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Immunity and infection > An introduction to innate immunity > Flashcards

An introduction to innate immunity Flashcards

1
Q

List the components of the innate and adaptive immune system

A

Innate immunity
* Physical barriers
– Skin, mucosal surfaces
* Chemical barriers
– pH, secreted factors
* Phagocytes
– Monocytes/granulocytes
* Inflammation; acute phase response
* Complement
* Cytokines/chemokines

Specific/adaptive immunity
* T lymphocytes
* B lymphocytes (antibody)
* Cytokines

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2
Q

Compare specificity of the Innate immunity and the Adaptive immunity

A

Innate immunity
non-specific, no antigen recognition

Adaptive immunity
involves very specific recognition of the particular
pathogen,

Innate involves recognition, but not as specific as
adaptive immunity

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3
Q

Comparison of the key characteristics of the innate and adaptive immunity

A
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4
Q

Describe neutrophils

A
  • Large cells (10-20 microns); only live about 2-3 days
  • 90% of granulocytes are neutrophils
  • Neutral staining cytoplasmic granules containing enzymes e.g. lysozyme
  • Phagocytic, kill bacteria by microbicidal mechanisms
  • Most important cell in non-viral infections
  • constitute the majority of leukocytes in the blood stream
    *have a characteristic multilobed nucleus
    Neutrophils have a large arsenal of enzymes and antimicrobial proteins stored in two main types of granule:
  • the primary (azurophilic) granules are lysosomes
  • the secondary granules contain lactoferrin and lysozyme
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5
Q

Describe Eosinophils

A
  • Contain prominent granules, which stain red with eosin
  • Granules contain a crystalline core cytotoxic for parasites; EOSINOPHIL BASIC PROTEIN
  • Important in immunity to helminth infections
  • Phagocytic,
    The major function of eosinophils appears to be the secretion of various toxic granule constituents following activation
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6
Q

Describe Basophils

A
  • <0.2% white blood cells, only go into tissues during inflammation
  • When stimulated, release substances that promote inflammation
  • Important in allergy
  • Not thought to phagocytose
  • Basophils and mast cells play a role in immunity against parasites
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7
Q

Describe Monocytes and Macrophages

A

Monocytes
* in blood 1-2 days
* Mononuclear leukocytes
* Phagocytic

Macrophages
* MCs in tissues = macrophages
* Up to 10x larger than MCs
* can live months or years mononuclear
* Characteristics of macrophages depend on tissue e.g. Kupffer cells in liver, microglia of brain
* Phagocytic, adherent

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8
Q

Recognition receptors on innate cells

A
  • Specificity from host molecule
    – e.g. IgG, complement components, chemokines
  • Inherent specificity (pattern recognition)
    – germline-encoded receptors for conserved molecular patterns
    – detects foreign invaders or aged/damaged host cells (apoptotic)
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9
Q

List Recognition receptors on innate cells:
specificity from host molecule and their outcomes

A
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10
Q

Describe Fc Receptors

A
  • Receptors for the Fc region of Ig
  • Expressed on many cell types
  • FcgR, alphaR, eR
  • Results in internalisation of Ab coated Ag
  • On Macrophages results in activation and production of reactive oxygen species
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11
Q

Describe Complement receptors

A
  • CR1-5
  • Diverse structures
  • CR1, CR3 (CR4) bind C3 cleavage products
    which are bound to pathogens, Immune
    complexes or other complement activators
  • Endocytic and activatory
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12
Q

Describe Chemokine receptors

A
  • 7 transmembrane receptors
  • Common family of membrane proteins
  • G-protein coupled
  • Recognise host chemokines and also microbial formyl-met peptides (starting sequence in protein synthesis)
  • Result in cell migration
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13
Q

describe pathogen-associated molecular
patterns (PAMPs)

A
  • Present only on pathogens and not on host cells
  • Essential for survival of pathogens
  • Invariant structures shared by entire class of
    pathogens
    the proteins which recognize them are PRRs
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14
Q

List Pattern recognition receptors, their ligand and outcome

A
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15
Q

Describe Lectin receptors

A
  • Eg Mannose receptor
  • Lectins bind carbohydrates
  • MR recognises terminal mannose and fucose
    (not present in human molecules)
  • MR is membrane bound cf soluble Mannan
    Binding Lectin in complement
  • Results in phagocytosis
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16
Q

Describe Scavenger receptors

A
  • Membrane bound PRRs
  • Bind to apoptotic cells/modified self molecules and responsible for ‘clearing up’ after an immune response. May affect M1/M2
  • Also bind bacterial cell walls
  • Recognise lipoproteins (lps)
  • Can mediate endocytosis
  • Main role is fine tuning TLR signalling (eg SR
    -A and TLR4 and TLR2 and CD36 in S.aureus
    and M.tb recognition).
17
Q

Compare all classes of scavenger receptors

A

No real structural homology between classes. Class A-I

Class A have collagen domain or C-type lectin domain.

