Immunology Flashcards

Question

Complement cascade

Answer 1

**3 pathways:** 1. _classic_: C1q activated by IgM/IgG/lipoteichoic acid/phosphocholine on organisms 2. _alternative_: C3b binds foreign surface 3. _lectin_: C4/C2 cleaved with activation by MBL and ficolins 1-3 **function:** 1. cytolysis 2. opsonisation 3. inflammation 4. immunse complex clearing **mechanism:** cascade of proteins in plasma with sequential activation and release of complement fragments **products:** _anaphylactoids_: C3a/C5a _MAC complex_: C5/6/7/8/9

Answer 2

- many associated AI conditions **C3 deficiency** - no C5a, inefficient opsonisation, recurrent infection puogenic organisms (meningococcus, pneumococcus, minigitidis) **_Deficiencies of control proteins_** **Factor I** (regulates both pathways) **Factor H** (assists dismantling alt p/w C3 convertase) **Properdin deficiency** - predisposed N.meningitidis meningitis **_Membrane complement control proteins_** **CD59**: prevents MAC development **CR1/CD46/DAF**: prevents C3bBb

Answer 3

**epidemiology:** 1/10,000, 10% familial, assoc IgA def **age:** 2 peaks 1-5yrs, 18-25yrs **mechanism:** B cells can't differentiate into plasma cells and secrete Ig **clinical:** (late onset) - enlarged LN, splenomegally (25%) - _recurrent infections_: encapsulated, sinopulmonary, bronchiectasis - _AI disease:_ cytopaenias, alopecia, gastric atrophy, arthritis, dermatomyositis, vascultis, lupus - _other:_ malabsorption, benign lymphoproliferative disease, non-caseating granuloma **diagnosis:** _low IgG_, normal IgM/IgA, normal T/B cells, impaired vaccination response **management:** IVIg, antibiotics, chest physio, avoid steroids

Answer 4

**definition:** falling neutrophils in 4 week cycles **clinical:** gingivostomatitis **diagnosis:** twice weekly FBC for 2 months **treatment:** supportive, GCSF

Answer 5

**mechanism:** thymic aplasia due to 3rd/4th pharyngeal pouch development defects - low CD3 T cells, increased proportion B cells - no lymphocyte response to mitogens clinical: - variable depending on complete/partial aplasia - in complete resembles SCID **diagnosis:** PHA no response **tx:** BMT, thymic tissue transplant

Answer 6

**type:** granulocyte **stimulating factor:** IL5 **function:** extracellular mediations - kill big organisms too large to be phagocytosed - degranulate and release enzymes in allergy

Answer 7

**class I** (90% child allergies): egg, milk, peanuts, tree nuts, fish, soy **class II:** kiwi, apples, carrots, peaches (analogues pollen) - all milk allergies develop by 12 months - all egg allergies develop by 18 months - median age for peanuts is 14 months **resolution:** - most outgrow milk/egg allergies (50% by 5 yrs) - peanut, nut, seafood don't resolve (90% for life)

Answer 8

**no parents**= 20% **1 parents**= 60% **2 parents**= 80%

Answer 9

**inheritance:** genetic/HLA association **risk:** 60% twin concordance eczema/asthma - no allergic parents: 20% risk - 1 allergic parents 50% risk - 2 allergic parents 66% risk **3 genes**: atopy (IgE/eosinophils), barrier, innate (pattern recognition)

Answer 10

Neutrophils/eosinophils/basophils - bone marrow - 70% of WBC in the circulation - live 2-3 days only

Answer 11

**age:** birth to 18 months, M\>F **pathogenesis:** syndrome of excessive inflammaiton and tissue destruction due to lack of normal inhibition of activated macrophages/lymphocytes - often defect in NK cells causing cell lysis **trigger:** infection or altered immune state **clinical:** fever - hepatomegally 95% - lymphadenopathy 33% - neurological sx 33% - rash 31% **diagnosis:** cytopaenia, elevated ferritin/LFTs, hypertriglyceridaemia, abnormal coags **treatment:** steriods, IVIG, chemotherapy, HSCT **prognosis:** fatal if untreated

