6, TNF-α, IL-12
Chemokines: CXCL8
94
What does TNF-α do in the inflammatory response?
Activates vascular endothelium
Increases vascular permeability which leads to increased entry of IgG, complement and cells to tissues and increase fluid drainage to lymph node
Leads to fever
Leads to mobilisation of metabolites
Can lead to shock
95
# Define
Natural Killer (NK) cells
a lymphocyte able to bind to certain tumour cells and virus-infected cells without the stimulation of antigens, and kill them by the insertion of granules containing perforin
96
97
# Define
RIG-like helicases
a type of intracellular pattern recognition receptor involved in the recognition of viruses by the innate immune system
98
# Define
Dendritic cell
antigen-presenting cells(also known as accessory cells) of the mammalian immune system. Their main function is to process antigen material and present it on the cell surface to the T cells of the immune system. They act as messengers between the innate and the adaptive immune systems.
99
# Definition
a cell filled with basophil granules, found in numbers in connective tissue and releasing histamine and other substances during inflammatory and allergic reactions.
Mast cell
100
Why is there an evolutionary advantage for offspring to have diversity in MHC?
To protect from disease
101
Which cells express MHC class II?
Antigen presenting cells
102
# Define
TNFα
a cell signaling protein (cytokine) involved in systemic inflammation and is one of the cytokines that make up the acute phase reaction.
103
# Define
MHC I
one of two primary classes of major histocompatibility complex (MHC) molecules and are found on the cell surface of all nucleated cells in the bodies of jawed vertebrates. They also occur on platelets, but not on red blood cells.
104
Why is MHC a major barrier to transplantation?
The immune system recognised allogeneic MHC as foreign
105
NK cells can kill stressed/infected cells that lose expression of \_\_\_\_\_\_\_\_
NK cells can kill stressed/infected cells that lose expression of MHC I
106
Which cells express MHC class I?
All nucleated cells (so not blood cells)
107
Only _________ cells can initated the adaptive immune response
Only **dendritic** cells can initated the adaptive immune response
108
What chemicals are used to kill microbes that have been phagocytosed?
ROS, NO and lysosomal enzymes
109
# Definition
a form of small leucocyte (white blood cell) with a single round nucleus, occurring especially in the lymphatic system
Lymphocytes
110
Which complement(s) are responsible for lysis of microbe?
C6-9
111
# Definition
an interleukin that acts as both a pro-inflammatory cytokine and an anti-inflammatory myokine
IL6
112
# Definition
a type of intracellular pattern recognition receptor involved in the recognition of viruses by the innate immune system
RIG-like helicases
113
What is CD4?
CD4 is a cell surface molecule that can bind, in a peptide independent manner, to MHC class II
114
What does CXCL8 do in the inflammatory response?
Chemotactic factor recruits neutrophils, basophils and T cells to site of infection
115
# Define
CD4+ T-cell
cells that help coordinate the immune response by stimulating other immune cells, such as macrophages, B lymphocytes(B cells), and CD8 T lymphocytes (CD8 cells), to fight infection
116
What do T-cells and B-cells recognise?
T-cells recognise peptide antigen presented by MHC
B-cells (antibody) recognises free antigens
117
Started onWednesday, 4 September 2019, 12:42 AM
StateFinished
Completed onWednesday, 4 September 2019, 12:44 AM
Time taken1 min 39 secs
Grade2.00 out of 4.00 (50%)
Question 1
Incorrect
Mark 0.00 out of 1.00
Question text
Pattern Recognition Receptor(s):
Select one:
a. Are generated by recombination of V, D and J gene segments during lymphocyte development
b. Signalling leads to increased phagocytosis, pro-inflammatory cytokine production, activation of the vascular epithelium and increased co-stimulatory activity by antigen presenting cells
c. Are cell surface membrane proteins that recognise Pathogen Associated Molecular Patterns (PAMPs) shared by pathogens
d. Recognise pathogens non-specifically
Feedback
Your answer is incorrect.
The correct answer is: Signalling leads to increased phagocytosis, pro-inflammatory cytokine production, activation of the vascular epithelium and increased co-stimulatory activity by antigen presenting cells
Question 2
Correct
Mark 1.00 out of 1.00
Question text
How many alleles of classical MHC class II molecules does an activated human dendritic cell typically express?
