Immune System Flashcards

Question

What are heteroantigens?

Answer 1

Foreign to the body: infectious agents, environmental substances and chemicals like drugs

Answer 2

Also called self-antigens, recognition triggers autoimmunity

Answer 3

Cells from same species but genetically different

Answer 4

Cells from a different species. Particular interest for transplantation field.

Answer 5

Antigenic epitope (determinant) – one antigen may have multiple epitopes, some of which may be immunodominant – majority of immune response is targeted at a certain set of epitopes.

Answer 6

A small chemical group, which when chemically conjugated to a large molecules (carrier protein) will alter its specificity creating a new epitope. A hapten cannot by itself stimulate antibody production, but can combine with antibody once linked to a carrier protein.

Answer 7

Cutaneous drug eruption: drug (ketoconazole) binds to a dermal protein which stimulates an Immune response.

Answer 8

A substance which, when combined with antigen, non-specifically enhances the immune response. May also have a depot effect allowing slow release of antigen.

Answer 9

2 heavy and 2 light chains, bound by disulphide bridges. At the end of each, there are domains labelled V, meaning variable. Variability is all located at ends, as this determines which antigen the molecule will bind to. Letter C means constant, domains which are the same across molecules.

Answer 10

By the heavy chain: - Gamma = IgG - Mu = IgM - Alpha = IgA - Delta = IgD - Epsilon = IgE Each with a kappa or lambda light chain.

Answer 11

Number of antigens an antibody can bind to

Answer 12

Single Y shaped unit, gamma heavy chain, valance 2, subclasses exist

Answer 13

Main serum Ig, for example, found in the blood. Diffuses easily to extravascular tissue.

Answer 14

- Fixes complement - Opsonin - Neutralise toxins, such as bacterial toxins - Main Ig in secondary immune response

Answer 15

Enhancing phagocytosis.

Answer 16

- 5 Y shaped units - Valence 10 - Mu heavy chain - Extra heavy chain domain (CH4) - J chain

Answer 17

Intravascular, stays in the blood due to large size

Answer 18

- Agglutinates particulate antigen - Fixes complement - Main Ig in early immune response - Important in bacteraemia

Answer 19

- Valence 4 - Monomer or dimer in serum (species dependent) - Dimer in mucosal secretions (all species) - Alpha heavy chain - Dimer linked by J chain - Subclasses exist

Answer 20

- Dimer at mucosal surfaces has secretory piece – provides protection from enzymatic degradation - Mucosal immune defence - Inhibits microbial attachment - Neutralises toxin - Weak opsonin

Answer 21

- 1 Y shaped unit - Valance 2 - Delta heavy chain - Found only on surface of immature B lymphocytes

Answer 22

- 1 unit, valence 2 - Epsilon heavy chain - Extra domain CH4

Answer 23

- Low level in serum - More in animals than man - Most bound to tissue mast cells or blood basophils

Answer 24

- Involved in parasite rejection - Involved in allergy

Answer 25

The antigenic epitope slots into a groove formed between the hypervariable regions of the heavy and light chains. Specific attachment – lock and key. Firm attachment – electrostatic forces, hydrogen bonds, hydrophobic forces and van der waal’s forces. Affinity – binding strength of antibody for its epitope.

Answer 26

Primary – where the immune system develops. Secondary – site of immune responses.

Answer 27

Bone marrow Ileal peyers patch Thymus Bursa of fabricius in birds

Answer 28

- Stem call – pluripotent - Origin of T and B lymphocytes - Site of maturation of B lymphocytes before export to secondary lymphoid tissues in humans, rabbits and rodents - Site of some B cell differentiation to plasma cells for antibody production in the humoral response

Answer 29

- Site of B cell maturation in most animal species - Found in the small intestine, domes without villi - Secondary follicle with germinal centres are where T cells are

Answer 30

- Site of B cell maturation in birds - Lymphoepithelial organ near cloaca Bursectomised chicks cannot make humoral immune response/cannot make antibodies

Answer 31

Anterior mediastinum in front of the heart. Involutes with age. Thymectomised or congenitally athymic (‘nude’) animals cannot mount cell-mediated immune responses. - Site of extramedullary T cell development – takes place outside bone marrow. - Cells generate cell mediated immunity. - Humans, rabbits and rodents have B cell maturation before circulation. - T cells arise in bone marrow and in all species migrate to thymus to complete maturation and then are circulated.

Answer 32

Encapsulated – spleen and lymph nodes Unencapsulated – mucosal lymphoid aggregates

Answer 33

- Encapsulated so has a capsule and then a subcapsular sinus below. - Afferent lymphatics is where immune cells arrive at lymph nodes. - Lymph nodes contain immune cells that perforate through the cell and exit via the efferent lymphatics. - B and T cells sit in cortex. - Primary follicles contain B cells that are inactive that are activated on immune response. - Paracortex is where T cells are between follicles.

Answer 34

Encapsulated: trabecula skeleton creates framework and there are areas of red pulp in between containing red blood cells, and areas of whit pulp where lymphocytes/B cells are. PALS, per-arteriolar lymphoid sheath is where T cells are found.

Answer 35

Secondary unencapsulated lymphoid tissue MALT – at the mucosal surfaces which are in contact with the environment. * Gastrointestinal (GALT) * Bronchial (BALT) * Nasal (NALT) * Conjunctival (CALT)

Answer 36

- Virgin or memory (inactive) - Little cytoplasm (large nucleus) - Few organelles - Condensed chromatin

Answer 37

- Stimulated by antigen - More cytoplasm - More organelles - Less condensed chromatin

Answer 38

- More endoplasmic reticulum - Clock face chromatin - Antibody production and secretion

Answer 39

1. Anatomical location 2. Function 3. Expression of surface molecules unique to each population

Answer 40

Expression of these molecules by individual cells in suspension or tissue can be determined using antibodies specific for the molecule of interest which are conjugated to a fluorochrome.

Answer 41

1. Antibody to SmIg conjugated to fluorochrome. 2. Added to unknown lymphocytes. 3. Antiserum labels SmIg in binding. 4. Expose to UV light to excite the fluorochrome. 5. Examine microscopically or count with a flow cytometer.

Answer 42

Used both clinically in labs and by immunologists in research labs: - Can take a single sample, stain antibodies, and begin looking at different immune cells and analyse their phenotypes. - Enables simultaneous measurement of up to 50 different characteristics of a single cell. - Identification and analysis of distinctive phenotypes in heterogenous populations.

Answer 43

Lymphocytes recirculate to maximise the chance of contact between an antigen and the appropriate responding populations of lymphocytes.

Answer 44

1. Tissue 2. Afferent lymphatics 3. Lymph nodes 4. Efferent lymphatics 5. Thoracic duct 6. Bloodstream 7. Can exit into required areas and tissues via HEVs (high endothelial venules)

Answer 45

Interaction between vascular addressins and homing receptors in the HEVs triggers diapedesis and turbulence, which increases the chance of interactions. Located in areas where lymphocytes exit tissues.

Answer 46

The common mucosal system: cells activated in response to an event at 1 mucosal surface can home to other mucosal surfaces.

Answer 47

Generation of colostral antibody

Answer 48

A series of plasma proteins (around 30) which when activated, interact sequentially forming a self-assembling enzymatic cascade generating biologically active molecules mediating a range of end processes.

Answer 49

1. Pattern recognition 2. Protease (enzymatic) cascade amplification and C3 and C5 convertase production 3. Inflammation 4. Enhanced phagocytosis/opsonisation 5. Membrane attack – lysis of microbial membranes

Answer 50

Once triggered, pathways get enzymatic cascades, each with different components of the cascade and all 3 result in the production of C3 convertase and C5 convertase.

Answer 51

Triggered by complexes between antigens and antibodies. For classical pathway, must have already had an immune response to produce antibodies. Antigen antibody complexes on the surfaces of pathogens.

Answer 52

1. Triggered by antigen-antibody complexes on a pathogen surface. Antibodies specific to antigen from previous immune response. 2. Binding of the first component, C1, which binds to part of the antibody at the CH2 region for complement fixation. 3. C1 is made up of several units and there is sequential activation of each component. 4. Active C1s component acts on the 2nd component, C4, causing C4 to split into 2 parts, a and b. 5. C4b becomes attached to bacterial surface and C4a stays in the serum. 6. C1s also acts on 3rd component, C2, which splits C2 into 2 parts, a and b. 7. C4b and C2a attach to each other on the pathogen surface and together they form the C3 convertase. 8. C3 convertase acts on C3, casing C3 to split into 2 components, a and b. 9. C3a stays in the serum and C3b goes to the pathogen surface. 10. C4b, C2a and C3b attach together on the pathogen surface and together form the C5 convertase.