Answer 12

**genetic:** AD haptoinsufficiency causing deficiency C1 esterase inhibitor - _type 1_: decreased C1 (30% normal conc) - _type 2:_ normal levels dysfunctional protein **pathogenesis**: uncontrolled activation of C1 which activates C4/C2 producing kinin - C3 normal **diagnosis:** reduced C4 **clinical:** variable frequency of attacks - recurrent oedema W/O urticaria - recurrent abdominal pain due to GI wall oedema **precipitants:** illness, stress, drugs, trauma, surgery **tx:** adrenaline _DOESNT WORK_ - replace purified C1 - bradykinin 2 receptor antagonist or kallikrein inhib

Answer 13

**genetics:** sporadic/AD **mechanism:** defect in STAT3 (TF) causing lack of Th17 then IL17 causing susceptibility to fungal infections **clinical triad:** 1) recurrent staph/candida infections: skin, joint, abscess 2) high IgE \>10,000 3) eosinophilia - course facies (broad nose/prominent upper lip), osteopaenia, hyperextensible, scoliosis, chronic eczema **associations:** lymphoma **diagnosis:** normal/elevated IgG/A/M, fewer memory T cells **treatment:** antibiotics

Answer 14

**incidence:** 1:500,000 males **genetics** **_type 1 (X linked): CD40L deficiency_** - onset 6 months - _symptoms_: sinopulmonary infections (encapsulated), opportunistic infection, neutropenia, lymphadenopathy, HSM **investigations:** - normal B cells - increased IgM, decreased IgA/IgG/IgE/memory cells - flow cytometry CD40L **complications:** malignancies (HCC, cholangiocarcinoma) **tx:** BMT, IVIg monthly

Answer 15

**pathophysiology:** poorly understood non IgE reactions **causes:** - vancomycin - contrast media - aspirin - dextran

Answer 16

**defect:** Foxp3 gene **pathophysiology:** defect in T cell regulation causing autoimmune and autoinflammation **clinical:** - fatal 1st few months - AI endocrinopathy, enteropathy, haem anaemia, ITP, neutropaenia - atopy: eczema, food allergy, eosinophilia - LN, SM

Answer 17

**definition**: inhibit self-reactive T cells **central:** thymus - AIRE (autoimmune regulatory gene): regulates negative selection - dysfunction: APS **peripheral:** - regulatory T cells (CD4/CD25/FOXP3): downregulates overactivation immune system via cell-cell contact - suppresses CD4/CD8 T cells, B cells and NK cells - dysfunction: IPEX syndrome (single X-linked defect)

Answer 18

**technique:** fluorescent enzyme immunoassay **pros/cons:** less sensitive, more specific, more expensive **benefits:** unaffected medications, people with anaphylaxis, dermatological conditions

Answer 19

**XLA:** dematomyositis, chronic echovirus encephalitis **Ataxia telangiectasia:** sinopulmonary infections, neuro deterioration, telangiectasia **Chediak Higashi:** oculocutaneous albinism, recurrent infection, TCP **C6/7/8 deficiency:** recurrent neisserial meningitis **CVID:** sinopulmonary infections, malabsorption, splenomegally, AI **IgA deficiency:** reaction to blood produces, assoc coeliac/UC/Crohn's **Myeloperoxidase deficiency:** thrush

Answer 20

**XL lymphoproliferative:** severe progression EBV **XLA:** paralysis post polio vaccine, no LN **Hyper IgE:** cutaneous/systemic staph infections, course facies **Chronic mucocutaneous candidiasis:** thrush, nail dystrophy, endocrinopathies **Cartilage hair hypoplasia: s**hort stature, fine hair, severe varicella

Answer 21

**DiGeorge:** hypocalcaemia, CVD, unusual facies **Leukocyte adhesion deficiency:** delayed cord separation, leukocytosis, recurrent infections **SCID:** diarrhoea, thrush, pneumonia, FTT **Wiskott Aldrich:** purpura, malaena, OM, eczema **X linked hyper IgM:** mouth ulcers, neutropaenia, infections

Answer 22

**B cell deficiency (no antibodies)** - pyogenic infections **T cell deficiency (no 2nd signal for B cells)** - opportunistic infections **Neutrophils (defect in respiratory burst)** - gingivitis/ulcers **NK deficiency (no cell-cell killing)**

Answer 23

**Ab deficient:** recurrent sinopulmonary/GI infections with polysaccharide encapsulated pyogenic organisms **T cell deficient:** infection with intracellular organisms (fungi, viruses, listeria) **Neutrophils/monocyte deficient:** high-grade bacterial infections (staph, gram -ve), invasive fungi/candidiasis **Complement C5-9:** disseminated neisseria

