Immunology Flashcards

(39 cards)

1
Q

What is a parasite

A

organism that lives in close association with another organism (the host), diverting the host’s resources to its own fitness, at a cost to the host.

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2
Q

Macro parasites

A

e.g. worms, ticks, fleas, parasitoids (flies or wasps)

considered as those that induce costs by diverting an individual’s resources directly from their bodies. These can be large ‘macroparasites’ that can be found on the body surface

macroparasites have low virulence, they can be costly, especially if the host is malnourished, but they rarely induce mortality directly. Exceptions are the parasitoids that lay their eggs in or on the body of an insect, with those larvae consuming the insect from the inside out, almost always resulting in mortality

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3
Q

Micro parasites

A
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4
Q
A

otherwise known as pathogens. These can also be fairly benign, e.g. the common cold, or incredibly virulent, e.g. Ebola. But costs can come in a form that is unlinked to mortality. An animal’s fitness can be impacted by increased mortality if they are young, but older individuals that have finished reproducing may not lose fitness by dying from infection. However, parasites can also directly or indirectly affect reproduction. Being sick can make you less likely to attract mates or hold a territory. Some parasites can even castrate their hosts so that the energy that would go into reproduction is instead diverted to the parasite.

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5
Q

Two categories of parasite

A

Classic
Brood

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6
Q

Brood parasites

A

Many animals provision resources to their offspring after they have detached from the parental body. This parental care provides a further source of energy that a parasite can exploit. The eponymous example of this parasitism of reproductive investment is performed by the common cuckoo (Cuculus canorus), which targets passerine hosts with post-hatching parental care. She removes a host egg upon laying her own in the nest, which hatches more rapidly than its adopted nestmates and promptly forcibly ejects all of the host’s own offspring from the nest, ensuring that all subsequent parental investment is directed exclusively towards the parasite. In contrast with classic parasitism, brood parasitism is a direct attack on the indirect fitness of the parent.

However, like classic parasitism, the costs of brood parasitism vary depending on the strategy of the parasite. For brood parasites, the magnitude of the costs are also a function of the level of parental investment in post-hatching care provided by the host. For example, in many cases of avian brood parasitism by cuckoos (Cuculus spp.) the combination of high levels of parental investment and an extremely virulent attack strategy by the parasite results in high parasite-induced costs for hosts.

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7
Q

Innate immunity

A

Non-specific defence
Includes cells and humoral components
‘Standing army’ protects an organism immediately upon infection

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8
Q

Adaptive immunology

A

(vertebrates only)
Memory of encountered infections - pathogen-specific response
Antibodies target pathogens in the bloodstream
T cells detect and kill infected cells

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9
Q

Behavioural defences against parasites- before

A

Avoidance, concealment, vigilance, grooming, hygienic behaviours, mobbing

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10
Q

Physical defences against parasitism - before

A

Fur, hair, skin, cuticle, gut lining, melanin, external secretions, nest architecture

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11
Q

Behavioural defences
Before parasitism – keeping them at bay

A

Avoidance, concealment, vigilance, grooming, hygienic behaviours, mobbing

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12
Q

Avoidance

A

First, animals can avoid parasites getting close by avoiding contaminated locations. In terms of classic parasites, individuals can avoid infection by shunning contaminated food e.g. grasshoppers [Jaronski 2013] or foraging/sleeping locations with a high risk of parasites e.g. termites [Mburu et al 2009] and badgers [Butler & Roper 1996] or by avoiding infected conspecifics as has been shown in mice [Kavaliers & Colwell 1995]. Some dung beetles specialise on carrion, but behave as they do with dung, collecting chunks and rolling it into a ball. However, carrion is a resource rich in microbial activity and a likely source of pathogens. To avoid this risk, beetles take the ball of meat that they will use for their babies away from the decomposing carcass where the threat of microbes is reduced. Some will roll the ball and tunnel up to 1m below the carcass where the risk of pathogens is greatly reduced compared to the surface.

