Host Responses to Microbial Infection Flashcards
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.
Peripheral tolerance
The _________ is a multimolecular cytoplasmic protease
The proteosome is a multimolecular cytoplasmic protease
Triggering PRR can lead to Type ___ interferon production
Triggering PRR can lead to Type I interferon production
Define
Scavenger receptors
receptors on macrophages and other cells that bind to numerous ligands, such as bacterial cell-wall components, and remove them from the blood
What is the name of the region of the MHC that the peptide sits?
Peptide-binding cleft
What are B-cell receptors composed of?
2 identical heavy chains and 2 identical light chains
Definition
one of three complement pathways that opsonize and kill pathogens. The pathway is triggered when the C3b protein directly binds a microbe
Alternative pathway
Which cells can display cross presentation? Why does it occur?
Only occurs in some highly specialised dendritic cell populations and it is thought to be criticaclly important in initiating CD8 T cell responses
What type of cells can Type I interferons activate?
NK cells
Dendritic cells
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
CD8+ T-cell
What are the two types of lymphocytes?
T-cells
B-cells
What is the main Nod-like receptor that recognises bacterial and viral DNA and RNA?
NLRP3
What does triggering PRR do to T cell immunity?
- Increases MHC expression and promotes antigen presentation
- Increases costimulation
- Promotes cytokine production
Where are adaptive immune responses initiated?
Initiated by dendritic cells in the secondary lymphoid organs (nodes and spleen)
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
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
True or False:
Antigen receptors are not germline encoded
True
Define
Alternative pathway
one of three complement pathways that opsonize and kill pathogens. The pathway is triggered when the C3b protein directly binds a microbe
Which protein families are PRRs encoded by?
Toll-like receptors (TLR)
Lectins
Scavenger receptors
NOD-like receptors
RIG-like helicases
What do CD4 cells differentiate into?
Thelper cells
Definition
conserved molecular structures produced by microorganisms and recognized as foreign by the receptors of the innate immune system
Pathogen associated molecular patterns (PAMPs)
How are peptides displayed on MHC I?
- 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
Define
Chemokines
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
Define
Ubiquitin
a compound found in living cells which plays a role in the degradation of defective and superfluous proteins. It is a single-chain polypeptide
What does IL-12 do in the inflammatory response?
Activates NK cells
Induces the differentiation of CD4 T cells into Thelper cells
What are the three types of antigen presenting cells?
Dendritic cell
Macrophage
B lymphocyte
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)
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
Define
Mannose binding lectin
a lectin that is instrumental in innate immunity as an opsonin and via the lectin pathway
Definition
a biochemical process in the blood that helps or ‘complements’ cells of the immune system to eliminate invading pathogens
Complement cascade
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
Which complement(s) are responsible for opsonisation and phagocytosis?
C3b
Definition
A protein that transports a peptide from the cytoplasm into the lumen of the endoplasmic reticulum
TAP
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
Which complement protein is the most potent?
C5a
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
How many different PRRs does a single innate immune cell express?
Many
Which region of the MHC does alleleic variation occur?
Peptide-binding region
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
What happens in the Alternative pathway?
C3 is activated and binds directly to the pathogen surface (via a chemical reaction) - non-specific
Define
TAP
A protein that transports a peptide from the cytoplasm into the lumen of the endoplasmic reticulum
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
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
What are the adhesion molecules that allow leukocytes to stably ashere?
Integrins
Define
Pathogen associated molecular patterns (PAMPs)
conserved molecular structures produced by microorganisms and recognized as foreign by the receptors of the innate immune system
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
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
What are the two major types of MHC?
Class I
Class II
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
True or False:
MHC is expressed co-dominantly
True
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
Define
IL6
an interleukin that acts as both a pro-inflammatory cytokine and an anti-inflammatory myokine
What are the first blood cell to arrive at the site of infection?
Neutrophils
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
What does activation of PRR lead to in innate immune cells?
- Inflammatory response
- Type I interferon production
- The oxidative burst
The T-cell receptor recognised peptide antigen presented by what?
