2. Innate Immunity Flashcards
LOs
innate vs adaptive immunity?
Innate Immunity:
1. Non-specific (no memory)
2. Immediate
Adaptive Immunity:
1. Specific (memory)
2. Delayed
INNATE IMMUNITY
- what organisms does it occur in?
- extra (make q)
1
* Exists in plants, invertebrates and fungi
as well as all vertebrates
2
* As a mark of its importance, most
pathogens have evolved mechanisms to
either subvert or avoid it
- non specific hence doesn’t recognise specific molecule, recognise all types of path, prod immediate response
- Evolutionary old
process/ steps of infection on physical barriers?
- pathogen adheres to surface (epithelium)
- local infection, penetration of epithelium
- induces local responses within tissue + local infection of tissues
- innate system then leads into adaptive immune response
MUCOSAL EPITHELIA
- what?
- where?
- why helpful?
1
include any secretory/ absorptive surfaces
2
usu gut, lungs, urogenital tract
3
- mucous coats microbes + makes it harder for microbes to adhere to the surface
- also traps microbes so can be cleared out
- mucus flows over surface continually, drawing microbes away
Epithelial barriers to infection examples
(MAIN BARRIERS)
MECHANICAL BARRIERS
~ epithelial cells bound together by tight junc to
prevent basolateral entry of microbes into
tissues
~ movement of air & cilia prevent microbes from
entering
CHEMICAL BARRIERS
~ fatty acid secretion on skin prevents microbes
survive
~ low pH & enzyme activity
~ salivary enzymes (lysozymes)
~ stomach acid (decreases pH, digest + destroy
microbes)
MICROBIOLOGICAL
~ ‘good’ flora - occupy niches so other bacteria
can’t & they prevent their survival by
competitive exclusion
ANTIMICROBIAL PEPTIDES
- secreted by/ come from?
- why/ when secreted?
- what do they do?
- secreted by epithelial cells
- target microbes
- can be as small as 20-30 peptides
- include alpha defensins
- include beta defensins
- Other proteins include lysozme, lactoferrin,
phospholipase A, histatins etc. - Secreted by epithelial cells naturally or upon
stimulation. - Most kill by damaging the microbial cell
wall/membrane
- Other proteins include lysozme, lactoferrin,
COMPLEMENT CASCADE
- possible pathways?
- what happens/ what is it?
- what does complement activation result in?
1
- classical pathway
- MB-lectin pathway
- alternative pathway
2
- CLASSICAL PATHWAY
~ antibody:antigen complexes
- MB-LECTIN PATHWAY
~ lectin binding to pathogen surfaces
- ALTERNATIVE PATHWAY
~ pathogen surfaces
all of these pathways result in complement activation
3
- recruitment of inflammatory cells
- opsonisation of pathogens
- killing of pathogens
MAKE Q OR DELETE???
CASCADE OF EVENTS
- collection of proteins aimed at detecting microbes + generating a response
- tissue fluid is rich in these proteins
CLASSICAL PATHWAY
1
activated by?
2
what does C1q interact with?
1
C1q component
2
* C1q interacts with
antibody:antigen complexes
- Can bind directly to pathogen surfaces
- Provides a link between innate and
adaptive immunity
classical pathway activation
C1 protein complex ( C1q, C1r, C1s ) associate and bind to antibody/antigen complex
Activates C1s Protein
- cleaves C4 and C2
Cleaves C4 protein into 2 parts - C4a + C4b
- C4b binds to microbial surface + C4a floats off
C4b binds to C2b = C4b2b on pathogen surface
- C2a acts as anaphylatoxin , stimulates inflammatory cells
C4b2b acts as a C3 convertase to cleave C3
- C3a acts as an a anaphylatoxin
-C3b binds to C4b2b complex
- multiple molecules of C3 can be cleaved, multiple C3b can bind to C4b2b complex
MANOSE-BINDING LECTIN PATHWAY
(M-B lectin pathway)
1
activated by?
2
what is lectin?
3
Is mannose visible?
- Similar to the Classical pathway
1
* Activated by Mannose-binding Lectin
2
* Lectin = carbohydrate-binding protein
(mannose = carbohydrate)
3
* ‘visible’ mannose is common on many pathogens but rare on vertebrate cells
ALTERNATIVE PATHWAY
1
when does it occur
2
initiated via?
3
extra points
- Discovered second
1
* Occurs in the absence of antibody
2
* Initiated via the spontaneous cleavage of C3
~ Does not require a pathogen-binding
protein
3
* Incorporates several specific components
* Can amplify the classical/MBL pathways
what happens during the alternative pathway?
what happens when complement cascade is completed?
