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* year 2 Clinical Pathology > core immunology > Flashcards

core immunology Flashcards

1
Q

what is the definition of a hypersensitivity reaction?

how many types are there?

A

undesirable, damaging, discomfort-producing and sometimes fatal reactions produced by the normal immune system
- directed at INNOCUOUS ANTIGENS in a PRE-SENSITISED host

nb all 4 types need presensitisation

four types

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2
Q

what are the 4 different types of hypersensitivity reactions?

how do they differ based on:

  • antibody produced?
  • type of antigen directed against?
  • response time?
A

type 1 - anaphylactic:

  • IgE
  • exogenous antigen
  • 15-30 mins

type 2 - cytotoxic

  • IgG, IgM
  • cell surface antigen
  • minutes-hours

type 3 - immune complex

  • IgG, IgM
  • soluble antigen
  • 3-8 hours

type 4 - delayed type

  • none (cell-mediated)
  • tissues + organs
  • 48-72 hours
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3
Q

what is erythroblastosis fetalis?

what type of hypersensitivity reaction is it?

A

haemolytic disease of the newborn (rhesus incompatibility)

type 2 (cytotoxic)

mothers anti-rh antibodies act against cell surface receptors on baby’s RBCs

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4
Q

what is goodpasture’s syndrome?

what is the mechanism?

what type of hypersensitivity reaction causes it?

A

aka anti-glomerular basement antibody disease

Abs attack the basement membranes of the kidneys and lungs leading to bleeding from the lungs and kidney failure

type 2 (cytotoxic)

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5
Q

what is allergic contact dermatitis?

what type of hypersensitivity reaction causes it?

A

immune reaction to touching something

eg certain metals (like in cheap earrings) or washing powders or tuberculin skin test

type 4 (delayed type)

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6
Q

what type of hypersensitivity reaction is seen in penicillin allergy?

A

type 2 (cytotoxic)

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7
Q

what type of hypersensitivity reaction is seen in farmers lung?

A

type 3 (immune complex)

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8
Q

what is serum sickness?

what type of hypersensitivity reaction is seen in serum sickness?

A

systemic reaction to antigens in transfused serum

type 3 (immune complex)

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9
Q

what is another name for ezcema?

A

atopic dermatitis

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10
Q

what is another name for hayfever?

A

allergic rhinitis

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11
Q

what makes up the atopic triad?

A
  • asthma
  • ezcema (atopic dermatitis)
  • hayfever (allergic rhinitis)

nb there is a genetic susceptibility factor but environement also plays a role

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12
Q

what is the hygiene hypothesis?

A

that stimulation by microbes is protective and helps modulate immune system

  • basically if you’re too clean then more likely to become atopic etc
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13
Q

what are the two types of T-helper cells, which type stimulates which parts of the immune system more?

which type of T-helper cells are more predominately seen in type 1 hypersensitivity reactions?

A

Th1 type

  • macrophages
  • T-killer cells

Th2 type

  • B-cells
  • eosinophils/mast cells

Th2 type

nb proportion of Th1:Th2 cells can change, changing someones susceptibility to becoming atopic

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14
Q

what are the two different types of allergic rhinitis?

symtpoms?

give some examples of common triggers

treatment? 2

A

perennial or seasonal

blocked/runny nose often with eye symptoms

seasonal is basically pollen

  • house mites
  • animal danders
  • antihistamines
  • nasal steroids
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15
Q

what is the late phase response in a type 1 hypersensitivity reaction?

how is this relevant to the pathogenesis of allergic asthma?

A

after mast cells + basophils have reacted to stimuli, eosinophils also produce a response (mediated by Th2 cells)

in childhood get initial IgE mediated response due to specific stimuli (norm dust mites) but this reactions goes away once stimulus has gone

however the late phase response damages the airways

these damaged airways are then HYPER-REACTIVE to non-allergic stimuli, eg fumes

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16
Q

what are anaphylaxoid reactions?

A

reactions that produce the same clinical picture with anaphylaxis but are not IgE mediated, occur through a direct nonimmune-mediated release of mediators from mast cells and/or basophils or result from direct complement activation.

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17
Q

what are the 5 most commonly used tests for allergy?

incl pros + cons

A

nb all of these have high false positive and negative rates

blood test looking for specific IgE

  • p: no risk to patient
  • c: patient not always convinced

skin prick test (SPT):

  • p: patients often more convinced + quicker result
  • c: slight risk to patient is are allergic

intra-dermal test:

  • more invasive that SPT
  • p+c: same as SPT

oral challenge test:

  • gold standard
  • start w tiny dose + slowly increase
  • p+ c: same as SPT

basophil activation test:

  • use patients basophils in utero to see what they react to
  • p+c: same as IgE blood test
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18
Q

when is immunotherapy indicated in people with allergies and when is it not?

