Immunology Flashcards
What type of virus is HIV
RNA retrovirus single stranded
Belongs to lentivirus family
Which cells do HIV infect
CD4+
- t helper cells
- macrophages
Pathogenesis of HIV
Attaches to CD4 via GP120 but uses co receptor either CCR5 or CXCR4
Replicates via a DNA intermediate
Integrates into host genome
HIV DNA transcribed to viral mRNA
Viral RNA translated to viral proteins
Packaging and release of mature virus
What can predict HIV disease progression
Initial viral burden after primary infection settles
What CD4 count defines AIDS
Less than 200
Response when recognise PAMP
Th1 and h17
How does immune system respond to toxins and helminthes
Detect a loss of function then get Th2 response
What are inborn errors of immunity
Heterogenous group of genetic disorders resulting in immune dysfunction and ill health
485 single defects already identified
What is the most common form of inborn errors of immunity
Antibody deficiency or B cell function
What gene defects result in suceptibility to mycobacterial and BCG infection
Gene defects in generation of IL-12 adn response to IFN-gamma
Leads to reduced production of TNF to activate oxidative pathways
What gives rise in critical influenza pneumonia susceptibility
Defects in TLR3 which is sensor of influenza A
What is in mucous from membranes which protects against microorganisms
IgA prevents bacteria and viruses from binding to epithelial cells
Lysozyme which breaks down cell walls
Lactoferrin which starves bacteria of iron
Which cells form part of innate immune response
Polymorphonuclear cells
Dendritic cells
Monocytes and macrophages
NK cells
Where are granulocytes produced
Bone marrow then migrate to site of injury
Other than cells what is included in the innate immune system
Complement
Acute phase proteins
Cytokins and chemokins
What are examples of pattern recognition receptors
TLR
RIG-1
What are monocytes and macrophages
Monocytes are produced by bone marrow and migrate to tissues where differentiate into macrophages
Function of macrophages
Phagocytosis
Present processed antigens to T-cells
What are mannose receptors
C-type lectin receptor found innate cells which detects pattern
What type of receptors are those detecting PAMPs
Fc receptors
What is opsonisation
Enables phagocytosis by marking the pathogen and making a bridge between it and phagocyte receptor
What are examples opsonins
Antibodies
Complement components
Acute phase proteins
What are 2 types of microbial killing
Non-oxidative- release bacteriocidal enzymes into phagolyosome
Oxidative- produce hydrochlorous acid
What forms pus
Phagocytosis depletes neutrophil glycogen store which results in cell death
As cell dies enzymes are released causing liquefaction of adjacent tissue
What is function of dendritic cells prior to phagocytosis
Found in peripheral tissue
Express Fc receptors for Ig to detect immune complexes
What mediates migration of dendritic cells to lymph node
CCR7
What are the components of the adaptive immune system
Humoral immunity
Cellular immunity
Chemokines and cytokines
What makes up humoral immunity versus cellular
Humoral- B lymphocytes and antibodies
Cellular- T lymphocytes
What are the primary lymphoid organs
Organs where lymphocytes develop
Bone marrow- both T and B haemopatoetic stem cells and where B cells mature
Thymus- where T cells mature
What are the secondary lymphoid organs
Sites where naive lymphocytes and microorganisms interact
Spleen
Lymph nodes
MALT
What do all T cells express
CD3+
When is the thymus most active
Foetal and neonatal stages of life
Involutes after pregnancy
HLA class 1 proteins
A, B, C
HLA class 2 proteins
THINK QPR:
DR, DQ, DP
Most important HLA matches
THINK DR. British Airways (BA)
In order
DR
B
A
When matching donors you want to minimise HLA differences
What does
- isograft
- allograft
- xenograft
- split graft mean
Iso- from a twin
Allo- from same species