Answer 53

1. Mannose-binding lectin binds mannose on pathogen surface 2. MBL, MASP-1, MASP-2, C4, C2 3. C3 convertase

Answer 54

1. Triggered by pathway surfaces 2. C3, B, D 3. C3 convertase

Answer 55

Peptide mediators of inflammation and phagocyte recruitment.

Answer 56

Binds to complement receptors on phagocyte for opsonisation of pathogens and removal of immune complexes.

Answer 57

C5b C6 C7 C8 C9 Membrane attack complex and lysis of certain pathogens and cells.

Answer 58

Where C5 convertase breaks down C5 and results in the membrane attack complex, which causes lysis of pathogens (occasionally cells).

Answer 59

Inflammation – due to the generation of bioactive substances, such as anaphylatoxins and chemoattractants. Removal of particulate antigens and immune complexes – enhanced phagocytosis. Cytolysis

Answer 60

- Smooth muscle contraction - Mast cell degradation - Vasodilation, local oedema, local influx of antibody and complement, cell extravasation - Neutrophil activation - Attracted to chemotactic gradient

Answer 61

1. Phagocytosis by non-specific adherence - IgM increases agglutinates particulate antigens and so there is a greater chance of interaction. 2. Opsonisation - specific binding between phagocyte receptors and pathogen antigens, as they are complementary. Complement involves as well further opsonisation. 3. Removal of immune complexes - antigen coated in C3b attached to red blood cell as they have receptors and circulate around in the blood attached. When supplying liver or spleen, antigens are removed.

Answer 62

- C5 split into C5a and C5b - C5b starts to sequentially assemble itself with final components of complement pathway, C6, 7, 8 and 9. Forms circular structure. - Circular structures are inserted into pathogen membranes and causes influxes of water and osmotic lysis.

Answer 63

Normal cells have membrane proteins which breakdown C3 convertase. This protects normal cells. For example. DAF, decay-accelerating factor. CD59 expressed widely on membranes and prevents formation of the MAC on normal cells.

Answer 64

Causes susceptibility to bacterial infections and get symptoms from prolonged immune response. High temperatures and recurrent infections could be signs.

Answer 65

An individual might have multiple polymorphisms that causes susceptibility to certain infectious diseases.

Answer 66

- Control/eliminate infection - Immunity and response to vaccination - Kill cancerous cells - Disease pathogenesis – transplant rejection, autoimmune disease, leukaemia/lymphoma - Therapeutic applications – cellular therapy against cancer

Answer 67

CD8+ T cells – killer T cells CD4+ T cells / TH / T helper cells - TH1 - TH2 - TH17 - TFH (follicular helper) CD4+ T regulatory cells – rather than stimulate an immune response, they dampen immune responses. In theory, could be used to treat autoimmune diseases.

Answer 68

T cells cannot recognise complex or whole antigens. T cells recognise small peptide fragments bound to Major Histocompatibility Complex molecules which are expressed at the cell surface

Answer 69

T cells express T cell receptors which are responsible for recognising cell surface peptide MHC. Therefore to trigger a T cell response, complex antigens must first be converted into a user friendly form.

Answer 70

Refers to the generation of small peptide fragments which are bound to major histocompatibility complexes and transported to the cell surface. 1. Antigen uptake 2. Antigen processing 3. Antigen presenting at the cell surface

Answer 71

CD8+ T cells see T cell epitopes presented by class I MHC, found on most nucleated cells: 1. Antigens found in the cytoplasm, viral, self or tumour, are referred to as endogenous or cytosolic antigens. 2. Endogenous (cytosolic) antigens are processed and presented with MHC class I molecules 3. Presented peptide fragments are usually 8-14 amino acids in length.

Answer 72

1. Peptide fragments of viral proteins are transported into the endoplasmic reticulum 2. Peptide fragments are bound by MHC class I and delivered to the cell surface

Answer 73

- The proteasome generates peptide fragments from cytosolic protein. During an immune response induced by interferon, modifications to the proteasome mean that it produces peptides that bind well to MHC class I. - TAP, Transporter associated with antigen processing, delivers peptides to the endoplasmic reticulum.

Answer 74

CD4+ helper T cells see T cell epitopes presented by class II MHC. MHC class II is found on antigen presenting cells: dendritic cells, macrophages, B cells.

Answer 75

1. Antigens taken up from outside the APC, extracellular pathogens and toxins, are referred to as exogenous antigen. 2. Exogenous antigens are processed and presented by MHC class II at the cell surface. 3. MHC class II molecules are found on specialised antigen presenting cells – dendritic cells, macrophages, B lymphocytes. 4. Presented peptide fragments are usually 15-24 amino acids in length.

Answer 76

Dendritic cells – several different types Macrophages B-cells

Answer 77

A range of cells hat can be induced to express MHC class II and present antigen when exposed to IFN-gamma.

Answer 78

- Activate naïve T cells, highly potent APCs - Large surface area to increase efficiency of antigen uptake - Widespread distribution – most epithelia and solid organs, such as the heart and kidneys - Phagocytosis – actively ingest antigens using complement receptors and Fc receptors - Micropinocytosis – engulf large amounts of surrounding fluid non-specifically. - Use pattern recognition receptors to recognise pathogen.

Answer 79

1. Dendritic cells take up microbial antigens and become activated in peripheral tissues. 2. Activated dendritic cells travel to the lymph nodes. 3. At the lymph nodes, the dendritic cells become mature and activate T cells. 4. CD maturation involves increased expression of MHC molecules, express co-stimulatory molecules and secrete cytokines. All 3 endow dendritic cells with a potent ability to activate naïve T cells.

Answer 80

- Recognise highly conserved microbial components referred to as pathogen associated molecular patterns or associated molecules patterns. - Sugars, proteins, lipids, nucleic acid motifs - Not easily altered by microbes to avoid detection

Answer 81

Soluble factors released by one cell that bind to specific receptors on the same cell or another cell leading to altered function. Important roles in all aspects of the immune response.

Answer 82

- Produced by many cell, and 1 cell can make many cytokines - Low MW proteins - Produced locally and transiently - Potent at picomolar concentrations - Have specific receptors - Binding alters target cell function - May have multiple actions

Answer 83

1. Haemopoietic, for example GM-CSF 2. Regulatory, for example IL-10 3. Cytotoxic, for example IFN 4. Autocrine, for example IL-2

Answer 84

Chemotactic recruitment of cells from blood into tissue.

Answer 85

- Defects in antigen processing are common in human tumours - Feline mammary carcinomas – reduced expression of MHC class I HC and proteosome components (LMP2 and LMP7) compared to normal mammary tissue. - May cause defective processing of some tumour antigens

Answer 86

- Bovine herpesvirus 1 (BoHV-1), pseudorabies virus and equid herpesviruses 1 and 4 encode a UL49.5 protein that inhibits TAP mediated peptide transport. - This impairs peptide loading of MHC class I molecules and represents an immune evasion mechanism.

Answer 87

Only activate at the right combination.

Answer 88

- Polygenic: contains several different copies MHCI and MHCII genes and all these genes are expressed at the same time. - Polymorphic: multiple variants (alleles) of each gene in the population - Every individual expresses a number of different MHC antigens. The specific set of MHC expressed by an individual is referred to as “tissue type”. Each set of MHC will be capable of presenting a different range of peptides

Answer 89

- Viral infection that affects a group of animals with different tissue types - Impact on being able to find transplant donors

Answer 90

- Every individual has two sets of MHC alleles called an “MHC Haplotype” - MHC gene expression is co-dominant - Greater diversity is possible with MHCII genes as different α and β chains may pair together to give distinct MHCII products - Fundamentally Mendelian - 1/4 chance of a sibling being a matched donor

Answer 91

- Chicken MHC is 1/20th of the size of the human MHC at only 19 genes - Chicken MHC has only a single classical class I and class II molecule expressed at high level - Single dominantly expressed MHCI and MHCII molecules confer resistance or susceptibility to particular pathogens (leading to strong genetic associations with infectious disease) - Chickens may live or die according to their dominantly expressed class I molecule

Answer 92

1. Graft Rejection 2. Associated with disease susceptibility, such as increasing the risk of developing a disease, especially autoimmune disease. 3. Association with disease resistance and production traits in livestock.

Answer 93

- Autografts: same individual - Isograft: genetically identical - Xenograft: different species (pigs) - Allograft: same species, different genetic constitution (most common)

Answer 94

- Alloreactivity is the recognition of peptides complexed with non-self MHC - It is estimated that 1 – 10% of all T-cells have the potential to be alloreactive which is why graft rejection can be so destructive. - Graft rejection may be acute (days to weeks) or chronic (months to years)

Answer 95

Canine rheumatoid arthritis Immune-mediated haemolytic anaemia (IMHA) Diabetes mellitus Lymphocytic thyroiditis Addison’s disease Chronic hepatitis in Dobermans Necrotizing meningoencephalitis Anal furunculosis Chronic superficial keratitis Susceptibility to leishmaniosis.