A

indications:

  • life-threatening reactions to wasp + bee stings
  • severe hayfever
  • animal dander allergy

not helpful:

  • multiple allergies
  • food allergy
  • allergic rashes (eg ezcema)
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19
Q

what is urticaria?

aka?

A

aka hives

incredibly itchy rash which norm resolves in couple of days

can be caused by food allergy, contact with certain plants, all sorts!

IgE mediated

nb similar to a nettle sting

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20
Q

what is angioedema

A

Angioedema is an area of swelling of the lower layer of skin and tissue just under the skin or mucous membranes. The swelling may occur in the face, tongue, larynx, abdomen, or arms and legs

often triggered by a food allergy or reaction to an insect bite etc

IgE mediated

“when I had my swollen lip”

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21
Q

what is stevens-johnsons syndrome?

what is the more severe form of the disease?

what normally triggers it?

A

Early symptoms include fever and flu-like symptoms. A few days later the skin begins to blister and peel forming painful raw areas. Mucous membranes, such as the mouth, are also typically involved. Complications include dehydration, sepsis, pneumonia, and multiple organ failure

toxic epidermal necrolysis (spectrum of disease)

allergic reaction to certain drugs

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22
Q

what is the difference between autoinflammation and autoimmunity?

A

autoinflammation:

  • problem with innate immune system
  • get random acute systemic inflammatory responses
  • very rare

autoimmunity

  • problem with adaptive immune system
  • manifests in lots of different ways
  • relatively common
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23
Q

variation/mutations in which proteins/genes increase susceptibility to autoimmune diseases?

A

MHC class 1 + 2

coded by HLA genes

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24
Q

which of these autoimmune conditions are ‘organ-specific’ and which are ‘systemic’:

  • graves disease?
  • MS?
  • RA?
  • SLE?
  • type 1 diabetes?
A

organ specific:

  • graves disease
  • MS
  • type 1 diabetes

systemic:

  • RA
  • SLE
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25
Q

mutation in which gene results in failure to develop regulatory T-cells -> severe immunity from birth?

A

FoxP3

nb this is X-linked recessive

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26
Q

apart from genetics, what other factors can affect likelihood of developing an autoimmune condition?

A
  • increased age
  • smoking
  • female
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27
Q

what is citrullination of proteins?

what autoimmune condition can it result in?

A

citraline is an exogenous amino acid which we ingest in our food

this can get incorporated into our proteins (replacing endogenous amino acids)

therefore the immune system may not recognise the protein any more due to this change and so attacks it

rheumatoid arthritis

nb smoking can also trigger cirullination

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28
Q

what are the two main groups of autoimmune conditions?

A

organ-specific

systemic

nb common to have more than one organ specific disease

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29
Q

what is the most common cause of hypothyroidism in the developed world?

A

hashimotos thyroiditis
- destruction of thyrpoid follicles by auto-antibodies

nb most common cause in developing world is iodine deficiency

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30
Q

what is the name of the auto-antibody in graves disease?

A

anti-TSH-autoantibody

this mimics TSH, inappropriately stimulating the thyroid

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31
Q

myasthenia gravis:

  • pathophysiology?
  • symptoms?
A

autoantibodies attack and destroy ACh recptors on muscle fibres at neuromuscular junction

weakness (gets worse throughout day), especially of eye and facial muscles

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32
Q

what is vitiligo?

A

autoimmune condition where you get autoantibodies against melanocytes in skin -> white patches of skin

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33
Q

what is the mechanism of pernicious anaemia?

A

autoantibodies against intrinsic factor (or parietal cells, which produce intrinsic factor)

B12 needs to bind to intrinsic factor in order to be absorbed

so can’t be absorbed

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34
Q

SLE:

  • type of hypersensitivity reaction?
  • most common symptoms? 3
  • possible complications? 4
A

type 3 (immune complex)

  • fatigue
  • malar rash (butterfly)
  • joint + muscle aches
  • pleural effusions
  • heart problems
  • nephritis
  • arthritis

immune complexes deposit in anyorgan, activate complement and cause inflammation

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35
Q

what type of autoantibody is found in SLE?

A

anti-nuclear antibodies (ANA)

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36
Q

why do you get the malar (butterfly) rash in SLE?