Select one:
a. 4: HLA-A, HLA-B, HLA-C, HLA-D
b. 6: 2 alleles of HLA-DP, 2 alleles of HLA-DQ, 2 alleles of HLA-DR
c. 3: HLA-DP, HLA-DQ, HLA-DR.
d. 1: HLA-class II
Feedback
Your answer is correct.
The correct answer is: 6: 2 alleles of HLA-DP, 2 alleles of HLA-DQ, 2 alleles of HLA-DR
Question 3
Incorrect
Mark 0.00 out of 1.00
Question text
Which one of the following statements about IgG is true?
Select one:
a. It is a low avidity and high affinity antibody isotype.
b. Greater levels are found in serum in week one post-infection relative to week three.
c. It is the only isotype found on the surface of B cells.
d. It is a potent trigger of anaphylaxis
Started onWednesday, 4 September 2019, 12:42 AM
StateFinished
Completed onWednesday, 4 September 2019, 12:44 AM
Time taken1 min 39 secs
Grade2.00 out of 4.00 (50%)
Question 1
Incorrect
Mark 0.00 out of 1.00
Question text
Pattern Recognition Receptor(s):
Select one:
a. Are generated by recombination of V, D and J gene segments during lymphocyte development
b. Signalling leads to increased phagocytosis, pro-inflammatory cytokine production, activation of the vascular epithelium and increased co-stimulatory activity by antigen presenting cells
c. Are cell surface membrane proteins that recognise Pathogen Associated Molecular Patterns (PAMPs) shared by pathogens
d. Recognise pathogens non-specifically
Feedback
Your answer is incorrect.
The correct answer is: Signalling leads to increased phagocytosis, pro-inflammatory cytokine production, activation of the vascular epithelium and increased co-stimulatory activity by antigen presenting cells
Question 2
Correct
Mark 1.00 out of 1.00
Question text
How many alleles of classical MHC class II molecules does an activated human dendritic cell typically express?
Select one:
a. 4: HLA-A, HLA-B, HLA-C, HLA-D
b. 6: 2 alleles of HLA-DP, 2 alleles of HLA-DQ, 2 alleles of HLA-DR
c. 3: HLA-DP, HLA-DQ, HLA-DR.
d. 1: HLA-class II
Feedback
Your answer is correct.
The correct answer is: 6: 2 alleles of HLA-DP, 2 alleles of HLA-DQ, 2 alleles of HLA-DR
Question 3
Incorrect
Mark 0.00 out of 1.00
Question text
Which one of the following statements about IgG is true?
Select one:
**a. It is a low avidity and high affinity antibody isotype.**
b. Greater levels are found in serum in week one post-infection relative to week three.
c. It is the only isotype found on the surface of B cells.
d. It is a potent trigger of anaphylaxis
118
True or False:
The innate immune system is non-specific
False
The innate immune system can distinguish between diacyl and triacyl lipopeptides
119
# Define
Lectins
any of a class of proteins, chiefly of plant origin, which bind specifically to certain sugars and so cause agglutination of particular cell types
120
# Define
T-cell
a lymphocyte of a type produced or processed by the thymus gland and actively participating in the immune response.
121
What are T-cell receptors composed of?
An alpha and a beta chain
122
What are the immunological consequences of complement activation?
Inflammation (leukocyte recruitment), opsonisation (phagocytosis) and bacterial lysis
123
# Define
IL12
an interleukin that is naturally produced by dendritic cells, macrophages, neutrophils, and human B-lymphoblastoid cells (NC-37) in response to antigenic stimulation
124
# Definition
a cytokine that provides one of the first lines of host defense against virus infection and can rapidly protect cell culture against infection by all FMDV serotypes
Type I interferon
125
Triggering PRR activates the oxidative burst in \_\_\_\_\_\_\_\_\_
Triggering PRR activates the oxidative burst in **phagocytes**
126
# Definition
adhesion molecules that allow leukocytes to roll on the vascular endothelium
Selectins
127
What receptors do NK cells have?
* Activated receptors that recognise stress ligands on infected cells
* Inhibitory receptors that recognise MHC I
128
How do innate immune cells recognised pathogens as foreign?
Pattern recognition receptors (PRR) recognise structures shared by many microbes
129
# Define
Type I interferon
a cytokine that provides one of the first lines of host defense against virus infection and can rapidly protect cell culture against infection by all FMDV serotypes
130
Why is the invariant chain essential in MHC II antigen processing?
