How is a normal infection response and protection carried out?
What are mucosal epithelia?
Secretory/absorption surfaces
Where are mucosal epithelia located?
They line externally exposed cavities of the body e.g. gut, lungs, etc.
Why do many mucosal epithelia secrete mucus?
Because mucus-coated microbes find it harder to adhere to surfaces
Mucus flows over the surface continually, drawing microbes away
What are antibacterial peptides?
Small peptides (typically from 70aa up)
Include alpha/beta defensins, S100As, cathepsins, cryptdins
Other proteins include lysozyme, lactoferrin, phospholipase A, histains etc.
What are antibacterial peptides secreted by and how do they kill?
Secreted by epithelial cells naturally or upon stimulation
Most kill by damaging the microbial cell wall/membrane
What are some other physical defences?
Tight junctions = tight barrier
Gut enzymes
Low/High PH
Mechanical actions e.g talking and chewing can help dislodge microbes from the Buccal surfaces
What is the classical pathway activated by and what does it do?
C1q component which interacts with antibody:antigen complexes
They can bind directly to pathogen surfaces as well and provides a link between innate & adaptive immunity
Describe the classical pathway activation:
C2a - acts as a anaphylatoxin which stimulates inflammation
C3a also has similar activity as C2a
What is the mannose-binding lectin pathway activated by?
Mannose-binding lectin (MBL) - This pathway is v similar to the classical pathway
What is lectin?
A carbohydrate-binding protein
When does the alternative pathway occur and how is it initiated?
Occurs in the absence of antibody and it can amplify the classical/MBL pathways by increasing C3b we see present on the surface of the microbe.
Initiated via the spontaneous cleavage of C3- doesn't require a pathogen-binding protein
Where is 'visible' mannose commonly located?
On pathogens (but rarely on vertebrate cells)
What do all pathways lead to activation of?
C3 & C5
How does C5b differ from C4b & C3b?
C5b doesn't covalently bind to the pathogen surface, unlike C4b & C3b
What affect do these small components from the complement system have?
Small component-cleavage products act on blood vessels to increase vascular permeability and cell-adhesion molecules (C3a, C5a and C4a)
What are C3a and C5a?
Inflammatory mediators- they recruit immune cells & activate others
Describe opsonisation.
- microorganisms have evolved coats/capsules to hide from phagocytic cells
-phagocytic cells however have receptors for complement proteins such as C3b. (Formed in one of the 3 complement pathways and attach onto the surface of the microbe)
-These receptors improve binding and recognition of the pathogen, allowing phagocytosis to occur regardless of them having coats to hide in
Describe the complement membrane attack complex.
What is the membrane attack complex (MAC) also known as?
The terminal pathway
The MAC directly lyses target cells (such as bacteria or infected cells) by creating pores in their membranes.
What are the 2 categories of Innate immune cells?
Myloid cells (shown in picture)
Lymphoid cells - majority are adaptive immune cells
What are the 3 points you need to remember about complement?
1. There are 3 pathways of activation
2. Purely an innate response
3. It leads to 4 events:
-recruitment of immune cells
-'opsonisation' of pathogens
-killing of pathogens
-activation of inflammation
What are the 2 main types of phagocytic cells?
1. Neutrophils- constitute ~75% of all immune cells in blood2. Monocytes/macrophages- monocytes in blood, macrophages in tissue
Dendritic cells are also phagocytic cells but used as a link to the adaptive immune system
How do phagocytic cells recognise pathogens?
Via opsonisation
Or by PRRs (pattern recognition receptors)
What do PRRs recognise?
PAMPs (pathogen associated molecular patterns),
they recognise a type of molecule rather than a specific molecule
What are the effects of pathogen recognition?
Phagocytosis
Secretion of inflammatory mediators
Secretion of cytokines
How does innate immune cell communication work?
By cytokines
What are cytokines?
Small glycoproteins similar to hormones but unlike hormones, they're not secreted by a specific organ, rather a wide variety of cells
Are cytokines specific to innate immunity?
No, they're common to both innate & adaptive although there are a few that are unique to only one
What are some different cytokine categories?
Pro-inflammatory cytokines
Anti-inflammatory cytokines
Growth factors/colony stimulating factors
Chemokines
Type I interferons
What do pro-inflammatory cytokines include and what do they induce?
-Induce many effects associated with inflammation
-induces swelling and oedema
Are anti-inflammatory cytokines actually anti-inflammatory?
Not necessarily, they're just antagonistic to pro-inflammatory cytokines
What do anti-inflammatory cytokines include?
IL-4 & TGF-beta
They can mediate the adaptive immune response
What are growth factor/CSF important in and what do they do?
Important in development of immune cells
Growth factors stimulate cell growth
CSFs stimulate differentiation into different cell types
What do chemokines do?
Attract/recruit immune cells to the site of infection or inflammation
Different cytokines attract different cell types
What are type I interferons produced by?
All cells in response to viral infection
What do type I interferons do?
1. Render surrounding cells non-permissive to infection/viral replication
2. Activate immune cells to destroy the infected cell
What is the timeline of innate immunity before adaptive immunity is activated?