A

when exposed to UV light, cells undergo apoptosis so you get nuclear antigens on the outside of the cell, then get an immune response to these

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37
Q

name 4 autoimmune connective tissue conditions (ie systemic)

A
  • SLE
  • scleroderma
  • polymyostitis
  • Sjogrens syndrome
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38
Q

what is the definition of:

  • sensitivity?
  • specificity?

incl formulas

A

sensitivity:

  • measure of how good the test is at identifying people with the disease
  • true positives / (true positives + false negatives)

specificity:

  • measure of how good the test is at correctly identifying people without the disease
  • true negatives / (true negatives + false positives)
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39
Q

what are the definitions of:

  • positive predictive value?
  • negative predictive value?

incl formulas

A

positive predictive value:

  • the proportion of people with a positive test who have the disease
  • true positives / (true positives + false positives)

negative predictive value:

  • the proportion of people with a negative test who do not have the disease
  • true negatives / (true negatives + false negatives)
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40
Q

name 7 non-specific markers of systemic inflammation

and whether they go up or down in systemic inflammation

A

go up:

  • ESR (will remain elevated for a time post-infection/inflammation)
  • CRP (goes up faster than ESR)
  • ferritin
  • fibrinogen
  • haptoglobin

go up or down (depending on disease):
- complement

go down:
- albumin (liver fouseson making complement instead)

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41
Q

what does ENA stand for?

what are they?

A

extractable nuclear antigens

basically the antigens which ANAs (anti-nuclear antigens) bind to

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42
Q

which test is highly sensitive for diagnosing SLE and which is highly specific?

which would you do first?

A

ANA (anti-nuclear antibodies) is highly sensitive but not very specific
- ie almost everyone with SLE will be positive but other stuff can have positive results

dsDNA (double stranded DNA) is highly specific but not very sensitive
- ie almost everyone with a positive result will have SLE but some people with SLE won’t get a positive result

do ANA first then dsDNA

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43
Q

what is rhematoid factor (RF)?

what condition can it go up in?

A

antibody against the Fc portion of IgG

rhematoid arthritis (70% sens + spec)
- nb can be seen in other stuff

pretty shit test

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44
Q

why is anti-CCP (ACPA) a more useful test than rhematoid factor? 2

A

it has a higher specificity

useful prognostic marker
- ACPA positive patients tend to have more severe and erosive disease

(therefore want to treat more aggressively)

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45
Q

what is ANCA?

what group of conditions is it a diagnostic marker for?
- examples? 3

how do these conditions tend to present?

A

anti-neutrophilic cytoplasmic antibodies (ANCA)

ANCA associated systemic vasculitidies (AASV)

  • granulomatosis with polyangitis (aka wegeners)
  • microscopic polyangitis
  • churg-strauss swyndrome
  • often have subacute/acute onset
  • typically present with pulmonary renal syndrome

nb these are types of systemic autoimmune conditions

nb ANCA is not overally specific or sensitive for these so largely a clinical diagnosis
- histopathology is gold standard

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46
Q

what antibodies can be detected in:

  • primary biliary cholangitis?
  • autoimmune hepatitis?
A

primary biliary cholangitis:
- anti-microbial antibodies

autoimmune hepatitis:

  • anti-smooth muscle antibodies
  • anti-liver/kidney/microsomal (LKS) antibodies

nb these antibodies may be present before clinical manifestation of disease

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47
Q

what is the defintion of immunodeficiency?

what’s the difference between primary and secondary immunodeficiency?

A

clinical situations where the immune system is not yet effective enough to protect the body against infection

primary:

  • inherent defect within the immune system
  • usually genetic

secondary:

  • immune system affected due to external causes
  • eg drugs, viruses
  • a lot more common
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48
Q

why does cystic fibrosis lead to immunodeficiency?

A

break down of ‘physical barriers’ to infection

normal method of expelling pathogens from lungs is comprmised

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49
Q

why does protein loss cause immunodeficiency?

give 3 examples of when immunodeficiency occurs secondary to protein loss

A

because need proteins to make antibodies etc

  • burns
  • malnutrition
  • protein loosing enteropathy

nb same thing happens when you start peeing out proteins, eg in chronic kidney disease

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50
Q

what types can result in immuno suppression?

A

all types

  • but especially lymphoproliferative disease or myeloma
  • as these have lots of cells replicating in bone marrow so think of it like there is no more space for normal immune cells to replicate
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51
Q

are natural killer cells part of the innate or adaptive immune system?

what is their role?

A

innate

kill virally infected cells

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52
Q

what type of cell is myeloma a cancer of?

A

aka multiple myeloma

plasma cells (ie mature B cells)

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53
Q

what does DMARDS stand for?

name an example

A

disease modifying ant-rhematic drugs

eg methotrexate

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54
Q

what types of drugs suppress the immune system? 5

A
  • steroids
  • DMARDS (disease modifying anti-rheumatic drugs
  • rituximab
  • anti-convulsants
  • myelosuppressive drugs
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55
Q

what is rituximab commonly indicated for? 2

A
  • RA

- b-cell cancers

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56
Q

what is the first line drug for RA?

