Immuno Flashcards
Reticular dysgenesis
Cause
Mutation
FBC findings
Failure of HSC differentiation
autosomal recessive adenylate kinase mutation
Everything is low except rbc
Kostmann syndrome
Severe congenital neutropenia
Failure of neutrophil precursors to differentiate
Autosomal recessive HAX mutation
Recurrent bacterial infections
Cyclic neutropenia
Failure of neutrophil differentiation
5 day period every three weeks where immunity fails and bacterial and fungal infections but good health in the interim
Autosomal dominant
ELA1 GENE
Leukocyte adhesion deficiency
CD18 deficiency ( beta 2 integrity) Granulocytes can’t extravate into infected tissues
Investigations for innate immune system
FBC- NEUTROPHIL COUNT
Leukocyte adhesion marker assay
dihydrorhodamine flow cytometry- fluorescence means oxidative killing
NBT- nitroblue tetrazolium test- if it turns blue oxidative killing
Encapsulated bacteria you are susceptible to in complement deficiency
Strep pneumoniae Haemophilus influenzae Klebsiella pneumoniae Neisseria meningitidus Salmonella typhi Cryptococcus neoformams Pseudomonas aerugosa
Common and terminal pathway deficiency
Cannot form MAC so susceptible to bacterial infections
CH50 and AP50 are abnormal
C3,5,6,7,8,9 are low
Classical pathway deficiency
C2 deficiency is common but C1q/r/s is also seen as is C4 deficiency
CH50 is abnormal
Associated with SLE because of CH50 abnormality
Alternative pathway deficiency
AP50 test is abnormal
Deficiency of factor P/I/B
Risk of infection with encapsulated bacteria
Lectin deficiency
MBL deficiency in 10%
Very common
SCID
X linked
Adenosine delaminates deficiency
Adaptive immunity disorder
Disorder in LYMPHOCYTE proliferation linked to IL2
Adaptive immune disorder
Di George syndrome
Cardiac dysfunction(ToF) Abnormal fancies Thymic aplastic Cleft palate and oesophageal atresia Hypocalcaemia due to low PTH
22Q11 DELETIONS
Adaptive immune disorder
Bare lymphocyte syndrome
Type 1 (rare) MHC I deficiency Type 2 MHC II deficiency In type 2 there are reduced CD4 cells and therefore reduced IgA and IgG as CD4 mediated class switching can’t occur Recurrent viral infections
Type 1 hypersensitivity reaction
IgE mediated
Anaphylaxis, eczema
Type 2 hypersensitivity
Antibody against a cellular antigen
Churg -Strauss,goodpastures, graves
Do a Coombes test
Type 3 hypersensitivity
Antibody against immune complex
SLE, RA, polyarteritis nodosa
Type 4 hypersensitivity
T cell mediated
Delayed onset
Contact dermatitis, Graft rejection, T1DM
Foreign antigen rejection order
HLA DR >B>A
Acute graft rejection
Donor APC presents donor MHC/ antigen to host T cell
Chronic graft rejection
Host APC present donor MHC/ antigens to host T cell
Bare lymphocyte syndrome
Defect in regulatory factor x or class 2 transactivator
Type 1 bare lymphocyte syndrome
No CD8+ T cells
What condition is bare lymphocyte syndrome associated with and when does it present?
Associated with primary sclerosis cholangitis
Presents at 3 months of age
Why do lymphocytes fail to develop in BLS?
There is no HLA expression in the thymus so lymphocytes can’t develop
Why are there low mature T cells in di George syndrome?
The thymus is absent so can’t mature lymphocytes
What are the T cell mediated immune deficiencies
Di George syndrome
Bare lymphocyte syndrome
How to treat T cell mediated immune deficiencies
Thymus transplant in Di George syndrome
Infection prophylaxis
Complement replacement
Which CD factors to T cells require for activation?
CD80
CD86
What are the B cell mediated immune deficiencies
Selective IgA deficiency
Bruton’s agammaglobulinaemia
Combined variable immune deficiency
Hyper IgM syndrome
Brutons agammaglobulinaemia
B cell mediated disorder
Inheritance
Mutation
Presentation
No antibodies
BTK gene
X linked tyrosine kinase mutation
FAILURE TO PRODUCE MATURE B CELLS, SYMPTOMS AT 3-6 MONTHS
Common variable immune deficiency
B cell mediated
IgA,IgE, IgG are low ( think AGE)
B cells do not differentiate
Many causes
Presents as failure to thrive, granulomatous disease and autoimmunity
Elective IgA deficiency
1/600 Caucasians
Recurrent respiratory and gastro infections
Vaccination is helpful
70% asymptomatic
Ig pattern in hyper IgM syndrome
IgM is high
Low IgA and IgG
Because B cells not present to make the ig
Mutation and inheritance in hyper IgM syndrome
X linked
Xq26 mutation
CD154, CD40, CD40L AND AICDA defect
Mechanism of disease in hyper IgM syndrome
Activated T cells cannot activate B cells to class switch therefore IgA and IgG aren’t formed but IgM is.
Less lymphoid tissue as no germinal centre
What conditions are you susceptible to in B cell deficiencies
Tetanus
Diphtheria
Some viral and bacterial infections
Treatment of B cell deficiencies
BMT transplant
Ig prophylaxis
If IgA deficiency then vaccination
WBC in SCID
Low B cell
Low T cell
Low antibodies
No B cell can be normal
How do you diagnose kostmannsyndrome
1) chronically low neutrophil count
2) bone marrow scan showing arrest of neutrophil precursor maturation
Treatment of kostmann syndrome
G-CSF
BMT
prophylactic abx
Chronic granulotomous disease
Reduced oxidative killing because NADPH is defective
Chronic granulotomous disease test and treatment
NBT test
DHR test
Infections you are susceptible to if chronic granulotomous disease
Catalase positive organisms Pseudomonas Listeria Aspergillus Candida E.coli Staph aureus Serattia
Treatment of chronic granulotomous disease
Prophylactic trimethoprim, itraconazole and interferon
Inflammatory cytokines
Il1
IL6
IL12
TNF
Anti inflammatory cytokines
TGF beta
IL10
What conditions are you predisposed to in cytokines deficiencies?
