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Primary Physiology > Haematology and Immunology > Flashcards

Haematology and Immunology Flashcards

1
Q

What proportion of protein content of erythrocytes is haemoglobin

A

95%

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2
Q

Significance of biconcave shape of rbc

A

High SA to volume ratio for efficient gas exchange
More deformable to navigate microvasculature

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3
Q

What is EPO
Function
Production
What stimulates epo production

A

A glycoprotein
Stimulates erythropoesis
Produced in kidneys but also liver
EPO production stimulated by corticosteroids, androgens, growth hormones, thyroxine
Also stimulated by hypoxia, haemorrhage, haemolysis, anaemia

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4
Q

Where are ertythocytes made, from what point?

A

Bone marrow from 7th month of gestation

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5
Q

What is the effect of haemoglobin on blood oxygen carrying capacity

A

Increases about 50x

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6
Q

Other than carrying o2 what else is Hb involved in transporting

A

Co2
H+

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7
Q

Where is myoglobin found
Function

A

Skeletal muscles
Oxygen store releasing it when needed

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8
Q

What are HbA molecules made up of
How are they held together?

A

2 alpha 2 beta chains bound by non-covalent salt links
4 covalently bound haem group

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9
Q

What is a haem group?

A

Porphyrin ring with central iron atom in ferrous (Fe2+) state

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10
Q

What are the relative configurations of oxy and deoxyhaemoglobin

A

Deoxyhaemoglobin is taut (T)
Binding of oxygen produces a more relaxed (R) state by breaking salt links in the links between alpha1 and beta2 + alpha2 and beta1

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11
Q

How do subsequent oxygen molecules binding to haemoglobin change in strength of bond? Why?

A

1st is weak as more salt links to break so needs more energy
Subsequent 2 molecules bond more strongly
4th molecule binds strongest

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12
Q

What does the changing affinity of Hb for oxygen mean for the oxyhemoglobin dissociation curve? How does this differ from myoglobin? Why?

A

Sigmoid shape
Myoglobin has only one chain thus has a hyperbolic shaped dissociation curve

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13
Q

What is the term for the binding of other molecules to Hb altering its oxygen binding capacity? What molecules do this?

A

Allosteric molecule
CO2 H+ 2,3-diphosphoglycerate (2,3-DPG)

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14
Q

How does CO2 allosterically influence haemoglobin oxyhaemoglobin dissociation curve

A

Converted to bicarbonate
Binds to terminal amino group
Moves oxygen dissociation curve to right (less saturation at given pp)

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15
Q

How does H+ influence haemoglobin oxyhaemoglobin dissociation curve

A

Taken up by deoxyhaemoglobin which has a higher affinity for H than oxyhaemoglobin shifting dissociation curve to right resulting in less saturation at given pp.

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16
Q

Name of effect caused by co2 and h causing right shift of oxyhaemoglobin dissociation curve

A

Bohr effect

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17
Q

What is 2.3DPG
Effect on hb

A

A product of glycolysis
Moves oxyhaemoglobin dissociation curve to right reducing affinity for oxygen 26-fold

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18
Q

What is the importance of 2.3DPG in context of blood transfusion

A

Decreased levels on storage by around 30% thus relative shift to left of dissociation curve and less oxygen released - mainly relevant in severe anaemia and heart disease patients.

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19
Q

Effect of temp on oxyhaemoglobin dissociation curve

A

Shifts to right releasing oxygen

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20
Q

Where are the genes for hb located

A

Alpha - short arm of 16
Beta - short arm of 11

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21
Q

What is the cause of sickle cell disease

A

Single base change resulting in single amino acid change on beta globin chain of Hb

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22
Q

What is the pathophysiology of sickle cell disease

A

HbS polymerises into crystals when deoxygenated causing membrane damage and misshapen RBCs
This shortens their survival time to 5-15 days causing haemolytic anaemia and results in obstruction in microcirculation

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23
Q

Effects of microcirculation obstruction in sickle cell

A

SSD crisis - Pain in joints, bones (marrow ischaemia), abdomen
Chest crisis - chest pain, fever, pulmonary infiltrates, hypoxia, PE
Stroke - esp in children…