A

methotrexate

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57
Q

what are PRRs?

what do they recognise?

give an example

A

pathogen recognition receptors (found on phagocytes)

they recognise:
- PAMPS (pathogen associated molecular patterns) - ie molecules on surface of pathogens

example of a PAMP
= lipopolysaccharide (found on many bacteria)

58
Q

what is the most clinically relevant type of PRR (pattern recognition receptor)?

what’s the name of the one which recognises lipopolysaccharide?

A

toll-like receptors

TLR4

nb TLR5 recognises flagellin = molecule found on bacteria’s flaggelum

59
Q

if someone has a chest infection what can the colour of the sputum tell you about the pathogen?

A

green = likely bacterial (full of dead neutrophils)

clear/white = likely viral

nb neutrophils die once they’ve ingested a bacteria

60
Q

why don’t you get a high blood macrophage count in a bacterial infection?

A

because macrophages are only found in tissues

- their precursors (monocytes) can be found in blood though

61
Q

what is the difference between a phagocyte and a macrophage?

A

a phagocyte is an umbrella term for any cell which ingests another

types of phagocytes:

  • monocytes/macrophages
  • neutrophils
62
Q

IRAK4 and MyD88:

  • what process are they involved in?
  • if they are deficient what can’t be produced?
  • how does this present clinically?
A

They are involved in the molecular cascade that occurs once a pathogen is recognised
- this cascade leans to inflammatory cytokines being produced

  • inflammatory cytokines (eg CRP)
  • recurrent bacterial infections (esp strep + staph) (eg meningtitis, pneumonia, arthritis)
  • poor inflammatory response
  • susceptibility to infection decreases with age

nb this affects the INNATE immune response

“IRAK4 = IRAQ, 4 rhymes with war”

“MyD88 = my dates are often not successful”

63
Q

where is CRP produced and due to what?

A

macrophages release IL1 which then travels to liver which thn produces CRP

64
Q

what is the treatment for IRAK4 or MyD88 deficiency?

A

prophylactic antibiotics

IV immunoglobulin, if severe

65
Q

what is a granuloma?

A

a collection of macrophages around a pathogen/foreign body which they are unable to ingest

  • so just try to wall it off instead
66
Q

chronic granulomatous disease (CGD):

- pathogenesis?

A

genetic mutation in one of the proteins which makes up the NADPH complex

NADPH complex is found on wall of phagolysosomes (in phagocytes) and produces the hypochlorus acid (ie bleech) which destroys ingested pathogen

in CGD this protein doesn’t function therefore macrophages + neutrophils can’t successfully kill pathogens and so granulomas form around any pathogens

67
Q

chronic granulomatous disease (CGD):

  • inheritence pattern?
  • clinical presentation?
A

X-linked recessive (gene for protein is on X-chromosome)

nb this condition affects the INNATE immune system

recurrent abscesses
- lung
- liver
- bone
- skin 
- gut
with unusual organisms, eg:
- staphylococcus
- klebsiella
- serretia
- aspergillus
- fungi
nb blood neutrophils, Igs + lymphocytes will probably all be normal
68
Q

chronic granulomatous disease:

  • test for?
  • treatment? 2
A

basically looking for ability of healthy neutrophils to reduce chemicals (Reduction Is Gain of electrons), can measure this using:

  • flow cytometry
  • nitro blue tetrazolium dye reduction (healthy neutrophils should go purple)
  • haemopoeitic stem cell transplant (aka bone marrow transplant)
  • antibiotics
69
Q

what are the three activation methods of the complement cascade?

what is the end product of the complement cascade?

A

classical pathway
- antibody binding sets of cascade

alternative pathway
- spontaneous activation of C3 sets off cascade

mannose-binding lectin pathway
- mannose-binding lectin binds to mannose residues on bacteria setting off cascade

MAC (membrane attack complex)
- creates pores in membranes of bacteria

nb also releases cytokines and some parts opsonise pathogens

70
Q

complement deficiencies:

  • how do they tend to present?
  • what is the test to diagnose?
A

recurrent meningitis
- esp neisseria meningitidus

nb more than one bacterial meningitis is NOT normal!

can also present as:

  • recurrent infections
  • myositis (muslce inflammation)
  • SLE

cover sheep RBCs with anti-sheep antibodies then mix with patient’s serum

  • complement proteins in serum should lyse RBCs (via classical pathway)
  • if don’t then problem with complement proteins

nb this is a problem with INNATE immune system

71
Q

what are the 4 methods by which binding of antibodies to antigens inactivates antigens?