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13
Q

Concealment and vigilance

A

Some parasites are mobile and actively seek out their hosts, parasite avoidance isn’t as simple as avoiding other parasitised individuals/locations. For example, a study on the hosts of brown-headed cowbirds found that more detectable hosts (e.g. those with longer nest-building visits, more male vocalisation near nests) were more likely to be parasitized [Banks & Martin 2001 ]. Given brood parasites’ active host searching behaviour, selection might favour hosts that attempt to conceal their locations. This has been shown in the European beewolf, a Sphecid wasp which is parasitised by a cuckoo wasp (Strohm et al 2001). Beewolf activity was temporally shifted during the day relative to cuckoo activity, such that beewolves were more active when cuckoo activity declined during the day (Strohm et al 2001). There is also evidence that the placement of the nest may have evolved to reduce the likelihood of brood parasites detecting or accessing the brood. For example, reed warblers have greater success when they nest further from the observation perches used by cuckoo females [Oien et al 1996], and potential open-nesting host species avoid using areas with vocal cues of cuckoo activity [Tolvanen et al 2017].

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14
Q

Grooming and hygienic behaviours

A

Grooming is an important anti-parasite measure. Some animals, like cats, are expert ‘self groomers’ whilst others have to enlist the help of friends. Mutual grooming is both an important antiparasite defence, friends can reach locations that you can’t, but has other benefits in terms of social cohesion in groups. Other spp use hired help, who will groom off parasites for the meal, such as oxpeckers and cleaner fish, though these mutualisms can shift to parasitism themselves when some cleaners start to keep wounds open to steal blood. A safer option is to enlist the help of something that won’t expect anything in return, such as a rock or a tree.

Many social insects also perform hygienic behaviours such as removing dead bodies from the nest that could spread disease, or barring others from entering the nest if they are likely to be infected.

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15
Q

Mobbing

A

So what about brood parasites? They can be deterred before they access the nest. Reed warblers will mob female cuckoos that appear near their nest. This has been tested with models that look like cuckoos or similar sized birds and cuckoos are mobbed more frequently. In addition, birds at greater risk of parasitism mob more than those in low risk areas. Mobbing is effective in that birds that mob more are less likely to end up with a cuckoo chick in their nest.

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16
Q

Melanin

A

Melanin can be incorporated into skin, cuticle, fur or feathers. Melanin has many functions, protection against UV, use in camouflage and signalling, but also has antimicrobial and antitoxin properties. Black skin is less susceptible to fungal infections than skin with low levels of melanin. This is true in caterpillars too. In fact, some species respond to high population densities, which are predictive of infection risk, by massively increasing the melanin content of their cuticle. This protects them against fungal infections and attack from macroparasites that enter via the skin

17
Q

External secretions

A

These physical defences can be further enhanced by chemical protection mechanisms. Sweat and organic acids on the skin, antimicrobials in the respiratory tract, and lysozymes in tears and saliva all help to kill microbes before they enter the body. Birds preen their feathers with a secretion from the uropygial gland, which has been shown to have antimicrobial activity and so protects the feathers from feather-degrading bacteria. Several animal species also use self-produced antimicrobials in the fabric of a nesting structure. For example, tungara frogs cover their eggs in a foam that contains a cocktail of antimicrobial chemicals and burying beetles prepare a vertebrate carcass for their offspring by covering it with antibacterial exudates. For example, the peacock blenny male covers his nest surface with mucus from his anal glands, which contains antibacterial activity, protecting the eggs from infection. Beewolves, a type of digger wasp, house streptomycete bacteria in their antennae, which they smear inside the brood cells. Larva pick up these bacteria and incorporate them into their cocoons, where they produce a suite of antimicrobials, protecting the pupae from fungal and bacterial infection.

18
Q

Nest architecture

A

Animals can create nests that parasites cannot enter or which allow for enhanced vigilance. Weaverbird nests, have a narrow entrance that makes it hard for cuckoos to gain access and social insects can have large nests that have few entrances. Many social insects post guards at the entrance to their nests, defending them against intruders, which can include ‘cuckoos’ or infected conspecifics. Just as burying beetles and tungara frogs protect their nests and offspring with cocktail of antimicrobial chemicals, wood cockroaches, that live in family groups inside decaying wood, coat the chambers with faecal pellets with antifungal properties. Other animals use naturally occurring antimicrobials in the structure of their nests. Starlings collect fresh greenery, rich in antibacterial phenolic compounds. Ants and bees collect resins from conifers and incorporate them into the nest to deter microbes.

