- 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

- cell 'drinking' - brings in nutrients - helps in osmoregulation - molecules internalised by NON SPECIFIC invagination of plasma memb - dep on external conc

Theme 2 - innate 2a Flashcards by P Sreekumar

describe innate immunity

what triggers it

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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what are the cells of the innate immune system

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

anatomical
physiological/chemical
phagocytic/endocytic
inflammatory

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describe anatomical barriers in innate immunity

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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describe physiological barriers in innate immunity

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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what do S100 proteins do

Psoriasin:

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

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what do surfactant proteins do

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

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what do defensins do

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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what are cathelicidins

antimicrobial peptides that disrupt microbial membranes (esp bacteria)
mainly on mucosal surfaces

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who had a key role in phagocytosis

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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what is cellular uptake for

what are the mechanisms used

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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what is pinocytosis

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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what is macro-pinocytosis

‘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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what is receptor-mediated endocytosis

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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what is phagocytosis

what carries it out

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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what are the 4 stages of phagocytosis

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1 recognition
2 ingestion
3 digestion
4 exocytosis

what happens in the DIRECT recognition stage of phagocytosis

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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

what does PRR stand for

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Pattern Recognition Receptors

what does PAMPs stand for

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Pathogen Associated Molecular Patterns

what does DAMPs stand for

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Damage Associated Molecular Patterns

what happens in the INDIRECT recognition stage of phagocytosis

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(opsonic)

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

give some exaples of PAMPs

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

in what situations may DAMPs be expressed

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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

what are the main types of PRRs

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C type lectin receptor
Scavenger receptors
Toll-like receptors

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

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

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

what do C type lectin receptors | what does the dectin-1 receptor do

- binds beta1-3 glucan | - expressed on a wide variety of myeloid lineage cells

what do C type lectin receptors | what does the DC-SIGN receptor do

- binds mannans on bacteria, fungi and parasites

what do scanvenger receptors do | where is SR-A found

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)

what do scanvenger receptors do | where is SR-B found

- includes CD36 on endothelium, DC, platelets, MC and macrophages - bind altered 'self' molecules eg ox LDL/vimentin - also recognises some PAMPs

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

- identified in Drosphila | - TLR4 identified using mous knockouts

describe toll like recepotrs

- 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

what are the other cytoplasmic PRRs | NOD

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

what are the other cytoplasmic PRRs | RIG-like

- bind viral dsRNA and so detect viral replication | - initiate anti-viral cytokine (type 1 interferons)

what are the other cytoplasmic PRRs | AIM-like and cGAS/STING

- Bind DNA molecules from bacteria and viruses | - Induce production of anti-viral and inflammatory cytokines

when NLRs and ALRs clump together what do they form

‘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

what is opsonisation

- 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

what is an antibody (Fc) receptors

- recognise the CONSTANT REGION of antiobodies - family of FcgammaR (recognise IgG) - Different varieties expressed on different phagocytes

what is an complement receptors

- 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

Theme 2 - innate 2a Flashcards

(38 cards)