Innate immunity 1 Flashcards
What is the host response aimed at?
Eradicating the pathogen
What does the protection mechanism of the immune system do?
Decides what is host and what is foreign organism
Decides what organisms are commensal and pathogenic
Decides what type of pathogen is causing danger and elicits immune response accordingly
What do many pathogens arise from?
A deleterious (to cause harm) immune response
What does the humoral component of the immune response involve?
Macromolecules, e.g., antibodies
What is the time frame of immediate innate immunity?
0-4 hours
What are the stages of immediate innate immunity?
Infection
Recognition by performed, non specific and broadly specific effectors
Removal of infectious agent
What is the time frame of early induced innate response?
4-96 hours
What are the stages of early induced innate response?
Infection
Recruitment of effector cells
Recognition of PAMPS (pathogen associated molecular patterns)
Removal of infectious agent
What is the time frame of the adaptive immune response?
More than 96 hours
What are the stages of the adaptive immune response?
Infection Transport of antigen to lymphoid organs Recognition by naive B and T cells Clonal expansion and differentiation to effector cells Removal of infectious agent
What sort of immune response do commensals elicit?
Low level- if any
What are the 5 groups of disease causing agent?
Bacteria Viruses Fungi Protozoa Helminths
What do disease symptoms depend on?
Where the pathogen replicates and the damage it causes
What do epithelial/endothelial cells and fibroblasts contribute to?
Innate immune response
What is innate immunity involved in?
The recruitment of immune cells to sites of infection
What does innate immunity rely on?
A limited number of gremlin encoded receptors to recognise ‘non self’
What sort of protection is epithelium?
An intrinsic, physical barrier
How are epithelial cells arranged?
Tightly packed cells joined by tight junctions
What prevents attachments of microorgnisms to epithelium?
Airflow.
In skin and gut, longitudinal flow of air
In lungs, movement of mucous by cilia
How do epithelial cells in various locations offer chemical protection?
Fatty acids in skin
Gut- low pH for pepsin
Skin, gut, lungs- antibacterial peptides
Eyes, nose- salivary enzymes (LYSOZYME)
What antimicrobials does saliva contain?
Lactoferrin
Lysozyme
Antimicrobial peptides
Immunoglobins (secretory IgA)
What does lactoferrin do?
Lactoferrin transfers iron to cells and controls levels of iron in blood and secretions. Bacteria need iron but lactoferrin removes it from them
How does lactoferrin effect bacterial pathogens?
It binds to the bacterial lipopolysaccharide and destabilises the bacterial membrane. It therefore disrupts the bilayer and creates osmotic stress.
How does lysozyme effect bacteria?
It cleaves the peptidoglycan, so breaks bacteria cell wall
Where is lysozyme found?
In tears, saliva, nasal secretions
What happens when lactoferrin and lysozyme work together?
It gives lysozyme better access to peptidoglycan layer
What size are antimicrobial peptides?
Very small
What parts do antimicrobial peptides have?
They are cationic and amphipathic , which means they have hydrophillic and lipophillic parts
What do antimicrobial peptides form?
They form pores, so can attach and disrupt membranes
At what concentration are antimicrobial peptides most effective?
In low concentrations
What are the major antimicrobial peptides found in the mouth?
B- defensins
Numan neutrophil peptides (HNP)
Cathelicidins
Psoriosin proteins (S100 family)
What is IgA?
An antibody but has a different role to normal antibodies as it does not require interaction between T and B cells
Where is IgA produced and found in high levels?
It is produced at mucosal surfaces, and is found in high levels in secretions
What can IgA bind to?
To antigens
To flagella to prevent motility
To bacterial toxins to neutralise them
What do cross links of IgA target and what does this do?
Targets macromolecules and bacteria, therefore trapping them and preventing effects on mucosa
How does IgA prevent attachment of bacteria to mucosal surfaces?