Answer 24

**chains:** 2 heavy (5 types) and 2 light chains (2 types) **heavy chain isotypes:** IgM, IgD, IgG, IgA, IgE **regions:** constant + variable regions linked disulfide bond - variable region contains hypervariability region **binding fragments:** 2 Fab portions and 1 Fc portion

Answer 25

- high concentrations IgA (10% protein) - tiny amount IgM/IgG declines day 5 - lymphocytes, macrophages, proteins with non-specific bactericidal activity, viral growth inihibitors, complement present **outcome:** decreased diarrhoea, OM, pneumonia, bacteraemia, meningitis in first year of BF babies

Answer 26

**Anti-polysaccharide response** - \<2yrs unable to form T indep immune response - young children prone to encapsulated organisms - improves with age

Answer 27

**staph aureus** (76-100% patients) - clinical: honey coloured, crusting, folliculitis, pyoderma - treat: culture, remove crust, topical mupirocin, oral AB, bleach baths **viral infections** - herpes simplex: eczema herpeticum - clinical: pain, pruritis, punch out erosions, haemorrhagic crus/veiscles, widespread lesions **fungal infections** - treat: standard topical or oral

Answer 28

**receptors:** **-** _TLR (toll like receptor)_: intracellular messaging via NK-kB - _CLR (C-type leptin)_: recognise CHO on microorganisms - _NLR (nod like receptor)_: detect intracellular changes - _RIG1:_ intracellular receptor **substrate:** PAMPs (peptidoglycans, bacterial DNA, LPS), DAMPs **location:** on APC **function:** acute phase response (IL1/IL6/TNF)

Answer 29

**onset:** peaks in late childhood **clinical:** cyclic exacerbations - itching, sneezing, rhinorrhoea, conjunctival inflammation, nasal congestion, allergic shiners **associations:** sinusitis, OM, eczema, asthma **diagnosis:** skin prick, RAST, eosinophils

Answer 30

**production:** released from many cell types in response to viral infection **types:** IFN-a (most), IFN-b **effect:** - induce resistance to viral replication in all cells - increase MHC-1 expression APC - activate DC/macrophages/NK cells

Answer 31

**2 purposes:** 1) Protection against infection 2) Suppression of inflammatory/immune process **product:** mainly IgG (small amounts IgA/IgM) from 20,000-50,000 blood donors **mechanism:** mostly anti-inflammatory response, but not understood **indications:** Bcell immune deficiencies (XLA,CVID, HyperIgM), SCID, DiGeorge, Wiskcott-Aldrich **dose:** 400mg/kg every 4 weeks **infusion rate related:** chills, headache, fatigue, malaise, nausea, vomiting, arthralgia, myalgia **less common:** abdo/chest pain, tachycardia, dyspnoea, BP change **rare:** anaphylaxis, septic meningitis, renal/pulm insufficiency, DIC screening for kids on IVIg: LFTs, Hep C

Answer 32

**incidence:** **pathogenesis:** - unknown etiology: ?post infective - medium blood vessel vasculitis **criteria (4 of 5 of):** 1. polymorphous rash 2. bilateral non purulent conjunctival injection 3. mucous membrane changes eg. dry lips, strawberry tongue 4. peripheral changes eg. erythema palms/soles, oedema hands/feed 5. cervical lymphadenopathy \>1.5cm - arthritis/arthralgia, liver dysfunction, jaundice, sterile pyuria **complications** - cardiac complications in up to 25% untreated - mild coronoary artery aneurysms on day 10 post fever (more likely - 25% of these will progress to true aneurysms, 1% giant aneurysms (\>8mm) - also myocarditions, ventricular dys, valvular regug, pericardial effusion **investigations** - ASOT/Anti DNAase B, ECHO, platelet count **treatment** - IVIg 2g/kg over 10 hours within first 10 days - aspirin 3-5mg/kg daily for 6-8 weeks **prognosis:** - 1% with CAA