Xeno- from different species
Split- shared by 2 recipients (liver)
Complications of Stem Cell Transplant (SCT)
Graft failure
Infections
Graft vs Host Disease (GVHD)
Relapse
What is Graft Vs Host Disease (GVHD)
Where donor cells recognise the patient as foreign
Acute GVHD presentation
Rash which can blister
GI- D&V with bloody diarrhoea
Liver- jaundice
Days to weeks
How is acute GVHD prevented
Methotrexate
Corticosteroids
Cyclosporin
Main prognostic factor for acute GVHD
Previous acute GVHD
What is pathology behind allergic reaction triggering
Normal epithelial function affected- breaking of epithelial barrier
Which route of transmission promtoes IgE sensitisation
Skin
Resp tract
If its oral it promotes IgG immune tolerance
What causes rapid onset symptoms in allergic reactions
Cross linking of IgE on the surface of mast cells and basophils
- release of histamine from granules
- release and synthesis of leukotrienes and prostaglandins
- pro-inflam cytokines which recruits inflam cells
- increases lymphatic flow to regional lymph nodes
- contraction of muscles in lungs and activation of sneezes and itches
What results in delayed symptoms of allergic reactions
Eosinophlic related tissue damage and cytokine release from Th2 T-cells (IL4, IL5, IL13)
What is most appropriate initial investigation for suspected peanut allergy giving urticaria and angioedema
Skin prick test
What allergic diseases will present in infancy and childhood
Dermatitis
Food allergy
Presentation of IgE allergic responses
Within 3-4 hours after exposure
Skin-angioedema, urticaria
Resp tract- cough, wheeze, nasal congestion
GI- D&V
Blood vessels- fainting, sense of impending doom
What is refractory anaphylaxis
No improvement in resp and cardio symptoms in response to 2 doses of IM adrenaline
What is the best lab test to diagnose anaphylaxis
Mast cell tryptase taken 30mins-2 hours after the initial symptoms start
What demotes a positive skin prick test
Wheal 3mm greater than negative control
What do sensitisation blood tests do
Detect IgE to whole allergen or a component of the allergen
What is function of compnoent resolved diagnostics
Test for IgE against the specific protein within a whole allergen
In essence identifies the exact protein to which someone is allergic to
How are allergic diseases diagnosed
Is made by a clinican based on epidemiology, history, exam, skin prick test (SPT) etc NOT a blood sensitisation test
These are necessary but not sufficient
If have a raised mast cell tryptase which fails to return to baseline afer anaphylaxis what could be causes
Systemic mastocytosis
Hereditary alpha tryptassaemia
What is gold standard for diagnosing food and drug allergies
Double blind oral food challenge tests
Anaphylaxis guidelines
ABCDE
Call for HELP
Remove trigger
Lie patient flat
IM adrenaline in anterolateral aspect of thigh
Establish airway and give oxygen
If no response
-IM adrenaline
- fluid bolus
Difference between food allergy and food intolerance
Allergy- adverse health effect arising from a specific immune response
Food intolerance- non-immune reactions which include pharmacological, metabolic
Examples of food intolerances
Food poisoning
Enzyme deficiencies- lactase
Pharmacological- caffeine, tyramine
Allergy mechanism in atopic dermatitis
IgE
Allergy mechanism in contact dermatitis
T cell mediated
What can differentiate between IgE sensitisation and IgE mediated allergy
Component resolved diagnostics
What can give delayed food induced anaphylaxis
Occur 3-6 hours after eating red meat
IgE antibody to alpha-1-3-galactose
What is the mechanism of oral allergy syndrome
When have hayfever, get cross reaction to some homologous proteins in apples, pears, carrots and nuts but not cooked
Presentation of oral allergy syndrome
Swelling and itch of lips and mouth
What does a positive blood sensitisation/SPT suggest
Sensitisation not allergy!