* The invariant chain blocks the peptide binding groove in the ER lumen (to prevent MHC II binding endogenous peptide)
* It directs MHC II to the MIIC vesicles, here it is degraded to form CLIP peptide which continues to block the groove
* CLIP is exchanged for exogenous peptides, a reaction catalysed by HLA-DM
131
# Definition
a lymphocyte able to bind to certain tumour cells and virus-infected cells without the stimulation of antigens, and kill them by the insertion of granules containing perforin
Natural Killer (NK) cells
132
# Definition
any of a class of proteins, chiefly of plant origin, which bind specifically to certain sugars and so cause agglutination of particular cell types
Lectins
133
# Define
Antigen presenting cells (APC)
a heterogeneous group of immune cells that mediate the cellular immune response by processing and presenting antigens for recognition by certain lymphocytes such as T cells
134
# Define
MHC II
a class of major histocompatibility complex (MHC) molecules normally found only on professional antigen-presenting cells such as dendritic cells, mononuclear phagocytes, some endothelial cells, thymic epithelial cells, and B cells. These cells are important in initiating immune responses.
135
# Define
Selectins
adhesion molecules that allow leukocytes to roll on the vascular endothelium
136
What molecules allow leukocytes to roll on the vascular endothelium?
Selectins
137
# Definition
a chemokine produced by macrophages and other cell types such as epithelial cells, airway smooth muscle cells and endothelial cells
CXCL8
138
# Define
Peripheral tolerance
the second branch of immunological tolerance, after central tolerance. It takes place in the immune periphery (after T and B cells egress from primary lymphoid organs). Its main purpose is to ensure that self-reactive T and B cells which escaped central tolerance do not cause autoimmune disease.
139
Proteins targeted for destruction are conjugated with which small protein?
Ubiquitin
140
Why is extreme MHC diversity important?
To make sure that all viral proteins can be displayed
141
MHC II tend to display *intracellular/extracellular* peptide
MHC II tend to display **extracellular** peptide
142
# Definition
a lectin that is instrumental in innate immunity as an opsonin and via the lectin pathway
Mannose binding lectin
143
# Definition
The primary pathway in the innate immune system, consisting of the activation of complement by an antigen-antibody complex
Classical pathway
144
How is complement activated?
Complement is activated in 3 ways:
* Alternative pathway
* Lectin pathway
* Classical pathway
145
Pattern Recognition Receptor(s):
Select one:
a. Are generated by recombination of V, D and J gene segments during lymphocyte development
b. Signalling leads to increased phagocytosis, pro-inflammatory cytokine production, activation of the vascular epithelium and increased co-stimulatory activity by antigen presenting cells
c. Are cell surface membrane proteins that recognise Pathogen Associated Molecular Patterns (PAMPs) shared by pathogens
d. Recognise pathogens non-specifically
Pattern Recognition Receptor(s):
Select one:
a. Are generated by recombination of V, D and J gene segments during lymphocyte development
**b. Signalling leads to increased phagocytosis, pro-inflammatory cytokine production, activation of the vascular epithelium and increased co-stimulatory activity by antigen presenting cells**
c. Are cell surface membrane proteins that recognise Pathogen Associated Molecular Patterns (PAMPs) shared by pathogens
d. Recognise pathogens non-specifically
146
What costimulatory molecules are displayed by antigen presenting cells?
CD80 and CD86
147
# Definition
membrane-bound vesicles, formed via a complex family of processes collectively known as endocytosis, and found in the cytoplasm of virtually every animal cell
Endosomes
148
What does IL-6 do in the inflammatory response?
Lymphocyte activation
Increased antibody production
Leads to fever
Induces acute-phase protein production
149
# Definition
a family of small cytokines, or signaling proteins secreted by cells. Their name is derived from their ability to induce directed chemotaxis in nearby responsive cells
Chemokines
150
# Definition
cells that help coordinate the immune response by stimulating other immune cells, such as macrophages, B lymphocytes(B cells), and CD8 T lymphocytes (CD8 cells), to fight infection
CD4+ T-cell
151
CD8+ T-cells recognised class __ MHC
CD8+ T-cells recognised class **I** MHC
152
Which of the branches of the immune system is essential early in infection?
Innate immune system
153
# Define
Endosomes
membrane-bound vesicles, formed via a complex family of processes collectively known as endocytosis, and found in the cytoplasm of virtually every animal cell
154
CD4+ T-cells recognised class __ MHC
CD4+ T-cells recognised class **II** MHC
155
What is cell mediated immunity?