Answer 96

Biological response to harmful stimuli aimed at removing that stimuli and promoting healing. Should be a local response.

Answer 97

- Type 1 reactions/anaphylaxis, such as vaccination reactions - Airway disorder, such as feline asthma or recurrent airway obstruction in horses - Autoimmune haemolytic anaemia in dogs - Sweet itch in horses

Answer 98

Vasodilation – caused by many mediators, such as histamine and prostaglandins Increased vascular permeability – caused by many mediators, such as histamine Exudation – fluid filters from the circulatory system into surrounding tissue. Carries leukocytes and components to proteolytic enzyme cascade, such as complement, coagulation, fibrinolytic and kinin systems.

Answer 99

- Histamine - Bradykinin - Nitric oxide - Cytokines – interleukins, interferons, chemokines, colony stimulating factors - Eicosanoids – prostaglandins, thromboxanes, leukotrienes - Other plasma proteins – complement, coagulation and fibrinolytic factors - Platelet activating factor - Neuropeptides

Answer 100

autocoids/local hormones. Released from cells upon stimulation. - Act on adjacent/local cells – paracrine - Act on cell that secreted hormone – autocrine

Answer 101

Keep them acting locally, done by 2 different pathways: 1. Diamine oxidase 2. Histamine-N-methyl-transferase

Answer 102

- Tissue repair, inflammation - Control of local blood supply - Contributes to allergic and anaphylactic reactions - Neurotransmission in the CNS - Gastric acid secretion

Answer 103

- High concentrations in the lungs, skin, GI tract and brain - Present in mast cells and basophils – contain granules densely packed with histamine, heparin, proteoglycans and serine proteases in a ratio of 1:3:6 - Neurones in the brain - Enterochromaffin like cells in the stomach

Answer 104

- Produced by bone marrow - Released as immature cells and then mature in tissue - Found beneath skin throughout the respiratory, digestive and urinary tracts.

Answer 105

1. Priming of mast cell: exposure to allergen creates IgE antibodies, which bind to mast cell IgE receptors. 2. 2nd exposure to allergen caused allergen to bind to IgE on mast cell surface. 3. Activates mast cell by: increasing intracellular calcium concentration or C3a and C5a complement components 4. Leads to degranulation and histamine release

Answer 106

Increase in cAMP by beta-adrenoreceptor agonists

Answer 107

Systemic vasodilation Increased vascular permeability Itching Bronchoconstriction Ileum contraction Effects on neuronal action potential firing

Answer 108

Increased IP3 and DAG, stimulating calcium ion release.

Answer 109

Stimulate gastric acid secretion Relax smooth muscle Speed up heart rate Inhibit antibody and cytokine production Inhibit neutrophil activation

Answer 110

Increased cAMP

Answer 111

Inhibits neurotransmitter release from neurones

Answer 112

Decreases cAMP

Answer 113

Regulates neutrophil release from bone marrow and chemotaxis in mast cells.

Answer 114

Decreases cAMP

Answer 115

- Used in treatment of allergy, such as hay fever and urticaria. - Orally active - Hepatic metabolism - There are no H1 antagonists licenced for vet use in the UK. Human drugs given with owner consent. - Have limited use in treating allergic disorders in animals. - Most useful if given before allergen challenge: feline asthma, allergic skin disorders relief of itching, motion sickness and mild sedation.

Answer 116

1st generation: average duration of 4-6 hours and crosses the blood brain barrier. Such as diphenhydramine, chlorphenamine, cyproheptadine and alimemazine. 2nd generation: longer duration of 12-24 hours and does not cross the blood brain barrier. Such as cetirizine, loratadine and acrivastine.

Answer 117

Inhibit gastric acid secretion. Treatment of gastric ulcers. For example, cimetidine, ranitidine, famotidine.

Answer 118

Used as research tools and have been human clinical trials on antagonists of H3 and H4 receptors.

Answer 119

Immediate or anaphylatc hypersensitivity – allergic reaction. Oversensitive reaction to an allergen producing an excessive inflammatory response.

Answer 120

- Whole body reaction of a previously sensitised animal to the sensitising allergen. - Life threatening - Produces immediate smooth muscle contraction, vasodilation, increased vascular permeability - Within 2 minutes, there is nausea, abdominal pain, palpitation, urticaria, difficulty in breathing, hypotension, inadequate circulation. - Within 4 minutes there is shock.

Answer 121

Epinephrine – immediate and subcutaneously. Intravenous administration also required to maintain intravascular volume and supply additional; medication. Chlorphenamine and promethazine – H1 receptor antagonists intravenously Glucocorticoids – no acute effect but suppress slow onset urticaria, bronchospasm, laryngeal oedema and hypotension.

Answer 122

Protein or polypeptides produced and released from immune cells during inflammation. Upregulated during inflammation

Answer 123

- Very potent – sub nanomolar (< 1 x 10-9 M) - More than 100 exist and they are split into 4 main groups: interleukins, interferons, chemokines and colony stimulating factors - Very complex – interact with each other, stimulate receptor upregulation for others - Act at kinase-linked receptors or GPCRs - Coordinate inflammatory response

Answer 124

- Generated from phospholipids - Precursors are 20 carbon fatty acids – eicosa = 20 C - They are not stored but generated on demand - They are prostaglandins, leukotrienes and thromboxane - Involved in many physiological processes with major involvement in inflammation - Target of several groups of drugs

Answer 125

PG = prostaglandin Letter = basic structure Number = number of carbon C=C double bonds PGD2, PGE2, PGF2alpha, PGI2 If arachnoid acid is precursor then 2 C=C bonds are present. If diet is rich is omega-3 fatty acids, then the precursor is slightly different to arachnoid acid. PGE3 and PGI3 have more of an inflammatory effect.

Answer 126

1. Arachidonic acid to PGG2 and PGH2 by cyclooxygenase. 2. PGH2 into PGI2, PGF2, PGD2, PGE2 and thromboxanes.

Answer 127

1 – constitutively expressed in most cells 2 – not normally present, expression induced inflammatory factors by cytokines for example.

Answer 128

- Relaxation of vascular smooth muscles and constriction at high concentrations. - Constriction of bronchial muscle - Relaxation of GI and uterine muscle

Answer 129

- Relaxation of vascular smooth muscle - Dilation and sometimes constriction of bronchial muscles - Hyperalgesia - Produces fever - Promotes platelet aggregation - Inhibition of gastric acid secretion - Increases gastric mucous secretion

Answer 130

Lower nociceptor threshold level. Sensitises receptors on afferent nerves to agents not usually causing pain.

Answer 131

- Constriction of vascular smooth muscle - Constriction of bronchial muscle in dogs and cats - Luteolysis in some species, such as cattle, and uterus contraction

Answer 132

- Relaxation (potent) of vascular smooth muscle - Hyperalgesia - Inhibit platelet aggregation - Modulates kidney function

Answer 133

Leukotrienes – produced in leukocytes, lung, mast cells and platelets. Triene of double bonds.

Answer 134

BLT for LTB4 – causes activation and targeting of leukocytes and cytokine production Cysteinyl-LTs – cause bronchoconstriction and vasodilation, coronary vasoconstriction and is particularly important in asthma

Answer 135

Mast cells, basophils Vasodilation and increased vascular permeability

Answer 136

Mast cells, leukocytes Vasodilation, pain, fever

Answer 137

Mast cells, leukocytes Increased vascular permeability, leukocyte activation and chemotaxis

Answer 138

Platelets Platelet aggregation and vasoconstriction

Answer 139

Non-steroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids H1 receptor antagonists and chondroprotective drugs

Answer 140

- Steroids secreted by adrenal gland - Outer layer of cortex/zona glomerulosa – secreted mineralocorticoids, such as aldosterone, regulate water and electrolyte balance - Middle layer/zona fasciculata – secretes mixture of glucocorticoids - Main glucocorticoids in humans is hydrocortisone/cortisol and in many animals, the main glucocorticoid is corticosterone

Answer 141

- Glucocorticoids released in pulsatile fashion, circadian rhythm, in humans highest in morning, declining to low in evening/night. - Produced from cholesterol, initial step regulated by ACTH

Answer 142

- Glucocorticoids bind to receptor in the cell cytoplasm - Glucocorticoid-receptor complex moves to nucleus - Increases or decreases gene transcription

Answer 143

- Decreased uptake and utilisation - Increased gluconeogenesis - Decreased protein synthesis - Increased protein catabolism - Redistribution of fat - Decreased absorption in GI tract - Increased excretion from kidney

Answer 144

Produces muscle weakness, hypotension, hypoglycaemia and weight loss.

