LO Flashcards
A blood type can donate to
A or AB
B blood type can donate to
B or AB
AB bloody type can donate to
AB
what blood type is universal?
O
A fresh frozen plasma can donate to
A or O
B fresh frozen plasma can donate to
B or O
AB fresh frozen plasma can donate to
A,B,AB,O
O fresh frozen plasma can donate to
O
pathophysiology of haemolytic disease of the newborn?
Rh D immunogenic stimulation of maternal Rh negative blood cells to produce antibodies against antigens of RH positive blood cells upon exposure resulting in IgG crossing the placenta.
treatment for haemolytic disease of the newborn?
Use of anti-D prophylaxis at any potential sensitising event (praevia, trauma) and routine at 28/40.
erythrocyte derives from
erythroblast->reticulocyte->erythrocyte
platelets arise from
megakaryocyte
neutrophils role
ingest and destroy pathogens bacteria and fungi
eosinophils role
parasites and allergy
stem cell growth regulated by
erythropoietin, G-CSF, thrombopoietin agonists
neutrophils growth hormonal stimulation by
Interleukins and Colony stimulating factors CSFs
reticulocyte count is the measure of
red cell production
full blood count constituents
hg RBC platelets WBC neutrophils lymphocytes monocytes eosinophils basophils
main haematological tests
clotting factors and clotting times, chemical assays for iron, B12, folate, marrow aspirate and trephine biopsy, lymph node biopsy, imaging (CT or plain film)
normal male 12-70 haemoglobin
140-180
normal male >70 haemoglobin
116-156
normal female 12-70 haemoglobin
120-160
normal female >70 haemoglobin
108-143
anaemia bone marrow pathophysiological points
cellularity, stroma, nutrients
anaemia red cell pathophysiological points
membrane, haemoglobin, enzymes
anaemia destruction pathophysiological points
blood loss, haemolysis, hypersplenism.
hypochromic microcytic matrix of investigations
serum ferritin
hypochromic microcytic low serum ferritin then..
iron deficiency
hypochromic microcytic normal serum ferritin then..
thalassaemia, secondary anaemia or sideroblastic anaemia
normochromic normocytic matrix of investigations
reticulocyte count
normochromic normocytic anaemia reticulocyte count normal
hypoplasia, marrow infiltrate
normochromic normocytic anaemia reticulocyte count increased
acute blood loss, haemolysis
macrocytic anaemia matrix investigations
bone marrow, B12 folate
macrocytic anaemia matrix if B12 and folate deficiency
megaloblastic
macrocytic anaemia matrix if no B12 or folate deficiency
myelodysplasia, marrow infiltrate drugs
inherited anaemia symptoms
anaemia, jaundice, splenomegaly, pigment gallstones.
general features of anaemia
tiredness, pallor, breathless ness, swelling of ankles, dizziness, chest pain. Must find out underlying causes whether bleeding, malabsorption, lymphadenopathy or splenomegaly.
MCH refers too
mean cell haemoglobin (colour)
MCV refers too
mean cell volume (Size)
iron metabolism
absorbed iron bound to either mucosal ferritin and lost or enters the duodenum via ferroportin to transferrin and then ferritin in the liver or haemoglobin
iron metabolism is regulated by
Regulated by hepcidin which is produced by the liver in response to high iron or inflammation to block the ferroportin
history for iron metabolism
dyspepsia, GI bleed, menorrhagia, diet, pregnancy. May have koilonychia, atrophic tongue and angular cheilitis
treatment for iron anaemia
diet, oral iron
haemoglobin consists of
two alpha chains and two beta chains with iron and a heme group in the centre of each
people inherit for haemoglobin
Inherit 2 alpha chains and 2 beta chains with gamma and delta parts
normal adults percentage for haemoglobin
(A97% 2A-2B: B2% 2A-2D: (F)foetal 1% 2A-2G)
homozygous alpha zero thalassaemia outcome
incompatible with life
beta thalassaemia major outcome
transfusion dependent anaemia: presents 3-6 months, expansion of ineffective bone marrow, bony deformities, splenomegaly, growth retardation. Requires blood transfusion 4-6* a week with chelation ( desferrioxamine) to prevent iron overloading
beta thalassaemia treatment
bone marrow transplantation
red cells breakdown in the reticuloendothelial system
with macrophages in spleen, liver, lymph nodes lungs etc.
