Innate Immune Defences & Inflammation 1 Flashcards
1
Q
What is Innate Immunity?
- … line of defence against infection
- Present at … and passed down …
- Occurs within … of … …
A
- First line of defence against infection
- Present at birth and passed down genetically
- Occurs within minutes of pathogen recognition
2
Q
… immunity is the first line of defence against infection
A
Innate immunity
3
Q
Innate Immunity is present at …
A
birth - passed down genetically
4
Q
How is innate immunity passed down?
A
genetically
5
Q
Innate immunity occurs within … of pathogen recognition
A
Innate immunity occurs within minutes of pathogen recognition
6
Q
The Innate Immune System is a … response
A
The Innate Immune System is a rapid response
7
Q
The Innate Immune System is a … response
A
The Innate Immune System is a rapid response
8
Q
Innate Immune Response - Immediate vs Induced Response
- The immediate innate immune response - … to … hours (pathogen recognised by preformed soluble effector molecules - pathogen can be eliminated and infection ends, mostly pathogen is not eliminated and will proceed with induced innate immune response)
- The induced innate immune repsonse - … hours to … days (activate cells in infected tissue - recruit effector cells to infected tissue - inflammation, fever etc)
A
- The immediate innate immune response - 0 to 4 hours (pathogen recognised by preformed soluble effector molecules - pathogen can be eliminated and infection ends, mostly pathogen is not eliminated and will proceed with induced innate immune response)
- The induced innate immune repsonse - 4 hours to 4 days (activate cells in infected tissue - recruit effector cells to infected tissue - inflammation, fever etc)
9
Q
Innate Immune Response - Immediate vs Induced Response
- The … innate immune response - 0 to 4 hours (pathogen recognised by preformed soluble effector molecules - pathogen can be eliminated and infection ends, mostly pathogen is not eliminated and will proceed with induced innate immune response)
- The … innate immune repsonse - 4 hours to 4 days (activate cells in infected tissue - recruit effector cells to infected tissue - inflammation, fever etc)
A
- The immediate innate immune response - 0 to 4 hours (pathogen recognised by preformed soluble effector molecules - pathogen can be eliminated and infection ends, mostly pathogen is not eliminated and will proceed with induced innate immune response)
- The induced innate immune repsonse - 4 hours to 4 days (activate cells in infected tissue - recruit effector cells to infected tissue - inflammation, fever etc)
10
Q
Innate Immune Response - Immediate vs Induced Response
- The immediate innate immune response - 0 to 4 hours (pathogen recognised by preformed … … molecules - pathogen can be eliminated and infection ends, mostly pathogen is not eliminated and will proceed with induced innate immune response)
- The induced innate immune repsonse - 4 hours to 4 days (activate cells in infected tissue - recruit … cells to infected tissue - inflammation, fever etc)
A
- The immediate innate immune response - 0 to 4 hours (pathogen recognised by preformed soluble effector molecules - pathogen can be eliminated and infection ends, mostly pathogen is not eliminated and will proceed with induced innate immune response)
- The induced innate immune repsonse - 4 hours to 4 days (activate cells in infected tissue - recruit effector cells to infected tissue - inflammation, fever etc)
11
Q
Innate Immune Response - Immediate vs Induced Response
- The immediate innate immune response - … to … hours (pathogen recognised by preformed soluble effector molecules - pathogen can be eliminated and infection ends, mostly pathogen is not eliminated and will proceed with induced innate immune response)
- The induced innate immune repsonse - … hours to … … (activate cells in infected tissue - recruit effector cells to infected tissue - inflammation, fever etc)
A
- The immediate innate immune response - 0 to 4 hours (pathogen recognised by preformed soluble effector molecules - pathogen can be eliminated and infection ends, mostly pathogen is not eliminated and will proceed with induced innate immune response)
- The induced innate immune repsonse - 4 hours to 4 days (activate cells in infected tissue - recruit effector cells to infected tissue - inflammation, fever etc)
12
Q
Characteristics of Innate Immunity
- … encoded - Inherited in …
- Expressed by all cells of a particular type - e.g macrophages
- Triggers … response
- Recognizes broad classes of pathogens
- Interacts with a range of molecular structures of a given type
- Does not encode in multiple gene segments
- Does not require gene rearrangement
- No Clonal distribution
- Able to discriminate between even closely related molecular structures
A
- Germline encoded - Inherited in genome
- Expressed by all cells of a particular type - e.g macrophages
- Triggers immediate response
- Recognizes broad classes of pathogens
- Interacts with a range of molecular structures of a given type
- Does not encode in multiple gene segments
- Does not require gene rearrangement
- No Clonal distribution
- Able to discriminate between even closely related molecular structures
13
Q
Characteristics of Innate Immunity
- Germline encoded - Inherited in genome
- Expressed by all cells of a particular type - e.g macrophages
- Triggers immediate response
- Recognizes … classes of pathogens
- Interacts with a … of molecular structures of a given type
- Does not encode in multiple gene segments
- Does not require gene rearrangement
- No Clonal distribution
- Able to discriminate between even closely related molecular structures
A
- Germline encoded - Inherited in genome
- Expressed by all cells of a particular type - e.g macrophages
- Triggers immediate response
- Recognizes broad classes of pathogens
- Interacts with a range of molecular structures of a given type
- Does not encode in multiple gene segments
- Does not require gene rearrangement
- No Clonal distribution
- Able to discriminate between even closely related molecular structures
14
Q
Characteristics of Innate Immunity
- Germline encoded - Inherited in genome
- Expressed by all cells of a particular type - e.g macrophages
- Triggers immediate response
- Recognizes broad classes of pathogens
- Interacts with a range of molecular structures of a given type
- Does not encode in multiple gene segments
- Does not require gene …
- No … distribution
- Able to discriminate between even closely related molecular structures
A
- Germline encoded - Inherited in genome
- Expressed by all cells of a particular type - e.g macrophages
- Triggers immediate response
- Recognizes broad classes of pathogens
- Interacts with a range of molecular structures of a given type
- Does not encode in multiple gene segments
- Does not require gene rearrangement
- No Clonal distribution
- Able to discriminate between even closely related molecular structures
15
Q
Characteristics of Innate Immunity
- Germline encoded - Inherited in genome
- Expressed by all cells of a particular type - e.g macrophages
- Triggers immediate response
- Recognizes broad classes of pathogens
- Interacts with a range of molecular structures of a given type
- Does not encode in multiple … …
- Does not require gene rearrangement
- No Clonal distribution
- Able to discriminate between even closely related molecular structures
A
- Germline encoded - Inherited in genome
- Expressed by all cells of a particular type - e.g macrophages
- Triggers immediate response
- Recognizes broad classes of pathogens
- Interacts with a range of molecular structures of a given type
- Does not encode in multiple gene segments
- Does not require gene rearrangement
- No Clonal distribution
- Able to discriminate between even closely related molecular structures
16
Q
Characteristics of Innate Immunity
- Germline encoded - Inherited in genome
- Expressed by all cells of a particular type - e.g macrophages
- Triggers … response
- Recognizes broad classes of pathogens
- Interacts with a range of molecular structures of a given type
- Does not encode in multiple gene segments
- Does not require gene rearrangement
- No Clonal distribution
- … to discriminate between even closely related molecular structures
A
- Germline encoded - Inherited in genome
- Expressed by all cells of a particular type - e.g macrophages
- Triggers immediate response
- Recognizes broad classes of pathogens
- Interacts with a range of molecular structures of a given type
- Does not encode in multiple gene segments
- Does not require gene rearrangement
- No Clonal distribution
- Able to discriminate between even closely related molecular structures
17
Q
Characteristics of Innate Immunity
- Germline encoded - Inherited in genome
- Expressed by all cells of a particular type - e.g macrophages
- Triggers immediate response
- Recognizes … classes of …
- Interacts with a range of … structures of a given type
- Does not encode in multiple gene segments
- Does not require gene rearrangement
- No Clonal distribution
- Able to discriminate between even closely related molecular structures
A
- Germline encoded - Inherited in genome
- Expressed by all cells of a particular type - e.g macrophages
- Triggers immediate response
- Recognizes broad classes of pathogens
- Interacts with a range of molecular structures of a given type
- Does not encode in multiple gene segments
- Does not require gene rearrangement
- No Clonal distribution
- Able to discriminate between even closely related molecular structures
18
Q
Innate Immune Memory (trained immunity)
- Conventional adaptive immune memory is present only in vertebrates, whereas innate immune memory is an ancient property of host defence present in plants, invertebrates and vertebrates
- Trained immunity occurs due to … modifications triggered by the initial infection.