Most commmon cause of secondary immunodeficiency worldwide
Malnutrition
Causes of secondary immunodeficiency
Malnutrition
Measles- get immune defects lasting months to years
TB
HIV
COvid
Haem cancers
Drugs
Drugs which cause immunodeficiency
Steroids
Cytotoxic agents- methotrexate, mycophenolate, cyclophosophamide, azathioprine
Calcineurin inhibitors- cyclosporine, tacrolimus
Anti-epileptics
DMARD
JAK inhibitors
Biologics
What is goods syndrome
Combined T and B cell defect with thymoma and antibody deficiency
What infections are those with Goods syndrome susceptible to
CMV
PJP
Mucocutaneous candida
Natural history of HIV
Acute phase where can have flu like illness
Asymptomatic but progressive
AIDS
Difference in transmission of HIV across disease course
Related to viral load in plasma
High in acute and aids but drops in asymptomatic
What is acute immune response to HIV
Induction of HIV-1 antibodies
CD8 T cell activation
How is HIV diagnosed if under 18 months
HIV RNA or DNA tests
What tests are done which can determine HIV treatment
Test for HLAB5701 to avoid prescribing abacavir as severe risk of SJS
Tropism test for CCR5 to determine if CCR5 antagonist therapy would work
What is first line for HIV in the UK
2 NRTI and 1 NNRTI
OR
2NRTI and INI
Mainly will change treatment due to drug toxicity rather than response
When likely to see PJP, toxoplasma and mycobacterium avium complex in HIV
PJP- CD4 less than 200
Toxoplasma- 100
MAC- 75
What is chronic benign neutropenia
Get a mild/moderate neutropenia common in african and middle eastern groups
Asymptomatic with no further investigation required
What is familial neutropenia
Adult onset severe neutropenia
Specific organ autoimmune disease
No increased infection risk
Which conditions give a severe congenital neutropenia
Kostmann syndrome
Cyclic neutropenia
What is genetic defect in cyclic neutropenia
Autosomal dominant- Neutrophil elastase
What is genetic defect of Kostmann syndrome
Autosomal recessive- HCLS-1 associated protein X-1 which prevents maturation of neutrophils
How do severe congenital neutropenias present
Present in first 3 months
Susceptible to oral, cutaneous and epithelial s. aureus infections, g-enteric bacteria and fungal infections
How are severe congenital neutropenias treated
G-CSF support
Stem cell transplantation
Pathophysiology of neutrophil leukocyte adhesion deficiency
Deficiency in CD18 which is used to remove neutrophils from circulation
What is result of luekocyte adhesion deficiency
delayed separation of umbilical cord
very high neutrophil counts in blood (20-100 x106/L)
Absence of pus formation
Pathophysiology of chronic granulomatous disease
Deficiency in NADPH oxidase which used to generate free radicals as such fail to kill certain bacteria
Get excessive inflammation from persistent recruitment of neutrophils and phagocytes causing granuloma formation
Presentation of chronic granulomatous disease
Granulomas
Hepatomegaly and lymphadenopathy
THINK: PLACESS where you don’t want granulomas
Recurrent infections from PLACESS often affecting skin
Pseudomonas
Listeria
Aspergillosis
Candida
Ecoli
S aureus
Serratia
Treatment of chronic granulomatous disease
Interferon gamma
Test for chronic granulomatous disease
Dihydrorhodamine (DHR) flow cytometry test. DHR is oxidized to rhodamine, which is strongly fluorescent, following interaction with hydrogen peroxide.
What are the 3 triggers for complement pathway
Immune complexes (antigen-antibody)
Bacterial endotoxin
Mannose binding lectin
How does classical complement system work
Immune complexes trigger C1 which begins cascade involving C1, C2 and C4. Ultimately activate C3
Pathophysiology of classical component deficiencies
These include deficiencies in C1q,2 and 4
This means that is failure to activate the complement system causing increased susceptibility to infections
What is link of classical complement deficiencies and SLE
If have deficiency of classical complement pathway then is accumulation of immune complexes which can deposit in the joints, skin and kidneys
Presentation of classical complement deficiencies
Susceptibility to infections namely Hib and strep pneumoniae
Severe skin disease
Co-existing SLE
Pathophysiology of alternative pathway deficiencies
Lack of factor B, D and P (properdin) mean less activation of terminal pathway from alternative pathway
Susceptibility of alternative pathway deficiencies
Encapsulated bacteria
Presentation of C3 deficiency
Increased suscpetibility to encapsulated bacteria infection