MHC
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
MHC I tends to display intracellular/extracellular peptides
MHC I tends to display intracellular peptides
What are the 2 major types of T lymphocyte?
CD4+ T-cells
CD8+ T-cells
True or False:
MHC is the same in everyone
False
MHC is highly polymorphic
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
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
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
Define
B-cell
a lymphocyte not processed by the thymus gland, and responsible for producing antibodies
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
Definition
adhesion molecules that allow leukocytes to stably adhere
Integrins
The adaptive immune system works via ______ selection
The adaptive immune system works via clonal selection
Definition
A type of immune cell that is one of the first cell types to travel to the site of an infection
Neutrophil
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
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.
Definition
a lymphocyte of a type produced or processed by the thymus gland and actively participating in the immune response.
T-cell
Definition
a cell signaling protein (cytokine) involved in systemic inflammation and is one of the cytokines that make up the acute phase reaction.
TNFα
What 3 signals from antigen presenting cells are needed by T-cells?
- Antigen + MHC
- Costimulation (CD80 and CD86)
- Cytokines to differentiate T cells into effector cells
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
What happens in the Classical pathway?
C3 is activated by antibody (IgM and IgG) bound to antigen
How many receptor types does each lymphocyte have?
One
When is self-tolerance developed?
During development of the immune system
Define
Integrins
adhesion molecules that allow leukocytes to stably adhere
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
What are the characteristics of activated/mature dendritic cells?
- Low phagocytosis
- High MHC II (high Ag presentation)
- High co-stimulation
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
What are Type I interferons?
Cytokines with potent antiviral activity
Which parts of microbes can be recognised by Toll-like receptors?
Diacyl lipopeptides
Triacyl lipopeptides
Flagella
LPS
CpG DNA
ssRNA
dsRNA
Dendritic cells activated by _______ migrate from the periphery to _________
Dendritic cells activated by PAMPs migrate from the periphery to draining lymph node
What are the Type I interferons?
IFNα
IFNβ
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)
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
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
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.
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
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
What are the two major branches of the immune syste?
Innate and adaptive
Define
Lymphocytes
a form of small leucocyte (white blood cell) with a single round nucleus, occurring especially in the lymphatic system
What pro-inflammatory cytokines and chemokines are involved in the inflammatory response?
Cytokines: IL-1, IL-6, TNF-α, IL-12
Chemokines: CXCL8
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
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
Define
RIG-like helicases
a type of intracellular pattern recognition receptor involved in the recognition of viruses by the innate immune system
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.
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
Why is there an evolutionary advantage for offspring to have diversity in MHC?
To protect from disease
Which cells express MHC class II?
Antigen presenting cells
Define
TNFα
a cell signaling protein (cytokine) involved in systemic inflammation and is one of the cytokines that make up the acute phase reaction.
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.
Why is MHC a major barrier to transplantation?
The immune system recognised allogeneic MHC as foreign
NK cells can kill stressed/infected cells that lose expression of ________
NK cells can kill stressed/infected cells that lose expression of MHC I
Which cells express MHC class I?
All nucleated cells (so not blood cells)
Only _________ cells can initated the adaptive immune response
Only dendritic cells can initated the adaptive immune response
What chemicals are used to kill microbes that have been phagocytosed?
ROS, NO and lysosomal enzymes
Definition
a form of small leucocyte (white blood cell) with a single round nucleus, occurring especially in the lymphatic system
Lymphocytes
Which complement(s) are responsible for lysis of microbe?
C6-9
Definition
an interleukin that acts as both a pro-inflammatory cytokine and an anti-inflammatory myokine
IL6
Definition
a type of intracellular pattern recognition receptor involved in the recognition of viruses by the innate immune system
RIG-like helicases
What is CD4?
CD4 is a cell surface molecule that can bind, in a peptide independent manner, to MHC class II
What does CXCL8 do in the inflammatory response?
Chemotactic factor recruits neutrophils, basophils and T cells to site of infection
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
What do T-cells and B-cells recognise?
T-cells recognise peptide antigen presented by MHC
B-cells (antibody) recognises free antigens
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