how is red cells recycled in the reticuloendothelial system
the globin amino acids are reused, haem is broken down into iron which is reused and haem which becomes biliverdin and then bilirubin which is bound to albumin in plasma (unconjugated).
principles of the direct antiglobulin test in assessing haemolysis
detects antibody or complement or red cell membrane: regents of anti-human IgG or anti-complement. Binds to antibodies on cells and causes agglutination, implies immunity basis for haemolysis.
membrane inherited anaemia pathophysiology
skeletal proteins responsible for maintain red cell shape and deformability
example of inherited membrane anaemia
hereditary spherocytosis, autosomal dominant defects causing spherical red cells that are removed by the reticuloendothelial system.
what does hereditary spherocytosis cause
anaemia, jaundice neonatal, splenomegaly, pigment gallstones
Treatment for hereditary spherocytosis
folic acid, transfusion, splenectomy
two types of inherited enzyme anaemia
Pentose Phosphate shunt
pentose phosphate shunt enzyme anaemia pathophysiology
phosphate dehydrogenase protects from oxidative damage via NADPH vital for glutathione that detoxifies free radicals. Absence results in blister and bite cells.
presentation of pentose phosphate shunt
neonatal jaundice, drug, broad bean or infection precipitated jaundice and anaemia with intravascular haemolysis, haemoglobinuria, splenomegaly and pigment gallstones.
pyruvate kinase deficiency presentation
reduced ATP, rigid cells, anaemia, jaundice, gallstones
pathophysiology of sickle cell
. Effected beta sickle chains when the RBC’s become deoxygenated they then turn permanently sickle; as a result there is haemolysis then endothelial activation, inflammation, coagulation activation, dysregulation of vasomotor tone and vaso-occlusion.
sickle cell anaemia inheritance
autosomal recessive
sickle cell anaemia presentation
painful bone crisis, chest crisis, stroke, hyposplenism, and infection risk, chronic haemolytic anaemia with gallstones and aplastic crisis, sequestration crisis
sickle cell anaemia pain crisis treatment
analgesia opiates, hydration, oxygen, maybe antibiotics for infection
sickle cell anaemia pain crisis long term managment
vaccination, penicillin, prophylaxis, folic acid. Episodic blood transfusion, hydroxycarbamide, bone marrow transplantation and gene therapy.
defects in haem synthesis pathophysiology
: mitochondrial defect resulting in sideroblastic anaemia or defects in cytoplasmic steps results in porphyria’s
acquired haemolytic anaemia types
immune (extravascular) or non-immune (intravascular)
haemolytic anaemia treatment
folic acid, immunosuppression via steroids, remove spleen, treat underlying causes consider transfusion.
blood clot formation physiology
vessel damage->exposure of subendothelial collagen with release of Tissue factor and Von-Willebrand factor, ADP, epinephrine and thrombin. Platelet then releases more VWF, thrombin, ADP, calcium and serotonin that forms the phospholipid surface for coagulation as its enzyme scramblase switches the membrane of the cell.
fibrin cascade physiology
exposure of tissue factor to V7, this then becomes activated and stimulate ten X, this can then produce thrombin from prothrombin, thrombin can then cleave fibrin from fibrinogen.
thrombin can go on to activate
activate factor 11 which activates factor 9 and 8 which leads to activation of factor ten and loads of thrombin.
natural anticoagulants
tissue factor pathway inhibitor, protein C and S, anti-thrombin
fibrinolysis clears up the clot via
via T-Pa and U-PA activating plasminogen into plasmin to cleave fibrin into fibrin degradation products -> D-Dimer.