A

neutralisation

  • blocks viral binding site
  • coats bacteria so can’t do anything

agglutination of microbes

precipitation of dissolved antigens (eg toxins)

activation of complement system (via classical pathway)

nb top three lead to phagocytosis and last one leads directly to cell lysis

72
Q

what is the technical term for when someone has no/very low levels of antibodies?

A

agammaglobulinaemia

“a gamma globulin aemia”

73
Q

primary antibody deficiency:

  • name an example?
  • mechanism?
  • mode of inheritence?
A

X-linked agammaglobulinaemia

a defect in Bruton’s Tyrosine Kinase (BTK)
- needed for B cell signalling + B cell maturation

BTK is downstream of the B-cell receptor
- if B cells can’t ‘use’ their B cell receptors then they get killed off before they leave the bone marrow

X-linked (clue’s in the name…)

74
Q

X-linked agammaglobulinaemia:

  • results on blood tests?
  • normal clinical presentation?
  • diagnostic test?
A

bloods

  • no B cells
  • no IgG, IgA or IgM
  • normal T cells

recurrent bacterial infection with pyogenic organisms
- eg get bronchiectasis due to repeated pneumonia

confirm suspision with genetics

75
Q

name 4 other B cell defects

explain them briefly

A

IgA deficiency

  • about 1 in 200 caucasian people have it
  • but only a few will be symptomatic
  • those who are asymptomatic have often compensated by producing more IgG

X-linked hyper IgM syndrome
- cell machineary can’t switch from making IgM to IgG (IgM is less effective)

Transient hypogammaglobulinaemia of infancy
- typically present at about 6 months, after maternal antibodies have ‘run out’

Common variable immunodeficiency (CVID)

  • diagnosis of exclusion following negative tests for other causes of very low levels of Ig
  • nb can also see high levels of autoimmune conditions with this as well (immune system is just not well balanced)
76
Q

what is the treatment for severe B cell defects?

A

antibiotics

then iv IgG for life

77
Q

Secondary antibody deficiency:

  • common cause?
  • mechanism?
  • treatment? 2
A

long-term immuno-suppressive drugs

if you take these drugs for a long time, though they normally only target one part of the immune system, immune cells stimulate eachother and so taking out one part, over time, suppresses other parts

  • > very low levels of antibodies in blood
  • > recurrent infections

nb you will see this!! increasingly common!
- though tend to get it with people who have been on the drugs for >20 years or so!

  • antibiotics
  • IV IgG replacement
78
Q

how would you ask a patient about cosanguity?

A

are your mum + dad related in any other way, apart from marriage?

79
Q

why are prematurely born babies immunocompromised?

A

because most of the antibodies which cross the placenta do so in the 3rd trimester

80
Q

which type of antibody can cross the placenta?

A

IgG

81
Q

SCID:

  • what does it stand for?
  • caused by a defect in?
  • example causes?
A

severe combined immunodeficiency

any sort of mutation which leads to no T cells

  • defect/absence of critical T cell molecule (eg TCR, common gamma chain
  • loss of communication (eg MHCII deficiency)
  • metabolic (eg adenosine deaminase deficiency

nb genetic cause is irrelevant in terms of treatment, only relevence is in testing relatives

82
Q

SCID:

  • clinical presentation?
  • diagnosis?
  • treatment?
A

recurrent infection with opportunistic infections

  • no T cells + suggestive history
  • paediatric emergency
  • antibiotics, antivirals, antifungals
  • asepsis - ‘bubble babies’

haemopoietic stem cells transplant (aka bone marrow transplant) is only cure

nb this is more severe than B cell deficiencies as B cells also need T cells to function properly, even though they may still be present

83
Q

what is the definition of immunomodulation?

what are the three types of desired effect?

A

the act of manipulating the immune system using immunomodulatory drugs to achieve a desired immune response

desired effect may be:

  • immunopotentiation
  • immunosuppression
  • induction of immune tolerance
84
Q

what is the definition of biologics?

what are the three main classes of these?

A

medicinal products produced using molecular biology techniques including recombinant DNA technology

  • substances that are (nearly) identical to the body’s own key signalling proteins
  • monoclonal antibodies
  • fusion proteins
85
Q

what are the main three forms of immunopotentiation?

