Immunology I Flashcards
Describe the work of Edward Jenner
cowpox vaccine conferred protection against smallpox
Describe the work of Robert Koch
- germ theory of disease
- hypersensitivity reaction (allergies)
Describe the work of Louis Pasteur
- fowl cholera vaccine
- rabies vaccine
What is the general function of the immune system?
recognise and respond to problems of infection, invasion or altered self
What is the function of the immune system with respect to infection
- 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)
Describe the principal components of an immune system
- recognition
- differentiation of different problems
- response
- effect
- integration
Describe recognition
a problem is evident
What are problems experienced by the immune system
pathogen types
Describe the generalised immune system
- signalling cascades
- cellular events
Describe signalling cascades
intra- and extra-cellular
Describe cellular events
differentiation, movement or proliferation
Describe the generalised effect of immune system
- directly lytic molecules
- binding molecules (block/agglutinate/opsonise)
Describe immune integration
ability to communicate and cross activate or regulate different parts of the immune system
Describe the evidence for anti-microbial mechanisms in bacteria
– restriction enzymes
– CRISPR-Cas systems
Describe the evidence for anti-microbial mechanisms in protozoa
- 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)
Describe bacterial restriction enzymes
- target specific non-self nucleic acid sequences
- can be induced
- may confer resistance to bacteriophages
Describe CRISPR-Cas9 systems
- clustered regularly interspersed short palindromic repeats
- uses RNA guides to target foreign sequences (typically DNA)
Describe the innovation of multicellularity
- allows survival of an individual in the face of loss of cells
- used to develop specialised cellular functions
What are the constraints associated with the innovation of multicellularity
- development of new sites for pathogen exploitation i.e. extracellular
- as complexity increases, new problems emerge of protection of surfaces and body fluids
Describe the basic process of vertebrate host immune engagement
- detection
- response
- outcome
- pathology (most is self-induced)
Describe vertebrate immune detection
- “Pattern Recognition” (self and
microbial) - initiates and directs response
Describe vertebrate immune response
- Innate
- Adaptive
Describe vertebrate immune outcome
- pathogen removal/killing
- control without removal (persistence)
How do we delineate between innate and adaptive immunity?
- time (rapid versus delayed reactions)
- different mechanisms (molecules, cascades, cell types)
- specificity (receptors)
Compare and contrast innate and adaptive receptors
- Toll-like receptors (innate)
- antibodies (adaptive)
Innate Immunity is
a feature of all organisms
Adaptive immunity emerged in
the vertebrates
Adaptive immune responses are
faster the second time around
Describe the innate immune system
- barriers
- tissue fluid systems
- cellular systems
Describe immune barriers
- mechanical (epithelial cell layers)
- chemical barriers (mucus, enzymes, pH, oils. antimicrobial peptides)
- microbiological (enteric microflora)
Describe immune tissue fluid systems
- complement cascades
- coagulation cascades
- iron-binding molecules
Describe cellular immune systems
- phagocytic cells (macrophages, neutrophils)
- lytic cells (Natural Killer cells)
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
Describe coagulation
- blood clotting enzyme cascade
- traps microbes
- tops blood loss
- initiates wound repair (re-establishing a barrier)
Describe Iron-binding molecules
- Lactoferrin and transferrin
- Compete with bacteria for iron, slows bacterial growth
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
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
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
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
PAMPs
Pathogen Associated Molecular Patterns
Describe Pattern Recognition by vertebrate Toll-like receptors
- triggers a wide array of pro-inflammatory effects
- use a common pathway for signal transduction
Describe the TLR-4 homodimer
- LPS agonist
- recognises Gram -ve bacteria
Describe the TLR-9 homodimer
- DNA with unmethylated CpG motifs agonist
- recognises bacteria
Describe the TLR-3 homodimer
- dsRNA agonist
- recognises viral RNAs
Describe the TLR-5 homodimer
- flagellin agonist
- Gram -ve bacteria
Describe the TLR-7 homodimer
- imidazoquinolones and ssRNA agonists
- recognises viral RNA
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
Describe Innate recognition of viruses
- TLR3 (dsRNA),
- TLR4 (RSV-Surface glycoproteins)
- TLR7/8 (ssRNA)
- RIG-I (dsRNA, cytoplasmic)
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
Describe Innate recognition of parasites
- TLR 2 (GPI anchors)
- TLR 4 (?) polymorphisms affect disease outcome
- TLR9 (Plasmodium hemozoin DNA)
Describe TLR recognition of Salmonella
- TLR5 recognises flagellin
- TLR4 recognises LPS
- TLR2 recognises lipopeptides
- TLR9 recognises CpG motifs
List some innate cells
- platelets
- erythrocytes
- eosinophil
- neutrophil
- basophil
- mast cell
- dendritic cell
- macrophage
- monocyte
- NK cells
List some adaptive cells
- T cells
- B cells
- plasma cells
Describe the macrophage
- phagocytosis & intracellular killing
- release of proinflammatory cytokines
- antigen presentation
- tissue repair
Describe dendritic cells
- antigen uptake in peripheral sites
- antigen presentation in lymph nodes
Describe neutrophils
- 40-75% of leukocytes
- phagocytosis
- intracellular killing
- inflammation and tissue damage
Describe eosinophils
- killing of antibody-coated parasites
- tissue damage in allergic reactions
Describe NK cells
release lytic granules that kill some virally infected cells
NK
natural killers
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
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
Describe acidification
- pH 3.5-4
- bacteriostatic or bactericidal
Describe toxic oxygen-derived products
- superoxide (O2-)
- hydrogen peroxide (H2O2)
- singlet oxygen (1O2.)
- hydroxyl radical (OH-)
- hypohalite (OCl)
Describe some toxic nitrogen oxides
Nitric oxide (NO)
Describe antimicrobial peptides
defensins and cationic proteins
Describe some immune enzymes
- NADPH-dependent oxidases
- lysozymes
- acid hydrolases
NADPH-dependent oxidases
generate toxic oxygen derivates
lysozymes
dissolve cell walls of some Gram positive bacteria
acid hydrolases
further digest bacteria
Describe immune competitors
- lactoferrin (binds Fe)
- vitamin B12-binding protein
List some soluble factors secreted by immune cells
- cytokines
- interleukin
- interferon
- tumour necrosis factor
- tumour growth factor
- chemokines
- antimicrobial peptides
Describe cytokines
soluble mediator produced by cells
Describe interleukin
soluble mediator produced by white blood cells
Describe interferon
soluble mediator that can induce a state that interferes with viral replication
Describe chemokines
- small chemotactic molecules
- organisation/homeostasis
- movement towards sites of infection
Describe antimicrobial peptides
small antimicrobial molecule
What are the functions of the soluble factors?
- communication
- organisation
- anti-pathogen effect
Give an example of a soluble factor produced?
macrophages producing pro-inflammatory cytokines
Describe chemotaxis
movement to site of inflammation, tissue damage and immune reactions
List some things that lead to inflammation
- pathogen recognition by macrophages
- activation of complement
- tissue damage
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