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24
Q

Long term complications of sickle cell disease

A

Anaemia
Cholelithiasis
Retinopathy
Leg ulcers
Renal impairment
Bone damage

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25
Q

Do sickle cell trait patients have any symptoms

A

Rarely - usually just high altitude e.g. unpressurised plane

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26
Q

Diagnosis of sickle cell disease

A

Protein electrophoresis

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27
Q

Treatment for sickle cell crisis

A

Analgesia
ABX if infectious source
Hydration
Oxygen only if hypoxia

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28
Q

Perioperative management of sickle cell disease

A

Consult at Haematologist to confirm diagnosis and possible antibodies from prior transfusions
Consider preoperative transfusion to reduce HbS
Attention to avoiding hypotension, hypothermia, acidosis, hypoxia
Prophylaxis of infection
Exsanguination of limb before tourniquet application

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29
Q

What is the genetic mechanism behind thallisaemia

A

Alphas usually gene deletion
Betas usually mutation resulting in abnormal processing

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30
Q

What are the genetic variabilities of alpha thalassaemia?

A

4 gene loci in any diploid cell for alpha chain, 2 on each chromosome
Loss of all 4 results in death in utero around 28-40 weeks

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31
Q

What genetic variations of beta thalassaemia are there?

A

There are 2 gene loci (one on each chromosome) in a diploid cell
Mutation can cause reduced or absent production
If absent or significantly reduced beta chains get beta thalassaemia major
If relatively reduced get beta thalassaemia trait

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32
Q

Pathophysiology of beta thalassaemia major
Management

A

Essentially no beta chain synthesis
When foetal haemoglobin decreases (alpha gamma) in first 6 months child becomes anaemic
Transfusion dependant with chelation to manage iron levels

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33
Q

Life expectancy of beta thalassaemia major with treatment

A

30s

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34
Q

Pathophysiology of beta thalassaemia trait

A

Asymptomatic with thalassaemia blood picture
Raised levels of HbA2
Iron deficiency

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35
Q

Haemoglobin chains in fetal and hba2

A

Fetal - alpha2 gamma2
HbA2 - alpha2 delta2

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36
Q

Proportion of different blood groups in uk
Responsible antibody for reaction

A

0 - 47%
A - 42%
B - 8%
AB - 3%

IgM

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37
Q

What can occur in around 25% of blood group A and AB patients

A

Lower than normal density of A antigens on membrane and thus can have anti A antibodies (though not usually clinically significant)

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38
Q

What proportion of people secrete blood antigens in saliva? How would you detect a blood group o in this manner

A

80%
All including O secrete a precursor ‘H’

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39
Q

When would a Rh-ve person become sensitised to rhesus antigens?

A

If transfused with Rh +ve blood or a mother bears a Rh+ve child

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40
Q

What antibodies are associated with Rh reactions? Significance in maternity?

A

IgG
Can cross placenta causing haemolytic disease of the newborn

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41
Q

What are the main Rh antigens? Most and second most important?

A

D most important
c second most important (but 20x lower immunogenicity than D)
Also C, E, e and up to 45 more
No d antigen (this represents absent Rh antigen)

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42
Q

How are group and saves performed

A

Establish abo and RhD status suing monoclonal typing reagents.
Reverse group by mixing patients serum with group A and group B red cells
Antibody screen

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43
Q

What is crossmatching

A

Patients serum tested directly against the unit of blood to be transfused

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44
Q

Transfusion reactions by category

A

Immediate life threatening:
Haemolytic transfusion reaction
Anaphylaxis

Delayed life threatening:
Bacterial infection
TRALI
Overload

Non life threatening:
Febrile non haemolytic transfusion reaction
Itch/urticaria

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45
Q

Antibodies most commonly associated with haemolytic transfusion reaction

A

Abo,
Rh
Duff
Kidd
Kell

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46
Q

Features of immediate haemolytic transfusion reaction
Mortality

A

Pain - cannula site, chest, back
Hypotension
DIC
Haemoglobinurea

Mortality rate 10%

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47
Q

Cause of anaphylaxis to blood transfusion

A

IgA depletion in host with anti IgA antibodies

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48
Q

Most Common organism for bacterial contamination of blood
Features of blood contaminated

