Innate Immunity Flashcards
What does humoral mean?
Driven by macromolecules e.g. antibodies
What doe cellular mean?
Does not involve macromolecules but driven by cells e.g. T cells
What are the five groups of disease causing agents?
- Bacteria
- Viruses
- Fungi
- Protozoa
- Helminths (worms)
Innate immunity is the first line of defence - how many days does it take to kick in?
1-4 days
What is meant by the innate immune system having no-memory or lasting protective immunity?
The body doesn’t remember what its innate immune system has been exposed to
When does innate immunity start in the body?
It is present from birth
Why is innate immunity seen as being effective?
Regular contact with potential pathogens which are destroyed within minutes or hours, only rarely causing disease
What is meant by the responses being non-specific?
Responses are broad spectrum - general inflammatory response to pathogens
What does innate immunity recruit to sites of infection?
Immune cells
What does the innate immune system rely on to recognise ‘non-self’ cells?
Relies on a limited number of germline encoded receptors
How is epithelium a physical barrier to infection?
Tightly packed cells creating a physical barrier
Stops microorganisms from invading the tissues - prevent pathogens crossing epithelia and colonising tissues
Name 5 molecules in saliva that protect against microorganisms?
- Antimicrobial peptides
- Immunoglobins
- Lactoferrin
- Lysozyme
- Cystatins
What are antimicrobial peptides also known as?
Host defence peptides
What size are host defence peptides?
Small ( less than 50 AA)
What is meant when saying host defence peptides have cationic and amphipathic parts?
There are hydrophilic and lipophilic parts
Are high concentrations of host defence peptides required for them to be effective?
No, they are effective in low concentrations
What do host defence peptides do to membranes?
Attach and disrupt membranes - can crack open membranes (specificity for microbial over host)
What are the 4 major families of host defence peptides?
- Beta-defensins
- Human neutrophil peptides
- Cathelicidins
- Psoriasin proteins
What does cationic mean?
Positively charged
Where is secretory IgA found?
- Produced at mucosal surfaces
- Unlike most other antibodies does not require interaction between B and T cells
How does IgA work?
- Binds to antigens
- Binds to flagella and can prevent motility
- Binds to and neutralises bacterial toxins
- Cross links target macromolecules and bacteria therefore trapping them and preventing effects on the mucosa
- Prevents attachment of bacteria to mucosal surfaces
- Directly by binding to specific adhesion molecules
- Indirectly due to negative charge and hydrophilic AA creating a ‘hydrophilic shell’
How does the body recognise danger?
By the use of an array of receptors - pattern recognition receptors
These are present on a variety of cells: immune cells and epithelial cells
Which receptors are activated by bacteria?
- Toll-like receptors
- NOD-like receptors
- Scavenger receptors
Which receptors are activated by viruses?
- Toll-like receptors
Which receptors are activated by fungal pathogens?
- Dectin and glucan receptors
What effects can the activation of receptors by microorganisms cause?
- Activate expression of genes that promote innate immune responses
- Aid internalisation of bacteria
- Promote phagocytosis of bacteria
- Promote activation of immune cells
What are toll-like receptors?
Pattern recognition receptors
- 10 identified in humans
Why are toll-like receptors successful?
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 readily be modified
What are Microbial (pathogen) associated molecular patterns (M(P)AMP’s) by toll like receptors?
Prevents microorganisms from evolving as if they try to modify themselves they are killed
What are different toll-like receptors activated by?
Different microorganisms
Name different antigens present on microorganisms?
- Lipoteichoic acid (LTA)
- Lipopolysaccharide (LPS)
- Lipoproteins (LP)
- Glycophosphatidylinositol (GPI)
Which toll-like receptors are found inside the cell?
3,7 and 9
What do we think are the functions of the 10 TLR found in humans?
- Evidence for role in viral infection
- Evidence as an ‘anti-inflammatory’ TLR
Which cells express pattern recognition receptors?
- Epithelial cells (keratinocytes/fibroblasts)
- All immune cells
What does signalling of PRR’s and activating immune cells cause them to directly do?
Promote cell functions e.g. phagocytosis
What does signalling of PRR’s induce cells to express?
- Cytokines
- Interferons (response to viruses)
- Chemokines
- Antimicrobial peptides (production of these is ramped up)
- Other enzymes and inflammatory mediators
What are cytokines?
Small proteins that are signalling molecules to co-ordinate immune responses
Cytokines are grouped into families by structure. What are the 3 main families of cytokines?
- Interleukin-1 family (e.g. IL-1alpha, IL-1beta)
- TNF family (e.g. TNF alpha)
- Interferons
What does autocrine mean?
Alter the behaviour of a cell from which they were secreted (can be released from cell but also acts upon cell)
What does paracrine mean?
Alter the behaviour of neighbouring cells (can be released and act upon neighbouring cells)
What does endocrine mean?
Enter circulation and alter behaviour of distant cells (cell can be released and act upon cells throughout the body)
What are the consequences of cytokine signalling? (what does the signalling of cytokines induce?)
- Cytokines and chemokines - shapes type of immune response
- Antimicrobials - Invading organisms
- Growth factors - Tissue remodelling and repair
- Receptors - Differentiation and proliferation
What do chemokines do?
- Small signalling proteins - rather than initiating signals these recruit immune cells to target areas in the body
- Predominantly involved in recruitment of immune cells to site of inflammation
Why are chemokines called that?
As they set up chemokine gradients
What are chemokines also known as?
Chemotactic cytokines
What are the 4 classes of chemokines?
- C chemokines (2 members)
- CC chemokines (31 members)
- CXC chemokines (18 members)
- CX3C chemokines (1 member)
How are chemokines classed into different groups?
Depending on the spacing of their first 2 cystine residues
How do different types of chemokines recruit different types of immune cells?
