core immunology Flashcards
what is the definition of a hypersensitivity reaction?
how many types are there?
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
what are the 4 different types of hypersensitivity reactions?
how do they differ based on:
- antibody produced?
- type of antigen directed against?
- response time?
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
what is erythroblastosis fetalis?
what type of hypersensitivity reaction is it?
haemolytic disease of the newborn (rhesus incompatibility)
type 2 (cytotoxic)
mothers anti-rh antibodies act against cell surface receptors on baby’s RBCs
what is goodpasture’s syndrome?
what is the mechanism?
what type of hypersensitivity reaction causes it?
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)
what is allergic contact dermatitis?
what type of hypersensitivity reaction causes it?
immune reaction to touching something
eg certain metals (like in cheap earrings) or washing powders or tuberculin skin test
type 4 (delayed type)
what type of hypersensitivity reaction is seen in penicillin allergy?
type 2 (cytotoxic)
what type of hypersensitivity reaction is seen in farmers lung?
type 3 (immune complex)
what is serum sickness?
what type of hypersensitivity reaction is seen in serum sickness?
systemic reaction to antigens in transfused serum
type 3 (immune complex)
what is another name for ezcema?
atopic dermatitis
what is another name for hayfever?
allergic rhinitis
what makes up the atopic triad?
- asthma
- ezcema (atopic dermatitis)
- hayfever (allergic rhinitis)
nb there is a genetic susceptibility factor but environement also plays a role
what is the hygiene hypothesis?
that stimulation by microbes is protective and helps modulate immune system
- basically if you’re too clean then more likely to become atopic etc
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?
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
what are the two different types of allergic rhinitis?
symtpoms?
give some examples of common triggers
treatment? 2
perennial or seasonal
blocked/runny nose often with eye symptoms
seasonal is basically pollen
- house mites
- animal danders
- antihistamines
- nasal steroids
what is the late phase response in a type 1 hypersensitivity reaction?
how is this relevant to the pathogenesis of allergic asthma?
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
what are anaphylaxoid reactions?
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.
what are the 5 most commonly used tests for allergy?
incl pros + cons
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
when is immunotherapy indicated in people with allergies and when is it not?
indications:
- life-threatening reactions to wasp + bee stings
- severe hayfever
- animal dander allergy
not helpful:
- multiple allergies
- food allergy
- allergic rashes (eg ezcema)
what is urticaria?
aka?
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
what is angioedema
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”
what is stevens-johnsons syndrome?
what is the more severe form of the disease?
what normally triggers it?
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
what is the difference between autoinflammation and autoimmunity?
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
variation/mutations in which proteins/genes increase susceptibility to autoimmune diseases?
MHC class 1 + 2
coded by HLA genes
which of these autoimmune conditions are ‘organ-specific’ and which are ‘systemic’:
- graves disease?
- MS?
- RA?
- SLE?
- type 1 diabetes?
organ specific:
- graves disease
- MS
- type 1 diabetes
systemic:
- RA
- SLE
mutation in which gene results in failure to develop regulatory T-cells -> severe immunity from birth?
FoxP3
nb this is X-linked recessive
apart from genetics, what other factors can affect likelihood of developing an autoimmune condition?
- increased age
- smoking
- female
what is citrullination of proteins?
what autoimmune condition can it result in?
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
what are the two main groups of autoimmune conditions?
organ-specific
systemic
nb common to have more than one organ specific disease
what is the most common cause of hypothyroidism in the developed world?
hashimotos thyroiditis
- destruction of thyrpoid follicles by auto-antibodies
nb most common cause in developing world is iodine deficiency
what is the name of the auto-antibody in graves disease?
anti-TSH-autoantibody
this mimics TSH, inappropriately stimulating the thyroid
myasthenia gravis:
- pathophysiology?
- symptoms?
autoantibodies attack and destroy ACh recptors on muscle fibres at neuromuscular junction
weakness (gets worse throughout day), especially of eye and facial muscles
what is vitiligo?
autoimmune condition where you get autoantibodies against melanocytes in skin -> white patches of skin
what is the mechanism of pernicious anaemia?
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
SLE:
- type of hypersensitivity reaction?