A

Yesinia enterocolitica
Purple colour or clotted

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49
Q

Cause of TRALI
Most associated with which product?
Features

A

Anti-leukocyte antibodies in donor plasma
FFP
Hypoxia, lung infiltration on CXR

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50
Q

Treatment of TRALI
Is there a risk of it reoccuring in the same patient

A

Methylprednisolone
No more than average - antibodies are in donor plasma

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51
Q

Commonest type of transfusion reaction
Cause?

A

Febrile reaction
Anti-leukocyte antibodies in recipient blood

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52
Q

Features of febrile non-haemolytic transfusion reactions
Management

A

Usually just fever, but can cause, nausea, vomiting, collapse, hypotension
Slow transfusion, paracetamol prior to transfusion. Consideration for leukodepletion of donor blood if reaction severe or persistent.

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53
Q

What are delayed haemolytic transfusion reactions

A

Slow activation of antibodies that had fallen to undetectable prior to transfusion. Slowly reactivate causing haemolysis with fever, anaemia and jaundice 4-14 days post transfusion

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54
Q

Rough platelet counts needed prior to invasive surgery/major trauma
What about op on critical sites (eye, spine, brain)
What should they be maintained at in bone marrow failure (reversible)

A

> 50
100
10

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55
Q

Indications for FFP

A

Massive transfusion if PT or APTT ratio prolonged or raised fibrinogen
Liver disease prior to surgery
Replacement of coagulation factor when specific concentrate not available
Bleeding in DIC
Plasmapheresis in TTP

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56
Q

Indications for cryoprecipitate

A

Emergency treatment for haemophilia and von willebrand disease when specific concetrates not available
Massive transfusion when fibrinogen low
Bleeding in DIC when fibrinogen low
Bleeding following thrombolysis

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57
Q

What is cryoprecipitate

A

Plasma derived blood product containing lots of fibrinogen (factor 1) and factors 8, 13, vWF and fibronectin

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58
Q

What is the feature of the coag cascade that causes large volume clotting

A

Amplifies

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59
Q

Basic features (physiological) involved in haemostasis

A

Blood vessel smooth muscle constriction
Platelet activation
Fibrin formation

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60
Q

Describe the trigger for extrinsic pathway of coagulation
What is it
Where is it in high concentrations

A

Release of tissue factor from outside vascular system by tissue damage
A lipoprotein cofactor
Brain, placenta, lung

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61
Q

Extrinsic pathway cascade

A

VII to VIIa
Tissue factor cofactor binds to VIIa
VIIa and TF cleaves X to Xa with the use of Ca
Xa enters common pathway

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62
Q

Intrinsic pathway activation

A

Exposure of blood to negatively charged subendothelial surfaces exposed by damaged vascular endothelium. Involves prekallikrein.

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63
Q

Cascade of intrinsic pathway of coagulation

A

XII to XIIa
XI to XIa
IX-IXa with Ca
IXa works with factor VIII as a cofactor to activate:
X to Xa with Ca

64
Q

What is the common coagulation cascade

A

Activate Xa with Va as cofactor causes prothrombin (II) to become thrombin
Thrombin causes fibrinogen to convert to fibrin monomers which form fibrin strands
Thrombin also activated XIII to XIIIa which cross links the fibrin strands stabilising it,

65
Q

Functions of thrombin

A

Cleaves fibrinogen
Activates factor XIII
Activates factors XII
Activates cofactors V and VIII
Induces platelet aggregation
Combines with thrombomodulin to activate protein C

66
Q

What is the PT?
What is it testing?
How?