Answer 145

May be autoimmune condition or caused by destruction of adrenal glands by chronic inflammation.

Answer 146

Excess of corticosteroids can be caused by prolonged glucocorticoid administration or excessive activity of adrenal glands. - Increased, excessive appetite - Distended abdomen - Coat problems – baldness, hair loss, hair thinning, discolouration - Polyuria and polydipsia

Answer 147

- Hyperglycaemia – decreased glucose uptake and utilisation and increased gluconeogenesis - Muscle wasting – decreased protein synthesis and increased protein catabolism - Osteoporosis – decreased calcium absorption in GI tract and increased calcium excretion from kidney

Answer 148

- Decreased movement of neutrophils from blood vessels - Decreased transcription of cytokine and cell adhesion factor genes - Decreased activation of mast cells, neutrophils, macrophages - Decreased activation of T helper cells - Decreased fibroblast function – reduced healing and repair - Decreased osteoblast (build bone) activity - Decreased transcription of many ILs, TNF-α, colony-stimulating factors, iNOS, IgG - Decreased histamine release from mast cells and basophils - Increased transcription of anti-inflammatory cytokines - Increased osteoclast activity Main effects: COX-2 expression increased during inflammation and produces prostanoids. Decreased COX-2 expression and increased lipocortin/annexin production, which acts to inhibit PLA2.

Answer 149

Glucocorticoids inhibit early inflammation response – redness, heat, swelling, pain, loss of function. And inhibit late inflammatory response – wound healing and repair.

Answer 150

- Treatment of inflammatory, immune or tumour related diseases - Emergency treatment of anaphylaxis, shock, asthma and trauma of CNS - Can be administered topically, orally, IV, IM or intralesional - Asthma - Recurrent airway obstruction - Eczema, rhinitis, allergic conjunctivitis - Hypersensitive states – severe allergic reactions to drugs or insect bites - Suppress graft rejection - Acute spinal injury

Answer 151

Suppression of response to infection Suppression of endogenous glucocorticoid production Metabolic actions Osteoporosis Cushing’s syndrome

Answer 152

1. Glucocorticoids suppress IL2 gene transcription 2. Prevent Th cell proliferation 3. Other drugs inhibit calcineurin activation to prevent IL2 production and Th proliferation, such as ciclosporin (aka cyclosporin) and tacrolimus. 4. Ciclosporin can be given (sometimes together with glucocorticoids) for immune suppression in humans after organ transplantation. Ciclosporin also used in vet practice, such as for atopic dermatitis in dogs but can cause kidney toxicity

Answer 153

Addison’s disease Systemic lupus erythematosus Haemolytic anaemia Myasthenia gravis Arthritis

Answer 154

T cells recognise small peptide fragments complexed with major histocompatibility complex molecules presented at the target cell surface.

Answer 155

A T cell receptor together with either a CD4 and CD8 co-receptor.

Answer 156

- TCR and co-receptors bind to different sites on the MHC molecules - A single MHC can be bound simultaneously by TCR and co-receptors - TCR is more peptide MHC recognition - CD4/CD8 enhances sensitivity - Unique systems has 1 ligand that the 2 receptors have 2 key interactions involved.

Answer 157

- Alpha-Beta-T cell receptors are made up of 2 transmembrane chains – alpha and beta. - Each chain contains a variable and a constant region - TCRs bind to the peptide binding platform of MHC and mediate peptide MHC recognition.

Answer 158

- Every individual possesses a large number of different TCRs. - Recent estimates suggest that every human has 25 million different TCRs. - Each TCR has its own unique antigen specificity. - This provides protection against a vast array of pathogens.

Answer 159

On recognition of antigen, individual TCRs undergo clonal expansion.

Answer 160

- Cross reactivity is effective immunity. - Cross reactivity caused pathogenesis of disease, such as the immunological basis of autoimmunity and transplant rejection. - Suggestion of cross reactivity being the underlying cause of autoimmunity has the mechanism ‘molecular mimicry’, microbial pathogens drive the expansion of self-reactive TCR clonotypes, causing autoimmune disease.

Answer 161

1. Binding of the TCR and co-receptors, CD4 or CD8, to foreign peptide MHC. 2. Co-stimulatory signal delivered by the same antigen presenting cell. CD28 on the T cell binds to B7 molecules on the APC. 3. APC produces cytokines, which influence pathway of differentiation and produce different subsets of effector T cells that carry out different effector function, CD4 T cells in particular.

Answer 162

Foci of interaction between T cells and antigen presenting cells. TCR-peptide MHC complexes concentrated here.

Answer 163

1. The TCR is expressed in association with the CD3 complex. 2. TCR-peptide MHC interaction results in phosphorylation of the immunoreceptor tyrosine based activation motifs in several CD3 chains. 3. Phosphorylation of CD3 is mediated by protein kinase. 4. Phosphorylated immunoreceptor tyrosine based activation motifs recruit and activate ZAP70, which triggers a cascade of signalling. 5. T cell signalling events lead to the activation of transcription factors in the nucleus, which result in proliferation and T cell effector function.

Answer 164

1. T cells undergo a physical transformation from a small lymphocyte into a lymphoblast. 2. Activated T cell starts to secrete cytokines and express cytokine receptors (IL-2 autocrine growth factor). 3. The activated T cell starts to divide which generates lost of T cells with the same TCR. 4. Most become effector cells but some also become memory cells, which are responsible for immunological memory.

Answer 165

- The T cell repertoire is generated by a process called somatic recombination. - This involves rearranging genes that encode parts of the complete alpha and beta chains. - The TCR-alpha locus: variable, joining and constant gene segments, V-alpha J-alpha C-alpha. - The TCR-beta locus: variable, diversity, joining and constant gene segments, V-beta D-beta J-beta C-beta.

Answer 166

1. 1 variable, diversity and joining region gene is selected (TCR). 2. The intervening intronic sequence is looped out and deleted. 3. The C region is added by RNA splicing after transcription.

Answer 167

- Different variable regions combine with variety of D and J regions in the beta chain and J regions in the alpha chain. This is combinatorial diversity. - The way the segments join is not precise, this is called junctional diversity. - Nucleotides may be added when the joins in the DNA are made. This is called N-nucleotide addition. - Different alpha chains can combine with different beta chains.

Answer 168

1. Migration form cortex to medulla of bone marrow. 2. Differentiation to express a TCR with either CD4 or CD8. 3. Positive selection of TCRs that can interact with peptide MHC complexes and others die by neglect. 4. Apoptosis of TCRs that ineract with high affinity for slf peptide MHC in negative selection.

Answer 169

99% of immature T cells die by apoptosis and cell debris is phagocytosed.

Answer 170

Subsets of CD4 T cells are specialised to provide help or different pathogens.

Answer 171

TH1 – activate macrophages enabling destruction of intracellular organisms. Stimulate cytotoxic effect cells, CD8 T cells and natural killer cells. TH2 – major role on providing B cell help to differentiate into plasma cells which secrete antibodies G, A and E. TH17 – recruit neutrophils to sites of infection. Essential in response to fungi. TFH – reside in lymphoid follicles. Important fr the formation and maintenance of germinal centres. Also in the regulation of B cell differentiation into plasma cells.

Answer 172

Immune responses can become polarised towards TH1 and TH2

Answer 173

- TH1 and TH2 responses are mutually antagonistic. - TH1 cells produce IFNgamma which inhibits TH2 cells, leading to cytotoxic cell mediated immunity. - TH2 cells produce IL-4 & IL-13 which inhibit TH1 cells, leading to humoral immunity.

Answer 174

Incorrect deviation is thought to contribute to pathology, such as a dog with leishmaniosis requires a strong TH1 polarization in order to control this protozoal infection. Failure leads to chronic multisystemic disease and death.

Answer 175

- All CD4 T-cells arise from a common naive CD4 T-cell precursor. - The way that antigen interacts with APCs (via PAMPs and PRRs) determines cytokine production by the antigen presenting cell, signal 3. - The variation in signal 3 causes naive CD4 T-cells to acquire different effector functions.

Answer 176

T-cells expressing CD8 differentiate into CD8 cytotoxic T-cells. CD8 T-cells kill their target cells on recognition of specific peptide Major Histocompatibility Complex Class I. Important for immunity against intracellular infection. Capable of killing cancerous cells.

Answer 177

- CD8 T-cells have specialized lysosomes that contain cytotoxic proteins. - These are called perforin, granzymes and granulysin. - Perforin forms pores in the cell membrane causing cell lysis. - Granzymes enter cells and stimulate apoptosis.

Answer 178

1. Target and cytotoxic cells form membrane interdigitations and intercellular ‘tight junctions’. 2. This forms a contained microenvironment in the narrow space between the cells.