What are the types of C3 deficiency
Primary from genetic deficiency
Secondary- get autoantibodies against C3
What is associated with C3 deficiency
Membranoproliferative glomerulonephritis
What is significance of mannose binding lectin deficiency
Very common however does not affect susceptibility to infection unless coinciding factor causing immunodeficiency like chemo or premature infant
Pathophysiology of Severe Combined ImmunoDeficiency (SCID)
Encompassing term for various mechanistic pathways however all relate to defects in the generation of lymphoid precursors in the bone marrow
Presentation of SCID
Present by 3 months of age
Opportunistic infections
Live vaccine infected (BcG and rotavirus)
Persistent candida infection
Failure to thrive
Peristent diarrhoea
Which infections are SCID normally susceptible
THINK: Opportunistic infections like in Goods Syndrome
Opportunistic- candida, PJP, CMV
Viral chest and GI infections- adenovirus, parainfluenza
RARELY BACTERIAL
Treatment for SCID
Stem cell transplant
Pathophysiology of DiGeorge syndrome
22q11 deletion
Congenital features of DiGeorge syndrome
CATCH
Cardiac abnormalities (TOF)
Atresia (oesophageal)
Thymic aplasia
Craniofacial defects (cleft palate)
Hypocalcaemia from hypoparathyroidism
Immune problems of DiGeorge syndrome
Thymic hypoplasia leading to reduced T cell counts
Increased incidence of autoimmune conditions and sino-pulmonary infections
How is IgA deficiency diagnosed
Serum IgA under 0.07g/L with normal Ig and B cell counts
Presentation of IgA deficiency
Most asymptomatic
Increased prevalence of allergic disorders and autoimmune diseases
Recurrent sino-pulmonary and GI infections
What is pathogenesis of common variable immune deficiency
Heterogenous conditions were is defect in B cell develpoment, maturation or function and fail to produce protective antibodies
Presentation of CVID
PRESENTS IN ADULTS
Recurrent sino-pulmonary infections with encapsulated bacteria
These can be so bad get bronchiectasis
Otitis media
Hib conjunctivitis
Enteric infections
Skin cellulitis, abscess HSV and VZV
Viral resp infections
Granulomatous infiltration
Autoimmune conditions common
Increased risk of B cell NHL and gastric cancers
Hallmarks of CVID
Increased infection susceptibility
Autoimmune conditions more prevalent
Granulomatous infiltration
Lymphoproliferative conditions common
Management of CVID
Normal human IVIG
Pathogenesis of X-linked agammaglobulinaemia
Mutation in bruton tyrosine kinase which is key in maturation of B cells
Presentation of x-linked agammaglobulinaemia
Presentation under 5
Recurrent bacterial infection of ENT, resp and GI
Encapsulated bacteria
Management of x linked agammaglobulinaemia
Normal human IVIg
Blood findings of x linked agammaglobulinaemia
Neutropenia
Reduction or absence of b cells
Absent of all Ig
MOst common cause of death in X linked agammaglobulinaemia
Acute or chronic lung disease
MOst common antibody deficiency
Selective IgA deficiency
What is immunopathology
Damage to the host caused by immune system
Difference between auto-inflammatory and auto-immune
Auto-inflammatory get activation of immate immune cells such as macrophages and neutrophils resulting in tissue damage
Auto-immune get activation of T and B cell responses in primary and secondary lymphoid organs
Genetic defect in familial mediterranean fever
Autosomal recessive loss of function mutation in MEFV which encodes pyrin-marenostrin
Leads to uncontrolled IL-1 production
Investigations for familial mediterranean fever
High CRP
High serum amyloid A
Send off to genetics lab for confirmation
Presentation of familial mediterranean fever
Periodic fevers lasting 48-96 hours associated with:
Abdominal pain due to peritonitis
Chest pain due to pleurisy and pericarditis
Arthritis
Rash
Treatment of familial mediterranean fever
Colchicine
IL-1 blocker
What does IPEX stand for
Immune dysregulation polyendocrinopathy enteropathy X-linked syndrome
Pathophysiology of IPEX
Mutations in Foxp3 which is needed for the development of CD25+ T reg cells. Menas is failure to negatively regulate T cell responses
How does IPEX present
Increased prevalence of autoimmune diseases
- DM
- Hypothyrodism
- enteropathy
- eczema
(Diarrhoea, DM, dermatitis)
What does ALPS stand for
Auto-immune lymphoproliferative syndrome
Pathophysiology of ALPS
Mutation in FAS pathway which is involved in apoptosis of lymphocytes
Presentations of ALPS
Very high lymphocytes
Splenomegaly and enlarged lymph nodes
Auto-immune diseases (typically cytopenias)