A
- Conventional adaptive immune memory is present only in vertebrates, whereas innate immune memory is an ancient property of host defence present in plants, invertebrates and vertebrates
- Trained immunity occurs due to epigenetic modifications triggered by the initial infection.
19
Q
Innate Immune Memory (trained immunity)
- Conventional adaptive immune memory is present only in vertebrates, whereas innate immune memory is an ancient property of host defence present in plants, invertebrates and vertebrates
- Trained immunity occurs due to epigenetic modifications triggered by the … …
A
- Conventional adaptive immune memory is present only in vertebrates, whereas innate immune memory is an ancient property of host defence present in plants, invertebrates and vertebrates
- Trained immunity occurs due to epigenetic modifications triggered by the initial infection.
20
Q
Innate Barriers to Infection
- … barriers - skin, respiratory tract, gastrointestinal tract
- … barriers - Complement, Defensins, Collectins
- … barriers - Innate Immune cells, Pattern Recognition Receptors (PRRs), Interferon
A
- Physical barriers - skin, respiratory tract, gastrointestinal tract
- Soluble barriers - Complement, Defensins, Collectins
- Induced barriers - Innate Immune cells, Pattern Recognition Receptors (PRRs), Interferon
21
Q
Innate Barriers to Infection
- Physical barriers - skin, respiratory tract, gastrointestinal tract
- Soluble - …, Defensins, Collectins
- Induced - Innate Immune cells, Pattern Recognition Receptors (PRRs), I…
A
- Physical barriers - skin, respiratory tract, gastrointestinal tract
- Soluble - Complement, Defensins, Collectins
- Induced - Innate Immune cells, Pattern Recognition Receptors (PRRs), Interferon
22
Q
Innate Barriers to Infection
- Physical barriers - skin, respiratory tract, gastrointestinal tract
- Soluble - Complement, Defensins, Collectins
- Induced - Innate Immune cells, … … … (PRRs), Interferon
A
- Physical barriers - skin, respiratory tract, gastrointestinal tract
- Soluble - Complement, Defensins, Collectins
- Induced - Innate Immune cells, Pattern Recognition Receptors (PRRs), Interferon
23
Q
Innate Barriers to Infection
- Physical barriers - …, respiratory tract, gastrointestinal tract
- Soluble - Complement, …, Collectins
- Induced - Innate Immune cells, Pattern Recognition Receptors (PRRs), Interferon
A
- Physical barriers - skin, respiratory tract, gastrointestinal tract
- Soluble - Complement, Defensins, Collectins
- Induced - Innate Immune cells, Pattern Recognition Receptors (PRRs), Interferon
24
Q
Innate Barriers to Infection
- Physical barriers - skin, respiratory tract, gastrointestinal tract
- Soluble - Complement, Defensins, Collectins
- Induced - … … cells, Pattern Recognition Receptors (PRRs), Interferon
A
- Physical barriers - skin, respiratory tract, gastrointestinal tract
- Soluble - Complement, Defensins, Collectins
- Induced - Innate Immune cells, Pattern Recognition Receptors (PRRs), Interferon
25
Q
Innate Barriers to Infection
- Physical barriers - skin, respiratory tract, gastrointestinal tract
- Soluble - Complement, Defensins, …
- Induced - Innate Immune cells, Pattern Recognition Receptors (PRRs), Interferon
A
- Physical barriers - skin, respiratory tract, gastrointestinal tract
- Soluble - Complement, Defensins, Collectins
- Induced - Innate Immune cells, Pattern Recognition Receptors (PRRs), Interferon
26
Q
These are all examples of … barriers to infection
A
Innate barriers to infection
27
Q
These are all examples of … barriers to infection
A
Innate barriers to infection
28
Q
Anatomical Barriers to Infection
- Skin has a dense layer of dead … that act as a physical barrier.
- In the respiratory tract mucus traps micro-organisms (importance demonstrated by Cystic fibrosis). In the lower airways there are collectins in the … that can activate complement.
- In the gut, people unable to secrete sufficient gastric acid have a high risk of salmonella infection.
- In the airway and lungs, sneezing and coughing help to expel mucus, whilst macrophages in the alveoli of the lungs can ingest pathogens.
- The intestine is colonised with ‘good’ bacteria that form your microbiome.
A
- Skin has a dense layer of dead keratinocytes that act as a physical barrier.
- In the respiratory tract mucus traps micro-organisms (importance demonstrated by Cystic fibrosis). In the lower airways there are collectins in the surfactant that can activate complement.
- In the gut, people unable to secrete sufficient gastric acid have a high risk of salmonella infection.
- In the airway and lungs, sneezing and coughing help to expel mucus, whilst macrophages in the alveoli of the lungs can ingest pathogens.
- The intestine is colonised with ‘good’ bacteria that form your microbiome.
29
Q
Anatomical Barriers to Infection
- Skin has a dense layer of dead keratinocytes that act as a … barrier.
- In the respiratory tract mucus traps micro-organisms (importance demonstrated by Cystic fibrosis). In the lower airways there are collectins in the surfactant that can activate complement.
- In the gut, people unable to secrete sufficient gastric acid have a high risk of salmonella infection.
- In the airway and lungs, sneezing and coughing help to expel …, whilst macrophages in the alveoli of the lungs can ingest pathogens.
- The intestine is colonised with ‘good’ bacteria that form your microbiome.
A
- Skin has a dense layer of dead keratinocytes that act as a physical barrier.
- In the respiratory tract mucus traps micro-organisms (importance demonstrated by Cystic fibrosis). In the lower airways there are collectins in the surfactant that can activate complement.
- In the gut, people unable to secrete sufficient gastric acid have a high risk of salmonella infection.
- In the airway and lungs, sneezing and coughing help to expel mucus, whilst macrophages in the alveoli of the lungs can ingest pathogens.
- The intestine is colonised with ‘good’ bacteria that form your microbiome.
30
Q
Anatomical Barriers to Infection
- Skin has a dense layer of dead keratinocytes that act as a physical barrier.
- In the respiratory tract mucus traps micro-organisms (importance demonstrated by Cystic fibrosis). In the lower airways there are collectins in the surfactant that can activate …
- In the gut, people unable to secrete sufficient gastric acid have a high risk of … infection.
- In the airway and lungs, sneezing and coughing help to expel mucus, whilst macrophages in the alveoli of the lungs can ingest pathogens.
- The intestine is colonised with ‘good’ bacteria that form your microbiome.
A
- Skin has a dense layer of dead keratinocytes that act as a physical barrier.
- In the respiratory tract mucus traps micro-organisms (importance demonstrated by Cystic fibrosis). In the lower airways there are collectins in the surfactant that can activate complement.
- In the gut, people unable to secrete sufficient gastric acid have a high risk of salmonella infection.
- In the airway and lungs, sneezing and coughing help to expel mucus, whilst macrophages in the alveoli of the lungs can ingest pathogens.
- The intestine is colonised with ‘good’ bacteria that form your microbiome.
31
Q
Anatomical Barriers to Infection
- Skin has a dense layer of dead keratinocytes that act as a physical barrier.
- In the respiratory tract mucus traps micro-organisms (importance demonstrated by Cystic fibrosis). In the lower airways there are collectins in the surfactant that can activate complement.
- In the gut, people unable to secrete sufficient gastric acid have a high risk of salmonella infection.
- In the airway and lungs, sneezing and coughing help to expel mucus, whilst … in the alveoli of the lungs can ingest pathogens.
- The intestine is colonised with ‘good’ bacteria that form your …
A
- Skin has a dense layer of dead keratinocytes that act as a physical barrier.
- In the respiratory tract mucus traps micro-organisms (importance demonstrated by Cystic fibrosis). In the lower airways there are collectins in the surfactant that can activate complement.
- In the gut, people unable to secrete sufficient gastric acid have a high risk of salmonella infection.
- In the airway and lungs, sneezing and coughing help to expel mucus, whilst macrophages in the alveoli of the lungs can ingest pathogens.
- The intestine is colonised with ‘good’ bacteria that form your microbiome.
32
Q
Anatomical Barriers to Infection
- Skin has a dense layer of dead keratinocytes that act as a physical barrier.
- In the respiratory tract mucus traps micro-organisms (importance demonstrated by … …). In the lower airways there are collectins in the surfactant that can activate complement.
- In the gut, people unable to secrete sufficient gastric acid have a high risk of salmonella infection.
- In the airway and lungs, sneezing and coughing help to expel mucus, whilst macrophages in the alveoli of the lungs can ingest pathogens.
- The intestine is … with ‘good’ bacteria that form your microbiome.
A
- Skin has a dense layer of dead keratinocytes that act as a physical barrier.
- In the respiratory tract mucus traps micro-organisms (importance demonstrated by Cystic fibrosis). In the lower airways there are collectins in the surfactant that can activate complement.