red thrombus consists of
fibrin and red cells causing back pressure arising from stasis and hypercoagubility in the venous pathway
diagnosis of red thrombus
pre-test probability wells and Geneva, D-dimer and imaging Doppler US, Potential for V/Q scan if pulmonary symptoms. Gold standard for pulmonary is CT angiogram
arterial thrombosis pathophysiology and presentation
white clot formed by the platelets and fibrin that goes on to result in ischaemia and infarction, secondary to atherosclerosis
red thrombus Doppler US signs
looking at compressibility of veins, enlargement and echogenic material.
environmental risk factors for arterial thrombus
age, smoking, sedentary lifestyle, hypertension, diabetes, obesity, hypercholesterolaemia.
environmental risk factors for venous thrombus
increasing age, pregnancy, hormonal therapy, tissue trauma, immobility, surgery, obesity, systemic disease, family history
heritable thrombophilia genetic risk factors
Factor V Leiden, prothrombin.
microvascular thrombus is
principally in disseminated intravascular coagulation. It is a mix of platelets and/or fibrin resulting in diffuse ischaemia.
DIC can be caused by
caused by septicaemia, malignancy, eclampsia, gangrene and organ failure. Leads to the consumption of platelets and clotting factors leading to bleeding
DIC can be treated by
Requires careful slow doses of anticoagulants to stop the consumption but avoid bleeding despite the increased PT time.
haemophilia history
bruising, epistaxis, post-surgical bleeding, menorrhagia, Post-partum, post trauma, severity of bleeding.
haemophilia features
haemarthrosis, muscle haematoma, CNS bleeding, retroperitoneal bleeding, post-surgical bleeding.
haemophilia complications
synovitis, chronic haemophilic arthropathy, neurovascular compression, stroke.
diagnosis for haemophilia
clinical prolonged APTT (Activated partial Thromboplastin Time), normal PT, reduced FVIII or FIX, genetic analysis
treatment for haemophilia bleeding diathesis
prophylactic for severe haemophilia recombinant coagulation factor replacement (FVIII/IX), DDAVP, tranexamic acid, future considerations of gene therapy, use of enisozimab.
treatment for haemophilia
splints, PT analgesia, synovectomy, joint replacement.
Von Willebrand disease treatment
tranexamic acid, topical application, OCP etc.
severe haemophilia percentage of coagulation factor activity
<1% is severe
moderate haemophilia percentage of coagulation factor activity
1-5% moderate
mild haemophilia percentage of coagulation factor activity
5-30%
haemophilia A and B is linked to
X chromosome
platelet type thrombocytopenia presents with
mucosal, epistaxis, purpura, menorrhagia, GI
decreased production thrombocytopenia presents with
marrow failure, aplasia, infiltration
increased consumption thrombocytopenia
immune ITP, non-immune DIC, hypersplenism
clinical presentation of thrombocytopenia
petechia, ecchymosis, mucosal bleeding, rare CNS bleeding.
immune thrombocytopenic purpura treatment
steroids, splenectomy, thrombopoietin analogues
liver failure acquired cause of haemostatic failure
loss of clotting factors (1,2,5,7,8,9,10,11) prolonged PT, APTT, reduced fibrinogen, cholestasis results in depleted vitamin K.
drugs that can cause haemostatic failure
warfarin, heparin, aspirin
haemorrhagic disease of the new born treatment
immature coagulation system, vit K deficient, treatable via vit k injection.
principles of leukaemogenesis
mutlii stage process that involves acquired genetic alteration in a long lived cell that confers a proliferative advantage enabling it to dominate the tissue. Depending on the behaviours of the mutations drastically different outcomes.
haematological malignancy can occur in what age groups?
occurs all age groups, adult males commonly more than females
acute haematological malignancy key points
: cells do not differentiate, bone marrow fails and rapidly fatal
chronic haematological malignancy key points
differentiate, no bone marrow failure, survivable for a few years
most lymphomas arise from
the stress of affinity maturations within the germinal centres of lymph nodes that B cells undergo mutations of immunoglobulin gene failure.