A

Prothrombin time
Tests extrinsic pathway

Citrate in sample
Add tissue factor
Add calcium to reverse citrate
Measure time to clot formation

67
Q

How may PT be presented as a result

A

As the raw PT
As an INR - normalised for differences between labs

68
Q

What is the conversion of PT to INR
Implication of the ISI of the TF used in uk being close to 1

A

INR = PT:mean normal PT ^ ISI
As isi around 1 in uk pt and INR often very similar

69
Q

Causes of raised PT

A

Anticoagulant drugs
Liver disease
Vit K deficiency
DIC
Massive transfusion
Inherited deficiency in VII, X or V
Heparin
Hypofibinoginaemia

70
Q

What is APTT
What is it testing
How

A

Tests intrinsic pathway
Plasma pre incubated with kaolin and phospholipid to mimic contact factors
Calcium to reverse citrate
Time to clot recorded

71
Q

Causes of prolonged APTT

A

Heparin
Liver disease
Contamination of sample with heparin
DIC
Massive transfusion
Inherited deficiency of XI, VIII, IX, X PK, HMWK
Hypofibinogenaemia

72
Q

Deficiencies in which factors cause prolongation of pt and APTT

A

X
V
II (prothrombin)

73
Q

Deficiencies of which factor only causes prolonged pt

A

VII

74
Q

Deficiencies of which factors only cause prolongation of APTT

A

XI, VIII, IX,

75
Q

What is the thrombin time test?
Reasons for prolongation

A

Tests the conversion of fibrin to fibrinogen
Adds thrombin to platelet poor plasma and measures time to clot

Most often spurious from heparin!
Hypofibrinogenaemia
Dysfibrinogenaemia
DIC

76
Q

Moa of warfarin

A

Inhibits Vit k reduction thus stops production of Vit k dependant clotting factors
II, VII, IX and X (1972)

77
Q

Moa of heparin

A

Enhances action of anti thrombin breaking down factors
IIa Xa XIIa XIa and IXa
Reduces platelet agrigation
Increases vascular permeability
Releases lipoprotein lipase

78
Q

Moa of lmwh

A

Inhibits Xa

79
Q

Moa of apixaban, fondaparinux, rivaroxaban

A

Inhibit Xa

80
Q

Moi dabigatran

A

Inhibits ii

81
Q

Issues with coag cascade intrinsic vs extrinsic models

A

Deficiency in some factors eg VIII cause prolonged APTT and bleeding
Others such as XII prolong APTT but don’t cause bleeding

82
Q

How does coagulation work with regards the cofactors V and VIII

A

Trace amounts of thrombin produced in absence of activated V and VIII
Thrombin then feeds back causing positive feedback activating V and VIII greatly increasing production

83
Q

Other than as cofactors what is the other effect of Va and VIIIa

A

Localise the reaction to surfaces

84
Q

Outside of the classical intrinsic extrinsic pathway what does VIIaTF complex do
Significance

A

Activates factor X as per the extrinsic pathway
Also activates IX
As IX activated when VIII activated massive amplification of cascade

85
Q

What are the natural coagulation inhibitors

A

Tissue factor pathway inhibitors
Serine protease inhibitors (e.g antithrombin)
Coagulation cofactor inhibitors (proteins C and S)

86
Q

What are tissue factor pathway inhibitors?
Effect

A

Rapidly inactivate VIIaTF complex
Force coagulation down the intrinsic route once started by the extrinsic

87
Q

How does the intrinsic pathway actually function in vivo?

A

No contact activation, this is lab only!
Thrombin once activated by extrinsic pathway activates factors XII and cofactor VIII

88
Q

How do serine protease inhibitors work
Main example

A

Antithrombin
Complexes with thrombin, Xa, XIIa, XIa, IXa inactivating them
Complex is then removed by liver

89
Q

Examples of Serine protease inhibitors that are not antithrombin

A

Alpha1 antitrypsin, c1 esterase inhibitors, heparin cofactor II

90
Q

How does the protein C system work in coagulation
Effect

A

Thrombin binds to thrombomodulin on cell wall
Protein C activated by thrombin thrombomodulin complex to activated protein C
Activated protein C with protein S cause inactivation of factors Va expand VIIIa by cleavage

Stops thrombosis propagating along wall of normal vessels close to point of injury