Answer 179

The cytotoxic granules move and become polarised. Cytotoxic granules are released at the site of cell contact.

Answer 180

- Are more sensitive to antigen - Express different cell surface markers - Are long-lived

Answer 181

- Widely distributed at body surfaces - When viruses infect cells, they produce interferon-alpha (IFN-alpha) - This cytokine activates NK cells to kill the virus-infected cell - Killer cell immunoglobulin-like receptors (KIRs) are the dominant form of activatory and inhibitory receptors in humans

Answer 182

1. Downregulation or loss of MHCI at surface. 2. So cell no longer engages the inhibitory receptor and no longer gives inhibitory signal to NK cell. 3. In addition, disease cells also express ligands which engage the activating receptors on these NK cells. 4. Activation of NK cells. 5. Perforin and granzymes are released.

Answer 183

- Have a T cell receptor made up of gamma and delta chains - Develop in the thymus - Found at mucocutaneous surfaces of the body - In some animals and many in blood (cattle, sheep, pig) - Prominent in spleen (dog) - Location suggests they are important in ‘front line defence’ of the body - Particularly responsive to bacterial antigen such as Listeria, E. Coli, S. Typhimurium and Mycobacterium

Answer 184

Aim is to harness the beneficial effects of T-cells and use them to treat diseases where there is an unmet need. Challenges: we need to improve our basic understanding of the immune system to overcome the challenges of using cellular therapy.

Answer 185

- T-cells have a potent ability to kill infected cells, especially useful in viral infections - T-cells have a potent ability to kill cancerous cells - T-cells can regulate the immune response, useful in autoimmunity and graft rejection - T-cell therapy may have a long lived effect, such as may be able to prevent cancer relapse

Answer 186

A treatment used to help the immune system fight diseases, such as cancer and infections with certain viruses. 1. T cells are collected from a patient and grown in the laboratory. 2. This increases the number of T cells that are able to kill cancer cells or fight infections. 3. These T cells are given back to the patient to help the immune system fight disease.

Answer 187

1. Isolate T-cells from blood & culture in vitro with cytokines. 2. T-cells are genetically modified using vectors that encode receptors or molecules that enhance response to cancer cells. 3. Most common vectors are gamma-retroviruses and lentiviruses engineered to be replication incompetent by the removal of genes that encode vital proteins. 4. Genes of interest are incorporated in the genome of T-cells.

Answer 188

It is possible to generate large numbers of cancer-specific CD8 T-cells in a very short space of time.

Answer 189

- Must identify a suitable MHCI restricted tumour rejection antigen - Must isolate a tumour specific TCR, which can be very challenging - This therapy is restricted by a specific MHCI so can only be used in a subset of patients

Answer 190

1. Operate in a non-major histocompatibility complex class I manner 2. Extracellular domain is a single chain antibody 3. Several different generations which vary in their cytoplasmic domains

Answer 191

T-cells within the immunosuppressive tumour microenvironment express a range of co-inhibitory receptors. - Engagement of these co-inhibitory receptors deliver a negative signal to the T-cells which prevents them from activating and destroying cancer cells. - Monoclonal antibodies that block PD-1 and CTLA-4 have been developed and are being used to treat humans with metastatic melanoma. - Amazing clinical responses have been seen in these patients although ~50% still do not respond so more work still required. - Other cancers are also being treated with these novel therapies e.g. lung cancers

Answer 192

- B and T cells are stimulated by different components of the same antigen. - T cells recognise processed peptide associated with MHC class I or II. - B cells recognise large, conformational determinants or epitopes, without the need to chop them up/no processed required. - May be free or non-specifically attached to the surface of an antigen presenting cell.

Answer 193

Thymus T cell independent – rare event Thymus T cell dependent – ~99% of antigens are T cell dependent

Answer 194

Results in B cell activation, which leads to maturation into plasma cells and antibody production, without requirement for T cell help.

Answer 195

T cell helps B cell become fully activated and there is no response to the antigen alone.

Answer 196

In the periphery – spleen, lymph node and mucosa – naïve B cells express both IgM and IgD, and there are binding sites to the same antigen.

Answer 197

1. BCR binds to an epitope 2. Co-stimulation: CD40L expressed by CD4 cells bind to CD40 on the B cell 3. Cytokine produced by CD4 cells binds to cytokine receptors on the B cell

Answer 198

- Transform into a lymphoblast - Ig class switch to IgG, IgA or IgE and no longer express IgM or IgD Clonal proliferation and differentiation into plasma cells and memory cells. Plasma cells then secrete antibody that has the same specificity as the orginal smIgM or smIgD.

Answer 199

1. Antigen presenting cells and T cells interact in the T cell areas of the secondary lymphoid tissues. 2. Activated T cells move into the follicles and interact with B cells in the germinal centre. 3. B cells that recognise antigens with high affinity, divide and mature into plasma cells, as long as they receive all 3 signals.

Answer 200

The BCR like the TCR, is unique for each B cell and a vast repertoire of BCRs exist to account for all the potential antigen exposure.

Answer 201

1. Naïve B cells begin by expressing surface membrane IgG and surface membrane IgM. 2. They interact with an antigen and activate, as they receive the 3 signals. 3. They then undergo class switching. 4. The activated B cell no longer expresses IgG or IgM. 5. They now express a single class of immunoglobulin. 6. It will then differentiate into a plasma cell and subsequently start to secrete that immunoglobulin, which has the same specificity as the original antibody expressed by the naïve B cell, but is now just a different class of antibody.

Answer 202

Gene rearrangement

Answer 203

1. Heavy chain genes 2. DNA rearrangement loops out introns 3. Transcription and alternative RNA splicing 4. Translation (happens twice to make sure RNA with a mu on the end and some with δ on the end) 5. Expression IgM and IgD are expressed at the cell surface. However, the VDJ genes are the same, for example, antibodies have the same binding specificity.

Answer 204

1. 2nd DNA rearrangement is cytokine driven. Switches based on what would give the most effective immune response. 2. mRNA transcription with RNA splicing 3. Translation 4. Expression as SmIgA

Answer 205

- As the antibody response matures, single nucleotide substitutions (point mutations) in Ig genes occur in somatic hypermutation. - Selection of B cells with high affinity BCRs from those with low affinity BCRs as the immune response matures and the antigen concentration decreases.

Answer 206

Refers to switching off an immune response. Also called down regulation Necessary to prevent unlimited and deleterious expansion of immune and inflammatory cascades. Prevents damage to normal tissue and protects our bodies.

Answer 207

1. Antigen usage 2. Antibody mediated suppression 3. Hormonal regulation 4. Suppressor T lymphocytes

Answer 208

1. Antigen 2. Immune response 3. Reduced antigen concentration 4. Reduced immune stimulation

Answer 209

a) Reducing antigen concentration – antibody combines with antigen, thereby reducing antigen concentration, which is linked to antigen usage/mechanism 1. b) Immune complexes of antigen an antibody are immunosuppressive – antigens and antibodies from immune complexes, which are then removed by phagocytes that subsequently release suppressive substances, such as PGE2.

Answer 210

The neuro-endocrine-immunological loop – effects that are mediated by soluble messenger proteins. - Stress > pituitary gland > adrenal cortex > cortisol > immune suppression - Cytokines > hypothalamus > temperature set point > fever - Some sex hormones can influence immune system.

Answer 211

T lymphocytes can suppress immune responses caused by other T and B lymphocytes. Also called regulatory T cells.

Answer 212

1. Inject mouse with high dose of foreign antigen 2. 4 days later, remove spleen from mouse and make lymphocyte suspension 3. Adoptive transfer to naïve recipient 4. Immunogenic dose of antigen 5. Makes weak serum Ab response to SRBC due to presence of suppressor T lymphocytes

Answer 213

CD4+ T cells are the majority – spontaneously arising or induced types CD8+ T cells less important – induced type

Answer 214

- By regulating the balance of TH1 vs TH2. - Natural suppressors include: CD4+ and CD25+ T reg - Induced suppressors: CD4+IL-10 producing Tr1 cells - The TGF-beta producing induced suppressors

Answer 215

Leishmaniosis is not endemic in the UK but can see cases form animals that have travelled abroad, transmitted by sand flies in protozoal infection. TH1 response is protective and TH2 response is not protective and results in severe disease.

Answer 216

CD4+, CD25+, FOXP3+ Treg - Always normally present in the body and require direct contact to work. - Control of unwanted immune responses, such as autoimmunity - Can be identified by the fact that they express CD25+ and FOXP3+ - Are found in humans and animals, such as cats, dogs and horses

Answer 217

IL-10 producing Tr1 are induced suppressors – induced by an immune response and are called Tr1 cells. Work via cytokines, not direct contact. Key cytokine is IL-10, which can be identified by their ability to produce IL-10. TGF- producing TH3 is important in ‘oral tolerance’. Induced and work via cytokines, not direct contact

Answer 218

An individual who has been sensitized to a particular antigen by repeated exposure over time is susceptible to developing an excessive immune response (hypersensitivity reaction) on subsequent exposure to the antigen. The same hypersensitivity mechanisms evolved for a useful purpose and are also utilised in appropriate immune responses to foreign antigen. They may be better considered as ‘immunopathological mechanisms’ rather than ‘hypersensitivity mechanisms’.