Lymphoma
Inheritance of ALPS
Autosomal dominant
What mutations is associated with Crohns disease
IBD1 gene of chr 16- NOD2 (most common)
CARD15
What are mixed pattern diseases
Involve mutations in both the innate and adaptive immune system
Main genetic allele associated with ank spond
HLA B27
Presentation of ank spond
Back pain worse in morning with stiffnesss
Large joint arthritis
Enthesitis- pain where ligaments/tendons insert
Management of ank spond
NSAIDS
Anti-TNF alpha
Anti- IL17
What are the types of immunological diseases
Monogenic auto-inflammatory
Polygenic auto-inflammatory
Mixed pattern diseases
Polygenic auto-immune diseases
Monogenic auto-immune diseases
What is the genetic association of goodpasture syndrome
HLA-DR15
What are 2 examples of genetic polymorphisms seen in polygenic autoimmune disease
Protein tyrosine phosphatase non-receptor 22
Cytotoxic t lymphocyte associated protein 4
What is Protein tyrosine phosphatase non-receptor 22 polymorphism associated with
SLE
RA
T1DM
What is Cytotoxic t lymphocyte associated protein 4 polymorphism associated with
Hashimotos
SLE
T1DM
What are the 4 hypersensitivity reactions
Type 1- IgE
Type 2- antibody reacts with cellular antigen
Type 3- antibody reacts with soluble antigen to form immune complex
Type 4- T-cell mediated
What is autoantigen in goodpastures
Noncollagenous domain of basement membrane collagen type IV
Anti glomerular basement membrane
What is the autoantigen in pemphigus vulgaris
Epidermal cadherin
Anti-desmoglein
Antibody in hashimotos
Anti thyroid peroxidase antibodies
Can get antithyroglobulin
NOTE IS VERY COMMON FOR PEOPLE IN GENERAL POPULATION TO HAVE
What type of immunological reaction is T1DM
Type IV
Get T cell infiltration of the pancreas
What are some of the antibodies in T1DM
Anti-islet cell antibodies
Anti-glutamic acid decarboxylase antibodies
Often predate the development of DM and do not play a role in diagnosis
Antibodies in pernicious anaemia
Anti gastric parietal cells
Anti intrinsic factor- most specific
Presentation of B12 deficiency
Macrocytic anaemia
Degeneration of spinal chord subacute
Peripheral neuropathy
OPtic neuropathy
Antibodies in coeliac
Anti tissue transglutaminase
Anti endomysial
Which antibody can be seen in IBD
P-ANCA
MORE UC THAN CROHNS
What are antibodies in primary biliary cholangitis
Anti mitochondrial antibody
ANA
Antibodies in Myasthenia gravis
Anti acetylcholine receptor
Anti-striational (if with myositis)
What antibody is seen in myasthenia gravis if concurrent myositis
Anti-striational
What antibody is seen in neuromyelitis optica spectrum
Anti aquaporin 4
What antibody is seen in optic neuritis
Anti myelin oligodendrocyte glycoprotein
What antibodies can be seen in encephalitis
Anti NMDA receptor
What antibodies can be seen if seizures
Anti GABA receptor
Normally underlying malignancy too
What are genetic predispositions to RA
HLA DR4
Peptidyl arginine deaminase as increases citrullination of proteins
Environmental predispositions to RA
Smoking
Gum infection with porphyromonas gingivalis as expresses peptidyl arginine deaminase which promotes citrullination
Which antibodies are present in RA
Anti cyclic citrullinated proteins- most sensitive
Rheumatoid factor- antibody against Fc portion of IgG
What are the antibodies present in SLE
- ANA
- Anti DsDNA
- anti Ro
-anti La - anti Sm
- anti U1RNP
What are the investigations done if psoitive ANA
Will do dsDNA
And extractable nuclear antigens
- anti Ro
-anti La
- anti Sm
- anti U1RNP
- scl70
- centromere
What are Ro, La, Sm and U1RNP all
Ribonucleoproteins- extractable nuclear antigens
What are the complement profiles of C3 and C4 in SLE
C4 reduced in active disease and severe disease
C3 only reduced in severe disease
What is seen in antiphospholipid syndrome
Recurrent thromosis
Recurrent miscarriage
Can get valvular disease
What antibodies test for in antiphospholipid syndrome
Anti-cardiolipin
Lupus anticoagulant
Anti beta 2 glycoprotein 1
Presentation of sjogrens
Dry eyes
Dry mouth
Arthralgia
Fatigue
Lip biopsy finding in sjogrens
B cell and T cell infiltration
CD4+ most prominent
What antibodies seen in sjogrens
Anti-Ro
Anti La
Speckled staining
What is risk of sjogrens or SLE with anti Ro antibodies during pregnancy
Can cross react with foetal cardiac tissue causing neonatal heart block
What antibody seen in polymyositis and dermatomyositis
Anti Jo-1 (anti t-RNA synthetase)
Speckled pattern
What are second line immune deficiencies tests
Measure concentration of vaccine antibodies
