Immunology I Flashcards

1
Q

Describe the work of Edward Jenner

A

cowpox vaccine conferred protection against smallpox

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2
Q

Describe the work of Robert Koch

A
  • germ theory of disease
  • hypersensitivity reaction (allergies)
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3
Q

Describe the work of Louis Pasteur

A
  • fowl cholera vaccine
  • rabies vaccine
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4
Q

What is the general function of the immune system?

A

recognise and respond to problems of infection, invasion or altered self

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5
Q

What is the function of the immune system with respect to infection

A
  • prevent invasion or colonisation
  • limit early proliferation and dissemination
  • restrict growth (post-spread)
  • kill or control pathogen
  • effect clearance
  • offer enhanced resistance to rechallenge (short and long
    term)
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6
Q

Describe the principal components of an immune system

A
  • recognition
  • differentiation of different problems
  • response
  • effect
  • integration
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7
Q

Describe recognition

A

a problem is evident

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8
Q

What are problems experienced by the immune system

A

pathogen types

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9
Q

Describe the generalised immune system

A
  • signalling cascades
  • cellular events
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10
Q

Describe signalling cascades

A

intra- and extra-cellular

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11
Q

Describe cellular events

A

differentiation, movement or proliferation

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12
Q

Describe the generalised effect of immune system

A
  • directly lytic molecules
  • binding molecules (block/agglutinate/opsonise)
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13
Q

Describe immune integration

A

ability to communicate and cross activate or regulate different parts of the immune system

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14
Q

Describe the evidence for anti-microbial mechanisms in bacteria

A

– restriction enzymes
– CRISPR-Cas systems

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15
Q

Describe the evidence for anti-microbial mechanisms in protozoa

A
  • induction of intracellular antiviral/antibacterial mechanisms
  • the ability to kill vacuolar organisms by production of
    reactive oxygen species (also used as a feeding system in amoeboid protozoa)
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16
Q

Describe bacterial restriction enzymes

A
  • target specific non-self nucleic acid sequences
  • can be induced
  • may confer resistance to bacteriophages
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17
Q

Describe CRISPR-Cas9 systems

A
  • clustered regularly interspersed short palindromic repeats
  • uses RNA guides to target foreign sequences (typically DNA)
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18
Q

Describe the innovation of multicellularity

A
  • allows survival of an individual in the face of loss of cells
  • used to develop specialised cellular functions
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19
Q

What are the constraints associated with the innovation of multicellularity

A
  • development of new sites for pathogen exploitation i.e. extracellular
  • as complexity increases, new problems emerge of protection of surfaces and body fluids
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20
Q

Describe the basic process of vertebrate host immune engagement

A
  • detection
  • response
  • outcome
  • pathology (most is self-induced)
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21
Q

Describe vertebrate immune detection

A
  • “Pattern Recognition” (self and
    microbial)
  • initiates and directs response
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22
Q

Describe vertebrate immune response

A
  • Innate
  • Adaptive
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23
Q

Describe vertebrate immune outcome

A
  • pathogen removal/killing
  • control without removal (persistence)
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24
Q

How do we delineate between innate and adaptive immunity?

