Innate Immune System 1 + 2 (31/01) Flashcards
1
Q
LO’s (bold = lecture 2)
A
- Describe the function and main features of the innate immune system
- Describe the protective role of acute inflammation and how it may be induced through innate and specific immune responses
3.Describe the various complement pathways
4.Describe the function of cytokines and describe some important examples
5.Describe the function of chemokines and describe some important examples
Describe the function of interferons and acute phase proteins
2
Q
To provide immunity, what four functions must the immune system carry out?
A
- Recognition: must be able to recognise foreign from self.
- Effector Functions: involves containment and elimination.
- Regulation: the immune response must not be too weak or strong.
- Memory: so a faster immune response happens in the future that is less energy expensive.
3
Q
What are the two subdivisions of the immune system?
A
- The innate immune sytem: this launches a non-specific response (it is the same despite what type of invader is recognised). However it is immediate.
- The adaptive immune sytem: this is specific to the invader, but is slower, requiring days to act. However, the advantage of the adaptive response is that it has memory.
4
Q
What does humoral mean?
A
Elements in the blood or other body fluids – non cellular
5
Q
In what two ways does the innate system provide a response?
A
- You have innate immunity and early induced innate immunity.
- Innate Immunity: 0-4h. Recognises invader using non-specific and broadly specific effectors.
- Early Induced Innate Immunity: 4-96h. Recognises invader through it’s molecular pattern. Causes inflammation and recruits effector cells.
- The adaptive immune system only happens after 96h is the innate IS fails to eliminate the infection.
6
Q
Describe the parts of the innate immune sytem?
A
- Physical barriers:
- skin: wind blows bacteria away, fatty acids and anti- bacterial peptides, have commensal bacteria (normal flora take up space so bad bacteria can’t invade).
- GI tract: flow of fluid pushes away bacteria, low pH, enzymes and anti- bacterial peptides. Also has commensal bacteria.
- lungs: bacteria trapped in mucas, moved by cilia, has anti bacterial peptides.
- eyes/nose: tears wash away bacteria in eyes, cilia in nose push away bacteria in nose. Have lysozymes to hydrolyse bacteria.
- Phagocytosis and Inflammation: if pathogens breach epithelia, they are spotted by macrophages and phagocytosed. Macrophages release cytokines (a molecule that changes the behaviour of another cell) like chemokines (causes migration and activation of other cells). These cytokines recruit neutrophils and monocytes from the bloodstream to the site of infection.
- Complement Pathways
- Induced Innate Responses
7
Q
Describe phogocytosis?
A
- Macrophages have receptors for bacterial characteristics.
- Mannose receptor
- Scavenger receptor
- Lipopolysaccharide (LPS) receptor (CD14)
- Glucan receptor
- Binding to receptor causes phagocyosis. The bacterial cell is internalised to form a phagosome within the macrophage.
- A lysosome fuses with the phagosome to hydrolyse the bacteria.
8
Q
What are the three roles of inflammation?
A
- Delivers effector cells to infection site to kill bacteria, because macrophages release cytokines which requite monocytes and neutrophils.
- Promotion of blood clotting at the site of infection to provide a barrier against further spread.
- Promotion of tissue repair.
* Cytokines also induce dilation of the blood vessel.
* Chemokines also induce production of adhesion molecules on the surface of the blood vessels. These anchor neutrophils and monocytes that would normally flow past.
* Neutrophils and monocytes migrate into tissue in a process known as extravasation. Monocytes differentiate into macrophages during extravasation. Net Result: Tissue phagocytes are reinforced and tissue becomes inflamed.
9
Q
The role of neutrophils in phagocytosis?
A
- Neutrophils are short lived phagocytes and normally die after one round of phagocytosis.
- They form the major component of pus in abscesses/boils caused by pyogenic bacteria.
10
Q
The role of dendritic cells in inflammation?
A
- Dendritic cells are abundant in the tissue underlying epithelium.
- Phagotyse pathogens, present them at lymph nodes to T cells. This is when they become mature.
- Because the T cells then begin the adaptive immune response, dendritic cells are said to bridge innate and adaptive immunity.
11
Q
What is a complement?
A
- These are plasma proteins that fight infections.
- They can oponise (change the surface of a pathogen) so it can be phagotosed.
- They can also start inflammation.
12
Q
What are the triggers for each complement pathway to begin?
A
- Classical Pathway: the trigger are antigen/antibody complexes, or the surface of pathogens.
- Alternative Pathway: the trigger is the surface of pathogens.
- Lectin Pathway: the trigger is carbohydrate on pathogen surfaces.
C3 convertase is made, and triggers the pathway to happen. The end result for all three pathways is the same (inflammation, oponisation or killing of the pathogen).
13
Q
Describe Alternative Pathway Activation
A
- The alternative pathway is initiated by the constant and spontaneous hydrolysis of C3 to C3a and C3b
- C3b is very unstable.
- The surface of bacteria / pathogens have abundant amino acids and hydroxyl groups that will stabilise C3b.
- Once C3b is stabilised on the pathogen surface, factor B is bound by C3b.
- Then, this is converted by factor D to form C3bBb on the pathogen surface. C3bBb acts as a C3 convertase.
- The C3bBb complex is stabilised by properdin.
- As C3bBb is a C3 convertase, the stabilised complex can rapidly convert C3 to C3b.
- A positive feedback loop of C3 conversion to C3b begins.
- This means large amounts of C3b are rapidly deposited on the pathogen surface by C3bBb.
- This C3b acts as an opsonin meaning that pathogens coated in C3b are rapidly phagocytosed by macrophages containing C3b receptors.
- C3bBb also converts another complement protein C5 to C5a and C5b. (So can C3b2Bb)
- C5a promotes inflammation.
- C5b adheres to the surface of the pathogen and bind C6,C7 and C8.
- C8 allows up to 16 C9 molecules to insert into the membrane of the pathogen forming a pore. This makes the pathogen lose its structural integrity.
- This is known as a the membrane attack complex.
14
Q
What prevents the complement system attacking our own cells?
A
A group of proteins present in blood plasma and on the surface of cells called complement control proteins prevent complement attacking our own cells.
15
Q
Describe Classical Complement Pathway
A
- The C1 complex is made up of C1q, C1r and C1s.
- The C1 complex binds to the pathagon using an antibodies on the pathogen surface that are natura (IgM) or adaptive.
- The C1 complex may bind directly to the surface of the pathogen also.
- This activates the C1r domain of the C1 complex.
- This then activates the C1s domain, allowing it to breakdown the C4 complement into C4 a and C4b.
- C4b then binds to the pathogen surface.
- C1s also cleaves C2 to C2a and C2b.
- C2a and C4b bind to form C4b2a on the pathogen surface.
- C4b2a is a C3 convertase.
- It forms lots of C3b which sticks to the pathogen’s surface and causes opsonisation.
- C4b2a can bind C3b to form C4b2a3b. This is a C5 convertase.
- C5a promotes inflammation.
- C5b binds C6, C7 and C8. C8 allows up to 16 C9 molecules to insert into the membrane of the pathogen forming a pore. This is the membrane attatck complex, killing the pathogen.