Different chemokines give out different signals - if they give out the right signal they get the right antibodies recruited
What is in charge of dictating and shaping immune responses?
- Cytokines and chemokines
- The immune system is all about balance - can ramp up response to get rid of threat but needs to know when to switch off
How do neutrophils know where to go to get to the site of infection?
- They are attracted along a CXCL8 (IL-8) gradient to site of inflammation
- They are attracted there by chemical signals that are released by other cells of the immune system or by invading microbes
What does diapedesis mean?
Pulling through - CD31 helps pull through neutrophils
Explain the process of neutrophil migration?
- At sites of injury, infection or inflammation, cytokines are released and stimulate endothelial cells that line adjacent blood vessels
- The endothelial cells then express surface proteins called selectins
- Selectins bind to carbohydrates displayed on the membrane pf the neutrophils causing them to stick to the walls of the blood vessels
- This binding interaction is of sufficiently low affinity that the neutrophils can literally roll along the vessel walls in search for points to enter the vessel
- There they adhere tightly and squeeze between endothelial cells without disrupting the vessel walls and then crawl out of the blood vessel into adjacent connective tissues
What are the 3 main families of adhesion molecules?
- Selectins
- Integrins
- Immunoglobin superfamily
What do adhesion molecules do?
Promote cell-cell interactions
What are adhesion molecules important for?
- Immune trafficking
- Also important for interactions between immune cells
What is the primary function for neutrophils?
To engulf and destroy invading pathogens
What is the degranulation function of neutrophils?
- Granules in cell vesicles containing numerous antimicrobial peptides and enzymes
- released upon activation of TLR’s
- Neutrophils engulf 1 or 2 bacteria and then die - they only last a few hours
What are the neutrophil NETs (neutrophil extracellular traps) function of neutrophils?
- Activation induces neutrophils to release proteins and some genetic material (chromatin) to form extra-cellular fibril matrix
- Traps pathogens
- Many antimicrobials also associated with the NET so bacteria ‘held’ whilst ‘administered’
What are the activated functions of macrophages?
- Phagocytosis and activation of bactericidal mechanisms
- Antigen presentation
What is the process of monocytes being converted into macrophages?
- Monocyte binds to adhesion molecules on vascular endothelium near site of infection and receives chemokine signal
- The monocyte migrates into the surrounding tissue
- Monocyte differentiates into a macrophage and migrates to the site of infection
What are macrophages defence against microbes?
- Phagocytosis
- Release of antimicrobials and enzymes
- Antigen presentation - link to adaptive immunity (long term protection) - where innate immunity stops and active immunity starts
After defending against microbes what do macrophages do?
- Clearance of damages tissue and cells; e.g. expended neutrophils
- Promote healing and repair responses
Granules are vesicles. What preformed mediators can they contain?
- Proteinases - enzymes that break down different protein agents
- Antimicrobials (AMPs, lactoferrin)
- Chemical mediators
What stimuli produce the release of granules?
- M(P)AMPs
- Compliment proteins
- Cytokines and other inflammatory mediators
What do mast cells produce?
Histamine
What do anti-histamines do?
Blocks the action of histamine, control the unwanted immune response to an antigen
Does degranulation play a role in allergy?
Yes
What are the functions of phagocytes?
Phagocytosis:
- Break down pathogens
- Removal of tissue
- Antigen presentation
- Safely break down and dispose of apoptotic cells
Name the 2 types of antigen-presenting cell?
Non-professional:
- Epithelial cells/fibroblasts/endothelial cells
Professional:
- Macrophages
- Dendritic cells
What is the link between innate and adaptive immunity?
Antigen presentation
Which 2 types of cells are key antigen presenting cells?
Monocytes and dendritic cells
What 4 enzymatic cascade systems are found in plasma?
- Complement
- Kinins
- Coagulation factors
- Fibrinolytic system
(these systems are interrelated and produce various inflammatory mediators)
How many plasma and cell surface proteins are fond in the compliment system?
More than 30
What is the function of compliment components in the enzymatic cascade system?
Act as a primary defence system against bacterial/viral pathogens (works in conjunction with antibodies - link to adaptive immunity)
Where do most plasma compliment proteins come from?
Liver hepatocytes but tissue macrophages contribute also to local levels
What are many complement proteins termed?
Acute phase proteins - any of the plasma proteins whose concentration increases or decreases by at least 25% during inflammation. They help mediate both positive and negative effects of acute and chronic inflammation
What are the 3 compliment pathways?
- Classical (antigen-antibody)
- Alternative (foreign cell surface)
- Lectin (recognising mannose on pathogen) (mannose is a sugar)
What is the compliment classical pathways initiating factor?
Antibody attached to microbe
What is the compliment alternative pathways initiating factor?
Microbial cell wall
What is the mannose binding lectin compliment pathways initiating factor?
Carbohydrates on pathogen surface
What are the compliment pathways innate defence functions?
- Trigger inflammation
- Attract phagocytes
- Opsonize antigens (make cell more susceptible to phagocytosis)
- Cause cell lysis
- Activate naïve B-lymphocytes
- Remove immune complexes
What are the range of effects anaphylatoxins have on immune responses?
Promote immune cell recruitment:
- neutrophils
- macrophages
Act on neutrophils:
- Degranulation
Act on macrophages:
- Promote cytokine expression
- Promote antigen presentation
- Promotes degranulation
Act on mast cells:
- Degranulation (histamine release)
Regulate adaptive immune responses:
- T-cells and B-cells
Where do the 3 complement pathways converge?
At production of C3 convertase
What does the downstream formation of membrane attack complex require?
Formation of C5 convertase
What does MAC do to bacteria?
Destroys bacteria by creating membrane pore