Answer 33

genetic: AR, 1/10,000,000 _LAD1:_ mutation 21q22.3 encoding CD18 integrin subunit - delayed cord separation 3-45days - increased WCC, infections but no pus, tooth eruptions (gingivitis/periodontitis), delayed wound healing, infections staph/gram - _LAD2 (_milder): CD11/CD18 intact but defective golgi apparatus and absent selectin ligand - neurologic defects, cranial facial dysmorphism, absent RBC ABO BG Ag _LAD 3:_ defect integrin adhesion/migration - bleeding disorder, delayed cord separation, soft tissue infection **diagnosis:** WCC\>20, flow cytometry for CD subtypes, blood group (Bombay) **management:** early BMT **prognosis:** death by 5 years 75%

Answer 34

**function** 1. Cleanse lymph 2. Alert immune system to pathogens **structure:** capsule, inner parenchyma, subcapsular sinuses - cortex: lymphoid nodules acquire germinal centre where B cells multiply and become plasma cells - medulla: medullary cords composed of lymphocytes, plasma cells, macrophages, reticular cells, reticular fibres **cell location:** - B cells in middle with dendritic cells - T cells on edge in the mantle/paracortical zone

Answer 35

**selectins:** rolling and tethering vessel wall **integrins:** moving from BV to tissue, stop the neutrophil to squeeze through endothelium **chemokines:** presented on vascular endothelium

Answer 36

**prevalence:** 25% WBC in peripheral blood **source:** derived from CD34 **stimulation of T/B/NK cells:** IL2 **stimulation T/NK cells:** IL7, IL15

Answer 37

**pathophysiology:** infiltrate of mature/immature lymphocytes, plasma cells and histiocytes in pulmonary tissue **associated:** HIV (17% perinatally acquired HIV) immune deficiencies, autoimmune disease **clinical:** - insidious onset cough, tachypnoea, finger clubbing but normal auscultation - LN, HSM and salivary gland enlargement **diagnosis:** hypergammaglobulinaemia, lung biopsy

Answer 38

**role:** release granules and hormonal mediators - mediate allergic and antiparasitic responses - NOT phagocytic **stimulation:** 1. direct injury: physical/chemical 2. IgE: surface receptor 3. Activated complement: common p/w **hormones:** tryptase, proteases, histamine, serotonin, heparin, chondroitin, thromboxane, PG D2, leukotriene, PAF, IL, TNF-a

Answer 39

**activation:** MBL on surface of bacteria **mechanism:** - binds to mannin, activates proteolytic enzymes, converts C4 to C4b, C4b binds C2b and forms C3 convertase

Answer 40

**subtypes:** HLA-DQ, HLA-DR, HLA-DP - loci highly variant and allow variation **location:** ONLY on antigen presenting cells **role:** present foreign antigens and activate CD4 Tcells **deficiency:** type 2 bare lymph syndrome, type of SCID

Answer 41

**subtypes:** HLA-A, HLA-B, HLA-C **location:** present on all nucleated cells except RBCs and some neuronal cells **role:** activate CD8 T cells **deficiency:** type 1 bare lymphocyte syndrome

Answer 42

**genetic:** AR, MPO gene missense mutation, 1/2000 **pathogenesis:** decreased production hypochlorous acid causing decreased early killing or gram +ve/-ve bacteria - neutrophils/monocytes use MPO independent mechanism to kill pathogens **clinical:** normal asymptomatic - rarely disseminated candidiasis

Answer 43

**onset:** most apparent \<1yr age **peak:** prevalence 8% at 1 year - 0.5-1.4% children: nut allergy - 1-2% egg allergy - 2.5% milk allergy - 0.4-1% wheat allergy (outgrow by adolescence) **resolution:** decreases to 4% by adulthood - most allergies outgrown except seafood/nuts **predictor resolution**: fall in IgE

Answer 44

Classic activity (normal at 3 months): CH100 Alternative activity (normal at 1 year): AH100 **CH50 test**: how much serum to lyse 50% RBC - measures entire complement p/w - different stimuli to test alternate pathways

Answer 45

- Ig transferred across placenta from 6 months - at term levels higher than in mother - levels drop rapidly after birth - infants\<1500g hypogammaglobulinaemic first week

Answer 46

Granulocyte **stimulating factor**: G-CSF **Kill bacteria via 2 mechanisms:** 1) Phagocytosis/Digestion 2) Respiratory burst: lysosomes degranulate into tissue causing tissues to make hydrogen peroxide. **receptor**: pattern recognition receptors (PRR) recognise pathogen assoc molecular patterns (PAMP)/danger assoc molecular patterns (DAMP) **test (nitroblue tetrazolium (NBT))** - activated neutrophils can reduce NBT producing dark blue crystals