Directly- by binding to specific adhesion molecules
Indirectly- due to negative charge and hydrophillic amino acids creating a ‘hydrophillic shell’
Where is secretory IgA produced?
At mucosal surfaces
What does the interaction between microbes and receptors initiate?
Innate immune responses
What are the receptors called and where are they present?
They are called pattern recognition receptors (PRR’s) and are present on immune cells and epithelial cells
What receptors (PRR’s) can bacteria bind with?
Toll-like receptors (TLR’s)
NOD-like receptors
fMLP
Scavenger receptors
What receptors (PRR’s) do viruses bind with?
Toll-like receptors (TLR’s)
What receptors (PRR’s) do fungal pathogens bind with?
Dectin and glucan receptors
What can interactions between microbes and receptors (PRR’s) do?
Activate the expression of genes that promote innate immune responses
Aid internalisation of bacteria
Promote phagocytosis of bacteria
Promote activation of immune cells
How many toll-like receptors have been identified in humans?
TCR’s are PRR’s, 10 identified in humans
How do toll-like receptors work?
They recognise constituents of microbial cell walls or pathogen-specific nucleic acids that are essential to the integrity, function or replication of microbes/viruses that cannot be readily modified
What are PAMP’s??
Pathogen associated molecular patterns (PAMP’s) are molecules associated with pathogens. PAMP’s bind to, and are recognised by toll-like receptors and pattern recognition receptors
What do PAMP’s activate?
PAMP’s activate innate immune responses by identifying some conserved non-self molecules. They contain features that body cells don’t have, such as lipopolysaccharide
Which TLR’s are found within the cell?
3,7 and 9
What does virus activation of TLR’s induce?
Can induce changes in gene expression, translation and transcription, which can activate molecules such as protein kinases
What are c-type lectin receptors essential for?
Anti-fungal immunity
What do c-type lectin receptors recognise?
Carbohydrates in fungal cell wall
What are the c-type lectin receptors?
Dectin 1&2
Mannose receptor
DG-SIGN
Mincle
What does activation of CLR’s (c-type lectin receptors) induce?
Changes in gene expression
What cells express PRR’s??
Epithelial cells (keratinocytes/fibroblasts) All immune cells
What does signalling of PRR’s activate?
Activates immune cells directly, promotes functions e.g., phagocytosis
What does signalling of PRR’s induce cells to express?
Cytokines
Interferones
Chemokines
Antimicrobial peptides
What are cytokines?
Small proteins, signalling molecules which coordinate immune responses
In what manner can cytokines act?
Autocrine- alter behaviour of cell from which they are secreted
Paracrine- alter behaviour of neighbouring cells
Endocrine- enter circulation and alter behaviour of distant cells
What are interferons?
A type of cytokine, important in anti-viral immunity
What do interferons do?
They stop viral replication, and promote immune response against virus infected cells
How do interferons stop viral infection?
They switch on expression of proteins in cells which inhibit replication
How do interferons promote immune response against virus infected cells?
They activate NK cells to kill the virus infected cells They increase synthesis and surface expression of MHC class 1, which targets infected cells for destruction by CD8 cytotoxic T cells
What are chemokines?
Small signalling proteins, chemotactic cytokines
Why are chemokines produced?
Due to TLR and NF-kB activation
What do chemokines do?
Mainly involved in recruitment of immune cells to site of inflammation
How are chemokines grouped?
Grouped into 4 classes, depending on spacing of their first 2 cysteine residues
What is the concentration of chemokines like?
In highest conc. towards threat. Immune cells follow the trail of the chemokine gradient
What are the 4 classes of chemokine and how many members does each have?
C chemokines- 2
CC chemokines- 31
CXC chemokines- 18
CX3C chemokines- 1
What do cytokines and chemokines dictate?
They dictate and shape immune response
How is the immune system balanced?
When there is threat- pro inflammatory molecules are produced
When threat is cleared- anti inflammatory molecules are produced to reduce the immune response