- most common symptoms? 3
- possible complications? 4
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
what type of autoantibody is found in SLE?
anti-nuclear antibodies (ANA)
why do you get the malar (butterfly) rash in SLE?
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
name 4 autoimmune connective tissue conditions (ie systemic)
- SLE
- scleroderma
- polymyostitis
- Sjogrens syndrome
what is the definition of:
- sensitivity?
- specificity?
incl formulas
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)
what are the definitions of:
- positive predictive value?
- negative predictive value?
incl formulas
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)
name 7 non-specific markers of systemic inflammation
and whether they go up or down in systemic inflammation
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)
what does ENA stand for?
what are they?
extractable nuclear antigens
basically the antigens which ANAs (anti-nuclear antigens) bind to
which test is highly sensitive for diagnosing SLE and which is highly specific?
which would you do first?
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
what is rhematoid factor (RF)?
what condition can it go up in?
antibody against the Fc portion of IgG
rhematoid arthritis (70% sens + spec) - nb can be seen in other stuff
pretty shit test
why is anti-CCP (ACPA) a more useful test than rhematoid factor? 2
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)
what is ANCA?
what group of conditions is it a diagnostic marker for?
- examples? 3
how do these conditions tend to present?
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
what antibodies can be detected in:
- primary biliary cholangitis?
- autoimmune hepatitis?
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
what is the defintion of immunodeficiency?
what’s the difference between primary and secondary immunodeficiency?
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
why does cystic fibrosis lead to immunodeficiency?
break down of ‘physical barriers’ to infection
normal method of expelling pathogens from lungs is comprmised
why does protein loss cause immunodeficiency?
give 3 examples of when immunodeficiency occurs secondary to protein loss
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
what types can result in immuno suppression?
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
are natural killer cells part of the innate or adaptive immune system?
what is their role?
innate
kill virally infected cells
what type of cell is myeloma a cancer of?
aka multiple myeloma
plasma cells (ie mature B cells)
what does DMARDS stand for?
name an example
disease modifying ant-rhematic drugs
eg methotrexate
what types of drugs suppress the immune system? 5
- steroids
- DMARDS (disease modifying anti-rheumatic drugs
- rituximab
- anti-convulsants
- myelosuppressive drugs
what is rituximab commonly indicated for? 2
- RA
- b-cell cancers
what is the first line drug for RA?
methotrexate
what are PRRs?
what do they recognise?
give an example
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)
what is the most clinically relevant type of PRR (pattern recognition receptor)?
what’s the name of the one which recognises lipopolysaccharide?
toll-like receptors
TLR4
nb TLR5 recognises flagellin = molecule found on bacteria’s flaggelum
if someone has a chest infection what can the colour of the sputum tell you about the pathogen?
green = likely bacterial (full of dead neutrophils)
clear/white = likely viral
nb neutrophils die once they’ve ingested a bacteria
why don’t you get a high blood macrophage count in a bacterial infection?
because macrophages are only found in tissues
- their precursors (monocytes) can be found in blood though
what is the difference between a phagocyte and a macrophage?
a phagocyte is an umbrella term for any cell which ingests another
types of phagocytes:
- monocytes/macrophages
- neutrophils
IRAK4 and MyD88:
- what process are they involved in?
- if they are deficient what can’t be produced?
- how does this present clinically?
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”
where is CRP produced and due to what?
macrophages release IL1 which then travels to liver which thn produces CRP
what is the treatment for IRAK4 or MyD88 deficiency?
prophylactic antibiotics
IV immunoglobulin, if severe
what is a granuloma?
a collection of macrophages around a pathogen/foreign body which they are unable to ingest
- so just try to wall it off instead
chronic granulomatous disease (CGD):
- pathogenesis?
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
chronic granulomatous disease (CGD):
- inheritence pattern?
- clinical presentation?
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
chronic granulomatous disease:
- test for?
- treatment? 2
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
what are the three activation methods of the complement cascade?
what is the end product of the complement cascade?
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
complement deficiencies:
- how do they tend to present?
- what is the test to diagnose?
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
what are the 4 methods by which binding of antibodies to antigens inactivates antigens?
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
what is the technical term for when someone has no/very low levels of antibodies?
agammaglobulinaemia
“a gamma globulin aemia”
primary antibody deficiency:
- name an example?