- In the gut, people unable to secrete sufficient gastric acid have a high risk of salmonella infection.
- In the airway and lungs, sneezing and coughing help to expel mucus, whilst macrophages in the alveoli of the lungs can ingest pathogens.
- The intestine is colonised with ‘good’ bacteria that form your microbiome.
33
Q
Anatomical Barriers to Infection
- Skin has a dense layer of dead … that act as a physical barrier.
- In the respiratory tract mucus traps micro-organisms (importance demonstrated by Cystic fibrosis). In the lower airways there are … in the surfactant that can activate complement.
- In the gut, people unable to secrete sufficient gastric acid have a high risk of salmonella infection.
- In the airway and lungs, sneezing and coughing help to expel mucus, whilst macrophages in the alveoli of the lungs can ingest pathogens.
- The intestine is colonised with ‘good’ bacteria that form your microbiome.
A
- Skin has a dense layer of dead keratinocytes that act as a physical barrier.
- In the respiratory tract mucus traps micro-organisms (importance demonstrated by Cystic fibrosis). In the lower airways there are collectins in the surfactant that can activate complement.
- In the gut, people unable to secrete sufficient gastric acid have a high risk of salmonella infection.
- In the airway and lungs, sneezing and coughing help to expel mucus, whilst macrophages in the alveoli of the lungs can ingest pathogens.
- The intestine is colonised with ‘good’ bacteria that form your microbiome.
34
Q
Tissue Damage
- Tissue resident cells detect the infection and release … innate immune effectors and cytokines to cause vasodilation and recruitments of further innate immune cells.
A
- Tissue resident cells detect the infection and release soluble innate immune effectors and cytokines to cause vasodilation and recruitments of further innate immune cells.
35
Q
Tissue Damage
- Tissue resident cells detect the infection and release soluble innate immune effectors and … to cause vasodilation and recruitments of further innate immune cells.
A
- Tissue resident cells detect the infection and release soluble innate immune effectors and cytokines to cause vasodilation and recruitments of further innate immune cells.
36
Q
Tissue Damage
- Tissue resident cells detect the infection and release soluble innate immune … and cytokines to cause … and recruitments of further innate immune cells.
A
- Tissue resident cells detect the infection and release soluble innate immune effectors and cytokines to cause vasodilation and recruitments of further innate immune cells.
37
Q
Soluble innate immune molecules
- … such as Lysozyme
- Disrupt bacterial cell walls; found in blood and tears
- Antimicrobial …
- Disrupt microbial membranes
- Collectins, ficolins and pentraxins
- Bind to pathogens targeting them for phagocytosis and activate complement
- Complement components
- Lyse bacteria, opsonise bacteria and induce inflammation
A
-
Enzymes such as Lysozyme
- Disrupt bacterial cell walls; found in blood and tears
- Antimicrobial peptides
- Disrupt microbial membranes
- Collectins, ficolins and pentraxins
- Bind to pathogens targeting them for phagocytosis and activate complement
- Complement components
- Lyse bacteria, opsonise bacteria and induce inflammation
38
Q
Soluble innate immune molecules
- Enzymes such as Lysozyme
- Disrupt bacterial cell …; found in blood and tears
- … peptides
- Disrupt microbial membranes
- Collectins, ficolins and pentraxins
- Bind to pathogens targeting them for … and activate complement
- Complement components
- Lyse bacteria, opsonise bacteria and induce inflammation
A
- Enzymes such as Lysozyme
- Disrupt bacterial cell walls; found in blood and tears
-
Antimicrobial peptides
- Disrupt microbial membranes
- Collectins, ficolins and pentraxins
- Bind to pathogens targeting them for phagocytosis and activate complement
- Complement components
- Lyse bacteria, opsonise bacteria and induce inflammation
39
Q
Soluble innate immune molecules
- Enzymes such as Lysozyme
- Disrupt bacterial cell walls; found in blood and tears
- Antimicrobial peptides
- Disrupt microbial membranes
- Collectins, ficolins and pentraxins
- Bind to pathogens targeting them for phagocytosis and activate …
- … components
- Lyse bacteria, opsonise bacteria and induce inflammation
A
- Enzymes such as Lysozyme
- Disrupt bacterial cell walls; found in blood and tears
- Antimicrobial peptides
- Disrupt microbial membranes
- Collectins, ficolins and pentraxins
- Bind to pathogens targeting them for phagocytosis and activate complement
-
Complement components
- Lyse bacteria, opsonise bacteria and induce inflammation
40
Q
Soluble innate immune molecules
- Enzymes such as Lysozyme
- Disrupt bacterial cell walls; found in blood and tears
- Antimicrobial peptides
- Disrupt microbial membranes
- Collectins, ficolins and pentraxins
- Bind to … targeting them for phagocytosis and activate complement
- Complement components
- Lyse bacteria, … bacteria and induce inflammation
A
- Enzymes such as Lysozyme
- Disrupt bacterial cell walls; found in blood and tears
- Antimicrobial peptides
- Disrupt microbial membranes
- Collectins, ficolins and pentraxins
- Bind to pathogens targeting them for phagocytosis and activate complement
- Complement components
- Lyse bacteria, opsonise bacteria and induce inflammation
41
Q
Soluble innate immune molecules
- Enzymes such as Lysozyme
- Disrupt bacterial cell walls; found in blood and tears
- Antimicrobial peptides
- Disrupt microbial …
- Collectins, ficolins and pentraxins
- Bind to pathogens targeting them for phagocytosis and activate complement
- Complement components
- Lyse bacteria, opsonise bacteria and induce …
A
- Enzymes such as Lysozyme
- Disrupt bacterial cell walls; found in blood and tears
- Antimicrobial peptides
- Disrupt microbial membranes
- Collectins, ficolins and pentraxins
- Bind to pathogens targeting them for phagocytosis and activate complement
- Complement components
- Lyse bacteria, opsonise bacteria and induce inflammation
42
Q
Soluble innate immune molecules
- Enzymes such as Lysozyme
- Disrupt bacterial cell walls; found in … and …
- Antimicrobial peptides
- Disrupt microbial membranes
- … , ficolins and pentraxins
- Bind to pathogens targeting them for phagocytosis and activate complement
- Complement components
- Lyse bacteria, opsonise bacteria and induce inflammation
A
- Enzymes such as Lysozyme
- Disrupt bacterial cell walls; found in blood and tears
- Antimicrobial peptides
- Disrupt microbial membranes
-
Collectins, ficolins and pentraxins
- Bind to pathogens targeting them for phagocytosis and activate complement
- Complement components
- Lyse bacteria, opsonise bacteria and induce inflammation
43
Q
These are all examples of … … immune molecules
A
These are all examples of soluble innate immune molecules
44
Q
Define opsonise
A
make (a foreign cell) more susceptible to phagocytosis.
45
Q
Lysozyme disrupts peptidoglycan
- Lysozyme is secreted by phagocytes and … cells from the small intestine
- Lysozyme is most effective against gram positive bacteria because LPS masks peptidoglycan in gram negative bacteria.
- Cleaves the bond between the alternating sugars that make up peptidoglycan
- Phospholipase A2 hydrolyses phospholipids in cell membrane to kill bacteria
A
- Lysozyme is secreted by phagocytes and paneth cells from the small intestine
- Lysozyme is most effective against gram positive bacteria because LPS masks peptidoglycan in gram negative bacteria.
- Cleaves the bond between the alternating sugars that make up peptidoglycan
- Phospholipase A2 hydrolyses phospholipids in cell membrane to kill bacteria
46
Q
Lysozyme disrupts peptidoglycan
- Lysozyme is secreted by phagocytes and paneth cells from the small intestine
- Lysozyme is most effective against gram … bacteria because LPS masks peptidoglycan in gram … bacteria.
- Cleaves the bond between the alternating sugars that make up peptidoglycan
- Phospholipase A2 hydrolyses phospholipids in cell membrane to kill bacteria
A
- Lysozyme is secreted by phagocytes and paneth cells from the small intestine
- Lysozyme is most effective against gram positive bacteria because LPS masks peptidoglycan in gram negative bacteria.
- Cleaves the bond between the alternating sugars that make up peptidoglycan
- Phospholipase A2 hydrolyses phospholipids in cell membrane to kill bacteria
47
Q
Lysozyme disrupts peptidoglycan
- Lysozyme is secreted by phagocytes and paneth cells from the small intestine
- Lysozyme is most effective against gram positive bacteria because LPS masks peptidoglycan in gram negative bacteria.