A
  • time (rapid versus delayed reactions)
  • different mechanisms (molecules, cascades, cell types)
  • specificity (receptors)
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25
Compare and contrast innate and adaptive receptors
- Toll-like receptors (innate) - antibodies (adaptive)
26
Innate Immunity is
a feature of all organisms
27
Adaptive immunity emerged in
the vertebrates
28
Adaptive immune responses are
faster the second time around
29
Describe the innate immune system
- barriers - tissue fluid systems - cellular systems
30
Describe immune barriers
- mechanical (epithelial cell layers) - chemical barriers (mucus, enzymes, pH, oils. antimicrobial peptides) - microbiological (enteric microflora)
31
Describe immune tissue fluid systems
- complement cascades - coagulation cascades - iron-binding molecules
32
Describe cellular immune systems
- phagocytic cells (macrophages, neutrophils) - lytic cells (Natural Killer cells)
33
Describe complement - the basics
- plasma based enzyme cascade - formation of deposits on microbial surfaces - lytic membrane attack complex - marking surface to assist interaction with immune cells - elements have chemotactic activity - effector for both innate and adaptive pathways
34
Describe coagulation
- blood clotting enzyme cascade - traps microbes - tops blood loss - initiates wound repair (re-establishing a barrier)
35
Describe Iron-binding molecules
* Lactoferrin and transferrin * Compete with bacteria for iron, slows bacterial growth
36
Describe complement cascades
- lectin and alternative pathways are innate cascades - classical pathway is an adaptive immune cascade - three pathways, same results: microbial lysis, enhanced phagocytosis
37
Describe the pattern recognition receptors (PRRs)
- innate receptors - lectins, Toll-like receptors, NOD-like receptors - genomically encoded in effective configuration - soluble, trans-membrane and cytoplasmic location - most animals have ~100-200 different receptors - each receptor expressed at high frequency - respond to PAMPs
38
Describe the adaptive receptors
- antibody, B cell or T cell receptors - formed by rearrangement of genomic segments - soluble or cell surface receptors - huge repertoire (>108 different specificities/person) - each receptor clonally expressed on very few cells, unless stimulated
39
Describe the families of PRRs
- Mannose binding lectin (tissue fluids) - Toll-like Receptors (transmembrane) - NOD1 and NOD2 (cytoplasmic) - Cell associated PRR-strong inducers of NFkB translocation to the nucleus
40
PAMPs
Pathogen Associated Molecular Patterns
41
Describe Pattern Recognition by vertebrate Toll-like receptors
- triggers a wide array of pro-inflammatory effects - use a common pathway for signal transduction
42
Describe the TLR-4 homodimer
- LPS agonist - recognises Gram -ve bacteria
43
Describe the TLR-9 homodimer
- DNA with unmethylated CpG motifs agonist - recognises bacteria
44
Describe the TLR-3 homodimer
- dsRNA agonist - recognises viral RNAs
45
Describe the TLR-5 homodimer
- flagellin agonist - Gram -ve bacteria
46
Describe the TLR-7 homodimer
- imidazoquinolones and ssRNA agonists - recognises viral RNA
47
Describe the TLR-2 (TLR-1,-6) heterodimers
- peptidoglycan, lipoarabinomannan, porins, bacterial lipoproteins, bacterial lipopeptides, yeast mannan, glycophosphatidyl-inositol anchor agonists - recognise Gram +ve bacteria, mycobacteria, Neisseria, yeast and trypanosomes
48
Describe Innate recognition of viruses
- TLR3 (dsRNA), - TLR4 (RSV-Surface glycoproteins) - TLR7/8 (ssRNA) - RIG-I (dsRNA, cytoplasmic)
49
Describe Innate recognition of bacteria
- TLR1/6 with 2 (cell wall components) - TLR4 (LPS) - TLR9 (CpG motifs in DNA) - NODs (cytoplasmic cell wall components) - Mannose receptors
50
Describe Innate recognition of parasites
- TLR 2 (GPI anchors) - TLR 4 (?) polymorphisms affect disease outcome - TLR9 (Plasmodium hemozoin DNA)
51
Describe TLR recognition of Salmonella
- TLR5 recognises flagellin - TLR4 recognises LPS - TLR2 recognises lipopeptides - TLR9 recognises CpG motifs
52
List some innate cells
- platelets - erythrocytes - eosinophil - neutrophil - basophil - mast cell - dendritic cell - macrophage - monocyte - NK cells
53
List some adaptive cells
- T cells - B cells - plasma cells
54
Describe the macrophage
- phagocytosis & intracellular killing - release of proinflammatory cytokines - antigen presentation - tissue repair
55
Describe dendritic cells
- antigen uptake in peripheral sites - antigen presentation in lymph nodes
56
Describe neutrophils
- 40-75% of leukocytes - phagocytosis - intracellular killing - inflammation and tissue damage
57
Describe eosinophils
- killing of antibody-coated parasites - tissue damage in allergic reactions
58
Describe NK cells
release lytic granules that kill some virally infected cells
59
NK
natural killers
60
Give some characteristics of macrophages
- slightly increased levels during inflammation - found in healthy tissues - variety of mature forms - slowly form granuloma with T-help - long-lived (months) - survive after phagocytosis
61
Give some characteristics of neutrophils
- rapid increase in numbers - found only in inflamed tissues - single mature form - rapidly form pus (cell debris and dead neutrophils) - short-lived (hours) - die after phagocytosis
62
Describe acidification
- pH 3.5-4 - bacteriostatic or bactericidal
63
Describe toxic oxygen-derived products
- superoxide (O2-) - hydrogen peroxide (H2O2) - singlet oxygen (1O2.) - hydroxyl radical (OH-) - hypohalite (OCl)
64
Describe some toxic nitrogen oxides
Nitric oxide (NO)
65
Describe antimicrobial peptides
defensins and cationic proteins
66
Describe some immune enzymes
- NADPH-dependent oxidases - lysozymes - acid hydrolases
67
NADPH-dependent oxidases
generate toxic oxygen derivates
68
lysozymes
dissolve cell walls of some Gram positive bacteria
69
acid hydrolases
further digest bacteria
70
Describe immune competitors
- lactoferrin (binds Fe) - vitamin B12-binding protein
71
List some soluble factors secreted by immune cells
- cytokines - interleukin - interferon - tumour necrosis factor - tumour growth factor - chemokines - antimicrobial peptides
72
Describe cytokines
soluble mediator produced by cells
73
Describe interleukin
soluble mediator produced by white blood cells
74
Describe interferon
soluble mediator that can induce a state that interferes with viral replication
75
Describe chemokines
- small chemotactic molecules - organisation/homeostasis - movement towards sites of infection
76
Describe antimicrobial peptides
small antimicrobial molecule
77
What are the functions of the soluble factors?
- communication - organisation - anti-pathogen effect
78
Give an example of a soluble factor produced?
macrophages producing pro-inflammatory cytokines
79
Describe chemotaxis
movement to site of inflammation, tissue damage and immune reactions
80
List some things that lead to inflammation
- pathogen recognition by macrophages - activation of complement - tissue damage
81
Describe the early induced responses
- pathogen entry triggers complement activation - cellular PRR activation with production of cytokines and chemokines - tissue-resident macrophages play a central role - vasodilation - increased vascular permeability - redness, heat and swelling - migration of inflammatory cells to tissue - escalation of inflammatory reaction - pain