Answer 219

Type I = immediate Type II = antibody dependent - Cytotoxic type - Anti-receptor type - (Sometimes considered as Type V) Type III = immune complex Type IV cell-mediated or delayed type hypersensitivity (DTH)

Answer 220

Sensitisation repeated exposure to antigen or allergen over time. - Allergens may be derived from: grass pollen, house dust mites, animal dander, food, bee venom. - Allergic reactions generally occur when sensitisation to an allergen occurs  development of allergen-specific IgE

Answer 221

1. Dendritic cell captures allergen, which is processed and presented by MHCII. 2. Dendritic cell migrates to local lymphoid tissue and triggers a T cell response (TH2). 3. TH2 response provides B cell help (IL-4,9 and 13) 4. Allergen specific N cells are activated > plasma cells that produce allergen specific IgE.

Answer 222

- Serum concentration of IgE is very low - Produced in small quantities - Short half-life (2 days) - Mostly found bound to the high affinity Fc-epsilon-RI on mast cells and basophils - Fc-epsilon-RI receptors are usually saturated with IgE despite low concentration of IgE in serum (high affinity)

Answer 223

Subsequent exposure to the same allergen will cross link IgE which is bound to mast cells resulting in mast cell degranulation and a Type I hypersensitivity reaction. - Allergen cross-links IgE bound to FceRI - Intracellular signalling pathway leads to degranulation

Answer 224

- Only occurs upon cross-linking of bound IgE - Cytoplasmic granules fuse with plasma membrane > release of chemical mediators - Inflammatory reaction is induced by release of granule contents (histamine) and secretion of newly formed mediators (prostaglandins, leukotrienes, cytokines) - Immediate symptoms – bronchoconstriction, vasodilation, pruritis, 5-60 mins - Late phase symptoms – recruitment, eosinophils and macrophages, 4-24 hours

Answer 225

Localised – - Cutaneous (flea allergy, insect bites) - Respiratory (asthma) - Intestinal (food allergy) Systemic - Anaphylaxis (bee sting, penicillin reaction - Severe and life threatening - Bronchoconstriction, laryngeal oedema, vasodilation

Answer 226

1. Lack of Treg activity 2. IgE production 3. Eosinophil attraction 4. Mast cell attraction

Answer 227

- Age - Parasitism? - Genetic - Microbial infection - Stress - Allergen exposure - Immune dysregulation - Allergy often has a genetic basis, certain breeds are susceptible - Other influences are important as well e.g. age of exposure

Answer 228

Suggestion that a lack of childhood exposure to pathogens and less childhood infections results in the increased incidence of allergy. In individuals where you get naturally exposed to different infections, this induces TEG cells as they secrete cytokines and allows for bystander suppression. Cleaner environments will result in reduces expansion of Treg resulting in more allergic reaction.

Answer 229

- Transfusing a DEA1- dog with DEA1+ blood, the dog will make an anti-DEA1 antibody response (induced alloantibody). - If a second transfusion of DEA1+ blood is given then the anti-DEA1 antibody will bind to the DEA1+ RBCs mediating cytotoxicity i.e. TYPE II Hypersensitivity. - Type B cats have naturally occurring anti-A antibody in their blood. If a type B cat is transfused with type A or AB blood this will result in a severe transfusion reaction.

Answer 230

The immune system destroys the dogs RBCs via antibody mediate cytotoxicity.

Answer 231

Triggers by production of antibody that can bind to a target cell in the body.

Answer 232

- Grave’s disease is hyperthyroidism in humans - TSH engages with TSH receptor causing to release thyroid hormones - In Grave’s disease, antibodies are developed that are specific to the receptors of TSH and cause stimulation of the receptor when it binds - Results in excessive hormone production/hyperthyroidism

Answer 233

Disease of the neuromuscular junction of humans, dogs and cats. - Dog or cat have muscle weakness and excessive fatigue - Disease occurs when nerve ending interact with the muscle motor end plate - Normally, Ach produced - In disease, produce antibodies specific to Ach receptors and blocks Ach from the receptor

Answer 234

- Sensitisation leads to circulating antibody - Exposure to high concentration antigen (antigen excess) - Results in the formation of small soluble immune complexes which are found in the blood and circulate around the body resulting in systemic disease

Answer 235

- Sensitisation which leads to an excessive IgG response - After an individual has become sensitized then subsequent local exposure to allergen will result in: - Local immune complex formation (Ag and Ab) - Triggers local inflammatory response

Answer 236

- Excess IgG response - Antigen enters where excess is - Immunocomplexes - Inflammation, most commonly in the respiratory tract

Answer 237

1. Immune complexes become deposited in the circulation 2. Cause vasodilation and vasculitis and inflammation. 3. Platelet aggregation 4. Microthrombi 5. Blood vessel occlusion 6. Ischaemic necrosis

Answer 238

- IC deposition occurs at certain predilection sites: small bore capillaries with a turbulent blood flow - Sites: renal glomeruli, uveal tract of the eye, skin at the junction between the epidermis and dermis, and synovium of the joints.

Answer 239

* Size of complex * If IC clearance mechanisms are overwhelmed * Nature of antigen * Nature of antibody * More likely to deposit at sites of high blood pressure & turbulent blood flow e.g. renal glomeruli * Damage to blood vessel walls (Endothelial lesions)

Answer 240

Causes a protein losing nephropathy

Answer 241

- Involves mononuclear cells & cytokines - Delayed in onset 24 - 72 hours - Delayed type hypersensitivity (DTH) - Contact allergy (mainly in humans)

Answer 242

1. APC take up antigen and present peptides, stimulating TH1 response 2. IFN-y and requirement of other immune cells CD8 and NK (this is what stimulates a type IV reaction)

Answer 243

Failure of the immune system to respond to a particular antigen. Neonatal tolerance is the 1st demonstration of tolerance.

Answer 244

- Share placental circulation but are genetically different - Each calf is exposed to each other’s alloantigens in utero - Become therefore tolerant to these alloantigens - Do not reject tissue grafts as a result

Answer 245

Calves exposed to viral antigens in utero become tolerised to the virus, are born with the infection and become persistently infected.

Answer 246

- Expose neonatal (new-born) mouse to foreign antigen by injection or transgenic expression - Are tolerant to the antigen - Immune system is tricked into thinking the antigen is self - Adult mouse would not mount an immune response to antigen

Answer 247

Tolerance can also be induced in adults. Experimental induction of tolerance to foreign antigens in adult animals.

Answer 248

High zone adult tolerance – a single high dose of antigen can induce tolerance in both T and B cells. Low zone adult tolerance: - Repeated injections of low dose antigen (dosage and route of admin is key) - Induces T cell tolerance - T cell more readily tolerised than B cells - If antigen is T dependent, B cells are effectively tolerant anyway

Answer 249

Failure to respond systematically to antigen previously given orally at specific dosage.

Answer 250

A foreign antigen is fed to a human or animal. When the same antigen is injected systematically then the individual will fail to respond.

Answer 251

- 1 group is fed ova – often used as an antigen to experimental approaches to tolerance - 1 group fed a different antigen, Derp1 - Dogs fed ova prior to immunisation get no immune response - Dog fed Derp1 have an immune response - So oral tolerance is established

Answer 252

- Systemic immune responses to an antigen are suppressed by feeding the antigen - Oral delivery of autoantigens or allergens may have therapeutic application - Could allow you to potentially treat autoimmunity?

Answer 253

- Failure of the immune system to recognise self-antigens - T and B cells are educated to render them tolerant to self - Breakdown of self-tolerance results in autoimmunity

Answer 254

1. Thymus selection of T cells to remove any autoreactive T cells from the population. 2. This is not always successful and make it out to the periphery so important to have peripheral mechanisms for autoreactive T cells. 3. These mechanisms are called peripheral tolerance. 4. One of which is T regulatory cells, which are thought to prevent autoreactive T cells getting out of control and causing damage. 5. There is also autoreactive T cell receive signal 1 and not signals 2 and 3, meaning it is unlike to activate and become anergic or die by apoptosis.

Answer 255

- Immature B cells encounter self-antigen in bone marrow? - Negative selection process? - Apoptosis of autoreactive clones? - Cannot activate without T cell help

Answer 256

Failure of self-tolerance resulting in activation of autoreactive cells which may produce pathology and disease.