- … the bond between the alternating sugars that make up peptidoglycan
- Phospholipase … hydrolyses phospholipids in cell membrane to kill bacteria
A
- Lysozyme is secreted by phagocytes and paneth cells from the small intestine
- Lysozyme is most effective against gram positive bacteria because LPS masks peptidoglycan in gram negative bacteria.
- Cleaves the bond between the alternating sugars that make up peptidoglycan
- Phospholipase A2 hydrolyses phospholipids in cell membrane to kill bacteria
48
Q
Lysozyme is most effective against gram … bacteria because LPS masks peptidoglycan in gram … bacteria.
A
Lysozyme is most effective against gram positive bacteria because LPS masks peptidoglycan in gram negative bacteria.
49
Q
Antimicrobial peptides - 3 Families
- …
- Produced in the oral cavity. Active against pathogenic fungi, e.g. Candida albicans
- Cathelicidins
- LL-37 broad-spectrum antimicrobial activity against both Gram-negative and Gram-positive bacteria
- Defensins
- 2 classes - alpha, beta defensins
A
-
Histatins
- Produced in the oral cavity. Active against pathogenic fungi, e.g. Candida albicans
- Cathelicidins
- LL-37 broad-spectrum antimicrobial activity against both Gram-negative and Gram-positive bacteria
- Defensins
- 2 classes - alpha, beta defensins
50
Q
Antimicrobial peptides - 3 Families
- Histatins
- Produced in the … cavity. Active against pathogenic fungi, e.g. Candida albicans
- Cathelicidins
- LL-37 broad-spectrum antimicrobial activity against both Gram-negative and Gram-positive bacteria
- …
- 2 classes - alpha, beta …
A
- Histatins
- Produced in the oral cavity. Active against pathogenic fungi, e.g. Candida albicans
- Cathelicidins
- LL-37 broad-spectrum antimicrobial activity against both Gram-negative and Gram-positive bacteria
-
Defensins
- 2 classes - alpha, beta defensins
51
Q
Antimicrobial peptides - 3 Families
- Histatins
- Produced in the oral cavity. Active against pathogenic fungi, e.g. Candida albicans
- C…
- LL-37 broad-spectrum antimicrobial activity against both Gram-negative and Gram-positive bacteria
- Defensins
- 2 classes - alpha, beta defensins
A
- Histatins
- Produced in the oral cavity. Active against pathogenic fungi, e.g. Candida albicans
-
Cathelicidins
- LL-37 broad-spectrum antimicrobial activity against both Gram-negative and Gram-positive bacteria
- Defensins
- 2 classes - alpha, beta defensins
52
Q
Antimicrobial peptides - 3 Families
- Histatins
- Produced in the oral cavity. Active against pathogenic fungi, e.g. Candida albicans
- Cathelicidins
- LL-… broad-spectrum antimicrobial activity against both Gram-negative and Gram-positive bacteria
- Defensins
- 2 classes - …, … defensins
A
- Histatins
- Produced in the oral cavity. Active against pathogenic fungi, e.g. Candida albicans
- Cathelicidins
- LL-37 broad-spectrum antimicrobial activity against both Gram-negative and Gram-positive bacteria
- Defensins
- 2 classes - alpha, beta defensins
53
Q
Antimicrobial peptides
- 3 families - Histatins, Cathlicidins, Defensins
- Cover epithelial surfaces, found in …
- Constitutively secreted by neutrophils, epithelial cells and paneth cells in the crypts of the small intestine
- Kill bacteria in minutes, by disrupting the membrane
- Also attack fungi, viruses (influenza and herpes virus)
- Inhibit DNA and RNA synthesis
A
- 3 families - Histatins, Cathlicidins, Defensins
- Cover epithelial surfaces, found in saliva
- Constitutively secreted by neutrophils, epithelial cells and paneth cells in the crypts of the small intestine
- Kill bacteria in minutes, by disrupting the membrane
- Also attack fungi, viruses (influenza and herpes virus)
- Inhibit DNA and RNA synthesis
54
Q
Antimicrobial peptides
- 3 families - Histatins, Cathlicidins, Defensins
- Cover epithelial surfaces, found in saliva
- Constitutively secreted by …, epithelial cells and … cells in the crypts of the small intestine
- Kill bacteria in minutes, by disrupting the membrane
- Also attack fungi, viruses (influenza and herpes virus)
- Inhibit DNA and RNA synthesis
A
- 3 families - Histatins, Cathlicidins, Defensins
- Cover epithelial surfaces, found in saliva
- Constitutively secreted by neutrophils, epithelial cells and paneth cells in the crypts of the small intestine
- Kill bacteria in minutes, by disrupting the membrane
- Also attack fungi, viruses (influenza and herpes virus)
- Inhibit DNA and RNA synthesis
55
Q
Antimicrobial peptides
- 3 families - Histatins, Cathlicidins, Defensins
- Cover epithelial surfaces, found in saliva
- Constitutively secreted by neutrophils, epithelial cells and paneth cells in the crypts of the small intestine
- Kill bacteria in …, by disrupting the membrane
- Also attack fungi, viruses (influenza and herpes virus)
- Inhibit DNA and RNA synthesis
A
- 3 families - Histatins, Cathlicidins, Defensins
- Cover epithelial surfaces, found in saliva
- Constitutively secreted by neutrophils, epithelial cells and paneth cells in the crypts of the small intestine
- Kill bacteria in minutes, by disrupting the membrane
- Also attack fungi, viruses (influenza and herpes virus)
- Inhibit DNA and RNA synthesis
56
Q
Antimicrobial peptides
- 3 families - Histatins, Cathlicidins, Defensins
- Cover … surfaces, found in saliva
- Constitutively secreted by neutrophils, epithelial cells and paneth cells in the crypts of the small intestine
- Kill bacteria in minutes, by disrupting the membrane
- Also attack fungi, viruses (influenza and herpes virus)
- Inhibit DNA and RNA synthesis
A
- 3 families - Histatins, Cathlicidins, Defensins
- Cover epithelial surfaces, found in saliva
- Constitutively secreted by neutrophils, epithelial cells and paneth cells in the crypts of the small intestine
- Kill bacteria in minutes, by disrupting the membrane
- Also attack fungi, viruses (influenza and herpes virus)
- Inhibit DNA and RNA synthesis
57
Q
Antimicrobial peptides
- 3 families - Histatins, Cathlicidins, Defensins
- Cover epithelial surfaces, found in saliva
- Constitutively secreted by neutrophils, epithelial cells and paneth cells in the crypts of the small intestine
- Kill bacteria in minutes, by disrupting the membrane
- Also attack fungi, viruses (influenza and herpes virus)
- Inhibit … and … synthesis
A
- 3 families - Histatins, Cathlicidins, Defensins
- Cover epithelial surfaces, found in saliva
- Constitutively secreted by neutrophils, epithelial cells and paneth cells in the crypts of the small intestine
- Kill bacteria in minutes, by disrupting the membrane
- Also attack fungi, viruses (influenza and herpes virus)
- Inhibit DNA and RNA synthesis
58
Q
Antimicrobial peptides
- 3 families - Histatins, Cathlicidins, Defensins
- Cover epithelial surfaces, found in saliva
- Constitutively secreted by neutrophils, epithelial cells and paneth cells in the crypts of the small intestine
- Kill bacteria in minutes, by disrupting the membrane
- Also attack …, … (influenza and herpes virus)
- Inhibit DNA and RNA synthesis
A
- 3 families - Histatins, Cathlicidins, Defensins
- Cover epithelial surfaces, found in saliva
- Constitutively secreted by neutrophils, epithelial cells and paneth cells in the crypts of the small intestine
- Kill bacteria in minutes, by disrupting the membrane
- Also attack fungi, viruses (influenza and herpes virus)
- Inhibit DNA and RNA synthesis
59
Q
Antimicrobial peptides kill bacteria how quickly?
A
in minutes - slowest takes 90 mins
60
Q
Antimicrobial peptides can also attack … and …
A
fungi and viruses (influenza and herpes virus)
61
Q
Antimicrobial peptides inhibit … and … synthesis
A
Antimicrobial peptides inhibit DNA and RNA synthesis
62
Q
… cover our epithelial surfaces and are present in the vernix caseosa and in the skin of the healthy new born
A
Defensins cover our epithelial surfaces and are present in the vernix caseosa and in the skin of the healthy new born
63
Q
Defensins cover our epithelial surfaces and are present in the vernix caseosa and in the skin of the … … …
A
Defensins cover our epithelial surfaces and are present in the vernix caseosa and in the skin of the healthy new born
64
Q
The only human cathelicidin is …, a peptide of … amino acids synthesized by macrophages, neutrophils, and epithelial cells (providing antimicrobial protection to our skin and the lining of our urinary tract).