91
Q

What is the most common inherited prothrombotic disorder
How does it work

A

Factor v Leiden
Changes binding site for activated protein c on factor v making it resistant to breakdown,

92
Q

What is the fibrinolytic cascade

A

Endothelial cells synthesise tPA (tissue plasminogen activators)
Release of tPA stimulated by venous occlusion, thrombin, adrenalin, vasopressin, strenous exercise
Plasminogen converted to plasminogen
Plasmin degrades fibrin (to products including ddimer)

93
Q

Medications that can influence fibrinolysis cascade

A

Streptokinase and urokinase can mimic tPA in converting plasminogen to plasmin
TXA stops action of plasmin on fibrin,

94
Q

Site of production and size of platelets
Lifespan?

A

Bone marrow from megokaryocytes
2-4 micrometers
8-14 days

95
Q

What are platelet granules called? What is in them?

A

Alpha granules
Factors v, x and protein s
vWF, fibrinogen
Platelet derived growth factor - aids tissue repair

96
Q

Function of platelets

A

Adhesion at site of injury
Aggregation
Surface for coagulation cascade
Release of alpha granules - coagulation, tissue repair

97
Q

What trigger platelet aggregation

A

ADP release from damaged tissues
thromboxane A2 released from the platelets
Both result in raised intracellular calcium
Exposure of glycoprotein IIb IIIa complex on platelet
Fibrinogen binds to this receptor and as it is dimeric bridges between platelets

98
Q

Pathway of thromboxane a2 synthesis

A

Phospholipase A2 releases arachidonic acid from phospholipids
COX converts arachidonic acid to prostaglandins
Thromboxane synthase converts prostaglandins into thromboxane A2

99
Q

What arachidonic metabolite is produced in endothelial cells in tissue damage
Effect

A

Prostacyclins
Vasodilation and platelet inhibition

100
Q

What is the role of vWF in clotting

A

vWF binds to exposed collagen and micro fibrils in damage vessels
Platelets adhear to the vWF via glycoprotein 1b receptor
This activates glycoprotein IIbIIIa complex allowing further platelet binding.

101
Q

What happens to platelets on binding

A

Change shape to spiky increasing reaction between platelets
Release alpha granules with coag factors and growth factors

102
Q

Functions of vWF

A

Platelet adhesion
Carrier for VIII

103
Q

What is vWF
Where is it made

A

Large multimer molecule
Made in endothelial cells and megakaryocytes
Stored in endothelial cells and platelet alpha granules

104
Q

Comments disorder causing bleeding tendency
Frequency
Types
Causes

A

vWF deficiency
1%
Types
1 - mild quantative
2 - qualitative
3 - severe quantitive

Poor platelet adhesion and reduced factor 8

105
Q

Lines of innate immune system and examples

A

First line Physical barriers - skin, mucus membranes, mucociliary
First line Chemical barriers - tears, saliva, gastric acid - contain substances like lysozyme
Second line cellular response - phagocytosis
Second line chemical response - complement, interferons

106
Q

What substances on bacteria activate the second line innate immune system

A

PAMPs - pathogen associated molecular patterns - common recognisable surface molecules

107
Q

What chemical in the serum binds to bacterial cell walls activating complement?

A

Mannan binding lectin

108
Q

What cells undertake phagocytosis of pathogens
Where are they found

A

Macrophages - recognise PAMPs, reside in tupissue or circulate as monocytes
Granulocytes - provide a rapid response to infection, don’t usually survive/persist
Dendritic cells - ingest pathogens to present to adaptive immune system (antigen presenting cells)

109
Q

What is the vesicle containing a phagocytosed pathogen called in a macrophage? What happens to it?

A

Phagosome
Merges with a lysosome containing proteolytic enyzmes, peroxidases, elastase,collagenase

110
Q

What process makes macrophages and neutrophils more efficient at phagocytosis

A

Opsonisation by compliment

111
Q

Other than compliment what else acts to opsonise pathogens

A

IgG

112
Q

What are cytokines
Production
Function in immune response
Examples

A

Peptides or glycopeptides
Released by t/b cells, macrophages etc
Signal to other immune cells
E.g. interleukins, interferons, CSFs, TNFs

113
Q

What are the three ways complement can be activated?