Answer 47

Innate immunity **direct cell-cell killing of intracellular pathogens:** microbes/cancer **mechanism:** 1. IgG coated microbes: via CD16 receptor 2. Killer inhibitory cells: no MHC1 on tumour/infected cells 3. Killer activating receptor

Answer 48

intermediate/delayed onset and assoc FTT **FPIES** (food protein induced enterocolitis) - cows milk, chicken, rice, egg when introduced - T cell mediated with onset 2 hours post exposure - vomiting/diarrhoea/hypotension **Dietary protein enteropathy** - cows milk most common - vomiting, diarrhoea, abdo distension, oedema, FTT - spectrum of disease **Dietary protein proctitis** - cows milk/soy milk - cell mediated - isolated blood stool resolve \<72hrs elimination **Food induced haemosiderosis (Heiner's syndrome) RARE** - recurrent pneumonia with pulm infiltrates (haemosiderosis) - cows milk, egg with FTT **Allergic eosinophilic esophagitis (mixed IgE/non IgE)** - cell mediated - chronic GORD, emesis, food refusal, abdo pain, dysphagia, irritability, weight loss, FTT, oedema, protein losing enteropathy - 50% patients atopic

Answer 49

**genetics**: loss of RAG gene function **pathophysiology:** oligocloncal proliferation of autoreactive T sells **clinical:** similar to GVHD **-** erythroderma, hepatosplenomegally, FTT, diarrhoea **diagnosis:** increased WCC/IgE with low other Ig, increased eosinophils **treatment**: BMT

Answer 50

**incidence:** 1/50,000 **genetic:** mutant PIG-A/T **pathophysiology:** deficiency membrane bound complement regulatory proteins CD59/CD55 making them susceptible to lysis **clinical:** recurrent intravascular haemolysis - chronic haem anaemia, BM failure, thrombosis, haemaglobinuria

Answer 51

**mechanism:** - logarithmic increase IgM day 4-10 during clonal expansion and Ab production - plasma cells form in hours - IgG peaks in days and lasts weeks to years - class switching and proportion of other antibodies increases with time - some B cells become memory cells and living in germinal matrix ready to produce fast secondary response with furthe exposure

Answer 52

**immediate: IgE** - usually within 1 hour **delated: T cells** - \>6 hours after starting medication - dalyed amoxycillin usually 7-10 days after starting **DRESS (drug reaction with eosinophilia + systemic symptoms)** - 1-12 weeks post starting

Answer 53

**incidence:** 1/50,000, M\>F **pathophysiology:** thymus not developed, failure T +/- B cells with no/low Ig and poor adaptive immunity **genetics:** _X-linked (47%):_ Xq13 encodes IL2/4/5/7/9 - B cells normal no. but defective - poor function post BMT due to abnormal cytokine R _ADA (adenosine deaminase) deficiency (15%):_ 20q13 - most profound lymphopaenia - T cell apoptosis and abnormal function - respond well to BMT _JAK3 deficiency (6%):_ signalling defect assoc Yc - poor B cell function post BMT **clinical:** small lymphoid tissue, early recurrent infections, diarrhoea (rotavirus/bacterial), pneumonia (PCP), persistent candida, sepsis - live vaccines can kill **diagnosis:** lymphopaenia, absent mitogen response to PHA, low Ig **treatment:** death \<1yr w/o stem cell transplant, need BMT within 3.5 months

Answer 54

SCID/hypogamma: deficiency C1q due to IgG deficiency Chronic membranoproliferative GN: C3 consumption Cirrhosis/hepatic failure Malnutrition/AN Sickle cell disease: defective alternative p/w Nephrotic syndrome Immune complex disorders: SLE, leprosy, endocarditis, malaria, EBV, dengue, hep B - induce complement consumption Bacteraemic shock IV contrast Burns

Answer 55

**memory cells:** display IgG/IgA/IgE on surface - no IgD - identified presence of CD27 - live in mucosal areas - 1% of total B cell population **secondary response**: - short lag period and rapid production isotypes other than IgM - high affinity Ig - derived from memory cells developed in primary response