A
The only human cathelicidin is LL37, a peptide of 37 amino acids synthesized by macrophages, neutrophils, and epithelial cells (providing antimicrobial protection to our skin and the lining of our urinary tract).
65
Q
Defensins
- …-… aa amphipathic peptides which means they have both hydrophilic and hydrophobic regions on their cell surface.
- Disulphide bonds stabilise the structure to have a positively charged region separated from a hydrophobic region
- Disrupt microbial membranes but not that of the host
A
- 35-40 aa amphipathic peptides which means they have both hydrophilic and hydrophobic regions on their cell surface.
- Disulphide bonds stabilise the structure to have a positively charged region separated from a hydrophobic region
- Disrupt microbial membranes but not that of the host
66
Q
Defensins
- 35-40 aa … peptides which means they have both hydrophilic and hydrophobic regions on their cell surface.
- Disulphide bonds stabilise the structure to have a positively charged region separated from a hydrophobic region
- Disrupt microbial membranes but not that of the …
A
- 35-40 aa amphipathic peptides which means they have both hydrophilic and hydrophobic regions on their cell surface.
- Disulphide bonds stabilise the structure to have a positively charged region separated from a hydrophobic region
- Disrupt microbial membranes but not that of the host
70
Q
Collectins, ficolins and pentraxins
- Collectins have globular lectin like heads that bind bacterial cell surface sugars. … acid hides mannose antigens on host cells.
- Ficolins (have a Fibrinogen like domain) recognise … compounds (COCH3) such as n-acetylglucosamine, a monosaccharide found in bacterial cell walls
- Pentraxins are cyclic multimeric proteins in the plasma. C-reactive protein (CRP) is used as a clinical measure of inflammation – CRP binds to phosphocholine on bacterial surfaces
A
- Collectins have globular lectin like heads that bind bacterial cell surface sugars. Sialic acid hides mannose antigens on host cells.
- Ficolins (have a Fibrinogen like domain) recognise acylated compounds (COCH3) such as n-acetylglucosamine, a monosaccharide found in bacterial cell walls
- Pentraxins are cyclic multimeric proteins in the plasma. C-reactive protein (CRP) is used as a clinical measure of inflammation – CRP binds to phosphocholine on bacterial surfaces
71
Q
Collectins, ficolins and pentraxins
- Collectins have globular lectin like heads that bind bacterial cell surface sugars. Sialic acid hides … antigens on host cells.
- Ficolins (have a Fibrinogen like domain) recognise acylated compounds (COCH3) such as n-acetylglucosamine, a monosaccharide found in bacterial cell walls
- Pentraxins are cyclic multimeric proteins in the plasma. …-… protein (…) is used as a clinical measure of inflammation – … binds to phosphocholine on bacterial surfaces
A
- Collectins have globular lectin like heads that bind bacterial cell surface sugars. Sialic acid hides mannose antigens on host cells.
- Ficolins (have a Fibrinogen like domain) recognise acylated compounds (COCH3) such as n-acetylglucosamine, a monosaccharide found in bacterial cell walls
- Pentraxins are cyclic multimeric proteins in the plasma. C-reactive protein (CRP) is used as a clinical measure of inflammation – CRP binds to phosphocholine on bacterial surfaces
72
Q
Collectins, ficolins and pentraxins
- Collectins have globular lectin like heads that bind bacterial cell surface sugars. Sialic acid hides mannose antigens on host cells.
- Ficolins (have a … like domain) recognise acylated compounds (COCH3) such as n-acetylglucosamine, a monosaccharide found in bacterial cell walls
- Pentraxins are cyclic multimeric proteins in the plasma. C-reactive protein (CRP) is used as a clinical measure of inflammation – CRP binds to phosphocholine on bacterial surfaces
A
- Collectins have globular lectin like heads that bind bacterial cell surface sugars. Sialic acid hides mannose antigens on host cells.
- Ficolins (have a Fibrinogen like domain) recognise acylated compounds (COCH3) such as n-acetylglucosamine, a monosaccharide found in bacterial cell walls
- Pentraxins are cyclic multimeric proteins in the plasma. C-reactive protein (CRP) is used as a clinical measure of inflammation – CRP binds to phosphocholine on bacterial surfaces
73
Q
Collectins, ficolins and pentraxins
- Collectins have globular lectin like heads that bind bacterial cell surface sugars. Sialic acid hides mannose antigens on host cells.
- Ficolins (have a Fibrinogen like domain) recognise acylated compounds (COCH3) such as n-acetylglucosamine, a monosaccharide found in bacterial cell walls
- Pentraxins are cyclic multimeric proteins in the plasma. C-reactive protein (CRP) is used as a clinical measure of inflammation – CRP binds to … on bacterial surfaces
A
- Collectins have globular lectin like heads that bind bacterial cell surface sugars. Sialic acid hides mannose antigens on host cells.
- Ficolins (have a Fibrinogen like domain) recognise acylated compounds (COCH3) such as n-acetylglucosamine, a monosaccharide found in bacterial cell walls
- Pentraxins are cyclic multimeric proteins in the plasma. C-reactive protein (CRP) is used as a clinical measure of inflammation – CRP binds to phosphocholine on bacterial surfaces
76
Q
Actions of Collectins, ficolins and pentraxins
- Soluble … … receptors
- Act as opsonins that bind to pathogens and infected cells targeting them for phagocytosis
- Activate complement through the classical pathway/lectin pathway
A
- Soluble pattern recognition receptors
- Act as opsonins that bind to pathogens and infected cells targeting them for phagocytosis
- Activate complement through the classical pathway/lectin pathway
77
Q
Actions of Collectins, ficolins and pentraxins
- Soluble pattern recognition receptors
- Act as … that bind to pathogens and infected cells targeting them for phagocytosis
- Activate … through the classical pathway/lectin pathway
A
- Soluble pattern recognition receptors
- Act as opsonins that bind to pathogens and infected cells targeting them for phagocytosis
- Activate complement through the classical pathway/lectin pathway
78
Q
Complement pathways converge on C3
- 3 different pathways - … pathway, … pathway, … pathway
- Converge on C3 convertase leading to downstream events that induce inflammation
A
- 3 different pathways - Classical pathway, Lectin pathway, Alternative pathway
- Converge on C3 convertase leading to downstream events that induce inflammation
79
Q
Complement pathways converge on C3
- 3 different pathways - Classical pathway, … pathway, Alternative pathway
- Converge on C3 convertase leading to downstream events that induce …
A
- 3 different pathways - Classical pathway, Lectin pathway, Alternative pathway
- Converge on C3 convertase leading to downstream events that induce inflammation
86
Q
Complement components
- Circulate as a …-form (…) in the blood
- Numbered in the order they were discovered, not in the order they are activated
- Some have proteolytic enzymatic activity
- On activation they split into a small and large fragments triggering an amplification cascade
- Normally ‘a’ is the small fragment - except c2a
A
- Circulate as a pro-form (inactive) in the blood
- Numbered in the order they were discovered, not in the order they are activated
- Some have proteolytic enzymatic activity
- On activation they split into a small and large fragments triggering an amplification cascade
- Normally ‘a’ is the small fragment - except c2a
87
Q
Complement components
- Circulate as a …-form (…) in the blood
- Numbered in the order they were …, not in the order they are …
- Some have proteolytic enzymatic activity
- On activation they split into a small and large fragments triggering an amplification cascade
- Normally ‘a’ is the small fragment - except c2a
A
- Circulate as a pro-form (inactive) in the blood
- Numbered in the order they were discovered, not in the order they are activated
- Some have proteolytic enzymatic activity
- On activation they split into a small and large fragments triggering an amplification cascade
- Normally ‘a’ is the small fragment - except c2a
88
Q
Complement components
- Circulate as a …-form (…) in the blood
- Numbered in the order they were discovered, not in the order they are activated
- Some have … enzymatic activity
- On activation they split into a small and large fragments triggering an amplification cascade
- Normally ‘a’ is the small fragment - except c2a
A
- Circulate as a pro-form (inactive) in the blood
- Numbered in the order they were discovered, not in the order they are activated
- Some have proteolytic enzymatic activity
- On activation they split into a small and large fragments triggering an amplification cascade
- Normally ‘a’ is the small fragment - except c2a
89
Q
Complement components
- Circulate as a …-form (…) in the blood
- Numbered in the order they were discovered, not in the order they are activated
- Some have proteolytic enzymatic activity
- On activation they split into a small and large fragments triggering an amplification cascade
- Normally ‘…’ is the small fragment - except …
A
- Circulate as a pro-form (inactive) in the blood
- Numbered in the order they were discovered, not in the order they are activated
- Some have proteolytic enzymatic activity
- On activation they split into a small and large fragments triggering an amplification cascade
- Normally ‘a’ is the small fragment - except c2a
90
Q
Complement components
- Circulate as a pro-form (inactive) in the blood
- Numbered in the order they were discovered, not in the order they are activated
- Some have proteolytic enzymatic activity
- On activation they split into a … and … fragments triggering an amplification cascade
- Normally ‘a’ is the small fragment - except c2a
A
- Circulate as a pro-form (inactive) in the blood
- Numbered in the order they were discovered, not in the order they are activated
- Some have proteolytic enzymatic activity
- On activation they split into a small and large fragments triggering an amplification cascade
- Normally ‘a’ is the small fragment - except c2a
92
Q
Complement Cascade
A
93
Q
Effects mediated by complement components
A
- Immune complexes bind CR1 receptors on the erythrocytes which transport them to phagocytes in the liver and spleen for removal.