- mechanism?
- mode of inheritence?
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…)
X-linked agammaglobulinaemia:
- results on blood tests?
- normal clinical presentation?
- diagnostic test?
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
name 4 other B cell defects
explain them briefly
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)
what is the treatment for severe B cell defects?
antibiotics
then iv IgG for life
Secondary antibody deficiency:
- common cause?
- mechanism?
- treatment? 2
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
how would you ask a patient about cosanguity?
are your mum + dad related in any other way, apart from marriage?
why are prematurely born babies immunocompromised?
because most of the antibodies which cross the placenta do so in the 3rd trimester
which type of antibody can cross the placenta?
IgG
SCID:
- what does it stand for?
- caused by a defect in?
- example causes?
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
SCID:
- clinical presentation?
- diagnosis?
- treatment?
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
what is the definition of immunomodulation?
what are the three types of desired effect?
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
what is the definition of biologics?
what are the three main classes of these?
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
what are the main three forms of immunopotentiation?
- immunization (active or passive)
- replacement therapies
- immune stimulants
passive immunization:
- definition?
- good things? 2
- problems? 3
- types? 2
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)
examples of passive immunisation? 5
- Hep B prophyaxis + treatment
- botulism
- VZV (in pregnancy)
- diptheria
- snake bites
active immunisation:
- definition?
- types? 4
- problems? 3
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
give 5 examples of replacement + immune stimulation therapies
- pooled human immunoglobulin (IV or SC)
- G-CSF/GM-CSF
- a-interferon
- B-interferon
- y-interferon
what is the mechanism of G-CSF/GM-CSF?
acts on bone marrow to increase production of mature neutrophils
what are the indications for:
- a-interferon? 1
- B-interferon? 1
- y-interferon? 2
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
name 5 types of drugs which suppress the immune system
- corticosteroids
- DMARDs
- biologic DMARDs
- cytotoxic agents
- anti-proliferative/activation agents
what are the two main types of endogenous corticosteroids?
glucocorticoids
- eg cortisol
mineralcorticoids
- eg aldosterone
what are the effects of corticosteroids which lead to immunosuppression? 6
- 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
why will someone on steroids have a high neutrophil count?
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
side effects of long-term corticosteroid use? 5
- altered carb + lipid metabolism (-> diabetes, hyperlipidaemia)
- reduced protein synthesis (-> poor wound healing)
- osteoporosis
- glaucoma + cataracts
- psychiatric complications (eg psychosis, mania, delirium, depression)
what is an allograft?
the transplantation of cells, tissues, or organs, to a recipient from a genetically non-identical donor of the same species
basically most transplants
indications of corticosteroids:
- autoimmune diseases? 3
- inflammatory diseases? 4
- malignancies? 1
- other? 1
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
list 4 types of drugs which target (+ suppress) lymphocytes?
antimetabolites
- azathioprine (AZA)
- mycophenolate mofetil (MMF)
Calineurin inhibitors
- ciclosporin A (CyA)
- tacrolimus (FK506)
M-TOR inhibitors
- sirolimus
IL-2 receptor monoclonal antibodies
- basiliximab
- daclizumab
side effects of calcineurin/mTOR? 8
- hypertension
- hirsutism (excessive body hair)
- nephrotoxicity
- hepatotoxicity
- lymphomas (often seen post-transplant)
- opportunistic infections
- neurotoxicity
- multiple drug interactions
main clinical use of calcineurin and mTOR?
allograft rejection
occassionally used for autoimmune but less so
antimetabolites:
- mechanism of action?
- side effects?
impair DNA production
cause significant cytopenias and affect any organs where cells are proliferating a lot
- eg gastritis, bone marrow suppression etc
name 2 other antimetabolites + cytotoxic drugs
- mechanism of action
side effects? 5
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)
cytotoxics, clinical uses:
- azathioprine (AZA) + mycophenolate mofetil (MMF)? 2
- methotrexate? 5
- cyclophosphamide? 2
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
DMARDs:
- stands for?
- types? 5
disease-modifying anti-rheumatic drugs
- anti-cytokines
- anti-B cell therapies
- anti-T cell activation
- anti-adhesion molecules
- complement inhibitors
anti-cytokines:
- sub-types? 3
- uses?