chronic lymphomas leukaemia pathophysiology
not an issue with the stem cell but a mature lymphoid cell originating in the germinal centre of the lymphoid tissue. Likely to have massively swollen lymph node as a result.
leukaemia difference to lymphoma
bone marrow involving stem cells, lymphoid progenitor, progenitor B, pre B, immature B cells
lymphoma difference to leukaemia
lymphoid tissue involving memory b cell, mature naïve B cell, plasma cell.
lymphadenopathy when it is haematological malignancy
consider leukaemia is rubbery localised and painless, or generalised and painless. Systemic symptoms include fever, drenching sweats, loss of weight, pruritis and fatigue.
indications for red cell transfusion
anaemia, prevent organ damage, improve quality of life in the patient with un-correctable anaemia, prepare a patient for surgery or speed up recovery, reverse damage by own cells
platelets infusion indications
thrombocytopenia , prophylactically to stop bleeding, dilutional thrombocytopenia, cardiopulmonary bypass, DIC if bleeding.
fresh frozen plasma indications
low coagulation factor
replacement of coagulation factors due to major haemorrhage, DIC In presence of bleeding, thrombotic thrombocytopenic purpura, replacement of coagulation factor deficiencies where factor concentrate unavailable.
cryoprecipitate indications
low fibrinogen
hypofibrinogenemia secondary to massive transfusion, DIC bleeding and fibrinogen <1g/L, bleeding associated with thrombolytic therapy causing hypofibrinogenemia, renal or liver failure with abnormal bleeding, inherited hypofibrinogenemia if fibrinogen concentrate unavailable
blood bank protocol
group and screen/Save cross match group specific blood two sample policy sample valid for 72 hours
main hazards of blood transfusion
haemolytic transfusion reaction
transfusion associated dyspnoea
transfusion associated circulatory overload.
likely reactions I being febrile with pyrexia, then allergic with urticaria.
chronic myeloid leukaemia features
anaemia, massive splenomegaly, weight loss, hyperleukostasis (venous congestion, altered consciousness, respiratory failure, fundal haemorrhage, gout (hyper metabolic state).
chronic myeloid leukaemia lab features
High WCC, high platelets, anaemia, blood film shows all stages of white cell differentiation and increased basophils, hypercellular bone marrow, presence of Philadelphia chromosome (9;22).
treatment of chronic myeloid leukaemia
tyrosine kinase inhibitors (imatinib, dasatinib, nilotinib), direct inhibitors of BCR-ABL, allogeneic transplantation only in TKI failures.
features of acute myeloid leukaemia
bone marrow failure, anaemia, thrombocytopenic bleeding (purpura, mucosal membrane bleeding), infection because of neutropenia.
investigations of acute myeloid leukaemia
blood count and film, bone marrow aspirate, cytogenics (karyotype), immunophenotyping of leukaemic blasts, CSF examination if symptoms, targeted molecular genetics for associated acquired gene mutations.
treatment of acute myeloid leukaemia
supportive care; chemo therapy (daunorubicin, cytosine arabinoside, gemtuzumab ozogamicin, CPX – 351), allogeneic stem cell transplantation, all trans retinoic acid and arsenic trioxide in low risk acute promyelocytic leukaemia, targeted treatments.
newer treatments for acute myeloid leukaemia
Newer Tx’s include targeted small molecules midostaurin tyrosine kinase inhibitors inhibiting FLT3.
polycythaemia vera features
headaches, itches, vascular occlusion, thrombosis, TIA, stroke, splenomegaly.
polycythaemia vera treatment
venesection to reduce haematocrit, aspirin, hydroxcarbamide(stem cell suppressor)/alpha interferon, Ruxolitinib (JAK2 inhibitor in in HC failures with systemic symptoms).
essential thrombocythemia features
raised platelet count, arterial and venous thromboses, digital ischaemia, gout, headache, mild splenomegaly
treatment with essential thrombocythemia
treated with aspirin and hydroxycarbamide or anagrelide.
paraprotein refers too
monoclonal immunoglobulin present in blood or urine. Sign of monoclonal proliferation of B lymphocyte/plasma cell.
paraproteins are associated with
renal failure cast nephropathy, hyper viscosity (bleeding retinal, oral, nasal, cutaneous can lead to risk of cardiac failure, pulmonary congestion), hypogammaglobulinemia (infection risk), amyloidosis (deposition of fibrillar protein), cardiac failure, carpal tunnel syndrome, autonomic neuropathy.
paraprotein’s are usually associated by which immunoglobulins
typically excess of IgG, IgA paraproteins by mature plasma cells.