The form of adaptive immunity that is mediated by T lymphcytes
156
Which complement(s) is responsible for initial inflammation?
C3a
157
# Definition
play a key role in the innate immune response by recognizing conserved pathogen associated molecular patterns(PAMPs) which are unique to each pathogen, and are essential molecular structures required for the pathogens survival.
Pattern Recognition Receptors (PRR)
158
# Definition
a lymphocyte not processed by the thymus gland, and responsible for producing antibodies
B-cell
159
What do CD8 cell differentiate into?
Cytotoxic T-cells
160
# Define
Complement cascade
a biochemical process in the blood that helps or 'complements' cells of the immune system to eliminate invading pathogens
161
# Definition
a large phagocytic cell found in stationary form in the tissues or as a mobile white blood cell, especially at sites of infection.
Macrophage
162
# Define
Neutrophil
A type of immune cell that is one of the first cell types to travel to the site of an infection
163
# Define
IL-1β
One of a group of related proteins made by leukocytes (white blood cells) and other cells in the body. Made mainly by macrophages, and helps the lymphocytes fight infections.
164
How many major class I and major class II genes are there?
3 Major class I genes: HLA-A, HLA-B and HLA-C
3 Major class II genes: HLA-DP, HLA-DQ and HLA-DR
165
What are the characteristics of quiescent/immature dendritic cells?
* Highly phagocytic
* Low MHC II (low Ag-presentation)
* Low co-stimulation
166
How many different major MHC genes do we each express?
12
Maternal: class I x 3 + class II x 3
Paternal: class I x 3 + class II x 3
167
# Define
Classical pathway
The primary pathway in the innate immune system, consisting of the activation of complement by an antigen-antibody complex
168
# Definition
a class of major histocompatibility complex (MHC) molecules normally found only on professional antigen-presenting cells such as dendritic cells, mononuclear phagocytes, some endothelial cells, thymic epithelial cells, and B cells. These cells are important in initiating immune responses.
MHC II
169
Which complement(s) are resonsible for late inflammation?
C5a
170
Where in the cell can PRRs be expressed?
Cell surface, endosomes and in the cytoplasm
171
# Define
Central tolerance
the process of eliminating any developing T or B lymphocytes that are reactive to self. Through elimination of autoreactive lymphocytes, tolerance ensures that the immune system does not attack self peptides
172
# Define
VDJ recombination
the process by which T cells and B cells randomly assemble different gene segments – known as variable, diversity and joining genes – in order to generate unique receptors (known as antigen receptors) that can collectively recognize many different types of molecule
173
What is CD8?
CD8 is a cell surface molecule that can bind to MHC class I in a peptide independent manner
174
What are the two types of tolerance developed to self-cells?
Central tolerance: self reactive lymphocytes are deleted during development in the thymus or bone marrow
Peripheral tolerance: Some self-reactive lymphocytes escape deletion. Peripheral tolerance mechanism keeps them in check
175
# Definition
receptors on macrophages and other cells that bind to numerous ligands, such as bacterial cell-wall components, and remove them from the blood
Scavenger receptors
176
# Define
Pattern Recognition Receptors (PRR)
play a key role in the innate immune response by recognizing conserved pathogen associated molecular patterns(PAMPs) which are unique to each pathogen, and are essential molecular structures required for the pathogens survival.
177
True or False:
PRR undergo VDJ recombination
False
They are germline encoded
178
How does triggering PRR lead to an inflammatory response?
* Bacteria trigger macrophages to release cytokines and chemokines
* Vasodilation and increased vascular permeability cause redness, heat and swelling
* Inflammatory cells migrate into tissue, releasing inflmmatory mediators that cause pain
179
Why is the secondary immune response always greater in magnitude?
Due to memory T and B cells generated during first contact with antigen
180
What type of protein are most complement? What does this allow?
Many complement proteins are proteases which cleave one another sequentially to form the complement cascade
181
How many hypervariable loops come together to form the antigen binding site?
6
182
# Definition
a group of pattern recognition receptors that are expressed in the cell cytosol. They can sense molecules that are associated with infection (for example, bacterial peptidoglycans) and induce inflammatory immune responses that help clear the infection
NOD-like receptors
183
# Define
CXCL8
a chemokine produced by macrophages and other cell types such as epithelial cells, airway smooth muscle cells and endothelial cells
184
What happens during costimulation?