Answer 257

- In normal individuals, you would expect to see autoreactive T and B cells being eliminated by peripheral mechanisms and not interact with self-cell and cause no autoimmunity. - We can take T cells and grow them in the lab against self-antigens.

Answer 258

- Can have a break down immunological tolerance - T regulatory cell are thought to play a role in tolerance so some defect in T regulatory cells causes lack of regulation and lead to activation to autoreactive T and B cells. - Attack of regular tissues and may have autoantibodies produced that also contribute to autoimmunity.

Answer 259

- Can involve almost all body systems - May be organ specific or multisystemic - Are highly important in humans - Occur in animals, particularly in dogs

Answer 260

IMHA (immune mediated haemolytic anaemia) IMTP (immune mediated thrombocytopenia) IMNP (immune mediated neutropenia) Pemphigus Polyarthritis Myasthenia gravis Thyroiditis Diabetes mellitus Systemic lupus

Answer 261

An immune response against auto-antigen: - Type II – cytotoxic or blocking antibodies - Type III – immune complex - Type IV – cell mediated

Answer 262

Immunological abnormalities Genetic background Age Gender Environmental triggers

Answer 263

- Loss of self-tolerance – such as lack of regulatory cells. - Expression of MHCII and peptide by target cells – self tissue becomes a target - Epidermal expression - IFN-gamma - can be triggered by infection

Answer 264

- Some human autoimmune diseases ae more common in particular races and can run in families - Autoimmune disease occurs in particular breeds of dog - Which genes are associated with autoimmune disease? - The major histocompatibility complex – certain MHCs seem to predispose individuals to immune diseases. - Preferential presentation of self-peptide - Linkage to other disease genes?

Answer 265

- Autoimmunity occurs in middle ages to older dogs and cats - As age changes in a dog, lymphocyte function, CD4 T cells and B cells decrease and CD8 T cells increase. - Hypothesis is that some of the CD4 T cells that disappear are regulatory.

Answer 266

Season and climate UV light Air pollution Diet and lifestyle Stress Drug administration Infection

Answer 267

TMS in Doberman and others – IMHA, IMTP and IMNP. Felimazole in cats – IMHA, IMTP and ANA.

Answer 268

Infection, concurrent or previous, triggers autoimmunity.

Answer 269

Injecting a susceptible strain of infectious agent or peptide antigen from microbe is enough to start autoimmunity and can be injected into another mouse and also develop autoimmunity.

Answer 270

Superantigens – non-specifically stimulate autoreactive T cells and B cells.

Answer 271

Infectious agent attached to cell surface, such as RBCs in mycoplasma infection. Cell destroyed secondary to immune response to microbe.

Answer 272

A response to infection results in antibodies which then circulate around the body and accumulate in certain organs, such as renal glomeruli, triggering a type III hypersensitivity reaction.

Answer 273

1. infection and tissue inflammation 2. T cell cytokine, IFN-gamma 3. MHC expression and self antigen 4. T cell recognises and attacks

Answer 274

1. Microbe and self-cell share antigenic component 2. Presentation of microbial antigen activates self T cell 3. Self B cell activated by microbial antigen

Answer 275

Immune system develops progressively in utero The immune system can be activated in utero

Answer 276

Blood lymphocytes can respond to mitogen in vitro in the 1st trimester, so: - Thymus develops - T cells in blood - Spleen - Blood SmIgM B cells - Complement - IFN-gamma/beta (antiviral)

Answer 277

Can make antibody to anaplasma, Leptospira, parainfluenza 3, rotavirus, parvovirus by day 100.

Answer 278

- Can make serum IgG - Blood SmIgG B cells - Can make serum IgM - Tonsil - Peyer’s patches

Answer 279

Can respond to campylobacter, chlamydia and E.coli beyond day 200. Normally born without serum Ig. Serum Ig at birth suggest in utero infection.

Answer 280

Depends on type of placentation. The classification of placenta according to how many cell layers separate the maternal and foetal circulation.

Answer 281

Epitheliochorial. Has lots of layers and then intact epithelium and trophoblast layer

Answer 282

Synepitheliochorial. Has uterine connective tissue and epithelium and some fusion of trophoblast cells and epithelium

Answer 283

Endotheliochorial. Has additional layer called maternal endothelium

Answer 284

Hemochorial. Has trophoblast as the main layer

Answer 285

- Born with serum IgG as adult level - Allows IgG to freely pass between maternal and foetal circulation and new-borns has a lot of IgG/similar to adult levels

Answer 286

- Small amount IgG (5-10% adult level) passes - Maternal antibody ca interfere with the way dogs and cats respond to vaccination

Answer 287

- Contact of maternal endothelium, uterine connective tissue, uterine epithelium and trophoblast. - No Ig transfer possible due to robust layer

Answer 288

- Contact of maternal endothelium, uterine connective tissue, uterine epithelium and trophoblast. - No Ig transfer possible due to robust barrier

Answer 289

Ruminants, horse and pigs have had no transfer of antibodies so are very vulnerable when born so very important for good colostral uptake.

Answer 290

Ruminant has lots of IgG and in non-ruminant has a dominating amount of IgA.

Answer 291

Gut permeability is increased from 6-24 hours. Colostral protein protected by: - Low proteolytic activity in the gut - IgA secretory component - Colostral trypsin inhibitors

Answer 292

Complement, but when this happen sit may be non-functional. May also be some absorption of maternal lymphocytes but not proven.

Answer 293

Lymphocytes can express fc receptors, the binding of which causes the uptake of antibodies from the colostrum. Can cause peak serum in circulation of animal within 24 hours and can cause transient proteinuria by some loss of the proteins by the neonatal glomeruli.

Answer 294

Ideally want IgA to stay in gut lumen, as they protect gut mucosa. In horse and pig, there is absorption of IgG and IgM and IgA stays within the gut mucosa. But in the ruminant, there is absorption of IgG and IgM, and IgA is absorbed and re-excreted back into the gut lumen.

Answer 295

- Colostral Ig inhibits development of neonatal immune response until maternal Ig is catabolised. - Neonates cannot respond to vaccine until this has occurred - Giving too early affects the ability to respond - Repeat vaccination of neonates accounts for variability in colostral intake and catabolism.

Answer 296

Vaccination at 8, 12 and 16 weeks to ensure that all are able to respond. - Vaccination too soon, internal antibody will interfere with the way the puppy or kitten will respond to vaccination. - Needs to be done before major susceptibility to certain infections. - This window varies between individuals and depends on the amount of colostrum absorbed.

Answer 297

Failure of passive/colostral transfer. Leads to enteric, respiratory disease or septicaemia. Immunodeficiency

Answer 298

- Premature at birth and no colostrum - Premature lactation with no loss colostrum - Poor quality colostrum - Failure to suckle - Failure to absorb - Adequate colostral transfer determine serum Ig concentration after 24 hours of life Treatment: administration of colostrum or plasma transfusion

Answer 299

Primary: congenital, inherited and rare. 16 weeks of age Secondary: acquired secondary to drugs, infectious, metabolic, neoplastic or inflammatory disease. Common.

Answer 300

- Chronic, recurrent infection in young, littermate animals - Infection at multiple sites - Failure to respond to standard antimicrobials - Infection with unusual agents

Answer 301

30 immunodeficiency diseases (breed associated) - Weimaraner immunodeficiency syndrome – IgG deficiency - CLAD – canine leukocyte adhesion deficiency (Irish setters) Congenital immunodeficiency in cats is rare.

Answer 302

- Isoimmune haemolytic anaemia - Can occur if the colostrum contains antibodies against the neonates erythrocytes - This can happen if dam has become sensitised to sire erythrocyte antigens or dam has spontaneously arising antibody that cross reacts with sire erythrocytes

Answer 303

- Given incompatible transfusion with Q+A+ blood (red blood cell antigens) - Sensitised to foal Q+A+ cells at first parturition - If mare is exposed to those antigens, it will cause an immune response and will produce antibodies against Q and A. - Could occur if mare has received a blood transfusion in the past containing Q and A (uncommon) or been expressed to red blood cells that express Q and A, which can happen after first parturition if the foal is Q and A positive. - Anti Q/A in colostrum - Haemolytic crisis in foal that is Q+A+

Answer 304

- Feline blood groups A, B and AB - All type B cats have high titred (antibody concentration) anti A - Type A cats sometimes have low titred anti-B - Neonatal isoerythrolysis can be caused in cats as a result: - A or AB kittens born to type B queens with colostral anti-A - Type B prevalent in Birman, Rex, BSH, Abyssinian, Persian and Somali

Answer 305

Rare in dog – but can be seen when sensitised DEA1- bitch mated to DEA1+ dog.