Class B have a CD36 domain

Class D LAMP domain Etc. Appear to all have clusters of cationic residues, centrally located. May account for binding to similar ligands. May be linked to FcRg ITAM

Endocytic receptors

18
Q

give examples of PAMPs and DAMPs

A
  • PAMPs such as TLR ligands
  • DAMPs such as ‘alarmins’, inc defensins, HMGB-1, ATP etc.
19
Q

Other Intracellular receptors than TLR

A

Recognise intracellular bacteria and viruses

NOD-like receptors (nucleotide binding and oligomerization domain)- bind dsRNA and also peptidoglycan

RIG-1- (retinoic acid inducible gene-1) like helicases (RLH)- recognise dsRNA intermediate of viral replication (also MDA-5)

Some NLRs can form the inflammasome.

20
Q

Describe the Inflammasome

A

A multiprotein oligomer complex which assembles in the cytoplasm after PAMP/DAMP detection. Can lead to activation of Caspases inc Caspase 1
which cleaves precursors to IL-1 and also IL-18

Composed of several intracellular PRRs including NOD-like receptor and can be triggered by PAMPs and DAMPs (DAMPs leading to ‘sterile’ inflammation.).

Leads to pyroptosis; Inflammatory cell death.

Linked to autoimmunity (MS, diabetes) and inflammation such as atherosclerosis. May simply be an exaggerated response to host-derived
factors.

21
Q

Describe Natural Killer cells (Large granular lymphocytes)

A
  • A group of lymphocytes that have the intrinsic ability to recognize and destroy some virally
    infected cells and some tumor cells.
  • 4% white blood cells
  • Collection of cells playing role between innate & specific immunity
  • Kill certain tumour & virally infected cells
  • Activated by FcR and KIR
  • Target cell destruction is caused by cytotoxic molecules called granzymes & perforins
22
Q

Describe natural killer T cells

A
  • Express NK and T cell markers, NK1.1 and TCR
    T cells: CD3 and have a unique ab TCR (expressing an invariant Va and Vb11
    CD16 and CD56 are used to distinguish NK cells
  • Restricted TCR alpha-chain usage (Valpha24 in Hu, 14 in Mo)
  • Intermediate TCR expression.
  • Recognises through CD1d (non-classical MHC1)
  • Produces Th1 and Th2 cytokines (IFNg and IL-4.)
  • Recognises lipids, glycolipids, hydrophobic peptides.
  • alpha-galactosylceramide and anti-tumour effect
23
Q

Describe gd T cells

A
  • Makes up ~10% peripheral blood MNC but up
    to 70% of mucosal T cells
  • Some express CD8 and CD4, most double
    negative
  • Restricted through MHC molecules as alphab
  • Some gd T cells are restricted through other
    molecules such as alpha3 butyrophilin
  • have a specific repertoire of TCRs biased towards
    certain bacterial/viral antigens
  • Can also recognise small aliphatic molecules
    (isoprenoid pyrophosphates and amines) which may represent a pattern recognition system
  • g chain consists of V, J and C regions
  • d chain consists of V, D, J and C regions
  • The effect of extensive junctional diversity increases the gd TCR repertoire to ~1019 possible receptors
    BUT Vg9Vd2 all seem to recognise IPP
24
Q

Describe DC targeted antigen delivery

A
  • DC-SIGN; lectins designed to target tumour
    Ag to DCs. Cross-presentation
  • DEC205- lectin receptor, anti-DEC205-ovalbumin complex endocytosed and antigen presented on Class1 and 2
  • FcgR mediated uptake- Ab conjugated to tumour antigen (lymphoma anti-Id)
  • Associated with cell mediated immunity
25
Q

Can the innate receptor be used clinically?
gd T cells

A
  • Have been shown to recognise non-peptide antigens
  • Have been shown to have broad cytotoxicity against tumour cells both allogeneic and autologous
  • Vg9Vd2 Recognise prenyl pyrophosphate ligands:
    can be over expressed on tumour cells eg B-cell
    lymphomas.
  • Zoledronic acid
  • Now in trials.
26
Q

TLR ant/agonists

A
27
Q

DC vaccines

A
  • HIV, Hep B & C peptides/native or transfected
    viruses-more than one epitope. But also therapeutic vaccination. More useful in cancer.
  • Used to be non-matured
  • TNF A
  • Complex cytokine cocktails including TLR
    agonists:
    Poly I:C; Aldara
28
Q

‘Virtually virally infected cell’

A
  • Induce death in a TC which will correctly stimulate the DC which endocytoses it.
  • TC will release signals which will activate/mature the DC.
  • Correct presentation of the TC peptides by the
    DC to the adaptive response.

Immunity and infection (29 decks)

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