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YEAR 2 S2 IMMUNO > Theme 2 - innate 2a > Flashcards

Theme 2 - innate 2a Flashcards

1
Q

describe innate immunity

what triggers it

A
  • first line of defence
  • fast
  • from birth
  • triggered by: tissue damage from TRAUMA or INFECTION causes series of CELLULAR and CHEMICAL events which aim to limit SPREAD, ELIMINATE microorganisms and repair damage
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2
Q

what are the cells of the innate immune system

A 
PHAGOCYTES 
- neutrophils
- monocytes and macrophages
- B cells
- mast cells 
- eosinophils 
ANTIGEN PRESENTING CELLS 
- monocytes
- macrophages
- dendritic cells 
- (B cells)
OTHERS
- NK cells
- innate lymphoid cells
- NKT cells
- gamma delta T cells
- eosinophils
- B1 cells
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3
Q

innate immunity comprises which 4 main types off defensive barriers/mechanisms

A
  • anatomical
  • physiological/chemical
  • phagocytic/endocytic
  • inflammatory
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4
Q

describe anatomical barriers in innate immunity

A

SKIN

  • mechanical barrier preventing entry of microbes
  • dead skin sloughs off
  • acidic (pH 3-5)
  • commensal microflora secrete BACTERIOCINS and METABOLITES eg LACTIC ACID

MUCOSAL SURFACES

  • cilia propulsion (nasal/bronchial)
  • mucus entrapment
  • secretions: urine, saliva, tears, milk
  • competition for ATTACHMENT and NUTRITION
  • epithelial cells joined by tight junctions
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5
Q

describe physiological barriers in innate immunity

A

TEMPERATURE
- fever inhibits bacterial growth and aids our enzymes
LOW pH
- acid of stomach
CHEMICALS MEDIATORS/ANTIMICROBIAL
- proteins/enzymes: Lysozyme (in tears/saliva, cleaves peptidoglycans in of bacterial cell walls), Lactoferrin (binds essential nutrients, inhibiting bac/fungal growth)
- peptides: Defensins, Cathelicidins, Histadin, Dermicin
- S100 proteins
- surfactant proteins

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6
Q

what do S100 proteins do

A

Psoriasin:

  • in secretions and on skin
  • disrupts microbial cell membranes
  • potent against E. coli but not S. aureus
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7
Q

what do surfactant proteins do

A
  • found mainly in resp tract
  • block bacterial surface components by BINDING to them
  • have lubricating function
  • SP-A, SP-D
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8
Q

what do defensins do

A
  • POSITIVELY charged polypeptides that bind NEG charged microbial structures eg LPS, LTA
  • aggregate to form pores in CYTOPLASMIC MEMBRANES
  • activate complement-classical pathway
  • found on skin and all mucosal surfaces
  • most abundant protein in neutrophil granules
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9
Q

what are cathelicidins

A
  • antimicrobial peptides that disrupt microbial membranes (esp bacteria)
  • mainly on mucosal surfaces
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10
Q

who had a key role in phagocytosis

A

Ilya Metchnikoff- found some specialised cells have a role in defence

  • studied ability of cells in transparent daphnia and starfish to SURROUND objects introduced to them
  • described phagocytosis as WBC ‘eating’ foreign particles
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11
Q

what is cellular uptake for

what are the mechanisms used

A
  • acquire nutrients
  • sample surrounding env
  • defence mech
    Mechanisms:
  • pinocytosis
  • macro-pinocytosis
  • receptor-mediated endocytosis/phagocytosis
    (most cells use PINO and RECEPTOR MEDIATED)
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12
Q

what is pinocytosis

A
  • cell ‘drinking’
  • brings in nutrients
  • helps in osmoregulation
  • molecules internalised by NON SPECIFIC invagination of plasma memb
  • dep on external conc
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13
Q

what is macro-pinocytosis

A
  • ‘larger gulps’
  • same functions as pinocytosis
  • potential role in recycling MEMBRANE RECEPTORS or PLASMA MEMBRANE
  • helps ANTIGEN processing for immune response
  • some microorganisms (viruses) use this to infect cells
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14
Q

what is receptor-mediated endocytosis

A
  • the SPECIFIC uptake of a LIGAND, GF, HORMONE, IMMUNE COMPLEX
  • clustering of receptors and association of CLATHRIN around ‘pits’ form endosomes
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15
Q

what is phagocytosis

what carries it out

A
  • carried out by specialised cells that INTERNALISE, KILL and DIGEST PARTICULATE matter
  • monocytes/macrophages, neutrophils, dendritic cells, eosinophils, B cells, mast cells
  • clustering of cell surface receptors
  • CYTOSKELETAL REARRANGEMENT and ENERGY
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16
Q

what are the 4 stages of phagocytosis

A

1 recognition
2 ingestion
3 digestion
4 exocytosis

17
Q

what happens in the DIRECT recognition stage of phagocytosis

A

DIRECT (non-opsonic)
- Pattern Recognition Receptors (PRRs) on phagocytes bind to Pathogen Associated Molecular Patterns (PAMPs) or to Damage Associated Molecular Patterns (DAMPs) on particles/microbes