IgM paraprotein associated with
lymphoma made by maturing B-lymphocytes
clinical presentation of myeloma
bone disease (lytic lesions, fractures, cord compression, hyper calcinemia, bone marrow failure), infections, anaemia, renal failure (CRAB)
investigations for myeloma
serum protein electrophoresis for identifying monoclonal gammopathy (paraprotein).
total immunoglobulin levels (heavy chain/Fc section)
immunofixation for identifying paraprotein class
light chains (assess imbalance in the urine)
diagnosis of myeloma requires
bone marrow biopsy with plasma cells
staging of myeloma
of albumin and beta-2 microglobulin
treatment for myeloma
chemo (Proteasome inhibitors), IMiDs (lenalidomide, pomalidomide), monoclonal antibodies, bisphosphonate therapy (zoledronic acid), RT, steroids, surgery (spinal decompression, long bone pinning), autologous stem cell transplant
presentation of neutropenic sepsis
fever no localising signs, rigors, >38.5 or 2*38 degrees, chest infection, skin sepsis, urinary tract infection, septic shock
gram positive febrile bacterial causes for immunosuppression
gram positive bacteria (60-70%); staphylococci MSSA, MRSA, coagulase negative, streptococci viridans
gram-negative bacilli causes for immunosuppression
Escherichia coli, Klebsiella ESBL, pseudomonas aeruginosa
fungal immunosuppression causitive agents
candida, aspergillus often deep-seated life-threatening lung, brain, liver, sinuses. Particularly likely to occur with monocytopenia and monocyte dysfunction.
lymphopenia patient presentation
atypical pneumonia (pneumocystis Jirovecii), CMV, Viral (shingles, mouth ulcers, adenovirus, EBV). Risk of fungal and atypical mycobacteria
prophylaxis for infection in immunosuppression
antibiotics, (ciprofloxacin), Anti-fungal (fluconazole), anti-viral (aciclovir), PJP (co-trimoxazole), growth-factors G-CSF for reversal of neutropenia, stem cell rescue/transplant, protective environment, I.V. immunoglobulin replacement, vaccination
sepsis broad spectrum antibiotics
Tazocin and gentamicin (negative affiliated), gram positive (vancomycin and teicoplanin), post 72 hours then add I.V. caspofungin, CT for source.
investigation for neutropenic fever
blood cultures, CXR, throat swab, sputum, FBC, renal and liver function, coagulation screen.
primary immunodeficiency refers too
congenital, part of the immune system is missing or abnormally functioning. Often caused by mutations, some by autoimmunity. Creates predisposition to infection and tumours.
secondary immunodeficiency refers too
acquired
examples of innate immunity disorders
chronic granulomatous disease
leukocyte adhesion deficiency
Chediak-Higashi syndrome
Toll-like receptor signalling defects
causes of primary immunodeficiency
mutations, polymorphisms, polygenic
mutation cause of primary immunodeficiency
rare and effect any part of the immune system causing severe disease.
polymorphism causes of primary immunodeficiency
2 or more variants of DNA that can affect any part of the immune system and generate an increased moderate risk for infection. Most common polymorphism if for HLA alleles which is essential for HMC antigen presentation.
polygenic causes of primary immunodeficiency
disorders caused by combined action of more than one gene. Common and affect mostly antibodies and may be caused by auto-immunity. Example being Common variable immunodeficiency CVID
B cell immune deficiency may be susceptible to
pygogenic bacteria, enteric bacteria, viruses and some parasites, encapsulated bacteria
T cell immune deficiency may be susceptible to
Pneumocystis Jiroveci, viruses, atypical mycobacteria, fungi, candida, EBC, CMV, Kaposi sarcoma
repeated infections with encapsulated bacteria is a sign of
defective antibody production. Antibody deficiency (IgG and IgA) leads to recurrent respiratory infection by pneumococcus or Haemophilus spp.