- All pathways lead to activation of C3 and C5
- C3a and C5a are inflammatory mediators – they recruit immune cells and activate others
C5b does not covalently bind to the pathogen surface, unlike C4b and C3b
Complement - Inflammatory mediator effects?
- makes it easier for immune cells to move up conc-grad
(low to high)
What happens during complement opsonisation?
- Many microorganisms have evolved coats or capsules to hide from phagocytic cells
- However, phagocytic cells such as macrophages and neutrophils have receptors for active complement proteins e.g. C3b
- These receptors improve binding and
recognition of the pathogen and subsequent
phagocytosis.
The Complement Membrane Attack Complex
what happens?
Complement cascade KEY POINTS?
1
pathways
2
leads to
1
* 3 pathways of activation
1. Classical pathway
2. M-B lectin pathway (mannose binding)
3. Alternative pathway
- Purely an innate response
2
* Leads to 3 events:
1. Recruitment of immune cells
2. ‘Opsonisation’ of pathogens
3. Killing of pathogens
cells involved in the innate immune system?
IMMUNE CELLS
cells / litre
- T-cells
- B-cells
- Monocytes
- neutrophils
1
* T-cells - 1.0 – 2.5 x 10^9 cells/litre
2
* B-cells - ~0.3 x 10^9 cells/litre
3
* Monocytes - 0.15 – 0.6 x 10^9cells/litre
4
* Neutrophils - 3.0 – 5.5 x 10^9 cells/litre
PHAGOCYTIC CELLS
1. MAIN TYPES INVOLVED IN INNATE IMMUNITY
- 3RD TYPE
1
* 2 main types –
- Neutrophils (also called PMNs –
Polymorphonuclear cells).
Constitute ~75% of all immune cells in the
blood - Monocyte/Macrophages
* Monocytes in the blood, Macrophages in
tissue
2
- 3rd type – Dendritic cells
- Linked with adaptive immunity
HOW DOES PATHOGEN RECOGNITION OCCUR?
- Can be via opsonisation i.e. with antibodies or Complement pathway
- Can also be via Pathogen Recognition Receptors - PRRs
What are PRRs?
- PRRs recognise Pathogen Associated Molecular Patterns (PAMPs)
- These are ‘types’ of molecules, rather than a specific molecule – i.e. C/G rich DNA, double stranded RNA, oligosaccharides, lipoproteins
etc - PRRs include Toll-Like Receptors (TLRs), C-Type Lectins (CLRs) and others
Effects of pathogen recognition
- Phagocytosis
- Secretion of inflammatory mediators
- Secretion of cytokines (= communication network)
CYTOKINES
- what?
- secreted by?
- involved in/ func?
1
* Small glycoproteins
* Similar to hormones
2
* Unlike hormones, they are not secreted by a specific organ – secreted by a wide variety of cells
3
* Involved in cellular communication
* Extensively involved in both innate and adaptive
immunity
categories/ types of Cytokines?
Several different categories:
- Pro-inflammatory cytokines
- Anti-inflammatory cytokines
- Growth factors/Colony Stimulating Factors
- Chemokines
- Type I Interferons
PRO-INFLAMMATORY CYTOKINES
- include?
- what do they induce?
1
IL-1a, IL-1b, TNFa and Interferon-g
IL = interleukins
- a = alpha
- b = beta
- g = gamma
2
- Induce many of the effects associated with
inflammation
– e.g. activation of macrophages
stimulation of inflammatory mediator release,
activation of adaptive immunity, pyrexia
ANTI-INFLAMMATORY CYTOKINES
- include?
- mediate what?
- Not necessarily anti-inflammatory
- Antagonistic to pro-inflammatory cytokines
1
* Include IL-4 and TGF-b
2
* They can mediate the adaptive immune
response
GROWTH FACTORS/ COLONY STIMULATING FACTORS
1. important for?
2. stimulate what?
1
* Important in development of immune cells
* CSFs stimulate differentiation into different cell types
2
* Growth factors stimulate cell growth!
what do chemokines do?
- Attract/recruit immune cells to the site of infection or inflammation
- Different chemokines attract different cell types
TYPE I INTERFERONS
- produced by?
- what do they do?
1
* Produced by all cells in response to viral
infection
2
* They:
1. Render surrounding cells non-permissive to
infection/viral replication
2.Activate immune cells to destroy the infected
cell
Timeline of infection?
- Physical barrier – e.g. Epithelium
- Natural humoral components – e.g.
Antimicrobial peptides, Complement - Pathogen recognition by Pattern
Recognition Receptors on cells - Recruitment and activation of
phagocytic cells - Activation of adaptive immunity