19
Q

Defences against parasites after parasitism - behavioural

A

Parasite ejection
Nest abondonment
Walling off
Self medication
Anorexia
Fever

20
Q

Defences against parasites after parasitism - physical

A

Immune response
Innate vs adaptive immunity

21
Q

Parasite ejection

A

Recognition in this case is primarily visual in birds and chemical in insects/fish. In many birds, egg recognition is highly evolved and this has led to evolved mimicry in cuckoos, which otherwise risk their eggs being rejected from a nest. Birds with no history of brood parasitism have not evolved complex egg recognition mechanisms.
Strangely, despite the exquisite egg matching that cuckoos of several species have perfected, their chicks usually look totally different from the hosts, but chick recognition and subsequent rejection is not common. Indigobirds mimic the distinctive mouth markings of the host nestlings to ensure they get fed by the parent. Bronze cuckoos in Australia which have evolved to mimic their hosts, have chicks which are nearly indistinguishable from the host chicks,

Chicks suspected of being parasites are grabbed by the scruff of the neck and flung from the nest.

22
Q

Nest abondonment
Walling off

A

Honeybees are susceptible to a nest parasite called the small hive beetle. It is devastating parasite, feeding on the stored food and brood. The beetles are hard to kill due to their tough exoskeletons but in cape honeybees, they are sometimes ‘walled off’ by being encapsulated in propolis, the material bees make from resin. In social insect colonies, infected individuals may take themselves out of the colony if they are going to die to reduce the risk of infection to nestmates. In the most extreme cases, hosts can even abandon a nest that is heavily infected with parasites as has been shown in ants and termites, these could be classic or brood parasites, thus killing the parasite by depriving it of hosts.
For example, brown-headed cowbird hosts have been shown to desert parasitized nests and Mason bees have been shown to abandon the tunnels they have been provisioning once one of the brood cells becomes parasitized. Similarly ants have been shown to abandon nests where a virulent species of Maculinea caterpillar has become established.

23
Q

Self medication

A

The food an animal eats can help to fight parasites, either because they are toxic to the parasite, because they are nutritionally incompatible with the needs of the parasite or because they enhance the immune system of the host. Infected animals should seek out the diet that gives the best chance of survival – in other words they should self-medicate. There is circumstantial evidence for self-medication in apes, who have been seen to eat balls of indigestible leaves, or the pith of a bitter fruit, potentially to expel intestinal parasites. The same fruit is used as a herbal medicine by humans in many parts of Africa.

24
Q

Anorexia

A

Often when we feel sick we don’t have much of an appetite. This phenomenon isn’t restricted to humans, it is found across taxa, from mammals to insects. It is specifically associated with parasitic infection, i.e. helminths, protozoa, bacteria, viruses and it is called Illness Induced Anorexia (IIA)