reduced phagocytes are associated with
Infections with staphylococci, gram-negative bacteria, and fungi are
complement defects predispose too
meningitis caused by Neisseria meningitidis
Recurrent Candida infection is suggestive of
TH17 defects
SCID reverse too
SCID – reverse combined immunodeficiency
SCID presentation
die within first few months of life without treatment. Have unusual infections, diarrhoea, unusual rashes. Family history of neonatal death or consanguinity.
SCID investigation
Very low lymphocyte count investigates with flow cytometry
antibody deficiency investigations
IgG, IgA and IgM should be measured, specific antibody testing, check complement and neutrophil function
SCID Tx
screen and stem cell transplant. Avoid live vaccines and prophylactic antibiotics
SCID Tx
prevent infection, prophylactic antibiotics, immunoglobulin replacement therapy
contrast types 1,2,3,4 hypersensitivity ABCD
A - Allergy
B – blood type
C - complexes
D – delayed
contrast 1,2,3,4 hypersensitivity with short summary (1/2 words)
anaphylaxis
cytotoxic
immune complex
delayed
IgE in type 1 hypersensitivity role
responsible for immediate hypersensitivity causing asthma or rhinitis
IgE pathway for production in type 1 hypersensitivity
Produced by B cells when stimulated by IL-4 via TH2 cells.
type 1 hypersensitivity pathophysiology
mediated through degranulation of mast cells and eosinophils reacting to allergen and IgE interactions. Release of prostaglandins and leukotrienes through cyclooxygenase and lipoxygenase pathways resulting in vasodilation and vascular permeability. Drop in blood pressure from the shift in fluids.
early allergy patho
degranulation of mast cells and eosinophils in response to allergen and IgE reactions
late allergy patho
migration of leukocytes to site in response to chemokines
atopy refers too
immediate hypersensitivity reaction to environmental antigens mediated by IgE = allergy
clinical effects of type 1 hypersensitivity
anaphylaxis, angioedema, urticaria, rhinitis, asthma, dermatitis, eczema
type 2 hypersensitivity pathophysiology
antibody mediated hypersensitivity as a result of IgG or IgM reacting with antigen present on the surface of cells. Interacts with complement or with Fc receptor on macrophages, there is then opsonisation of target cells and immune mediated haemolysis
clinical relevance of type 2 hypersensitivity
alloimmune haemolysis with ABO transfusion and rhesus antigen, autoimmune haemolysis induced by infection, drugs, or as a part of systemic autoimmune disease SLE, malignant B cells (Grave’s disease and hyperthyroidism), Goodpasture syndrome
type 3 hypersensitivity pathophysiology
immune complex disease involving IgG as a result of binding to antigens and causing damage at the site or elsewhere. Failure of clearance through the complement system and phagocytes results in increased vascular permeability, neutrophil infiltration, inflammation, mast cell degranulation and thrombi formation
clinical effects of type 3 hypersensitivity
glomerulonephritis (rapid onset renal failure, nephrotic syndrome, Farmer’s lung)
pathophysiology of type 4 hypersensitivity
slowest form of hypersensitivity mediated by T cells, takes 2-3 days. macrophages release cytokines (IL-12) and initiate inflammation, presentation of antigens to T cells and they proliferate and attack site of inflammation. Secretion of Tumour necrosis factor TNF stimulate much of the damage.
clinical effects of type 4 hypersensitivity
Rheumatoid arthritis (delayed hypersensitivity persistent TH1 and TH17 reactions), Multiple sclerosis
central tolerance refers too
thymus for eliminating T cells and bone marrow for B cells.