If antibodies are low then can offer vaccination wit pneumovax II and tetanus and measure response
This is a criteria for IgG in replacement some conditions
Which vaccines are used to investigate immune deficiency
Pneumovax II
Tetanus
How is HIV diagnosed (options available)
4th gen ELISA then to confirm use western blot
Rapid point of care tests available which provide answer in 20 minutes however less sensitive than 4th gen test
If in acute HIV have suspicion of HIV but serological tests negative what use
HIV RNA tests
How is HIV monitored
Viral load
CD4 count
What is viral load set point
3-6 months after initial infection a steady state HIV-1 viral concentration is observed in blood
Used to predict long term outcomes
When is ART offered to prevent infection
Prevent transmission to seronegative partners
Pregnancy
Following inadvertant exposure follwoing occupational exposure or high risk sex
What are the phases of T cell mediated transplant rejection
Phase 1- presentation of donor HLA by an APC
Phase 2- T cell activation and inflammatory cell recruitment
Phase 3- effector phase with organ damage
What are phases of antibody mediated rejection
Phase 1- B cells recognise foreign HLA
Phase 2- proliferation and maturation of B cells with anti HLA antibodies
Phase 3- effector phase where antibodies bind to graft endothelium
Graft biopsy of t cell mediated rejection
Inerstitial inflammation and tubulitis
Arteritis
Graft biopsy of antibody mediated rejection
Antibody deposition
Complement deposition
All in endothelium
Which antibodies can exist in antibody mediated rejection
Anti-HLA
Anti-A or anti-B
Where can anti-HLA antibodies seen in organ rejection arise from
Anti-HLA are not naturally occuring
- pre formed- prev transplant, pregnancy, transfusion
- post formed- arise from transplant
How can rejection be prevented by tissue typing
ABO and HLA tissue-matching
Screen for anti-HLA antibodies
What induction agents are given for baseline suppression in prevention of graft rejection
Anti CD52- alemtuzumab
OKT3- muronomab-CD3
Anti-CD25 (IL2-R)- daclizumab
As well as induction agents which baseline immunosuppression agents are given to prevent SOT rejection
Calcineurin inhibitor
Mycophenolate or azathioprine
+/- steroids
How can organ rejection be detected
Monitor organ function ie creatinine
Screen for antibodies (anti-HLA)
How is T cell mediated organ rejection treated
IV steroids
OKT3- muronomab-CD3
How is antibody mediated rejection treated
IVIG
PLasma exchange
Rituximab
How is drug toxicity treated of immunosuppressive agents treated
Reduce dose
If are immunocompromised and then contract a viral infection how is it treated
Reduce dose
What is moa of tacrolimus and cyclosporin
Calcineurin inhibitor- needed for T cell proliferation
What is MOA of azathioprine
Prevents purine (adenine and guanine) synthesis
What is moa of mycophenolate motefil
Prevents guanine synthesis by inhibiting inosine-5’-monophosphate dehydrogenase (5-IMD)
Anti-proliferative affecting T>B cells
What is MOA of methotrexate
Inhibits dihydrofolate reductase which so is anti folate
What is MOA of daclizumab
IL-2 receptor antibody, targets CD25
What is MOA of rituximab
Anti-CD20 which depletes mature B cells but not plasma cells
What is MOA of muromonab-CD3
Blocks CD3 on T cells
What is MOA of alemtuzumab
Binds to CD52- blocks all T cell production
Which immunosuppressive agent is strongly linked with JC virus
Mycophenolate motefil
What is main side effect of calcineurin inhibitors
Gingival hypertrophy
What is main side effect of cyclophsophamide
Haemorrhagic cystitis due to excretion product acrolein
What is MOA of cyclophoshamide
Alkylates guanine which inhibits DNA synthesis
What is MOA of corticosteroids
Inhibits phospholipase A2
What is MOA of infliximab
TNF-alpha inhibitor
What is MOA of denusomab and what used in
Anti-RANK ligand
Osteoporosis
How is contact dermatitis diagnosed
Patch testing
What is immunopathology of an allergic reaction
if an allergen is taken up by a macrophage, it is processed
intracellularly and peptides are presented via major histocompatibility
complex on the cell surface to T cells of the TH2-cell (E) subclass. TH2-
cell secrete IL-4, which stimulates B cell (B) proliferation. TH1-cells (D)
do not play a role in the pathogenesis of type I hypersensitivity but do
contribute to type IV hypersensitivity reactions. B cells in turn produce
allergen-specific antibodies of the IgE variety. IgE binds to mast cells
(A) via the Fc receptor.