- Some components are termed anaphylatoxins because they can cause anaphylactic shock (C3a, C4a and C5a).
- Changes induced by complement components leads to recruitment immune cells to the site of the infection and increases phagocytic capacity.
94
Q
Classical pathway (Complement)
- Initiated by … activation
- C… is a complex of three proteins: C…q, C..r and C..s
- The structure of C… is dominated by C…q
- a large molecule of 18 polypeptides that form six collagen like triple helix structures
- This was the first complement pathway to be discovered.
- C.. complex is stabilised by Ca2+ ions.
A
- Initiated by C1 activation
- C1 is a complex of three proteins: C1q, C1r and C1s
- The structure of C1 is dominated by C1q
- a large molecule of 18 polypeptides that form six collagen like triple helix structures
- This was the first complement pathway to be discovered.
- C1 complex is stabilised by Ca2+ ions.
95
Q
Classical pathway (Complement)
- Initiated by C1 activation
- C1 is a complex of three proteins: C1q, C1… and C1…
- The structure of C1 is dominated by C1q
- a large molecule of 18 polypeptides that form six collagen like triple helix structures
- This was the first complement pathway to be discovered.
- C1 complex is stabilised by Ca2+ ions.
A
- Initiated by C1 activation
- C1 is a complex of three proteins: C1q, C1r and C1s
- The structure of C1 is dominated by C1q
- a large molecule of 18 polypeptides that form six collagen like triple helix structures
- This was the first complement pathway to be discovered.
- C1 complex is stabilised by Ca2+ ions.
96
Q
Classical pathway (Complement)
- Initiated by C1 activation
- C1 is a complex of three proteins: C1q, C1r and C1s
- The structure of C1 is dominated by C1…
- a large molecule of 18 polypeptides that form six collagen like triple helix structures
- This was the first complement pathway to be discovered.
- C1 complex is stabilised by Ca2+ ions.
A
- Initiated by C1 activation
- C1 is a complex of three proteins: C1q, C1r and C1s
- The structure of C1 is dominated by C1q
- a large molecule of 18 polypeptides that form six collagen like triple helix structures
- This was the first complement pathway to be discovered.
- C1 complex is stabilised by Ca2+ ions.
97
Q
Classical pathway (Complement)
- Initiated by C1 activation
- C1 is a complex of three proteins: C1q, C1r and C1s
- The structure of C1 is dominated by C1q
- a large molecule of 18 polypeptides that form six collagen like triple helix structures
- This was the first complement pathway to be discovered.
- C1 complex is stabilised by …+ ions.
A
- Initiated by C1 activation
- C1 is a complex of three proteins: C1q, C1r and C1s
- The structure of C1 is dominated by C1q
- a large molecule of 18 polypeptides that form six collagen like triple helix structures
- This was the first complement pathway to be discovered.
- C1 complex is stabilised by Ca2+ ions.
98
Q
Classical pathway: Activation (Complement)
- Triggered when C1 binds to the … region of an antibody – antigen complex
- C1 must bind at least 2 … domains
- IgM is the most efficient at activating complement as it has 5 … domains. IgG1 and IgG3, and to a lesser extent IgG2 can also activate complement when close together bound to antigen
A
- Triggered when C1 binds to the Fc region of an antibody – antigen complex
- C1 must bind at least 2 FC domains
- IgM is the most efficient at activating complement as it has 5 Fc domains. IgG1 and IgG3, and to a lesser extent IgG2 can also activate complement when close together bound to antigen
99
Q
Classical pathway: Activation (Complement)
- Triggered when C1 binds to the Fc region of an antibody – antigen complex
- C1 must bind at least … FC domains
- IgM is the most efficient at activating complement as it has … Fc domains. IgG1 and IgG3, and to a lesser extent IgG2 can also activate complement when close together bound to antigen
A
- Triggered when C1 binds to the Fc region of an antibody – antigen complex
- C1 must bind at least 2 FC domains
- IgM is the most efficient at activating complement as it has 5 Fc domains. IgG1 and IgG3, and to a lesser extent IgG2 can also activate complement when close together bound to antigen
100
Q
Classical pathway: Activation (Complement)
- Triggered when C1 binds to the Fc region of an antibody – antigen complex
- C1 must bind at least 2 FC domains
- … is the most efficient at activating complement as it has 5 Fc domains. IgG1 and IgG3, and to a lesser extent IgG2 can also activate complement when close together bound to antigen
A
- Triggered when C1 binds to the Fc region of an antibody – antigen complex
- C1 must bind at least 2 FC domains
- IgM is the most efficient at activating complement as it has 5 Fc domains. IgG1 and IgG3, and to a lesser extent IgG2 can also activate complement when close together bound to antigen
106
Q
Serum IgM - Complement
- Serum IgM cannot bind C1 as it has a … conformation, the shape changes on binding antigen to reveal binding sites for C1q
A
- Serum IgM cannot bind C1 as it has a planar conformation, the shape changes on binding antigen to reveal binding sites for C1q
107
Q
Serum IgM cannot bind C1 as it has a planar conformation, the shape changes on binding antigen to reveal binding sites for C1…
A
Serum IgM cannot bind C1 as it has a planar conformation, the shape changes on binding antigen to reveal binding sites for C1q
108
Q
Serum … cannot bind C1 as it has a planar conformation, the shape changes on binding antigen to reveal binding sites for C1q
A
Serum IgM cannot bind C1 as it has a planar conformation, the shape changes on binding antigen to reveal binding sites for C1q
109
Q
Classical pathway: Amplification
- Binding C1q with the Fc domain causes a conformational change in C1…
- C1s is cleaved and can activate C2 and C4 splitting into their large and small fragments
- C3 convertase (C4b2a) can then activate over 200 C3 molecules producing a massive amplification of the signal
- C4b, C2a and C3b fragments form the C5 convertase that activates C5 leading to the membrane attack complex
A
- Binding C1q with the Fc domain causes a conformational change in C1r
- C1s is cleaved and can activate C2 and C4 splitting into their large and small fragments
- C3 convertase (C4b2a) can then activate over 200 C3 molecules producing a massive amplification of the signal
- C4b, C2a and C3b fragments form the C5 convertase that activates C5 leading to the membrane attack complex
110
Q
Classical pathway: Amplification
- Binding C1q with the Fc domain causes a conformational change in C1r
- C1… is cleaved and can activate C2 and C4 splitting into their large and small fragments
- C3 convertase (C4b2a) can then activate over 200 C3 molecules producing a massive amplification of the signal
- C4b, C2a and C3b fragments form the C5 convertase that activates C5 leading to the membrane attack complex
A
- Binding C1q with the Fc domain causes a conformational change in C1r
- C1s is cleaved and can activate C2 and C4 splitting into their large and small fragments
- C3 convertase (C4b2a) can then activate over 200 C3 molecules producing a massive amplification of the signal
- C4b, C2a and C3b fragments form the C5 convertase that activates C5 leading to the membrane attack complex
111
Q
Classical pathway: Amplification
- Binding C1q with the Fc domain causes a conformational change in C1r
- C1s is cleaved and can activate C… and C… splitting into their large and small fragments
- C3 convertase (C4b2a) can then activate over 200 C3 molecules producing a massive amplification of the signal
- C4b, C2a and C3b fragments form the C5 convertase that activates C5 leading to the membrane attack complex
A
- Binding C1q with the Fc domain causes a conformational change in C1r
- C1s is cleaved and can activate C2 and C4 splitting into their large and small fragments
- C3 convertase (C4b2a) can then activate over 200 C3 molecules producing a massive amplification of the signal
- C4b, C2a and C3b fragments form the C5 convertase that activates C5 leading to the membrane attack complex
112
Q
Classical pathway: Amplification
- Binding C1q with the Fc domain causes a conformational change in C1r
- C1s is cleaved and can activate C2 and C4 splitting into their large and small fragments
- C.. convertase (C4b2a) can then activate over 200 C… molecules producing a massive amplification of the signal
- C4b, C2a and C3b fragments form the C5 convertase that activates C5 leading to the membrane attack complex
A
- Binding C1q with the Fc domain causes a conformational change in C1r