A
  • immunization (active or passive)
  • replacement therapies
  • immune stimulants
86
Q

passive immunization:

  • definition?
  • good things? 2
  • problems? 3
  • types? 2
A

transfer of specific, high-titre antibody from donor to recipient.

good things:

  • provides immediate protection
  • can be given to immunocompromised

problems:

  • protection is transient + not long-lasting
  • risk of transmission of viruses
  • serum sickness

types:

  • pooled specific human immunoglobulin
  • animal sera (antitoxins + antivenoms)
87
Q

examples of passive immunisation? 5

A
  • Hep B prophyaxis + treatment
  • botulism
  • VZV (in pregnancy)
  • diptheria
  • snake bites
88
Q

active immunisation:

  • definition?
  • types? 4
  • problems? 3
A

to stimulate the development of a protective immune response + immunological memory

  • weakened forms of pathogens
  • killed inactivated pathogens
  • purified materials (proteins, DNA)
  • adjuvants

problems:

  • allergy to any vaccine component
  • limited usefullness in immunocompromised
  • delay in achieving protection
89
Q

give 5 examples of replacement + immune stimulation therapies

A
  • pooled human immunoglobulin (IV or SC)
  • G-CSF/GM-CSF
  • a-interferon
  • B-interferon
  • y-interferon
90
Q

what is the mechanism of G-CSF/GM-CSF?

A

acts on bone marrow to increase production of mature neutrophils

91
Q

what are the indications for:

  • a-interferon? 1
  • B-interferon? 1
  • y-interferon? 2
A

a-interferon
- main use in Hep C (though now much better treatments for Hep C

B-interferon
- used in MS

y-interferon

  • can be useful in treatment of certain intracellular infections (atypical mycobacteria)
  • chronic granulomatous disease
92
Q

name 5 types of drugs which suppress the immune system

A
  • corticosteroids
  • DMARDs
  • biologic DMARDs
  • cytotoxic agents
  • anti-proliferative/activation agents
93
Q

what are the two main types of endogenous corticosteroids?

A

glucocorticoids
- eg cortisol

mineralcorticoids
- eg aldosterone

94
Q

what are the effects of corticosteroids which lead to immunosuppression? 6

A
  • decreased neutrophil margination
  • reduced production of inflammatory cytokines
  • inhibition phospholipase A2 (reduced arachidonic acid metabolites production)
  • lymphopenia
  • decreased T cell proliferation
  • reduced Ig production (long term effect)

nb action is not very targeted

95
Q

why will someone on steroids have a high neutrophil count?

A

as the steroids block the neutrophils being able to ‘stop, drop + roll’ into tissues (margination) it means there is a high amount in the blood

96
Q

side effects of long-term corticosteroid use? 5

A
  • altered carb + lipid metabolism (-> diabetes, hyperlipidaemia)
  • reduced protein synthesis (-> poor wound healing)
  • osteoporosis
  • glaucoma + cataracts
  • psychiatric complications (eg psychosis, mania, delirium, depression)
97
Q

what is an allograft?

A

the transplantation of cells, tissues, or organs, to a recipient from a genetically non-identical donor of the same species

basically most transplants

98
Q

indications of corticosteroids:

  • autoimmune diseases? 3
  • inflammatory diseases? 4
  • malignancies? 1
  • other? 1
A

autoimmune:

  • connective tissue diseases
  • vasculitis
  • RA

inflammatory:

  • crohn’s
  • sarcoidosis
  • giant cell arteritis
  • polymyalgia rheumatica

malignancies:
- lymphoma

other:
- allograft rejection

nb in the majority of situation, steroids are now used in conjunction with other immunosuppressants

99
Q

list 4 types of drugs which target (+ suppress) lymphocytes?

A

antimetabolites

  • azathioprine (AZA)
  • mycophenolate mofetil (MMF)

Calineurin inhibitors

  • ciclosporin A (CyA)
  • tacrolimus (FK506)

M-TOR inhibitors
- sirolimus

IL-2 receptor monoclonal antibodies

  • basiliximab
  • daclizumab
100
Q

side effects of calcineurin/mTOR? 8

A
  • hypertension
  • hirsutism (excessive body hair)
  • nephrotoxicity
  • hepatotoxicity
  • lymphomas (often seen post-transplant)
  • opportunistic infections
  • neurotoxicity
  • multiple drug interactions
101
Q

main clinical use of calcineurin and mTOR?

A

allograft rejection

occassionally used for autoimmune but less so

102
Q

antimetabolites:

  • mechanism of action?
  • side effects?
A

impair DNA production

cause significant cytopenias and affect any organs where cells are proliferating a lot
- eg gastritis, bone marrow suppression etc

103
Q

name 2 other antimetabolites + cytotoxic drugs

  • mechanism of action

side effects? 5

A

Methotrexate
- folate antagonist

cyclophosphamide
- cross link DNA

(both basically prevent cells replicating)

  • bone marrow suppression
  • gastric upset
  • hepatitis
  • susceptibility to infections
  • cystitis (just cyclophosphamide)
  • pneumonitis (just methotrexate)
104
Q

cytotoxics, clinical uses:

