Immunology Flashcards

Question

What is inflammation, and what are the cardinal signs ?

Answer 1

Inflammation - itis * non specific response to cell damage * a process by which cells of the immune system and their products are concentrated at a site of damage/ infection * the purpose is to aid eradication or repair of damaged tissue The five cardinal signs * heat * swelling * pain * loss of function * redness

Answer 2

Three events of inflammation 1. blood supply to site increases 2. capillary permeability increases 3. leukocytes migrate to the site of inflammation

Answer 3

PAMPS = pathogen associated molecular patterns

Answer 4

Initiation of inflammation * PAMPS (pathogen associated molecular patterns) on invading microorganisms are recognised by the body * PAMPS are recognised by **Toll like receptors (TRL)** found on microphages, DC, mast cells and mucosal epithelial cells (sensor cells) * signals from TLR acitivate genes that are involved in the production of cytokines IL-1, IL-6 and TNF alpha being the major proinflammatory cytokines * sensor cells DC, mast cells and macrophages turn on genes associated with inflammation

Answer 5

Cell derived * preformed sequesterd and released (mast cell histamine) * synthesised as needed prostaglandins, cytokines Histamine * secreted by Mast cells, when they are stimulated or injured * potent action on venules, arterioles and capillaries * vasodilation, venular endothelial contraction and junctional widening Prostaglandins and leukotrrienes * synthesised from Arachidonic acid (eicosanoids) * prostaglandins and thromboxine cycloxygenase pathway cause vasodilation and prolong odema (aspirin, NSAIDS) * Leukotrienes via lipoxygenase pathway, chemotaxis, vasoconstrictors cause increased vascular permeability * may result in the sensation of pain

Answer 6

plasma derived inflammatory mediators Complement, kinins, and coagulation factors * Kinins (bradykinin) - vasodilation, increased permeability and pain * sentinel cells (macrophages) produce cytokines that have local and systemic effects

Answer 7

Nitric oxide * short acting soluble free-radical gas with many functions * produced by endothelial cells and macrophages * causes vascular smooth muscle relaxation and vasodilation * kills microbes in activated macrophages

Answer 8

IL-2 Cytokines * activates NK cells * induces the differentiation of CD4 T cells into TH1 cells

Answer 9

The complement system * group of proteins * circulate in the blood or can be induced * help to recruit phagocytes to the site of inflammation and activate them * bind to receptors on phagocytes helping to remove the agent of infection from them * form pores in the invaders or infected cells membrane * activate mast cells to release histamine and other factors * complement proteins include C3, C5, C4 upto 30 + proteins

Answer 10

Phagocyte migration into tissue * neutrophils exit blood first followed by monocytes which develop into macrophages in tissues * complement factors, prostaglandins are all chemotactic (attract) neutrophils * PUS = dead and dying neutrophils, tissue debris and remaining pathogens Leucocyte movement into tissue * interaction between activated endothelium and molecules on the leukocyte * tight binding triggered by cytokines/chemokines - enhance ability of leucocyte to adhere to their receptor on endothelium * crossing of endothelial cell wall * direction of migration follows gradient of cytokines/chemokines

Answer 11

Fever High levels of cytokines (!L-1, IL-6 and TNF) reset the hypothalamic set point - leading to an overall increase in body temperature Positive effects * indicates infection * accompanies inflammation * stimulates phagocytosis * slows bacterial growth * decreases iron in blood levels Negative effects * in extreme cases may lead to protein or enzyme degradation * interuption of normal biochemical reactions

Answer 12

Acute inflammation * within minutes of tissue insult * neutrophils (PMNs) than monocytes * redness, swelling, pain, loss of function and heat If the pathogen is not eliminated continued recruitment of inflammatory cells increase concentration of phagocyte derived molecules cytokines in plasma. - leading to chronic inflammation - granuloma (may be present, infection can not be eliminated so the body walls it off to prevent spread). - tissue destruction by inflammatory cells - attempts at repair with fibrosis and angiogenesis (new vessel formation). Occurs when the acute phase can not be resolved - acute phase is not resolved (ulcer) - prolonged toxic agent exposure (silica) - autoimmune disease (thyroiditis)

Answer 13

Chronic inflammation * lymphocyte, macrophage and plasma cell (mononuclear infiltration) * Granuloma - may be present (a collection of immune cells formed when the immune system attempts to wall off substances it perceives as foreign) * tissue destruction be inflammation cells * attempts at repair fibrosis and angiogenesis (new vessel formation).