Answer 56

The _MOST COMMON_ primary immune defect **Incidence:** 1/700, familial or acquired, defect unknown, AD **diagnosis:** absent IgA +/- IgG subclass **clinical:** usually asymptomatic, recurrent sinopulmonary infections, sprue like syndrome **associations:** atopy, GI disease, CVID, AI, malignancies **complications:** _ANAPHYLAXIS_ to blood products due to IgA antibodies

Answer 57

**mechanism:** systemic immune mediated hypersensitivity vasculitis **cause:** foreign proteins **pathophysiology:** Ag and Ab combine to form immune complex that get stuck in blood vesells or tissue and activate complement and granulocytes - results in migration of neutrophils, release of vasoactive substances and tissue damage **clinical:** 7-10 days post exposure - fever, malaise, rash, myalgia, LN, arthralgia, arthritis, nausea, diarrhoea - lasts 1-2 weeks **rare associations:** carditis, GN, guillaine barre, peripheral neuritis **diagnosis:** immune complexes, low C3/C4, high ESR, mild proteinuria/haematuria treatment: analgesia, steroids, antihistamines

Answer 58

**benefits:** rapid, sensitive, cost effective **mechanism:** tiny amounts allergen into skin in contact with cutaneous mast cells - mast cells have IgE, degranulate and release histamine, produces wheal (peak 20mins) - late phase reactions 1-2 hr post **positive:** wheal\> histamine control wheal (3mm) at 10 minutes **negative predictive value:** 95% change no allergy - BUT 50% have positive test with no clinical allergy **note:** infants have less positive reactions **contraindication:** high risk anaphylaxis, recent anaphylaxis, meds (ACEi, beta blockers)

Answer 59

**hyperacute 1% graft loss** - preformed recipient Ab to HLA/ABO blood group attach graft endothelium - within minutes of transplant **acute (5% graft loss)** - within days - recipient CD4/CD8 T cell mediated bind donor APC with self Ag - assoc HLA match **chronic (69% graft loss)** - after 1 year - T cell + Ab - characterised by interstitial fibrosis, thickening graft vessels, narrow lumina and graft failure

Answer 60

**trigger:** T cell recognises APC with MHC bound Ag **costimulation:** APC B7 binds Tcell CD28 **inhibition:** CTLA-4 **effect:** 1. proliferation: IL2 with clonal expansion (blocked by calcineurin inhibitors) 2. differentiation of naive T cells 3. functional differentiation 4. memory cells

Answer 61

eg. vaccines **role:** some molecules (polysaccharide/lipopolysaccharide) **negatives:** poor memory B cell response/maturation AB and no isotype switching **polysaccharide vaccines:** - crosslink BCR directly activating B cells and produce IgM - eg. HiB, meningococcal, pneumococcal - _adding protein_: tricks B cell to break down to peptide and display on MHCII to T cells causing cytokine production

Answer 62

**_SELECTION_** **positive:** those binding MHC weakly are selected **negative:** those binding MHC strrongly are deleted or become regulartory **apoptosis:** those not binding MHC die **_TOLERANCE_** **central:** AIRE genes produce low level tissue specific Ag in thymus to allow selection of binding T cells **peripheral:** **-** chronic expression self Ag w/o costimulatory molecules - clonal ignorance in immune privileged sites - suppression by regulatory T cells: IL2 R (CD 25+), foxp3 gene, blocks IL2 transcription, reinforces inhib cytokines (CTLA4, IL10)

Answer 63

**Lymphocyte subsets** - lymphopaenic kids: 70% CD3+ Tcells - CD4/CD8 subsets **CXR:** for absent thymus **Candida skin testing**: positive with erythema/induration **PHA:** phytohaemagglutinin - mitogen usually stimulates T cell proliferation