* APC display costimulatory molecules CD80 and CD86 (B7.1 and B7.2)
* These interact with the T cell molecule CD28
* CD28 transduces signals (signal 2) that synergise with signal 1 and lead to T cell proliferation
185
# Definition
a compound found in living cells which plays a role in the degradation of defective and superfluous proteins. It is a single-chain polypeptide
Ubiquitin
186
What is crosspresentation?
* Crosspresentation is an exception to the MHC I/endogenous antigen, MHC II/exogenous antigen rule.
* Here exogenous antigen escapes the phagolysosome, and enters the cytoplasm
* It then enters the ER and therefore the class I pathway
187
# Define
Adaptive humoral mediated immunity
the form of adaptive immunity that is mediated by B lymphocytes
188
# Define
Granzymes
serine proteases released by cytoplasmic granules within cytotoxic T cells and natural killer (NK) cells. They induce programmed cell death (apoptosis) in the target cell, thus eliminating cells that have become cancerous or are infected with viruses or bacteria
189
# Define
IgA
an antibody that plays a crucial role in the immune function of mucous membranes
190
# Define
IgD
an antibody isotype that makes up about 1% of proteins in the plasma membranes of immature B-lymphocytes where it is usually co-expressed with another cell surface antibody called IgM
191
# Define
IgE
a type of antibody produced by the immune system. If you have an allergy, your immune system overreacts to an allergen by producing this antibody type
192
# Define
IgG
a type of antibody. Representing approximately 75% of serum antibodies in humans, it is the most common type of antibody found in blood circulation
193
# Define
IgM
one of several isotypes of antibody (also known as immunoglobulin) that are produced by vertebrates. It is the largest antibody, and it is the first antibody to appear in the response to initial exposure to an antigen
194
# Define
Opsonisation
the molecular mechanism whereby molecules, microbes, or apoptotic cells are chemically modified to have a stronger attraction to the cell surface receptors on phagocytes and NK cells
195
# Define
Perforin
a pore forming cytolytic protein found in the granules of cytotoxic T lymphocytes (CTLs) and Natural Killer cells (NK cells)
196
# Define
Plasma cells
white blood cells that originate in the bone marrow and secrete large quantities of proteins called antibodies in response to being presented specific substances called antigens
197
# Define
Th1
A type of T-helper cell that produce interferon-gamma, interleukin (IL)-2, and tumour necrosis factor (TNF)-beta, which activate macrophages and are responsible for cell-mediated immunity and phagocyte-dependent protective responses
198
# Define
Th17
play a critical role in the induction of the tissue inflammation and tissue destruction that are hallmarks of many immune-inflammatory diseases
199
# Define
Th2
A type of T-helper cell that produce IL-4, -5, -10, and -13 and help regulate humoral immune responses to extracellular parasites and bacterial infections
200
# Definition
the form of adaptive immunity that is mediated by B lymphocytes
Adaptive humoral mediated immunity
201
# Definition
serine proteases released by cytoplasmic granules within cytotoxic T cells and natural killer (NK) cells. They induce programmed cell death (apoptosis) in the target cell, thus eliminating cells that have become cancerous or are infected with viruses or bacteria
Granzymes
202
# Definition
an antibody that plays a crucial role in the immune function of mucous membranes
IgA
203
# Definition
an antibody isotype that makes up about 1% of proteins in the plasma membranes of immature B-lymphocytes where it is usually co-expressed with another cell surface antibody called IgM
IgD
204
# Definition
a type of antibody produced by the immune system. If you have an allergy, your immune system overreacts to an allergen by producing this antibody type
IgE
205
# Definition
a type of antibody. Representing approximately 75% of serum antibodies in humans, it is the most common type of antibody found in blood circulation
IgG
206
# Definition
one of several isotypes of antibody (also known as immunoglobulin) that are produced by vertebrates. It is the largest antibody, and it is the first antibody to appear in the response to initial exposure to an antigen
IgM
207
# Definition
the molecular mechanism whereby molecules, microbes, or apoptotic cells are chemically modified to have a stronger attraction to the cell surface receptors on phagocytes and NK cells
Opsonisation
208
# Definition
a pore forming cytolytic protein found in the granules of cytotoxic T lymphocytes (CTLs) and Natural Killer cells (NK cells)
Perforin
209
# Definition
white blood cells that originate in the bone marrow and secrete large quantities of proteins called antibodies in response to being presented specific substances called antigens
Plasma cells
210
# Definition
A type of T-helper cell that produce interferon-gamma, interleukin (IL)-2, and tumour necrosis factor (TNF)-beta, which activate macrophages and are responsible for cell-mediated immunity and phagocyte-dependent protective responses
Th1
211
# Definition
play a critical role in the induction of the tissue inflammation and tissue destruction that are hallmarks of many immune-inflammatory diseases
Th17
212
# Definition
A type of T-helper cell that produce IL-4, -5, -10, and -13 and help regulate humoral immune responses to extracellular parasites and bacterial infections
Th2
213
What do Th1 cells do?