  • azathioprine (AZA) + mycophenolate mofetil (MMF)? 2
  • methotrexate? 5
  • cyclophosphamide? 2
A

azathioprine (AZA) + mycophenolate mofetil (MMF)

  • most autoimmune diseases (SLE, vasculitis, IBD etc)
  • allograft rejection

methotrexate

  • RA
  • psoriatic arthritis
  • polymyositis
  • vasculitis
  • graft vs host disease (follow transplant)

cyclophosphamide

  • vasculitis (v good for this)
  • SLE
105
Q

DMARDs:

  • stands for?
  • types? 5
A

disease-modifying anti-rheumatic drugs

  • anti-cytokines
  • anti-B cell therapies
  • anti-T cell activation
  • anti-adhesion molecules
  • complement inhibitors
106
Q

anti-cytokines:

  • sub-types? 3
  • uses?
A

anti-TNF

  • RA
  • other inflammatory conditions (crohn’s, psoriasis, ankylosing spondylitis

anti-IL-6 (tocilizumab)

  • RA
  • adult onset stills disease (AOSD)

anti-IL-1

  • adult onset stills disease (AOSD)
  • autoinflammatory syndromes
107
Q

why are you at increased risk of contracting TB when on anti-TNF drugs?

A

because TNF is essential fo forming granulomas

108
Q

Rituximab:

  • cell targeted?
  • mechanism of action?
  • uses? 3
A

B cells with CD20 on their surface

  • so only kills B cells in the blood (not cells in bone marrow or plasma cells)
  • so, when stop drugs, more B cells can replicate from bone marrow

nb mode of action is probably a bit more complex than this

  • lymphomas
  • leukaemias
  • transplant rejection
  • autoimmune condition
109
Q

what is adoptive immunotherapy?

when is it used? 4

A

bone marrow transplant and stem cell transplants (nb slightly different things)

  • immunodeficiencies (eg SCID)
  • lymphomas + leukaemias
  • inherited metabolic disorders (osteopetrosis)
  • autoimmune diseases
110
Q

give 3 examples of immunomodulators used to treat allergy?

A
  • allergen specific immunotherapy
  • anti-IgE monoclonal treatment
  • anti-IL-5 monoclonal treatment

nb topical/inhaled steroids are also used as are immunosuppressants occasionally

111
Q

allergen specific immunotherapy:

  • indications?
  • mechanism of action?
  • side effects?
A
  • allergic rhinoconjunctivitis not controlled on max medical therapy
  • anaphylaxis to insect venoms
  • switching of immune response from Th2 (allergic) to Th1 (non-allergic)
  • development of T reg cells and tolerance

basically expose person to allergen in slightly higher quantities

  • localised and systemic allergic reactions
112
Q

what does the suffix -mab indicate?

A

monoclonal antibody

113
Q

omalizumab:

  • what is it?
  • used to treat? 2
  • possible side effect?
A

monoclonal antibody against IgE

  • asthma
  • chronic urticaria (hives) + angioedema

may cause severe anaphylaxis

114
Q

Why are patients with burns immunocompromised?

what pathogens are they particularly at risk from?

A

skin is an essential barrier to infection
- this is broken in burns

  • staph aureus (esp is person is a nasal carrier)
  • pseudomonas
  • group A strep (though less these days)
115
Q

which organism are people with chronic granulomatous disease paricularly at risk from?

A

staph aureus

“get a lot of granulomas on skin”

nb this is a qualitative defect of neutrophils’ killing power

116
Q

neutropenia (quantitative defect):

  • causes? 3
  • organism especially at risk from?
A
  • chemo
  • bone marrow malignancy
  • aplastic anaemia

pseudomonas
- >50% of those with pseudomonal infections will die in 24hrs if not treated

nb also at higher risk of other bacterial/viral/fungal infections

117
Q

why are patients on chemo at high risk of e. coli infections?

A

chemo can cause ulcers in bowel (as attacks rapidly dividing cells, eg in gut)

so then e coli from gut can spread into the blood of the neutropenic patient

118
Q

what is a good antibiotic for covering gram negative?

A

gentamicin

119
Q

which organisms tend to cause central line infections in neutropenic patients?

A

coag neg staph

120
Q

If a patient known to have neutropenia gets a suspected bacterial infection, what should be the first and second line treatment?

A

1st line:
- antipseudomonal penicillin (norm pipericillin tazobactam)
+/- gentamicin (good gram -ve)

2nd line:
- carbapenem (eg merapenem)

if that doesn’t work then consider a fungal or viral cause

121
Q

apart from giving antibiotics what other treatment can be given to patients with neutropenia when they get an infection?