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
why are you at increased risk of contracting TB when on anti-TNF drugs?
because TNF is essential fo forming granulomas
Rituximab:
- cell targeted?
- mechanism of action?
- uses? 3
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
what is adoptive immunotherapy?
when is it used? 4
bone marrow transplant and stem cell transplants (nb slightly different things)
- immunodeficiencies (eg SCID)
- lymphomas + leukaemias
- inherited metabolic disorders (osteopetrosis)
- autoimmune diseases
give 3 examples of immunomodulators used to treat allergy?
- allergen specific immunotherapy
- anti-IgE monoclonal treatment
- anti-IL-5 monoclonal treatment
nb topical/inhaled steroids are also used as are immunosuppressants occasionally
allergen specific immunotherapy:
- indications?
- mechanism of action?
- side effects?
- 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
what does the suffix -mab indicate?
monoclonal antibody
omalizumab:
- what is it?
- used to treat? 2
- possible side effect?
monoclonal antibody against IgE
- asthma
- chronic urticaria (hives) + angioedema
may cause severe anaphylaxis
Why are patients with burns immunocompromised?
what pathogens are they particularly at risk from?
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)
which organism are people with chronic granulomatous disease paricularly at risk from?
staph aureus
“get a lot of granulomas on skin”
nb this is a qualitative defect of neutrophils’ killing power
neutropenia (quantitative defect):
- causes? 3
- organism especially at risk from?
- 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
why are patients on chemo at high risk of e. coli infections?
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
what is a good antibiotic for covering gram negative?
gentamicin
which organisms tend to cause central line infections in neutropenic patients?
coag neg staph
If a patient known to have neutropenia gets a suspected bacterial infection, what should be the first and second line treatment?
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
apart from giving antibiotics what other treatment can be given to patients with neutropenia when they get an infection?
granulocyte stimulating factors (GCSF)
opportunistic infections that tend to affect people with T-cell deficiencies:
- bacterial? 2
- viral? 3
- fungal? 2
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
what type of cryptococcal infection is seen in patients with T-cell deficiencies?
cryptococcal meningitis
esp in HIV patients
where do most people contract listeria monocytogenes from?
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
hypogammaglobulinaemias:
- causes? 3
- bacteria at high risk from?
- parasite at high risk from?
- treatment?
- congenital (eg X-linked)
- multiple myeloma
- burns
usually encapsulated bacteria (eg streptococcus pneumoniae)
parasite (eg giardia lamblia)
treatment
= immunoglobulin
what sort of organisms are people with a complement deficiency most at risk of?
why?
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
what type of organism is neisseria meningitidis?
gram negative diplococci
nb is faculatively intracellular
function of the spleen?
source of compliment + antibody producing B cells, removes opsonised bacteria from blood
- also breaks down old RBCs
splenectomy:
- reasons why?
- organisms susbsequently at risk from? 2
- treatment? 3
- 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)
what does the degree of immunosuppression given following organ transplant depend on? 2
- how closely donor + recipient are matched
- organ transplanted
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?
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
does blood group matching matter in organ donation
yes, poor outcomes following donation where blood group is not the same
what is another name for MHC proteins
what types of cells are MHC class 1 proteins found on?
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
in terms of matching HLA/MHC proteins is the closest match needed for bone marrow transplants or solid organ transplants?
closest match needed for bone marrow transplants
nb lower immunosuppression needed for closer matches
what is the inheritence pattern of MHC proteins?
Mendelian inheritance
nb MHC proteins are highly polymorphic
what is anti-mitochondrial antibody a specific test for?
primary biliary sclerosis aka primary biliary cholangitis
what is nitroblue tetrazolium test a diagnostic test for?
chronic granulomatous disease
what is anti-CCP a specific test for?
rheumatoid arthritis
what is the gold standard test for food allergy?
oral challenge test
what is often one of the first signs of scleroderma?
raynauds phenomenon
nb can also be a part of SLE
nb primary raynauds, which is idiopathic, is more common
what might an anaphylactoid reaction be brought about by?
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
what is the difference between mast cells and basophils?
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
