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2052 DYLAN > innate immune system > Flashcards

innate immune system Flashcards

1
Q

Key components of the innate immune system

A
  • Epithelial barriers
    • Phagocytes
      ○ Neutrophiles, monocytes, macrophages, dendritic cells
    • Innate cell of type 2 immunity
      ○ Mast cells, eosinophils, basophils
    • Innate lymphoid cells
      ○ ILC1,2,3 and Nk cells
    • Innate T cells
      ○ Nk cells
      Complement
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2
Q

Innate vs Adaptive

A
  • Day 0
    ○ Billions of IIC respond
    ○ Only tens of adaptive immune cells can respond
    ○ 2 weeks post
    • Adaptive immune response increases
    • PRR broadly specific and cannot distinguish between PAMPS
    • Antigen receptors unique and specific
      The innate immune response has no conventional memory
  • each innate immune cell can express many PRR
  • adaptive immune cell express a single Ag receptor
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3
Q

Physical barriers prevent pathogen entry

A
  • Epithelial cells express PRR upon activation and secrete chemokines and cytokines to recruit IIC
    • Mucosal epithelial cells can secrete antimicrobial compounds
      ILC3 and th17 can secrete IL-22 which promotes defensin secretion, epithelial cell proliferation and barrier integrity
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4
Q

Mucociliary transport

A
  • Epithelial cells from a barrier
    • Goblet cells secrete mucus
    • Cilia
      ○ Protrude luminal surface of epithelial cells
      ○ Move mucus
      ○ Defected in smokers, anaesthetics, infections, CF
      § Recurrent respiratory infections
      CF fills airway with thick mucus blocking airway and allowing bacteria to stick and not move out
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5
Q

Complement

A

A series of serum proteins (C1-C9) that collectively form a biochemical pathway

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6
Q

Alternative pathway

A

non-specific chemical reaction

- C3 spontaneously hydrolyses to form C3a and C3b
- C3b then form a C3 convertase which triggers the rest of the pathway
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7
Q

Classical pathway

A

activate by complexes of antibody with antigen

- C1q recognises IgG or IgM bound to antigen
- C1q also contains proteases that cleave C4
- C2 is then cleaves generated the C3 convertase
- C3b converts the C3 convertase into a C5 convertase
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8
Q

Lectin pathway

A

triggered by recognition of unique microbial carbohydrates

- Mannose binding lectin (MBL) is a soluble PRR that binds to mannose found on surface of microbes
- Proteases associated with MBL cleave C4
- The rest is the same as the classical pathway
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9
Q

lysis by complement

A

C5 gets cleaved into C5a and C5b
C5a is a very potent pro-inflammatory factor
C5b stuck on microbe surface initiates assembly of membrane attack complex (MAC) comprised of C5b, C6, C7, C8 and C9
Mac generates pores in membrane causing lysis by osmotic shock

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10
Q

inflammation by complement

A

Proteolysis of C3 and C5 release C3a and C5a
Leucocytes have receptors for C3a and C5a
C3a and C5a are chemo attractants

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11
Q

opsonisation by complement

A

All complement pathways deposit C3b on cell surface
Phagocytes have receptors for C3b
A microbe covered in C3b recognised by complement receptor, activating phagocyte leading to phagocytosis

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12
Q

macrophages

A
  • Long lived
    • All tissues
    • Antigen presenting
    • Can differentiate
      ○ M1 inflammatory macrophages secrete pro-inflammatory cytokines
      M2 anti-inflammatory macrophages wound healing immunoregulation
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13
Q

monocytes

A
  • Mononuclear phagocyte
    • Upon inflammation and infection, monocytes leave and differentiate into macrophages
      Monocyte arrive slower than neutrophils (2-3 days vs 2-3 hours)
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14
Q

Neutrophils

A
  • Most common
    • Short lived
    • Rapidly migrate out of circulation to site
    • Non presenting antigen
    • Effective killers of rapidly growing extracellular organisms
      ○ Phagocytosis
      ○ Degranulation
      § Release granules that contain ant-bacterial proteins
      ○ Neutrophil extracellular traps (NETS) that are a DNA web released, trap and destroy extracellular bacteria
      Some bacteria escape by secreting DNAse
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15
Q