A

granulocyte stimulating factors (GCSF)

122
Q

opportunistic infections that tend to affect people with T-cell deficiencies:

  • bacterial? 2
  • viral? 3
  • fungal? 2
A

bacterial:
- listeria monocytogenes
- mycobacteria
“both of these are INTRAcellular, therefore B cells can’t get to them!”

viral:

  • HSV
  • CMV
  • VZV

fungal:

  • candida spp
  • cryptococcus spp
123
Q

what type of cryptococcal infection is seen in patients with T-cell deficiencies?

A

cryptococcal meningitis

esp in HIV patients

124
Q

where do most people contract listeria monocytogenes from?

A

food proucts with unpasteurised milk in
- eg brie, camembert, feta

nb this why pregnant women are told not to eat this as meningitis caused by listeria is a common cause of meningitis in neonates

125
Q

hypogammaglobulinaemias:

  • causes? 3
  • bacteria at high risk from?
  • parasite at high risk from?
  • treatment?
A
  • congenital (eg X-linked)
  • multiple myeloma
  • burns

usually encapsulated bacteria (eg streptococcus pneumoniae)

parasite (eg giardia lamblia)

treatment
= immunoglobulin

126
Q

what sort of organisms are people with a complement deficiency most at risk of?

why?

A

encapsulated

eg:

  • neisseria meningitidis
  • streptococcus pneumoniae
  • haemophilus influenzae type B

as complement cascade normally play a large role in neutralising these through direct attack with MAC and opsonisation

127
Q

what type of organism is neisseria meningitidis?

A

gram negative diplococci

nb is faculatively intracellular

128
Q

function of the spleen?

A

source of compliment + antibody producing B cells, removes opsonised bacteria from blood
- also breaks down old RBCs

129
Q

splenectomy:

  • reasons why?
  • organisms susbsequently at risk from? 2
  • treatment? 3
A
  • traumatic injury
  • surgical
  • functional (eg sickle cell disease)

encapsulated organisms
- eg N meningitidis, S pneumoniae, H influenzae type B

Malaria

  • vaccinations
  • prophylactic penicillin (to guard against s pneumoniae)
  • education (seek help if unwell, take antimalarials etc)
130
Q

what does the degree of immunosuppression given following organ transplant depend on? 2

A
  • how closely donor + recipient are matched

- organ transplanted

131
Q

what sort of infections could someone be especially at risk from during the process of organ transplantation:

  • surgery + hosp admission?
  • organ receipt?
  • initial 3 months post?
  • after 3 months?
A

surgery + hosp admission
- staph aureus wound infection

organ receipt
- low pathogenicity organisms in the organ eg toxoplasmosis

initial 3 months post
- opportunistic infection during initial immunosuppression eg CMV, aspergillus

after 3 months?
- later opportunistic infection eg VZV, listeria

132
Q

does blood group matching matter in organ donation

A

yes, poor outcomes following donation where blood group is not the same

133
Q

what is another name for MHC proteins

what types of cells are MHC class 1 proteins found on?

A

HLA

human leukocyte antigens

  • nb called leukocyte as initially only found on WBCs but now realise they are on every NUCLEATED cell

nb MHC class 2 are only found on antigen-presenting cells

134
Q

in terms of matching HLA/MHC proteins is the closest match needed for bone marrow transplants or solid organ transplants?

A

closest match needed for bone marrow transplants

nb lower immunosuppression needed for closer matches

135
Q

what is the inheritence pattern of MHC proteins?

A

Mendelian inheritance

nb MHC proteins are highly polymorphic

136
Q

what is anti-mitochondrial antibody a specific test for?

A

primary biliary sclerosis aka primary biliary cholangitis

137
Q

what is nitroblue tetrazolium test a diagnostic test for?

A

chronic granulomatous disease

138
Q

what is anti-CCP a specific test for?

A

rheumatoid arthritis

139
Q

what is the gold standard test for food allergy?

A

oral challenge test

140
Q

what is often one of the first signs of scleroderma?

A

raynauds phenomenon

nb can also be a part of SLE

nb primary raynauds, which is idiopathic, is more common

141
Q

what might an anaphylactoid reaction be brought about by?

A

anaesthetic induction agents

nb -oid means resembling!

an anaphylactoid reaction is a reaction which doesn’t involve IgE but mast cells are degranulated by some other mechanism

142
Q

what is the difference between mast cells and basophils?

A

basophils circulate in the blood and mast cells are stationary in the tissue

“a MAST is stationary”

nb basophils are NOT immature mast cells (like monocytes and macrophages), they have different lineages! - they perform the same role as eachother, one does it in the blood and the other in the tissues

* year 2 Clinical Pathology (11 decks)

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