Answer 14

Adaptive immunity components * T and B cells * as lymphocytes develop in (bone marrow B cells) and (Thymus T cells each cell acquires an antigen receptor that is randomly generated, individual and unique * this is how the large pool of lymphocytes in the body can collectively recognise any Ag the individual is likely to encounter in their life time. The four key antigen receptors * TCR = T cell receptor * BCR = B cell receptor * MHC class 1 = every nucleated cell * MHC class 2 = APCs * each is constructed using immunoglobulin domains as building blocks - and each binds antigen through the use of variable domains

Answer 15

The two branches of adaptive immunity Humoral immunity * antibody mediated * Produced by B lymphocytes and plasma cells Cell mediated immunity * T lymphocytes * T helper cells help B cells make antibody * T helper cells also help T cells with a molecule CD4 on their surface * killer or cytotoxic T cells - kill infected cells or tumor cells with CD8 molecule on their surface

Answer 16

T and B cells recognise their antigen differently * B cells recognise free intact or native antigen * B cells acquire Ag via its BCR, process Ag than present Ag to helper T cells via MHC * T cells recognise antigen only when they processed peptides complexed to MHC molecules displayed on the surface of an APC * MHC-1 cytotoxic T cell; MHC-2 Helper T cell

Answer 17

Immune cell interactions of the lymph node * APCs prrsent antigen to T lymphocytes * Helper T cells help B cells to produce antigen * Helper T cells interact with Killer T cells Note T cells are located in the paracortex and B cells are located in the cortex.

Answer 18

Antigen presentation to T cells is affected by location **Exogenous antigen** Ag coming from outside the APC are predominantly loaded onto MHC class 2 recognised by CD4 T helper cells Endogenous peptides * Ag peptides within the cell are predominantly loaded onto MHC class 1 * recognised by CD8 class 2 T cells T cells * successful stimulation of T cells requires multiple signals and is highly regulated * depending on the antigen, the T cell may be activated by signals from multiple TCRs or by appropriate costimulation

Answer 19

T helper cell types Naive CD4 when activated by APC/Ag may differentiate into any one of a number of different effector cells with different functions (produce different cytokines) **TH1 cells** * activate infective macrophage * help B cells for antibody production * target microbes which exist in macrophage vessicles **Th2 cells** * provide help to B cells in antibody production * especially antibody switching to IgE for helminth parasites **TH17** * enhance neutrophil response and promote barrier integrity (skin, intestine) **CD4 Regulatory** * suppress T cell response

Answer 20

Type one hypersensitivity - immediate hypersensitivity * immediate Mast cells and IgE are significant players * eg allergy, anaphylaxis Phase one * individual is first senesitised to allergen * allergen specific B cells make IgE (TH2 make IL4 to make IgE) * IgE binds to mast cells Phase two * upon subsequent exposure to allergen mast cells degranulate * rapid release of inflammatory molecules from mast cells - histamine, heparin, serotonin * synthesis of other mediators leukotrienes, PGS The result * compounds release cause constriction of smooth muscle (airways) * vasodilation (oedema) * acute inflammation, nerve ending (puritis, itch) * initial symptoms are rapid 15-20mins, late response 4-24hrs * can be localised or systemic

Answer 21

Conditions of type one hypersensitivity * allergy, asthma, hay fever, allergic conjunctivitis Clinical signs * hay fever, conjunctivitis, hayfever * rash * itchy skin * wheezing stridor * asthma * swollen lips toungue or face

Answer 22

Atopy * geneitic predisposition to type one hypersensitivity * type one hypersensitivity is generally encounted at mucosal surfaces * atopic individuals have a predisposition to overactive TH2 immunity and high levels of IL-4 and IgE * TH2, IL-4, IgE and eosinophils (effectors) are the main players in type one hypersensitivity * AG involved in allergies is referred to as allergins *