A

Classical pathway - antigen antibody complex activate pathway
Mannose binding lectin pathway - MBL binds to mannose and fructose on cell wall activating pathway
Alternative pathway - direct activation by antigens on bacterial cell wall

114
Q

Where are complement molecules synthesised

A

Liver

115
Q

What are the functions of the complement system?

A

Opsonisation of bacteria and immune complexes
Activation and attraction of phagocytes
Lysis of target with membrane attack complex
Activation of adaptive immune response

116
Q

Initial step in complement cascade

A

C3 cleaved to C3a and C3b

117
Q

Function of C3a

A

Stimulates mast cell degranulation and smooth muscle contraction

118
Q

Function of C3b

A

Attaches to microorganism/immune complex
Opsonisation
Focal point for start of membrane attack complex

119
Q

How does a membrane attack complex form

A

Forms around C3b
Initial cleavage of C5 to C5a and C5b
C5b aggregates with C6+7 forming hydrophobic complex attaching to plasma membrane.
Then binds c8 and C9 penetrating the cell causing lysis.

120
Q

What does the leftover C5a from the membrane attack complex formation do?

A

Causes inflammation, same as C3a but also neutrophil activation, chemotaxis, increased capillary permeability.

121
Q

What happens to the membrane attack complex and nearby structures
How is it stopped

A

Can attach to any nearby membrane causing lysis - a bystander effect
Proteins such as vitronectin deactivate it

122
Q

What organs/systems form the adaptive defence system

A

Thymus
Spleen
Peripheral lymphoid and lymphatics

123
Q

Where do t and b cells originate and develop

A

Both originate in bone marrow from haemopoietic stem cells
T cells mature in thymus
B cells in bone marrow

124
Q

What are the two component responses of the adaptive immune system

A

Humoral - mediated by B cells
Cellular - mediated by T cells

125
Q

How are T cells activated

A

Antigens presented by antigen presenting cells in peripheral lymphoid tissue - usually dendritic cells presenting small peptides from ingested pathogens.

126
Q

How do dendritic cells present antigens

A

As a complex with class II major histocompatibility complex (MHC)

127
Q

Other than dendritic cells what other cell types can be antigen presenting cells

A

Endothelial and epithelial cells

128
Q

What are major histocompatability proteins?
Function

A

Protein markers on the surface of all cells
Distinguish self from non self
Coded by the major histocomplatability complex of genes

129
Q

How do class I mhc proteins work

A

Present self antigens for recognition. If cell invaded by pathogen would display the pathogenic antigen

130
Q

Key functions of antibody mediated response in adaptive immunity

A

Activates complement system
Inactivates toxins produced by microbes
Inactivate viruses

131
Q

How does the antibody mediated response work

A

Antigen binds to surface immunoglobulin of specific B cell
Antigen processed and expressed on MHC protein
B cell now interacts with helper T cell (already activated by APCs)
T helper cell releases stimulators cytokines
B cell proliferates to produce plasma cells and B memory cells (as do some t helper cells)
Plasma cells produce antibodies for release

132
Q

What is the structure of an antibody

A

2 heavy and 2 light chains binding at a hinge region
The light chain region is variable and thus forms a highly specific binding site.

G,E and D exist as monomers, A as dimer, M as pentimer

133
Q

How is such variability in antigen binding sites on antibodies achieved

A

Immunoglobulin gene rearrangement
A variable gene (1 of 100) joins a joining gene (1 of 6) and a diversity gene (1 of 30) to produce a unique gene in each B cell. Further diversified with point mutations and recombination inaccuracies.

134
Q

What are the phases of a PRIMARY antibody response? Which types are seen?

A

Lag phase - little response
Logarithmic increase
Plateau
Decline back to low/undetectable

Mainly consisting of IgM with IgG slightly later

135
Q

What are the phases of a SECONDARY antibody response? Which types are seen?