25
Fever
For ectotherms- fever has to be achieved behaviourally
26
Innate immunity after parasitism
Innate immunity: recognition, humoral or cellular immune upregulation, adaptive immunity
27
Recognition
recognising which cells are ‘self’ and which are ‘non-self’ is key to initiating a successful immune response.
28
Insects- recognition
we have our invading parasites. The examples here are fungi, bacteria and protozoa for single celled parasites and parasitoid eggs/larvae or nematodes as macroparasites. All contain what we call PAMPs, or pathogen associated molecular patterns, which are recognised by PRRs, or pattern recognition receptors. Different PAMPs bind to different PRRs. For fungi and bacteria PAMPs are components of cell walls such as lipopolysacharides, beta 1,3 glucan or peptidoglycans. For protozoa and macroparasites these include collagen fragments, glycolipids, glycoproteins, Reactive Oxygen Species and calcium. As large parasites often cause damage upon invading the body’s interior, signals of damage will also trigger recognition of possible parasitism. PRRs can be free in the blood (called hemolymph in insects) or bound to cells. Humoral receptors include Peptidoglycan recognition proteins, c-type lectins, Leucine rich repeat proteins, Beta glucanase receptor proteins and thioester proteins. Some of these receptors bind to the surface of a parasite making it more apparent to immune cells, called ‘opsonisation’. Cellular receptors also include PGRPs, Toll like receptors, the protein Dome and integrins which are use in cell-cell recognition and adhesion. Recognition triggers an immune response via a series of signalling pathways that are triggered by different PAMPs. The major pathways in insects are Toll, which responds to fungi and G+ve bacteria and Imd which responds to G-ve bacteria, and JAK/STAT which are triggered by viruses, damage or stress. Opsonisation also triggers the cellular responses to parasites.
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Major recognition pathways in insects
Toll, which responds to fungi and G+ve bacteria and Imd which responds to G-ve bacteria, and JAK/STAT which are triggered by viruses, damage or stress. Opsonisation also triggers the cellular responses to parasites.
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Immune regulation in insects
Parasite recognition therefore results in immune responses, which can be humoral or cellular. The humoral response includes lysozymes and antimicrobial peptides (AMPs). Lysozymes are constitutively present in the gut and hemolymph in insects. Toll or Imd activation results in the production of AMPs, which are produced by the fat body or blood cells to inhibit growth or kill bacterial or fungal cells. PAMPs also directly stimulate the activation of phenoloxidases, which catalyse the production of melanin. Components of the PO cascade can act as opsonins. The PO cascade also results in the production of toxic quinones which can directly attack parasites. The second response is the cellular response, blood cells release PO, components of the cascade sticks to pathogens and makes blood cells more likely to stick to them. Spreading cells, called plasmatocytes in some species and lamellocytes in others (!) then form a capsule around the invader, PO itself binds to the surface of these blood cells and hardens and melanises the capsule. Plasmatocytes and granulocytes will also phagocytose fungal and bacterial cells and form nodules around smaller clumps of cells which have been tagged by opsonins.
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Recognition in mammals
PAMPs recognised by mammals are basically the same, and they are recognised by one of several classes of PRRs, some of which are transmembrane, and some cytoplasmic. These are CLR-C type lectin receptors, TLR, Toll like receptors, NLRs which are nucleotide binding like receptors and RLRs which are RIG 1 like receptors. All recognise different PAMPs in different locations and trigger different immune pathways.
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Immune regulation in mammals
In mammals the humoral response is mediated by NF-kB signalling, which results in the production of a range of cytokines, Interleukins which trigger the inflammatory response and the proliferation of immune cells, and other cell signallers and regulators. NF-kB also results in the maturation and differentiation of immune cells. Lysozymes are constitutively present in saliva and tears in vertebrates and are active in plasma. Natural ‘antibodies’ or immunoglobulins also circulate and are produced by B cells in the absence of pathogens. TLR and TNF pathways also result in the production of AMPs, which are produced by the immune cells to inhibit growth or kill bacterial or fungal cells. PAMPs also directly stimulate the activation of the complement cascade, components of which act as opsonins and which can form pores in microbial membranes, inducing lysis. In addition to secreting elements of the humoral response, the cellular response is phagocytic, macrophages, neutrophils/heterophils, basophils and eosinophils phagocytose fungal and bacterial cells and form nodules around smaller clumps of cells which have been tagged by opsonins. T lymphocytes recognise and destroy pathogens. Natural killer cells are also key in immune surveillance, targetting viruses and body cells that have been compromised by intracellular pathogens.
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Insects vs mammals