- C1s is cleaved and can activate C2 and C4 splitting into their large and small fragments
- C3 convertase (C4b2a) can then activate over 200 C3 molecules producing a massive amplification of the signal
- C4b, C2a and C3b fragments form the C5 convertase that activates C5 leading to the membrane attack complex
113
Q
Classical pathway: Amplification
- Binding C1q with the Fc domain causes a conformational change in C1r
- C1s is cleaved and can activate C2 and C4 splitting into their large and small fragments
- C3 convertase (C4b2a) can then activate over 200 C3 molecules producing a massive amplification of the signal
- C4b, C2a and C3b fragments form the … convertase that activates … leading to the membrane attack complex
A
- Binding C1q with the Fc domain causes a conformational change in C1r
- C1s is cleaved and can activate C2 and C4 splitting into their large and small fragments
- C3 convertase (C4b2a) can then activate over 200 C3 molecules producing a massive amplification of the signal
- C4b, C2a and C3b fragments form the C5 convertase that activates C5 leading to the membrane attack complex
114
Q
Classical pathway: Amplification
- Binding C1q with the Fc domain causes a conformational change in C1r
- C1s is cleaved and can activate C2 and C4 splitting into their large and small fragments
- C3 convertase (C4b2a) can then activate over 200 C3 molecules producing a massive amplification of the signal
- C4…, C2… and C3… fragments form the C5 convertase that activates C5 leading to the membrane attack complex
A
- Binding C1q with the Fc domain causes a conformational change in C1r
- C1s is cleaved and can activate C2 and C4 splitting into their large and small fragments
- C3 convertase (C4b2a) can then activate over 200 C3 molecules producing a massive amplification of the signal
- C4b, C2a and C3b fragments form the C5 convertase that activates C5 leading to the membrane attack complex
116
Q
Lectin pathway (Complement)
- Antibody …, activated by ficolins and … binding lectin (MBL)
- MBL binds … residues on carbohydrates and glycoproteins on bacteria and some viruses
- Similar downstream mechanism to the classical pathway
- Upon binding MBL forms a complex with MASP-1 and MASP-2 (serine proteases)
- Active complex cleaves C2 and C4
A
- Antibody independent, activated by ficolins and mannose binding lectin (MBL)
- MBL binds mannose residues on carbohydrates and glycoproteins on bacteria and some viruses
- Similar downstream mechanism to the classical pathway
- Upon binding MBL forms a complex with MASP-1 and MASP-2 (serine proteases)
- Active complex cleaves C2 and C4
117
Q
Lectin pathway (Complement)
- Antibody independent, activated by … and mannose binding lectin (MBL)
- MBL binds mannose residues on carbohydrates and glycoproteins on bacteria and some viruses
- Similar downstream mechanism to the classical pathway
- Upon binding MBL forms a complex with MASP-1 and MASP-2 (serine proteases)
- Active complex cleaves … and …
A
- Antibody independent, activated by ficolins and mannose binding lectin (MBL)
- MBL binds mannose residues on carbohydrates and glycoproteins on bacteria and some viruses
- Similar downstream mechanism to the classical pathway
- Upon binding MBL forms a complex with MASP-1 and MASP-2 (serine proteases)
- Active complex cleaves C2 and C4
118
Q
Lectin pathway (Complement)
- Antibody independent, activated by ficolins and mannose binding lectin (MBL)
- MBL binds mannose residues on carbohydrates and glycoproteins on bacteria and some viruses
- Similar downstream mechanism to the classical pathway
- Upon binding MBL forms a complex with …-1 and …-2 (serine proteases)
- Active complex cleaves C2 and C4
A
- Antibody independent, activated by ficolins and mannose binding lectin (MBL)
- MBL binds mannose residues on carbohydrates and glycoproteins on bacteria and some viruses
- Similar downstream mechanism to the classical pathway
- Upon binding MBL forms a complex with MASP-1 and MASP-2 (serine proteases)
- Active complex cleaves C2 and C4
119
Q
Lectin pathway (Complement)
- Antibody independent, activated by ficolins and …
- … binds mannose residues on carbohydrates and glycoproteins on bacteria and some viruses
- Similar downstream mechanism to the classical pathway
- Upon binding … forms a complex with MASP-1 and MASP-2 (… proteases)
- Active complex cleaves C2 and C4
A
- Antibody independent, activated by ficolins and mannose binding lectin (MBL)
- MBL binds mannose residues on carbohydrates and glycoproteins on bacteria and some viruses
- Similar downstream mechanism to the classical pathway
- Upon binding MBL forms a complex with MASP-1 and MASP-2 (serine proteases)
- Active complex cleaves C2 and C4
126
Q
Alternative pathway (Complement)
- C3 spontaneous … into C3… and C3…
- C3b binds to a cell membrane and factor B, making it susceptible to cleavage by factor D to Bb
- C3bBb has a half-life of 5 min, unless it binds the serum protein properdin, which extends it half-life to 30 min by protecting it from proteases
- C3b,Bb can hydrolyse more C3 creating more C3b which can amplify the signal
A
- C3 spontaneous hydrolyses into C3a and C3b
- C3b binds to a cell membrane and factor B, making it susceptible to cleavage by factor D to Bb
- C3bBb has a half-life of 5 min, unless it binds the serum protein properdin, which extends it half-life to 30 min by protecting it from proteases
- C3b,Bb can hydrolyse more C3 creating more C3b which can amplify the signal
127
Q
Alternative pathway (Complement)
- C3 spontaneous hydrolyses into C3a and C3b
- C3b binds to a cell membrane and factor …, making it susceptible to cleavage by factor … to Bb
- C3bBb has a half-life of 5 min, unless it binds the serum protein properdin, which extends it half-life to 30 min by protecting it from proteases
- C3b,Bb can hydrolyse more C3 creating more C3b which can amplify the signal
A
- C3 spontaneous hydrolyses into C3a and C3b
- C3b binds to a cell membrane and factor B, making it susceptible to cleavage by factor D to Bb
- C3bBb has a half-life of 5 min, unless it binds the serum protein properdin, which extends it half-life to 30 min by protecting it from proteases
- C3b,Bb can hydrolyse more C3 creating more C3b which can amplify the signal
128
Q
Alternative pathway (Complement)
- C3 spontaneous hydrolyses into C3a and C3b
- C3b binds to a cell membrane and factor B, making it susceptible to cleavage by factor D to Bb
- C3bBb has a half-life of … min, unless it binds the serum protein properdin, which extends it half-life to … min by protecting it from proteases
- C3b,Bb can hydrolyse more C3 creating more C3b which can amplify the signal
A
- C3 spontaneous hydrolyses into C3a and C3b
- C3b binds to a cell membrane and factor B, making it susceptible to cleavage by factor D to Bb
- C3bBb has a half-life of 5 min, unless it binds the serum protein properdin, which extends it half-life to 30 min by protecting it from proteases
- C3b,Bb can hydrolyse more C3 creating more C3b which can amplify the signal
129
Q
Alternative pathway (Complement)
- C3 … hydrolyses into C3a and C3b
- C3b binds to a cell membrane and factor B, making it susceptible to cleavage by factor D to Bb
- C3bBb has a half-life of 5 min, unless it binds the serum protein properdin, which extends it half-life to 30 min by protecting it from proteases
- C3b,Bb can hydrolyse more C3 creating more C3b which can … the signal
A
- C3 spontaneous hydrolyses into C3a and C3b
- C3b binds to a cell membrane and factor B, making it susceptible to cleavage by factor D to Bb
- C3bBb has a half-life of 5 min, unless it binds the serum protein properdin, which extends it half-life to 30 min by protecting it from proteases
- C3b,Bb can hydrolyse more C3 creating more C3b which can amplify the signal
130
Q
The … pathway (complement) - Involves four serum proteins: C3, complement factor B (circulates in the blood), factor D (secreted by adipocytes), and properdin (released by monocytes and neutrophils).
A
The Alternative pathway (complement) - Involves four serum proteins: C3, complement factor B (circulates in the blood), factor D (secreted by adipocytes), and properdin (released by monocytes and neutrophils).
131
Q
The Alternative pathway (complement) - Involves four serum proteins: C3, complement factor … (circulates in the blood), factor … (secreted by adipocytes), and properdin (released by monocytes and neutrophils).
A
The Alternative pathway (complement) - Involves four serum proteins: C3, complement factor B (circulates in the blood), factor D (secreted by adipocytes), and properdin (released by monocytes and neutrophils).