Answer 23

Type one hypersensitivity - immediate hypersensitivity * immediate Mast cells and IgE are significant players * eg allergy, anaphylaxis Phase one * individual is first senesitised to allergen * allergen specific B cells make IgE (TH2 make IL4 to make IgE) * IgE binds to mast cells Phase two * upon subsequent exposure to allergen mast cells degranulate * rapid release of inflammatory molecules from mast cells - histamine, heparin, serotonin * synthesis of other mediators leukotrienes, PGS The result * compounds release cause constriction of smooth muscle (airways) * vasodilation (oedema) * acute inflammation, nerve ending (puritis, itch) * initial symptoms are rapid 15-20mins, late response 4-24hrs * can be localised or systemic

Answer 24

Eosinophils role in type one hypersensitivity * large numbers of eosinophils are attracted to mast cells degranulation products * large presence of eosinophils at site is regarded as a hall mark of type one hypersensitivity * eosinophils degranulate to release their own products - contribute to inflammation * further increase type one response TH2 and mast cells produce IL5 eotaxins which mobilise eosinophils from the bone marrow.

Answer 25

Anaphylaxis * occurs when the hypersensitivity becomes systemic, whole body allergic reaction * condition may become life threatening * occurs when a patient sensitised to an allergen is exposed to further dose (eg bee stings) * systemic vasodilation causes hypotension * skin, RIT, GIT, cariovascular, CNS

Answer 26

Clinical signs of anaphylaxis * medical emergency * pale gums * limbs feel cold * elevated HR * weak pulse * dyspnoea shortness of breath * bronchoconstriction * systemic dilation of blood vessels - hypotension * increase in vascular permeability - urticaria * contraction of smooth muscle diarrhoea and cramps

Answer 27

Diagnose * history breed, age, diet, environment * ELISA IgE * intradermal skin testing Treat - corticosteroids, prevent exposure to allergen, immuotherapy (TH2 to TH1)

Answer 28

Type two - AB mediated cytotoxic hypersensitivity Occurs when antibody reacts with the surface of normal cells * normal cells will then be destroyed by complement or cytotoxic cells * complement deposition result in lysis of the cell - rapid * lesions may develop as a result of cell destruction - delayed The main players = IgG (or IgM) + complement, macs (phagocytosis), or NK cells eg incompatible blood transfusions or organ transplants, autoimmune haemolytic anaemia

Answer 29

TH1 = IL-2, IFN-Y and TNF-alpha TH2 = IL-4 and IL-5

Answer 30

Type three hypersensativity Immune complexes are formed as a result of antigen antibody complexes and this activates complement * sensitization with antibody = increase in circulating antibody * localised or systemic response * immune complexes activate complement locally * immune complexes may become deposited in blood vessel walls Phagocytic cells may be recruited * phagocytic cells release oxidants and other enzymes causing causing acute inflammation and tissue damage Examples = serum sickness, Arthus reaction, Lupus

Answer 31

Type four delayed type hypersensitivity Is cell mediated (T cells) has delayed onset (24-72 hours) * sensitisation phase generates TH1 cells and AG specific memory T cell * subsequent exposure to the sensitising Ag leads to reactivation of these memory cells >TH1 * these cells home to the tissue site of Ag exposure and release IFNY and other cytokines chemokines * this leads to recruitment of other memmory cells including MACs and granulocytes causing tissue damage Some antigens when injected into the skin induce a slow developing inflammatory resonse, sometimes used to assess exposure of an individual to Ag - Q fever test, contact dermatitis, contact hypersensitivity

Answer 32

Red flags of immune deficiency * affects particular breed * affects young animal, only after maternal antibody has waned * unusual frequencies of infection * chronic recurrent infection * infection in multiple body sites * failure to respond to vaccination * failure of infection to respond to standard antimicrobial treatment