Activate macrophages to kill intracellular bacteria
214
What do Th2 cells do?
Destroy helminths
215
What do Th17 cells do?
Mobilise neutrophils to kill rapidly proliferating extracellular bacteria
216
What three signals from antigen-presenting cells are required by T-cells?
1. Antigen + MHC
2. Costimulation (CD80 and CD86)
3. Cytokines to differentiate T-cells into effector cells
217
What do CD4+ cells do?
Activation of macrophages, B-cells and other cells
218
What do CD8+ cells do?
Killing of infected cells; macrophage activation
219
What are the major types of CD4 T-cells?
Th1
Th2
Th17
220
Which cytokines are produced by Th1 cells in response to intracellular pathogens?
IFNγ
221
Which cells are activated by the IFNγ released by Th1 cells?
Macrophages (mainly)
222
What is the role of Th1 cells in disease?
Autoimmunity
Chronic inflammation
223
Which cytokines are produced by Th2 cells in response to parasites?
IL-4
IL-5
IL-13
224
Which cells are activated by the IL-4, -5 and -13 produced by Th2 cells?
Eosinophils
225
What is the role of Th2 cells in disease?
Allergy
226
Which cytokines are produced by Th17 cells in response to extracellular pathogens?
IL-17
IL-22
227
Which cells are activated by the IL-17 and -22 produced by Th17 cells?
Neutrophils
228
Which CD4 cells are important for fighting bacteria and viruses?
Th1 and Th17 cells
229
Do CD4 T-cells recognise peptides displayed from MHC I or MHCII?
MHCII
230
Which categorie of interferon does IFNγ fit into?
Type II interferon
231
Which cytokines are required for the maturity of Th1 cells from Th0 precurosors?
IL-12
IFNγ
232
Which cytokines are required for the maturity of Th2 cells from Th0 precurosors?
IL-4
233
Which cytokines are required for the maturity of Th17 cells from Th0 precurosors?
TGFβ
IL-6
IL-23
IL-1β
234
Which cells produce the cytokines responsible for the differentiation of Th0 cells?
Dendritic cells (and other immune cells)
235
Early in an immune response, _________ are a source of IL-12 and ___________ a good source of IFNγ
Early in an immune response, **dendritic cells** are a source of IL-12 and **natural killer cells** a good source of IFNγ
236
Early in an immune response, ___________ and _____________ are a good source of IL-1, -6 -23 and TGFβ
Early in an immune response, **dendritic cells** and **macrophages** are a good source of IL-1, -6 -23 and TGFβ
237
Which cells have receptors for IFNγ? What does activation do?
Macrophages have receptors for IFNγ
IFNγ activates macrophages to become superb killers of intracellular microorganisms
238
What is the second way (other than IFNγ) that Th1 cells activate macrophages?
Th1 cells express CD40 ligands for which macrophages have a receptor for
239
What do macorphages do in response to activation from a Th1 cell?
Increase production of cytokines: TNFα, IL-1 and -12
This induces production of antimicrobial agents: NO and O2-
Increased expression of MHC and costimulatory molecules
240
How does the IL-17 produced by Th17 cells act indirectly to mobilise neutrophils?
* Acts directly on non-immune cells and causes them to secrete chemokines
* Chemokines attract and activate neutrophils
* Neutrophils phagocytose and kill rapidly growing extracellular bacteria
241
What does the IL-22 produced by Th17 cells do to epithelial cells?
Increases their integrity
242
Which molecule is responsible for mediating neutrophil rolling?
Selectins
243
How many types of CD8+ effector cells are there? List them
1
Cytotoxic T-lymphocyte
244
Cytotoxic T-lymphocytes recognise and destroy infected cells by ____________ \_\_\_\_\_\_\_\_\_\_\_
Cytotoxic T-lymphocytes recognise and destroy infected cells by **inducing apoptosis**
245
Which MHC do CTLs recognise?
