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BDS2 HHD - Immunology > 2. Innate Immunity > Flashcards

2. Innate Immunity Flashcards

1
Q

LOs

A
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2
Q

innate vs adaptive immunity?

A

Innate Immunity:
1. Non-specific (no memory)
2. Immediate

Adaptive Immunity:
1. Specific (memory)
2. Delayed

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3
Q

INNATE IMMUNITY

  1. what organisms does it occur in?
  2. extra (make q)
A

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
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4
Q

process/ steps of infection on physical barriers?

A
  • 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
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5
Q

MUCOSAL EPITHELIA

  1. what?
  2. where?
  3. why helpful?
A

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

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6
Q

Epithelial barriers to infection examples
(MAIN BARRIERS)

A

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

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7
Q

ANTIMICROBIAL PEPTIDES

    • secreted by/ come from?
    • why/ when secreted?
  2. what do they do?
A
    • 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
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8
Q

COMPLEMENT CASCADE

  1. possible pathways?
  2. what happens/ what is it?
  3. what does complement activation result in?
A

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

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9
Q

MAKE Q OR DELETE???

A

CASCADE OF EVENTS

  • collection of proteins aimed at detecting microbes + generating a response
  • tissue fluid is rich in these proteins
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10
Q

CLASSICAL PATHWAY

1
activated by?

2
what does C1q interact with?

A

1
C1q component

2
* C1q interacts with
antibody:antigen complexes

  • Can bind directly to pathogen surfaces
  • Provides a link between innate and
    adaptive immunity
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11
Q

classical pathway activation

A

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

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12
Q

MANOSE-BINDING LECTIN PATHWAY
(M-B lectin pathway)

1
activated by?

2
what is lectin?

3
Is mannose visible?

A
  • 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

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13
Q

ALTERNATIVE PATHWAY

1
when does it occur

2
initiated via?

3
extra points

A
  • 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

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14
Q

what happens during the alternative pathway?

A
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15
Q

what happens when complement cascade is completed?

A
  • 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

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16
Q

Complement - Inflammatory mediator effects?

A
  • makes it easier for immune cells to move up conc-grad
    (low to high)
17
Q

What happens during complement opsonisation?

A
  • 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.
18
Q

The Complement Membrane Attack Complex

what happens?

A
19
Q

Complement cascade KEY POINTS?

1
pathways

2
leads to

A

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

20
Q

cells involved in the innate immune system?

A
21
Q

IMMUNE CELLS
cells / litre

  1. T-cells
  2. B-cells
  3. Monocytes
  4. neutrophils
A

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

22
Q

PHAGOCYTIC CELLS
1. MAIN TYPES INVOLVED IN INNATE IMMUNITY

  1. 3RD TYPE
A

1
* 2 main types –

  1. Neutrophils (also called PMNs –
    Polymorphonuclear cells).
     Constitute ~75% of all immune cells in the
    blood
  2. Monocyte/Macrophages
    * Monocytes in the blood, Macrophages in
    tissue

2
- 3rd type – Dendritic cells
- Linked with adaptive immunity

23
Q

HOW DOES PATHOGEN RECOGNITION OCCUR?

A
  • Can be via opsonisation i.e. with antibodies or Complement pathway
  • Can also be via Pathogen Recognition Receptors - PRRs
24
Q

What are PRRs?

A
  • 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
25
Q

Effects of pathogen recognition

A
  • Phagocytosis
  • Secretion of inflammatory mediators
  • Secretion of cytokines (= communication network)
26
Q

CYTOKINES

  1. what?
  2. secreted by?
  3. involved in/ func?
A

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

27
Q

categories/ types of Cytokines?

A

Several different categories:

  1. Pro-inflammatory cytokines
  2. Anti-inflammatory cytokines
  3. Growth factors/Colony Stimulating Factors
  4. Chemokines
  5. Type I Interferons
28
Q

PRO-INFLAMMATORY CYTOKINES

  1. include?
  2. what do they induce?
A

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

29
Q

ANTI-INFLAMMATORY CYTOKINES

  1. include?
  2. mediate what?
A
  • Not necessarily anti-inflammatory
  • Antagonistic to pro-inflammatory cytokines

1
* Include IL-4 and TGF-b

2
* They can mediate the adaptive immune
response

30
Q

GROWTH FACTORS/ COLONY STIMULATING FACTORS
1. important for?
2. stimulate what?

A

1
* Important in development of immune cells
* CSFs stimulate differentiation into different cell types

2
* Growth factors stimulate cell growth!

31
Q

what do chemokines do?

A
  • Attract/recruit immune cells to the site of infection or inflammation
  • Different chemokines attract different cell types
32
Q

TYPE I INTERFERONS

  1. produced by?
  2. what do they do?
A

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

33
Q

Timeline of infection?

A
  1. Physical barrier – e.g. Epithelium
  2. Natural humoral components – e.g.
    Antimicrobial peptides, Complement
  3. Pathogen recognition by Pattern
    Recognition Receptors on cells
  4. Recruitment and activation of
    phagocytic cells
  5. Activation of adaptive immunity

BDS2 HHD - Immunology (7 decks)

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