Which C proteins involved in membrane attack complex
C5b through to 9
What is presentation when defect in terminal pathway forming membrane attack complex
Defects in C5b through to 9 lead to recurrent infection with encapsulated bacteria
What is difference between a mature and immature dendritic cell
Immature- phagocyte
Mature- antigen presenting cell
Which cells derive from monocytes
Macrophages
When on what drug do you get repeated mouth and lip swelling after procedures
ACEi
Which vaccines are given to the elderly
Pneumococcal PPV
Shingles
Flu
Which cells are involved in adaptive immune response to vaccines
APC presents to specific receptor effector T-cell
which then proliferate
Specific antigen binds toIgm b-cells which undergo proliferation to memory b-cells and plasma cells with high affinity antibodies
Which antigen confers immunity to Influenza vaccine
Haemoagglutinin
How does tuberculin test work
Inject tuberculin into arm and measure induration width 48 hours later
How do conjugate vaccines work
Contain a weak antigen alongside a stronger antigen to trick immune system into generating stronger response to weaiker antigen
When is interferon alpha given to boost immune response
Hep B and C
When is IL-2 given to stimulate T cell response
Renal cell cancer
When are haematopoietic stem cells given
SCID
Leukocyte adhesion defect
Haem malignany
Which organisms are bloods for IVIG screened for
HIV
Hep B and C
Indications for antibody replacement
Primary AB deficiency
- X linked agammaglobulinaemia
- X linked hyper IgM syndrome
- CVID
Secondary deficiency
- CML
- myeloma
When are specific abs given
Hep B exposure from sex/needlestick etc HBSag
Rabies exposure from a bite
VZV in pregnant women
Suspected tetanus exposure
What is adoptive cell transfer
Can give specific T cells to a recipient
Types pf adoptive cell transfer
Virus specific T cells
Tumour infiltrating T cells
Tcell receptor T cells
Chimeric antigen T cells
What is virus specific t cell therapy
Take allogenic or autologous T cells
Expose to antigen
Grow them and give back to recipient
When is virus specific T cell therapy used
EBV related B cell lymphoproliferative disease
Persistent viral infection in immunocompromised
How does tumour infiltrating lymphocyte therapy work
Excise a tumour
Identify lymphocytes which have infiltrated tumour and expand them
Blood features of coeliac
IDA
- hypochromic and microcytic
Megaloblastic
- hypersegmented
- macrocytosis
Hyposplenism
- howell-jolly bodies
Hyposplenism causes
Coeliac
SLE
SCD
IBD
What exact antigen does anti-tissue transglutaminase respond to
Gliadin
What type of antibodies are anti-TTG and endomysial
IgA
Where take biopsy in coeliac
Deeper duodenum as presence of brunners gland distorts biopsy
Define atopy and anaphylaxis
Atopy- tendancy to produce IgE
Anaphylaxis- allergic reaction with an A,B or C definition
Person had anaphylaxis then a few hours later has same symptoms, what cause
Anaphylaxis is biphasic
What is used to measure complement
C3 and C4
CH50
AP50
What is livedo reticularis seen in
Antiphospholipid- net like discolouration of legs
Non serological blood findings of APL
Thrombocytopenia
Prolonged APTT
How is renal disease monitored in SLE
Urine dip
Why get recurrent infections in myeloma
Suppression of BM expansion by IgG
Why get anaemia in myeloma
Plasma cells crowd out the BM
What are T-cell receptor T cells and chimeric antigen receptor cell therapy
Involves the insertion of genes into T-cells which provokes development of T cell receptors on their surface which can bind to ligands on tumour cells
Difference between chimeric antigen receptor cell therapy and t-cell receptor T cell therapy
In chimeric the genes inserted are made up of recombinant genes
Use of chimeric antigen receptor T cells
Can get T cells to express receptors which bind to CD19 of some non-hodgkin lymphomas and b lymphocytes in ALL
Which cell is most affected by steroids
CD4+
Side effects of antiproliferative immunosuppressants
BM suppression
Infection
Malignancy
What is MOA of rapamycin/sirolimus