18
Q

what does PRR stand for

A

Pattern Recognition Receptors

19
Q

what does PAMPs stand for

A

Pathogen Associated Molecular Patterns

20
Q

what does DAMPs stand for

A

Damage Associated Molecular Patterns

21
Q

what happens in the INDIRECT recognition stage of phagocytosis

A

(opsonic)

- receptors on phagocytes bind OPSONINS coating the surface of particulate matter/microbes

22
Q

give some exaples of PAMPs

A

LPS on G-ve
glycolipids, peptidoglycans and lichotechoeic acid on G+ve
Flagellin

23
Q

in what situations may DAMPs be expressed

A
  • our own cells that have gone wrong
  • cell may have undergone necrosis and released ssRNA
  • short chain f.a in diet
  • if a cell is apoptotic then it may express PHOSPHATIDYLSERINE, RNA, HDL and VITRONECTIN on surface of damaged/apoptosic cells
  • clearing and tissue/limb development
24
Q

what are the main types of PRRs

A

C type lectin receptor
Scavenger receptors
Toll-like receptors

Others:
NOD-like receptors
RIG-like recepotrs
AIM2-like receptors

25
Q

what does lectin have specificity for
what do C type lectin receptors
what does the mannose receptor do

A
  • lectin has specificity for CARBOHYDRATE
    Mannose receptor:
  • bind mannose
  • on surface of most macrophages and DCs
  • 8 extracellular domans and cytoplasmic tail
26
Q

what do C type lectin receptors

what does the dectin-1 receptor do

A
  • binds beta1-3 glucan

- expressed on a wide variety of myeloid lineage cells

27
Q

what do C type lectin receptors

what does the DC-SIGN receptor do

A
  • binds mannans on bacteria, fungi and parasites
28
Q

what do scanvenger receptors do

where is SR-A found

A

they bind APOPTOTIC/NECROTIC cells
- mainly bind DAMPs
SR-A
- found on all macrophages and some endothelial cells, binds modified low density LIPOPROTEIN (eg ox LDL)

29
Q

what do scanvenger receptors do

where is SR-B found

A
  • includes CD36 on endothelium, DC, platelets, MC and macrophages
  • bind altered ‘self’ molecules eg ox LDL/vimentin
  • also recognises some PAMPs
30
Q

identified in what
how
what was identified
what do toll-like receptors do

A
  • identified in Drosphila

- TLR4 identified using mous knockouts

31
Q

describe toll like recepotrs

A
  • leucine rich repeats of external domain specific for a set of PAMPs or DAMPs
  • can be HOMO or HETERO dimers
  • memb bound but some sample the contents of endocytic vesicles
  • most cells have INTRACELLULAR TLRs- detect DNA/RNA associated with viruses and induce TYPE I INTERFERONS (cytokines w/ antiviral effects)
  • cell surface TLRs expressed by IMMUNE cells and strongly associated w/ bac/fungal inf
  • MOs, Mφs and DCs have all TLRs
  • B cells, T cells and granulocytes have fewer Endothelium, adipocytes etc only express TLR4
32
Q

what are the other cytoplasmic PRRs

NOD

A

NOD-like receptors

  • Family of 23 members divided into 3 main groups (B,C and P)
  • interact with intracellular PAMPs and DAMPs
  • Activate the NFkB pathway and autophagy
33
Q

what are the other cytoplasmic PRRs

RIG-like

A
  • bind viral dsRNA and so detect viral replication

- initiate anti-viral cytokine (type 1 interferons)

34
Q

what are the other cytoplasmic PRRs

AIM-like and cGAS/STING

A
  • Bind DNA molecules from bacteria and viruses

- Induce production of anti-viral and inflammatory cytokines

35
Q

when NLRs and ALRs clump together what do they form

A

‘inflammasome’resulting in the production of pro-inflammatory cytokines such as Interleukin-1 and 18 (IL-1 and IL-18) – this can result in a special form of self-death called pyroptosis

36
Q

what is opsonisation

A
  • post recognition, attachment may be enhanced by OPSONINS such as IgG (antibody), fragments of Complement and lectins
  • opsonin ‘coats’ microbe/cell
  • Acute phase proteins (C reactive protein-CRP) have structure similar to Complement component 1 & activate Classical Complement pathway by attaching to microorganisms
  • AB, complement and lectin receptors on phagocytes mediate INGESTION through binding to the opsonins
37
Q

what is an antibody (Fc) receptors

A
  • recognise the CONSTANT REGION of antiobodies
  • family of FcgammaR (recognise IgG)
  • Different varieties expressed on different phagocytes
38
Q

what is an complement receptors

A
  • bind components of classical, alternative and lectin complement pathways
  • CR1, CR2, CR3, CR4, C3a/4a and C5aR are expressed by a variety of phagocytes•Main ones involved in phagocytosis are CR1, 3 and 4

YEAR 2 S2 IMMUNO (14 decks)

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