132
Q
The Alternative pathway (complement) - Involves four serum proteins: C3, complement factor B (circulates in the blood), factor D (secreted by adipocytes), and … (released by monocytes and neutrophils).
A
The Alternative pathway (complement) - Involves four serum proteins: C3, complement factor B (circulates in the blood), factor D (secreted by adipocytes), and properdin (released by monocytes and neutrophils).
133
Q
The Alternative pathway (complement) - Involves four serum proteins: C3, complement factor B (circulates in the …), factor D (secreted by adipocytes), and properdin (released by … and …).
A
The Alternative pathway (complement) - Involves four serum proteins: C3, complement factor B (circulates in the blood), factor D (secreted by adipocytes), and properdin (released by monocytes and neutrophils).
134
Q
Alternative pathway (Complement)
- C3 … hydrolyses into C3a and C3b
- C3b binds to a cell membrane and factor B, making it susceptible to cleavage by factor D to Bb
- C3bBb has a half-life of 5 min, unless it binds the serum protein …, which extends it half-life to 30 min by protecting it from proteases
- C3b,Bb can hydrolyse more C3 creating more C3b which can … the signal
A
- C3 spontaneous hydrolyses into C3a and C3b
- C3b binds to a cell membrane and factor B, making it susceptible to cleavage by factor D to Bb
- C3bBb has a half-life of 5 min, unless it binds the serum protein properdin, which extends it half-life to 30 min by protecting it from proteases
- C3b,Bb can hydrolyse more C3 creating more C3b which can amplify the signal
135
Q
Complement pathways - Overview
A
136
Q
Terminal complement components
A
137
Q
Membrane attack complex
- MAC forms a … that inserts into the membrane allowing diffusion of ions and small molecules, … moves into the cell killing it
- Human cells have soluble and cell surface associated proteins that prevent MAC formation
A
- MAC forms a pore that inserts into the membrane allowing diffusion of ions and small molecules, water moves into the cell killing it
- Human cells have soluble and cell surface associated proteins that prevent MAC formation
138
Q
Membrane attack complex
- MAC forms a pore that inserts into the membrane allowing diffusion of ions and small molecules, water moves into the cell killing it
- … cells have soluble and cell surface associated proteins that prevent MAC formation
A
- MAC forms a pore that inserts into the membrane allowing diffusion of ions and small molecules, water moves into the cell killing it
- Human cells have soluble and cell surface associated proteins that prevent MAC formation
139
Q
Complement pathway summary
A
140
Q
Complement inhibitors
- Unwanted … if no inhibitors
- Hereditary Angioedema : C1 inhibitor deficiency
- Classical complement cascade easily activated but can be treated with an injection of C1 inhibitor
A
- Unwanted inflammation if no inhibitors
- Hereditary Angioedema : C1 inhibitor deficiency
- Classical complement cascade easily activated but can be treated with an injection of C1 inhibitor
141
Q
Complement inhibitors
- Unwanted inflammation if no inhibitors
- Hereditary Angioedema : C… inhibitor deficiency
- Classical complement cascade easily activated but can be treated with an injection of C… inhibitor
A
- Unwanted inflammation if no inhibitors
- Hereditary Angioedema : C1 inhibitor deficiency
- Classical complement cascade easily activated but can be treated with an injection of C1 inhibitor
142
Q
Hereditary … : C1 inhibitor deficiency
A
Hereditary Angioedema : C1 inhibitor deficiency
143
Q
Hereditary Angioedema : … inhibitor deficiency
A
Hereditary Angioedema : C1 inhibitor deficiency
144
Q
Complement deficiency
- Patients deficient of components of the complement pathway experience … …
- MBL deficiency causes serious pyogenic infections in neonates and children
- C3 deficiency is the most severe leading to successive severe infections
- Patients deficient of C8 are prone to infection with Neisseria meningitis
A
- Patients deficient of components of the complement pathway experience recurrent infections
- MBL deficiency causes serious pyogenic infections in neonates and children
- C3 deficiency is the most severe leading to successive severe infections
- Patients deficient of C8 are prone to infection with Neisseria meningitis
145
Q
Complement deficiency
- Patients deficient of components of the complement pathway experience recurrent infections
- … deficiency causes serious pyogenic infections in neonates and children
- C3 deficiency is the most severe leading to successive severe infections
- Patients deficient of C8 are prone to infection with Neisseria meningitis
A
- Patients deficient of components of the complement pathway experience recurrent infections
- MBL deficiency causes serious pyogenic infections in neonates and children
- C3 deficiency is the most severe leading to successive severe infections
- Patients deficient of C8 are prone to infection with Neisseria meningitis
146
Q
Complement deficiency
- Patients deficient of components of the complement pathway experience recurrent infections
- MBL deficiency causes serious pyogenic infections in neonates and children
- … deficiency is the most severe leading to successive severe infections
- Patients deficient of C8 are prone to infection with Neisseria meningitis
A
- Patients deficient of components of the complement pathway experience recurrent infections
- MBL deficiency causes serious pyogenic infections in neonates and children
- C3 deficiency is the most severe leading to successive severe infections
- Patients deficient of C8 are prone to infection with Neisseria meningitis
147
Q
Complement deficiency
- Patients deficient of components of the complement pathway experience recurrent infections
- MBL deficiency causes serious pyogenic infections in neonates and children
- C3 deficiency is the most severe leading to successive severe infections
- Patients deficient of … are prone to infection with Neisseria meningitis
A
- Patients deficient of components of the complement pathway experience recurrent infections
- MBL deficiency causes serious pyogenic infections in neonates and children
- C3 deficiency is the most severe leading to successive severe infections
- Patients deficient of C8 are prone to infection with Neisseria meningitis
154
Q
Complement deficiency in SLE
- …% of people deficient for C4 develop the autoimmune disease systemic lupus erythematosus (SLE)
- C4 deficiency means less C3b (C4b2a is C3 convertase)
- C3b bound to immune complexes binds to CR1 on erythrocytes which transports them to phagocytes in the liver and spleen.
- Phagocytes recognise the immune complexes via their Fc receptors and engulf them
A
- 90% of people deficient for C4 develop the autoimmune disease systemic lupus erythematosus (SLE)
- C4 deficiency means less C3b (C4b2a is C3 convertase)
- C3b bound to immune complexes binds to CR1 on erythrocytes which transports them to phagocytes in the liver and spleen.
- Phagocytes recognise the immune complexes via their Fc receptors and engulf them
155
Q
Complement deficiency in SLE
- 90% of people deficient for C4 develop the autoimmune disease systemic … … (SLE)
- C4 deficiency means less C3b (C4b2a is C3 convertase)
- C3b bound to immune complexes binds to CR1 on erythrocytes which transports them to phagocytes in the liver and spleen.
- Phagocytes recognise the immune complexes via their Fc receptors and engulf them
A
- 90% of people deficient for C4 develop the autoimmune disease systemic lupus erythematosus (SLE)
- C4 deficiency means less C3b (C4b2a is C3 convertase)
- C3b bound to immune complexes binds to CR1 on erythrocytes which transports them to phagocytes in the liver and spleen.
- Phagocytes recognise the immune complexes via their Fc receptors and engulf them
156
Q
Complement deficiency in SLE
- 90% of people deficient for C… develop the autoimmune disease systemic lupus erythematosus (SLE)
- C… deficiency means less C3b (C…b2a is C3 convertase)
- C3b bound to immune complexes binds to CR1 on erythrocytes which transports them to phagocytes in the liver and spleen.
- Phagocytes recognise the immune complexes via their Fc receptors and engulf them
A
- 90% of people deficient for C4 develop the autoimmune disease systemic lupus erythematosus (SLE)
- C4 deficiency means less C3b (C4b2a is C3 convertase)
- C3b bound to immune complexes binds to CR1 on erythrocytes which transports them to phagocytes in the liver and spleen.
- Phagocytes recognise the immune complexes via their Fc receptors and engulf them
157
Q
Complement deficiency in SLE
- 90% of people deficient for C4 develop the autoimmune disease systemic lupus erythematosus (SLE)
- C4 deficiency means less C3b (C4b2a is C3 convertase)
- C3b bound to immune complexes binds to CR1 on erythrocytes which transports them to phagocytes in the … and …
- Phagocytes recognise the immune complexes via their … receptors and engulf them
A
- 90% of people deficient for C4 develop the autoimmune disease systemic lupus erythematosus (SLE)
- C4 deficiency means less C3b (C4b2a is C3 convertase)
- C3b bound to immune complexes binds to CR1 on erythrocytes which transports them to phagocytes in the liver and spleen.
- Phagocytes recognise the immune complexes via their Fc receptors and engulf them