mTOR inhibitor which prevents T cell proliferation via IL-2
What is MOA of jakinibs
Inhibit JAK-STAT signalling which prevents production of cytokines
What are JAKinibs used in
Psoriasis
RA
Ank spond
What are PDE4 inhibitors used in
Psoriasis
What is MOA of PDE4 inhibitors
Modulates cytokine release
MOA of basilixumab and daclizumab
Binds to IL2R/CD25 reducing T cell proliferation
MOA of abatecept
Reduces costimulation of T cells via CD28
MOA of vedolizumab
Binds to alpha 4 beta 7 integrin which inhibits leukocyte adhesion
MOA of tocilizumab
IL-6 receptor antibody
What is tocilizumab (IL-6 antibody) used for
RA
MOA of secukinumab
Anti-IL17
MOA of guselkumab
Anti-IL23
MOA of mepolizumab
Anti-IL5
Use of mepolizumab
Eosinophilic asthma
What is most common classical pathway deficiency
C2
What are the most common SCIDs
X-linked SCID most common
Adenosine deaminase deficiency 2nd most common
Pathophysiology of X-linked SCID
Defective gamma chain on IL-2 leading to no t-cells and NK cells but immature B-cell production
Blood findings of x-linked SCID
Low T-cells and NK cells
Normal B cells
Pathophysiology of ada deficiency
Adenosine deaminase deficiency which is enzyme involved in leukocyte deficiencies
Low all b and t cells
Blood findings of ADA deficiency
Low T and NK cells
Low B cells
Inheritance of hyper IgM syndrome
x-linked recessive
Presentation of hyper IgM
Failure to thrive
Recurrent bacterial infections
PJP infection
What are the polygenic auto-inflammatory disease
IBD
Osteoarthritis
GCA
Takayasus arteritis
What are the mixed pattern disease
Ank spond
Psoriatic arthritis
Behcets disease
What does speckled mean when it comes to antibodies
Under immunofluorescence it means the nucleus is speckled with antibodies
What ENA have speckled appearance
Ro
La
U1RNP
What gel and coombs in RA
4
3 if RF positive
Difference between direct and indirect antigen detection in transplant rejection
Direct- donor APC presents foreign antigen to host T cells (acute)
Indirect- host APC presents foreign antigen to T cells like in infection
How to remember which cells antiproliferative agents affect the most
B cells
- cyclophosphamide
T cells- ones which have T in
- azathioprine
- mycophenolate motefil
Can include tacrolimus here too
MOA of ustekinumab
Anti-IL12 and IL-23
Name for beef tapeworm
Taenia saginata
What is the target of the antibody P-ANCA?
Myeloperoxidase
What is the target of the antibody C-ANCA?
Proteinase 3
What hematological cells create a “respiratory burst” in order to kill phagocytosed pathogens?
Neutrophils- done by NADPH oxidase
What is the worst SCID
Reticular dysgenesis
What is the minimum number of Fc receptors on the surface of mast cells that must bind to an antigen to cause mast cell degranulation
2
Which cell surface receptor allows cells of the innate immune system to bind to immunoglobulins?
Fc
What test can be used to identify the allergens in allergic rhinitis?
Skin prick
Antibodies in diffuse systmeic sclerosis
Topoisomerase (Scl70)
Fibrillarin
What is the maximum number of viral capsids that a molecule of IgM, IgA and IgG may bind to?
IgM- 10
IgA- 4
IgG- 2
What is use of natalizumab
Relapsing remitting MS
MOA of natalizumab
Targets alpha4integrin
T helper cells involved in bacterial versus allergies
Bacterial infections- T helper 1 cells
Allergies- T helper 2 cells
Monoclonal vs polyclonal antibodies
Monoclonal antibody = a solution of identical antibodies Polyclonal antibody = a solution of mutliple antibodies with different affinities for the same antigen (or target molecule)
What is example of integrase inhibitor
Dolutegravir
What chemical is responsible for urticaria and swelling in allergy
Histamine
What is latex food syndrome
Latex food syndrome is an IgE mediated type 1 hypersensitivity reaction to fruits and seeds, that is caused by cross-reactivity to latex antigens.
HLA association of DM
DR3 and DR4
HLA association of goodpastures
DR15
Presentation of hereditary angioedema
Recurrent bouts of swelling around mouth and neck
Pathophysiology of herditary angioedema
Acquired C1-inhibitor deficiency