peripheral tolerance refers toon
mature lymphocytes that recognise mature self-antigens in peripheral tissues die via apoptosis
autoimmune disease essentially refers to
break down of self-tolerance, self-antigens provoking an immune response through autoreactive T cells or autoantibodies (2,3,4 reactions)
peripheral factors for auto-immunity
inappropriate access to self-antigens, increased local expression of co-stimulatory molecules, altered presentation of self-molecules
genetic factors for auto-immunity
common polymorphisms of HLA association, AIRE mutations
environmental factors for auto-immunity
infections, drugs and UV radiation
inflammatory pathogenesis for auto-immunity
inflammation resulting in increased proteolytic enzymes resulting in peptides being presented to responsive T cells. Once tolerance has broken down just results in further exposure and acceleration of tissue damage
infection pathogenesis for autoimmunity
antigen breakdown and presentation changes, upregulation of co-stimulation, molecular mimicry
drugs autoimmunity pathogenesis
molecular mimicry, genetic variation in drug metabolism
skin radiation autoimmunity pathogenesis
trigger for skin inflammation, modification of self-antigen
non-organ autoimmune disease
multiple organs, associated with auto-immune responses against self-molecules through-out the body, intracellular molecules involved in transcription and translation
organ specific autoimmune disease
restricted to one organ, endocrine glands
major differences between donor and recipient
ABO compatibility
recipient must not have anti donor human Leukocyte antigens
Donor should match the HLA status of the recipient
immunosuppressive drugs for preventing graft rejection
immunosuppressive drugs prevent rejection if given at time of transplantation; corticosteroids, T cell signalling blockers (cyclosporine and tacrolimus), IL-2 blockade (Basilixamb and rapamycin), anti-proliferative (azathioprine, mycophenolate)
hyper acute organ rejection
preformed antibodies binding to ABO blood group or HLA class 1 antigens on graft, triggers type 2 hypersensitivity reaction and graft is destroyed by vascular thrombosis
acute rejection organ pathogenesis
type 4 hypersensitivity, donor dendritic cells stimulate an allogeneic response in local lymph node and T cells proliferate into donor organ. Usually result of HLA mismatch.
chronic organ rejection pathogenesis
allogeneic reaction mediated by T cells resulting in repeated acute rejections or recurrence of auto-immune disease
afferent phase of organ rejection
donor MHC molecules on passenger leucocytes (dendritic cells) recognised by recipients CD4+ T cells
effector phase of organ rejection
CD4+ T cells recruit effector cells responsible for the damage to the tissue
define graft versus host disease
Donor T cells respond to allogeneic recipient antigens, mismatches in major or minor histocompatibility antigens. given immunosuppressive drugs to prevent. Often involves skin, gut, liver and lungs
direct immunosuppressive therapy refers too
direct (targeted) antibodies that detect antigen on tumour and destroy target
indirect immunosuppressive therapy refers too
immune system activation to destroy the tumour.
passive infusions refer too
infusion of gamma globulins to reduce infection, or passive infusion of antibody specific to the toxins such as with snake or spider bites
cytokine therapies refer too
form of indirect immunotherapy. Modulated cytokines (GM-CSF, pegylated IFN-Alpha, IL-2) use for specific cancer
rituximab refers mechanism and use
first line for non-hodgkin’s lymphoma, specific for CD20 on sub population of B cells.
infliximab mechanism and use
anti-TNF therapy used for ankylosing spondylitis, Crohn’s disease and ulcerative colitis by blocking TNF
Herceptin use
; binds to HER2 on cancer cells for breast cancer
checkpoint inhibitors refer too
form of indirect immunotherapy; unlock gateway to adaptive immune system for powerful anti-tumour responses. Such as anti PD1/PD-L1 antibodies
T cell immunotherapy
take samples of autologous T cells and allow them to overgrow with samples of the tumour for 2- 3 weeks, test for reactivity, if positive then culture and re-infuse.
dendritic cell vaccine refers too
form of indirect immunotherapy; take sample from patient, culture cells with cytokines that promote APC function and transfuse with APC after uptake of tumour antigen.
CAR-T cells refer too
engineered to express antigen-targeted receptors specific for tumour antigens