Class I MHC
246
How do CTLs destroy infected cells?
The release cytotoxic granules towards the target cells that contains perforin and granzymes
247
What does perforin (released by CTLs) do?
Perforin enables the granzymes to enter the target cell
248
What do granzymes (released by CTLs) do?
Granzymes activate the target cells apoptotic pathways leading to cell death
249
What type of MHC does B-cells recognise?
Trick question ;)
No MHC is needed, they recognise free antibodies
250
What are activated B-cell called?
Plasma cells
251
What are the 5 types of Antibody isotypes?
IgM
IgD
IgG
IgE
IgA
252
How many types of antibody light chains are there?
2
λ and κ
253
What is the funciton of IgD?
Receptor of naive B-cells
Not secreted
Function obscure
254
What is the function of IgM?
Receptor of naive B-cells
Pentamer, hexamer
The first antibody secreted in the adaptive immune response
Low affinity
High avidity (10 antigen-binding sites!)
Best antibody at activating complement
255
Which antibody has low affinity but high avidity?
IgM
256
Which antibody is a pentamer?
IgM
257
What is the function of IgA?
2 subclasses
Major antibody in mucosal surfaces
258
Which antibody is a dimer?
IgA
259
What is the function of IgG?
4 subclasses
Major serum antibody
Fixes complement
Opsonisation
Meonatal immunity
260
What is teh function of IgE?
Specialised to fight helminths
Causes allergy
Interacts with mast cells, eosinophils and basophils
261
In what ways do antibodies fight infectious disease?
1. Nautralisation (only high affinity IgG and IgA)
2. Opsonisation (IgG and IgA; also IgM via complement)
3. Lysis (Only IgG and IgM)
262
What antibody is secreted from plasma cells if there is no help from other immune cells?
IgM
263
What antibody is secreted from plasma cells if there is T-cell help?
IgG
IgA
IgE
264
What is the first type of antibody produced in response to infection?
IgM
265
B-cells present antigens to T-cells on which type of MHC?
MHC II
266
T-cells stimulate B-cells with _______ and \_\_\_\_\_\_\_\_
T-cells stimulate B-cells with **CD40L** and **cytokines**
267
Which cytokine drives isotype switching to IgG?
IFNγ
268
Which cytokine drives isotype switching to IgE?
IL-4
269
Which cytokine drives isotype switching to IgA?
TGFβ
270
Which PRR are important for recognising viral PAMPs?
* Endosomal PRRs
* TLR-3, -7 and -9
* Cytoplasmic PRRs
* E.g. Rig-like helicases
271
Which type of IFN inhibits viral replicaiton?
Type I IFN
272
What is the role of Type I interferons in acquired immunity?
Type I IFNs inhibit viral replication
Type I IFNs also acitvate dendritic cells and NK cells
273
What do the activating and inhibitory receptors of NK cells recognise?
**Activating receptors:** stress ligands on infected cells
**Inhibitory receptors:** Class I MHC
274
MHC class I presentation is particularly important for which pathogen type?
Viruses
275
\_\_\_\_\_\_\_\_\_\_\_\_\_ are the principal cellular effector mechanism in anti-viral immunity
**Cytotoxic T-cells** are the principal cellular effector mechanism in anti-viral immunity
276
Which antibodies can block viral attachment and entry into cells?
IgA (mucosa)
IgG (blood)
277
Once a virus has entered a host cell, which immune cells are needed?
CTLs and NK cells
278
Which parts of the bacteria are commonly used as PAMPs?
Pili
Capsule
Cell wall
279
Which cytokine promotes Th1 differentiation and cytotoxic activity in CTLs and NK cells?
IL-12
280
What are some examples of bacteria that cause disease almost exclusively by the release of toxins?
Vibro cholerae
Corynebacterium diptheriae
Bordetella pertussis
Bacillus anthracis
281
How does Uropathogenic E. coli (UPEC) causes disease?
1. UPEC pili bind specifically to receptors expressed by the bladder epithelium
* Type 1 pili (FimH at the pilin tip) to bind to specific mannose-containing glycoproteins in the urinary tract
2. UPEC secrete toxins
3. After binding UPEC invade bladder epithelial cells
* FimH binds to integrins (an adhesion molecule)
282
The type of immunity effective against bacteria will vary with bacterial pathogenesis. What is important for extracellular microbes?