Answer 64

**production/maturation:** in the thymus - TCR (2 chains: a and b) assoc CD3 complex binds Ag - rearrange TCRs via splicing and express TCR/CD3 - selected causes apoptosis in 95% T cells - differentiate from cortex to medulla to blood - form CD4 or CD8 and travel to LN/spleen - require APC B7 binding Tcell CD28 receptor for activation **CD4 (helper cells)** _Th1 (stimulated IL12):_ - activated Ag in MHC II - secrete IFN-g/TNF activating macrophages/NK cells and B cell Ab secretion - protection bacterial/viral _Th2 (stimulated IL 4)_: - activated Ag in MHC II - secrete IL4, IL5, IL6, IL13 and activate mast cells/eosinophils/basophils and B cell Ab secretion - protection parasites _Th17 (stimulated TGFb, IL6, IL23):_ - secrete IL17 - causes inflammation, protection fungal, causes psoriasis **CD8 (cytotoxic)** - viral peptide in MHC I complex - induce cell death via injecting granzymes into cell which activates caspase - release cytokines (IFNg, TNFa) into surrounds - protection fungi (non systemic)

Answer 65

**cause:** 1. Immunocompromise: donor lymph not destroyed by recipient T cells 2. Specific HLA mismatch: recipient doesn't recognise donor as non-self, but donor recognises and mounts response **clinical:** 4-30d post transfusion, diarrhoea, vomiting, anorexia, cough, pancytopaenia **diagnosis:** biopsy of skin, satellite dyskeratosis **prognosis**: ALWAYS fatal **prevention:** use irradiated blood products

Answer 66

**definition:** delayed maturation of antibody production with low IgG +/- IgA **incidence:** common in preterm infants less than 6 months, males 60%, assoc atopy **mechanism:** delay in normal synthesis of Ig unti after maternal IgG catabolism **outcome:** resolved by 4 years **treatment:** antibiotic prophylaxis, rarely IVIg

Answer 67

**mechanism:** Ag exposure causing IgE mediated activation of mast cells and basophils causing release of vasoactive substances (histamine, prostaglandin, leukotrienes) **clinical:** anaphylaxis, angioedema, bronchospasm, urticaria

Answer 68

**incidence:** rare **timing:** usually 5-10 days post high dose exposure **mechanism:** drug acts as an Ag and directly binds cell's antibody causing injury **examples:** hemolytic anaemia, thrombocytopaenia, neutropaenia

Answer 69

**incidence:** uncommon **onset:** 1 or more weeks to develop with high dose drugs **mechanism:** drug binds drug specific IgG and forms complexes that deposit and cause damage to joints, blood vessels, glomeruli - deposition of immune complexes causes complement activation and recruitment or neutrophil **examples:** serum sickness (fever, urticarial rash, arthralgia, lymphadenopathy, low complement)

Answer 70

**mechanism:** NOT Ab mediated, Ag exposure directly activates T cells causing tissue injury **examples:** contact dermatitis, some morbilliform reactions, severe exfoliate dermatoses (SJS), interstitial nephritis, drug induced hepatitis

Answer 71

**incidence:** 20% population **clinical:** pruritic erythematous plaque **causes:** - infection (viral, bacterial, fungal) 80% - ingestion (medical, food) - injection/infusion - inhalation **onset:** acute \<6 weeks chronic \>6 weeks **mechanism**: mast cell release mediators **systemic disorders:** urticarial vasculitis, mastocytosis, SLE, RA, Sjogrens, cutaneous small vessel vasculitis, malignancies

Answer 72

**allergy due to egg ovalbumin component** - avoid influenza, rabies, yellow fever, Q fever **Influenza:** vaccines\<1microg ovalbumin safe but still small risk anaphyaxis

Answer 73

**definition:** X linked recessive B/T cell defect **genetic:** Xp11.23, WASP **clinical:** thrombocytopaenia, eczema, immunodef - 1st year: atopic dermatitis, recurrent infections (pneumonia, meningitis, OM, PJP, HSV) with encapsulated organisms/viruses **diagnosis:** LARGE platelets, leukopaenia, low IgM, high IgA/E, normal IgG, poor Ab response to mitogens **associations:** AI, malignancies esp EBV associated **treatment:** monthly IVIg

Answer 74

**incidence:** 1/4000 **genetics:** XLR q22 deletion (1/3 new mut) **defect:** Bruton tyrosine kinase deficiency causes blockade at Pre-B-1 stage **diagnosis:** ALL Ig \<95^th centile - _NO_ circulating B cells but pre B-cells in marrow - normal T cell function, neutropaenia 20% - poor vaccination response, BTK on flow cytometry **clinical (early onset 6 months):** - small tonsils, no LN, no spleen - recurrent sinopulmonary infections with pyogenic/encapsulated infections - progressive dermatomyositis, malabsorption **management:** chest physio, IVIg