Phagocytosis

A
  • PRR specialised in uptake bind to microbes
    • Microbial uptake into phagosome
    • Phagosome fuses with lysosome, degrading the microbe
      Mycobacteria block phagolysosome fusion + acid resistant
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16
Q

4 major classes of PRR’s

A
  • Toll-like receptors (TLR)
    • Rig-like helicases (RLH)
    • Nod-like Receptors (NLR)
      C type Lectin receptors (CLR)
17
Q

TLR

A
  • Expressed on surface or in endosomes

Recognise PAMPS from a diversity of pathogens

18
Q

CLR

A
  • Expressed on surface
    • Recognise polysaccharides expressed by pathogens
      ○ Dectin-1 glucan, fungal cell wall
      ○ Dectin-2 mannan, fungal cell wall
      DC-sign n-linked mannan expressed in mycobacteria and viruses
19
Q

RLH

A
  • Located on cytoplasm

Recognise viral dsRNA

20
Q

NLR

A
  • Cytoplasmic

Damage associated molecular patterns (DAMPS)
Are released upon cellular damage

21
Q

5 pillars of inflammation

A
  • Heat
    • Redness
    • Swelling
    • Pain
      Loss of function
22
Q

Tissue resident macrophages activated via pattern recognition

A
  • Cytokines activate vascular endothelium leading to vasodilation and increase in vascular permeability (redness, heat, swelling)
    • Chemokines recruit leucocytes (pain, loss of function)
    • Neutrophils are the first to arrive
      Monocytes take 2-3 days
23
Q

Inflammasome

A
  • Multimeric complex comprised of NLR, the adaptor protein and protease caspase 1
    • Structure forms after the NLR binds its ligand
    • Cleaves IL-1b
      ○ Requires 2 signals
      § PRR recognition leads to transcription and translation of Pro-IL-1b
      Cleavage of Pro-IL-1b by inflammasome
24
Q

Stages in leucocyte recruitment

A
  1. Cytokines activate vascular endothelium
    1. Selections: adhesion molecules allow leucocytes to roll on the vascular endothelium
    2. Chemokines: activate integrins to become high affinity
    3. Integrins: adhesion molecules that allow leucocytes to stably adhere
  2. Leucocyte transmigrate out of vasculature and follow chemotactic gradient towards the site of infection
25
Q

Triggering PRR leads to type I interferon production

A
  • Type 1 interferons (IFNa and IFNb) are cytokines with potent antiviral activity
    • Signalling through type I receptor
      ○ Inhibits viral protein
      ○ Degrades viral RNA
      ○ Inhibits viral gene expression and virion assembly
    • Type I also activate
      ○ NK cells
      Dendritic cells
26
Q

NK cells

A
  • Innate equivalent of CD8 cells

Activated by IFN

27
Q

Dendritic cells

A
  • Bridge between innate and adaptive immune system
    • Activate naïve t cells
    • Morphology maximises contact with T cells
    • Short life
      Only APC to active naïve T cells
28
Q

MHC

A
  • Class 1 presented by all nucleated cells

- Class 2 presented by only professional antigen presenting cells

29
Q

MHC signal recognition

A

Peptide displayed is recognised by t cell receptor

30
Q

Costimulation

A
  • CD80 and CD86 interact with T cell CD28

CD28 transduces signals (signal 2) that synergise with signal 1 and lead to T cell proliferation

31
Q

Cytokine production

A

Dendritic cells secrete cytokines to drive t cell differentiation

32
Q

Dendritic cells

A 
- Quiescent/ immature 
		○ High phagocytic 
		○ Low mhc II
		○ Low costimulation
	- Mature
		○ Low phagocytic
		○ High mhc II
		○ High costimulation
Activated by PAMPs
33
Q

triggering PRR on dendritic cells

A

○ Increases MHC and antigen expression
○ Increases cytokine production
Increases costimulation

2052 DYLAN (12 decks)

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