Humoral immunity plus Th17 cells are important for extracellular microbes
283
The type of immunity effective against bacteria will vary with bacterial pathogenesis. What is important for intracellular microbes?
Cellular immunity (Th1 cells and CTLs) are important for intracellular pathogens
284
Which type of Th cells are important against obligate intracellular organisms?
Th1 responses are important against obligate intracellular organisms
285
What changes induced in activated macrophages?
* Increased production of cytokines:
* TNF- , IL-1 (pro-inflammatory)
* IL-12, IFN-(Th1 differentiation)
* Production of antimicrobial agents such as lysosomal enzymes, NO, ROS
* Increased expression of MHC and costimulatory molecules
286
What type of immunity tends to be irrelevant for obligate intracellular organisms? Why?
Humoral immunity tends to be irrelevant for obligate intracellular organisms.
These organisms are rapidly phagocytosed via multiple receptors
Antibodies can’t penetrate cell membranes
287
Which cells are of critical importance for extracellular bacteria? Why?
Th17 cells are of critical importance for extracellular bacteria
Th17 cells secrete IL-17
IL-17 leads to the production of proinflammatory cytokines and chemokines; which leads to a rapid influx of neutrophils
288
Both ________ and ___________ are opsonins which can bind to the bacterial surface and make it more recognisable to phagocytes
Both **complement** and **antibody** are opsonins which can bind to the bacterial surface and make it more recognisable to phagocytes
289
What can high affinity antibodies do in response to bacterial infection?
High affinity antibodies can neutralise bacterial toxins
High affinity antibodies can prevent bacterial colonisation
290
291
Comparing the innate and adaptive immune systems:
Select one:
a. Innate immune cells express many different Pattern Recognition Receptors, Adaptive immune cells express an antigen receptor of unique specificity
b. Innate immune cells are all generated in the bone marrow, adaptive immune cells are all generated in the thymus
c. Innate immune responses generate memory that is essential in vaccination
d. Adaptive immune cells kill pathogens as they are highly phagocytic
Comparing the innate and adaptive immune systems:
Select one:
**a. Innate immune cells express many different Pattern Recognition Receptors, Adaptive immune cells express an antigen receptor of unique specificity**
b. Innate immune cells are all generated in the bone marrow, adaptive immune cells are all generated in the thymus
c. Innate immune responses generate memory that is essential in vaccination
d. Adaptive immune cells kill pathogens as they are highly phagocytic
292
How many alleles of classical MHC class II molecules does an activated human dendritic cell typically express?
Select one:
a. 6: 2 alleles of HLA-DP, 2 alleles of HLA-DQ, 2 alleles of HLA-DR
b. 3: HLA-DP, HLA-DQ, HLA-DR.
c. 1: HLA-class II
d. 4: HLA-A, HLA-B, HLA-C, HLA-D
How many alleles of classical MHC class II molecules does an activated human dendritic cell typically express?
Select one:
**a. 6: 2 alleles of HLA-DP, 2 alleles of HLA-DQ, 2 alleles of HLA-DR**
b. 3: HLA-DP, HLA-DQ, HLA-DR.
c. 1: HLA-class II
d. 4: HLA-A, HLA-B, HLA-C, HLA-D
293
Which one of the following statements about IgG is true?
Select one:
a. It is a low avidity and high affinity antibody isotype.
b. Greater levels are found in serum in week one post-infection relative to week three.
c. It is the only isotype found on the surface of B cells.
d. It is a potent trigger of anaphylaxis
Which one of the following statements about IgG is true?
Select one:
**a. It is a low avidity and high affinity antibody isotype.**
b. Greater levels are found in serum in week one post-infection relative to week three.
c. It is the only isotype found on the surface of B cells.
d. It is a potent trigger of anaphylaxis
294
Concerning B cell responses:
Select one:
a. The isotype first secreted by B cells is high affinity IgM
b. All B cell responses require T cell help
c. IFNg drives switching to some subclasses of IgG
d. Cytokine secretion by T cells is sufficient to drive isotype switching
Concerning B cell responses:
Select one:
a. The isotype first secreted by B cells is high affinity IgM
b. All B cell responses require T cell help
**c. IFNg drives switching to some subclasses of IgG**
d. Cytokine secretion by T cells is sufficient to drive isotype switching