A

Short lag
Logarthimic rise 10 times greater than primary response
Prolonged plateau
Slow decline

Almost entirely IgG

136
Q

How do T cells detect antigens presented to them?
Constituents of this? How is it variable

A

T cell receptor
Alpha and beta chain
Similar variability to antibody production in B cells 3 domains vjd segments

137
Q

Types of T cells

A

Cytotoxic
Helper
Regulatory

138
Q

What occurs on binding of TCR with MHC-antigen complex

A

Exchange of cytokines including IL1
Release of cytokines to stimulate t helper cells (proliferation) and macrophages (MHC expression) resulting in positive feedback

139
Q

What other T cell receptors are required to make a strong enough bind to activate between MHC and TCR, what do they bind to

A

CD4 receptor - recognises MHC 1
CD8 receptor - recognises MHC 2

140
Q

How do T cells deal with viral infected cells?

A

Cytotoxic T cells Bind to MHC presenting antigen and induce apoptosis

141
Q

How do natural killer cells work?

A

Identify tumour associated antigens and antibody coated cells inducting apoptosis

142
Q

Elements of inflammation

A

Hyperaemia - increased blood flow
Exudation - increased capillary permeability
Emigration of leukocytes - phagocytes then lymphocytes along chemotactic gradient

143
Q

Mediators of inflammation

A

Kinins
Histamine
Leukotrines
TNF
Complement

144
Q

Originator molecule for kinins
Example of kinin
Effects of kinin

A

Prekalikrein
Bradykinin
Vasodilation, increased permeability, pain

145
Q

Where are histamine and leukotriens released from?
Function

A

Basophils and tissue equivalent mast cells
Increased vascular perm inability
Chemotactic

146
Q

What happens at sites of inflammation to drive neutrophil migration

A

Activated endothelial cells by mediators like TNF
Change in adhesion molecule expression and neutrophils adhere to vessel wall
Increased permeability and neutrophils migrate out of vessel down chemotactic gradient along collagen etc using other adhesion molecules to move

147
Q

How do neutrophils contribute to furthering inflammation

A

Release platelet activation factor triggering platelets to release their inflammatory mediators and activate other neutrophils

148
Q

What releases TNF
Function

A

Macrophages and lymphocytes on presence of pathogens
Activates endothelial cells

149
Q

Why is inflammation procoagulant

A

Platelet activation by PAF released by mast cells and neutrophils
TNF mediated activation of endothelium becoming procoagulant

150
Q

What does activated endothelium do in inflammation?

A

Smooth muscle relaxation from nitric oxide release
More permiable
Procoagulant
Allows adhesion of neutrophils

151
Q

Which bits of complement are inflammatory mediators
What do they causes

A

C3a and C5a
Mast cell degranulation
Smooth muscle contraction
Increased capillary permeability
Neutrophil activation

152
Q

What is type 1 hypersensitivity?
Characteristics

A

IgE release from B cells on first exposure binding to mast cells
Subsequent exposure antigen binds to mast cells bound IgE
Immediate response with degranulation resulting in allergy, in severe cases anaphylaxis when there is widespread as opposed to localised release,

153
Q

What is an anaphylactoid reaction

A

Certain drugs bind directly into mast cells - not via IgE - causing degranulation

154
Q

What drives type 2 hypersensitivity
Example

A

IgG or IgM interact with complement to produce target cell damage
E.g. goodpasture’s

155
Q

What is a type 3 hypersensitivity reaction
Diseases associated

A

Immune complex formation that cannot be adequately cleared
Deposition with subsequent complement activation
Associated with hep B, dengue, RA, SLE, cryoglobulinaemia, cutaneous vasculitis, polymyositis, polyarteritis nodosa

156
Q

Type 4 hypersensitivity reaction
Characteristics and trigger
Example

A

Cell mediated
>12 hours to develop
Commonly caused by hapten (molecule to small to induce immune response)
Eg Granulomatous hypersensitivity - TB, leprosy, schistosomiasis, sarcoidosis, leishmaniasis
Continued t helper cell activation but macrophages unable to destroy antigen causing granuloma formation,

Primary Physiology (15 decks)

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