Answer 33

Two types of immune deficiency Primary immune deficiency * inherited, congenital * mutation in a gene encoding a molecule of the immune system * clinical signs appraent early in life * breed suceptability * defects in inate or adaptive immunity * relatively rare * best characterised in horses and dogs Secondary immune deficiency * acquired (not born with the disease) * cytotoxic drugs, viral infections, exercise, tumors, age, medical therapy or chronic disease

Answer 34

Immuosenescence * age related decline in immune function * relative decrease in circulating CD4 cells * fewer naive cells leave the thymus and bone marrow * older animals still have high anytibody titres and IgA * good recall but reduced ability to amount a primary immune response (vaccine) * may increase susceptability to infection, autoimmunity and neoplasia

Answer 35

Autoimmunity Normally the immune system dose not attack its own cells * it can distinguish self antigens from non-self antigens * tolerance to self antigen sis determined during the maturation process of T and B cells * sometimes autoreactive T lymphocytes escape this process and enter lymphoid organs Regulation has failed and lymphocytes respond to self antigen * characterised by tissue damage result of hypersensitivity reactions * type one diabetes, thyroiditis

Answer 36

Function of an antibody * enhance phagocytosis * enhance complement mediated killing * neutralise toxins * prevent pathogen attachment

Answer 37

Immunodeficiency = impairment in function of part or parts of the immune system, that renders the immunodeficient individual susceptible to disease

Answer 38

Primary immunodeficiency * Inherited * A mutation in a gene encoding a molecule of the immune system * inherited, congenital (present from birth) *clinical signs appear early in life * severe disease often depends on having two copies of the disease (homozygote) * breed susceptibility > relatively rare (secondary immune deficiencies more common) Secondary immunodeficiency * Acquired * can affect animals of any breed, relatively common compared to immunodeficiency one

Answer 39

Primary immune deficiency - CLAD/BLAD canine/bovine leukocyte adhesion deficiency - Cyclical neutropenia - Defects in the granules of neutrophils (NK and CTLS) - defects of the adaptive immune system

Answer 40

CLAD/BLAD canine, bovine leukocyte adhesion deficiency Primary immune deficiency * Lack of adhesion molecules (integrins) * mutation prevents white blood cells from adhering to the vascular endothelium, preventing them from leaving the blood vessels and eliminating harmful bacteria and viruses * can not gain access to inflamed tissues * juvenile animals particularly suffer often fatal * marked blood neutrophilia, severe multisystem infections Dog red setters, Frisian Holstein cows PCR diagnostic test

Answer 41

Primary immune deficiency Cyclical congenital neutropaenia Affects bone marrow - neutrophils, platelets and monocytes may be affected * stem cell growth factor defects * cyclic fluctuation in the number of white blood cells * the number of neutrophils falls sharply 10-12 days, then returns to normal * episodes of infection grey collie syndrome, pups rarely live beyond three years of age Defects in granules of neutrophils Rare Chediak Higashi syndrome * poor bactericidal activity, making the animal suspectable to bacterial infections * melanin granules may also be affected * blue smoke Persian cat, Hereford cattle, killer whales, mink and humans *

Answer 42

Primary immune deficiencies Defects of the adaptive immune system - primary immune deficiency - B lymphocyte deficiency animals are more likely to die from extracellular bacterial infections (German shepherd, Sharpei) * T cell deficiency more likely to die from viral infections Combined T and B deficiencies *rare usually result in death * certain T cell deficiencies impact Ab production eg thymic function * defect in antigen receptor sites affect both T and B cells.

Answer 43

Immunodeficiency Impairment in function of part or parts of the immune system, that renders the immunodeficient individual more susceptible to disease

Answer 44

Primary immune deficiency A mutation in a gene encoding a molecule of the immune system - inherited, congenital (there from birth) - clinical signs often appear early in life - severe disease often depends on having 2 copies of the gene, ie homozygous - disease less severe in heterozygotes - breed susceptability - relatively rare compared to secondary immune deficiency - most common and best describe in horses and dogs

Answer 45

Primary immune deficiency 1) CLAD/BLAD canine/bovine leukocyte adhesion deficiency 2) cyclic congenital neutropenia 3) defects in granules of neutrophils 4) defects of the adaptive immune system