Once parasites have been recognised, immune pathways are triggered that result in the production of antimicrobial peptides in insects and mammals and cytokine signalling via NK-kB in mammals. If we compare the major AMP pathways in insects, Toll and Imd, with the TLR and TNF pathways in mammals there is conservation among the Drosophila and mammalian innate immunity NF-κB pathways. Homologs are marked with circles of the same colour at the left of each component. Notice the striking homology of components between species, though some homologs are positioned in different pathways. The subcellular localization of homologous proteins is also conserved. AMPs: Antimicrobial Peptides; Duox: Dual oxidase; GPCRs: G-Protein-Coupled Receptors; NLRs: NOD-like Receptors; Nox: NADPH oxidase; PGN: peptidoglycan; PAMPs: Pathogen-Associated Molecular Patterns; PGRPs: Peptidoglycan Recognition Proteins; ROS: Reactive Oxygen Species; TLR: Toll-like Receptors; TNF: Tumor Necrosis Factor. Antiviral immunity also follows very similar pathways in insects and mammals, showing remarkable homology, particularly via the IL6 route which triggers the proliferation and differentiation of stem cells.
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Adaptive immunity in mammals
Overlaid on the innate immune response is the adaptive immune response in vertebrates. With the exception of red blood cells, all cells in the vertebrate body express the Major Histocompatibility Complex (MHC), which can bind fragments of molecules, known as antigens, and present them on their surface. These antigens can be self or non-self, and it is the non-self antigens that are recognized by the adaptive system. The adaptive immune system comprises lymphocytes which come in two major forms, B- and T-cells. Macrophages and dendritic cells that have engulfed parasites, chop them up and display the antigens on their surface via the MHC, presenting them to the T-cells (Janeway et al., 2001). Antigen recognition activates specific T-cells that then either form cytotoxic T-cells or helper T-cells. Upon activation, cytotoxic T-cells mature and replicate, producing an army of lymphocytes that actively seek out body cells infected with parasites and kill them. In contrast, helper T-cells have no phagocytic or cytotoxic function and instead act as mediators of the immune response by secreting cytokines to mature other T-cells and B-cells or recruit cells of the innate system to the site of infection (Janeway et al., 2001). B-cells differ from T-cells in that they will recognize antigens in their native form, not only when they are bound to the MHC. Upon recognition of an antigen, B-cells will engulf the antigen and display it on its own MHC. This will then be recognized by matching helper T-cells, which will produce cytokines to help the B-cells to replicate and mature into antibody-producing plasma cells. These plasma cells live for 2-3 days, secreting antibodies that bind to antigens, making them easier targets for the killer cells of the innate system and the humoral response (Janeway et al., 2001). Over the timecourse of an infection, innate immune responses occur immediately, within hours. Adaptive responses take up to a week to reach full effectiveness. Once antigens are eliminated, excess activated immune cells undergo apoptosis but some of the activated B- and T-cells form memory cells that remain in the body and can be quickly activated upon subsequent infection by the same parasite.
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Secondary immune response
This produces a faster, stronger response to secondary infection, essentially rendering the host immune. Memory can last for years, even a lifetime. It is this effect that vaccination harnesses, by triggering the initial immune response and the creation of memory cells, but to the antigen and not the full pathogen. Removing the need for the body to undergo dangerous infections before it develops a truly effective immune response. But how can the vertebrate adaptive immune system recognize every possible pathogen that could be encountered? The system is incredibly powerful, a combination of somatic mutations and genetic recombination of antigen receptor gene segments allows a small number of genes to produce over a trillion different antibody molecules. These are randomly generated before birth and enable the immune system to react to an almost unlimited array of antigens (Rajewsky, 1996).
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Adaptive immunity in insects
Do invertebrates have any immune memory, even in the absence of true adaptive immunity? Inverts undergo what is known as immune priming.The two major phenomena underlying the capacity of invertebrates to mount a more effective defensive response after priming are the recall response (upper part) and the immune shift (lower part). As a general mechanism (centre part), priming is expected to induce epigenetic reprogramming that, upon challenge, determines improved clearance of parasites and enhanced survival. At the level of the whole organism (left part), memory can encompass mechanisms leading to an increase in the number of immune cells at the site of reaction (haematopoiesis, mitosis, haemocytosis), and also the capacity of transferring resistance across generations. At the cellular level (right part) it is also possible to observe increased effector functions in individual cells (e.g., an increased phagocytic rate vs. phagocytic index). Mechanisms that are observed both at the global and cellular levels (lower part) encompass the increased production of soluble immune mediators and the shift of immune response from an initial protective reaction (e.g., phagocytosis) to a more effective mechanism (encapsulation). One potential mechanism for immune memory is alternative splicing of products from the DSCAM gene family. DSCAM is an immunoglobulin that is found on blood cells, which detects and binds to non-self. DSCAM occurs in humans where there are only two isoforms, but with alternate splicing can produce up to 18000 isoforms in the insects so far examined, with different immune challenges producing a different array of DSCAM proteins. This is nowhere near the capacity of the MHC, but is nonetheless potentially very effective.
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2 parts of adaptive immunity in insects
Recall response Immune shift
38
Immune priming
Based on cell proliferation and increased functionality Insects
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What is unique to insect immunology
The presence of PO