Answer 306

- Subclinical disease but may develop tail tip necrosis - 1-3 weeks post-partum - Severe haemolytic anaemia (Coombs positive) - Jaundice - Haemoglobinuria - Weakness, lethargy - Reluctance to suckle - Death within first few days of life

Answer 307

- Prevent at risk mating by blood typing sire and dam - Determine level of anti-A in dam serum before birth by titrating against sire RBC - Prevent susceptible kittens access to colostrum for 24 hours after birth - Type A foster queen - Colostrum replacement with type A cat serum

Answer 308

Potential for hypersensitivity if given repeatedly. Preformed antibody prevents recipient immune response.

Answer 309

The delivery of an antigen to induce an immune response and establish immunological memory.

Answer 310

- Cheap to produce - Stable - No side effects - Induce a protective immune response - Include range of epitopes to stimulate multiple clones of T and B cells - Induce immunological memory

Answer 311

- Whole pathogen vaccines - Virulent - for example, orf in sheep - Attenuated - Heterologous

Answer 312

So cannot cause disease. Done by heat, chemicals, alter growth conditions (medium, animal species), or (modern) genetic modification to attenuate the organism, for example, by modifying or deleting virulence genes.

Answer 313

Antigenically related but adapted to another species (for example, measles – distemper, no longer used).

Answer 314

Whole pathogen vaccine. Organism is antigenically intact but unable to replicate, due to formalin, alcohol or alkylating agents.

Answer 315

Live: - Induce better immunity - Fewer doses - No adjuvant - Greater risk of reversion to virulence or contamination - Less stable Killed: - Multiple doses - Must be administered with an adjuvant - Stable - Economical

Answer 316

Contain only specific metabolites or structural proteins from an organism that are known to cause an immune response.

Answer 317

Low immunogenicity (need adjuvant), monospecific immune response – although none currently available. Type of subunit vaccine*

Answer 318

Subunit vaccines can be made using recombinant DNA technology. DNA encoding protein is inserted into a bacterial plasmid. Produce recombinant antigen protein.

Answer 319

Harmless viruses are used to deliver the genetic code of the antigens to cells of the body resulting in the production of protein antigens which stimulate an immune response. Viral vectors may be replicating or non-replicating.

Answer 320

- mRNA is injected into the body and taken up by cells where it is translated by the cell into antigens, which stimulates an immune response. - mRNA only lasts for a very short period of time (days) and is then broken down naturally and removed by the body.

Answer 321

Can be produced much ,ore rapidly than conventional vaccines which is a major advantage in a pandemic situation. Made using synthetic production methods, offering flexibility of pathogens are rapidly evolving.

Answer 322

Not very stable so need to be stored at a very low temperature, such as -70 degrees.

Answer 323

- Much more stable than mRNA vaccines - No licensed DNA vaccines currently - Often administered using a technique called electroporation to allow the DNA vaccine to be taken up by cells. - After DNA has entered cells, it is then translated into mRNA and subsequently protein antigens are made resulting in stimulation of an immune response.

Answer 324

Differentiation between infection and vaccination

Answer 325

- Problem with FMD vaccination - Problem with FIV vaccine - (Fort dodge) - ospA Borrelia vaccine (recombitek lyme, merial) - IBR vaccine (infectious bovine rhinotracheitis) (gE negative mutant). Bayovac IBR, bayer

Answer 326

Needle injection Needle-free – transdermal delivery Mucosal – intranasal Aerosolization – poultry Feed or water – poultry In ovo – into eggs, poultry Immersion – fish

Answer 327

- Should be tailored to the individual animal or herd. Not every animal needs every vaccine. - Vaccines should be considered as core or non-core. All animals should receive core vaccines, but not every animal needs every non-core vaccine. - As many animals as possible within a population should be vaccinated with core vaccines in herd immunity. - Young animals require a series of priming vaccines followed by a 12 month booster.

Answer 328

- Transient post-vaccinal illness - Transient post-vaccinal immunosuppression - Local injection listen reactions - Hypersensitivity reactions

Answer 329

- Not be given to pregnant animals unless licensed - Avoid giving vaccines to sick animals with weakened immune systems - Decisions on vaccination should be made in consultation with clients and considering data sheets and vaccination guidelines. - Always read and understand vaccine data sheet and guidelines. - Keep records of vaccination and report any adverse reactions to the company and/or VMD. - One dose fits all and animal size is irrelevant. - Vaccines rarely lead to adverse effects. - All licensed veterinary vaccines have proven quality, safety and efficacy.

Answer 330

- Inappropriate administration - Administration to immunosuppressed animal - Batch of subnormal efficacy - Genetic non-responder

Answer 331

- Control and possibly elimination of infectious disease - Bring disease under control and tackle pandemics

Answer 332

- Viral pathogen in domestic species - Infects the epithelial cells of the gut - Will cause diarrhoea such as calf scours

Answer 333

- Physical barrier – the epithelium - Intestinal secretions, such as mucus and bile salts - IgA and complement - Enzymes, such as lysozyme

Answer 334

Innate immunity – non-specific defence, such as macrophages and natural killer cells.

Answer 335

1. Viruses often use receptors expressed by normal cells to gain entry and begin replication 2. Infected cell expresses viral Ag on MHC class I. The virus particle is broken down into peptide fragments which presented at the cell surface by MHCI. 3. Infected cell releases IFN-alpha/beta. This makes the uninfected cell produce anti-viral proteins for resistance. 4. Dendritic cells takes up virus particles. Migrate to the local draining lymph node, such as mesenteric lymph. Then triggers an adaptive immune response.

Answer 336

For intracellular pathogens, need to stimulate a cytotoxic T cell response. In the lymph nodes: 1. Antigen presenting cell, the dendritic cell has taken up viral antigens and has arrived at local lymph nodes. 2. Dendritic cells can stimulate CD8 and CD4 T cells, as it can pick up MHCI and II. 3. Dendritic cells also stimulating TH1 response which further stimulate CD8 T cells by producing IFN-gamma. 4. B cells stimulated by T helper cells, producing antibodies. 5. Once stimulated, immune cells need to home back to site of infection.

Answer 337

T and B cells that have clonally expanded in the mesenteric lymph nodes must get to the site of infection. - Achieved by the recirculation pathway - Activated cells go into the lymph and then blood. - Then find adhesion molecules on endothelial cells and home to site of infection. - Specific immune cells arrive at the site of infection.

Answer 338

To get through gut epithelium, E.coli must overcome physical barrier (bile, gut flora and gut motility for example) and cells of innate immune response.

Answer 339

E.coli bind to K88 and K99 pilus receptors to colonise the gut surface. Gamma-delta T cells provide protection to gut epithelium, particularly in ruminants.

Answer 340

Local toxins act on the intestinal tract causing a net loss of fluid into the tract, causing metabolic diarrhoea. Systemic toxins are endotoxins, which may cause serious symptoms. Local inflammation caused by bacteria that invade the intestinal wall.

Answer 341

Adaptive immunity is required. APC transport Ag to Peyer’s Patch or mesenteric lymph nodes. Stimulate TH2 response, which provide help to stimulate B cells that can produce specific E.coli antibodies in the lymph nodes. The adaptive immune response must then home back to the site of infection.

Answer 342

1. Parasite antigens released and taken up by antigen presenting cells. 2. Parasites are large but release antigens that can be picked up by dendritic cells. 3. APC transport Ag to Peyer’s Patch or mesenteric lymph nodes to trigger an adaptive immune response.

Answer 343

1. APC present antigen and cause TH2 response, that stimulate B cells to produce specific antibodies. 2. Activate parasite-specific immune response in PP/LN. 3. Immune cells must home back to specific site of infection. 3. Lymphocyte homing back to the site of infection. 4. Plasma cells produce parasite specific IgG and IgE.

Answer 344

1. IgE binds to mast cells dje to mast cell high affinity for igE receptors. Causes: - Eosinophil infiltration - Oedema, degranulation, vasodilation, local inflammation - IgE sensitises mast cells 2. Inflammation makes parasite detach 3. Goblet cell produce mucous to coat parasites to make it more difficult for worm to persist.

Answer 345

1. IgG/E binds parasite and recruits phagocytes 2. Extracellular degranulation of phagocytes damages parasites 3. IgG neutralise parasite products

Answer 346

An obligate intracellular protozoan pathogen which infects macrophages and replicates inside them. Infected macrophage or dendritic cells transport antigen to regional draining lymph nodes.

Answer 347

1. Infected macrophage transports antigen to regional LN. 2. Activate leishmania specific immune response in lymph node. 3. A TH1 response is required for an effective response against leishmania. TH1 release IFN-gamma, to activate ,macrophages to cause intracellular killing of leishmania. 5. Plasma cells binds to antigens to mediate complement mediated lysis. 6. These immune cells must home back to site of infection.

Immune System Flashcards

(372 cards)