Salmonella
BCG
atypical mycobacterium
TB
What do cytokines do
They signal between T cells and macrophages
Stimulate NAPDH oxidative killing
Activate TNF
Treatment of anaphylaxis
Elevate legs 100%O2 IV was 100mcg hydrocortisone Salbutamol IM adrenaline 500mcg IV chlorphenamine 10mcg IV fluids Seek help
Investigations in allergy
Ski. Prick test( positive test is wheal greater than 2mm than negative control- dilutant)
RAST ( check IgE response)
Component resolved diagnostics- tests specific IgE response to a specific allergen protein
Challenge test
What do you measure in an acute allergy reaction?
Mast cell tryptase (peaks 1-2 hours and baseline at 6 hours)
Limited cutaneous scleroderma
AKA CREST SYNDROME
Calcinosis Raynauds Esophageal dysmotility Sclerodactily Telangectasia
+ primary pulmonary hypertension
Antibody in crest syndrome
Anticentromere ab
Diffuse scleroderma
Crest+ pulmonary six+ GIT sx+ renal sx
Topoisomerase ab
Scl70 ab
RNA polymerase I, II, III ab
Fibrillarin ab
Sjorens syndrome ab
Anti ro and anti la
Sjorens syndrome symptoms
Dry mouth, dry eyes, PNS and pancreatic dysfunction
Keratoconjunctivitis sicca and xerostomia
IPEX syndrome
What does IPEX stand for
Immune dysregulation, polyendocrinopathy, enteropathy, X linked inheritance and autoimmune diseases
How is IPEX inherited
X linked recessive
Typical conditions in IPEX sufferers
Alopecia univeralis
Bulbous pemphagoid
Eczematous dermatitis
Nail dystrophy
Coeliac disease antibodies
What type of ab are they?
EMA
TGT
BOTH OF THESE ARE IgA
Antigliadin (IgG)
What condition is coeliac disease associated with (3)
Down’s syndrome
Dermatitis herpetiformis
T cell lymphoma
What HLA molecules are associated with with 95% of coeliac disease
DQ8
DQ2
What is the pathology in atopic dermatitis (infantile eczema)
Beta defensin defect which predisposes to staph aureus superinfection
Treatment for infantile eczema (atopic dermatitis)
PUVA phototherapy
Emollient cream
Steroid
Topical antibiotics
How to diagnose food allergy
Food diary
RAST
skin prick test
Food challenge
What is latex food syndrome
Foods such as avacado and chestnut have latex like properties so latex allergy sufferers get IgE mediated symptoms when they eat them
Signs of allergic rhinitis
Anosmia Sneezing Blueish nasal mucosa Rhinitis Nasal obstruction
Causes of acute urticaria
50% idiopathic
Viral illness
Febrile illness
Allergen
Pathology of acute urticaria
Resolves in 6 weeks
IgE mediated
Wheals
Component resolved diagnostics for peanut allergy
Ara h8 allergic to peanut and stone fruit but reaction is only oral
Ara h2- v allergic to peanuts
Pathology and diagnosis of haemolytic disease of the newborn
Path: maternal IgG mediated reticulocytosis and anaemia
Positive Coombs test
What is the antigen for HDN
Antigens on foetal rbc
Treatment of HDN
Maternal plasma exchange
Exchange transfusion
Evans syndrome
Autoimmune haemolytic anemia plus ITP
What is the pathology in AIHA
Complement mediated destruction of rbc
Also by Fcr, phagocytes and autoantibody
Anaemia
Diagnosis and treatment of AIHA
Positive Coombes test
Anti rbc autoantibody
Treat with steroids
Autoimmune thrombocytopenic purpura antigen (2) and antibody
Antigen glpIIb
Antigen: glp IIIa
Anti platelet antibody
Treatment of autoimmune thrombocytopenic purpura
IVIG
steroids
Splenectomy
Anti D antibody
Antigen for goodpastures syndrome
Non collagenous domain of basement membrane collagen type 4
Pathology of goodpastures syndrome
Pulmonary haemmorage and glomerulonephritis
Which immunoglobulin mediated goodpastures syndrome
IgG
Diagnosis of goodpastures syndrome (2)
Anti GBM antibody
Linear smooth IF Staining of IgG deposits on basement membrane
Antigen for pemphigus vulgaris
Epidermal cadherin
Which ig antibody mediates pemphigus vulgaris
IgG
Symptoms of pemphigus vulgaris
Non tense blistering of skin and Bullae
How do you diagnose pemphigus vulgaris
Immunoflourescance showing IgG deposition
Treatment of pemphigus vulgaris
Steroids
Immunosuppression
Graves’ disease
Anti TSH-R ab
Causes hyperthyroidismism
Treat with carbimazole and propylthiouricil
Myasthenia gravis antigen
Ach-R
Symptoms of myasthenia gravis
Muscle fatigue
Double vision
Diagnosis of myasthenia gravis
Tensilon test
EMG
anti ach-r antibodies
Treatment of myasthenia gravis
Neostigmine
Pyridostigmine
If severe IVIG and plasmapheresis
Antigen for acute rheumatic fever
M protein on group a strep
Symptoms, diagnosis and treatment of rheumatic fever
Myocarditis, Sydenham’s chorea and arthritis
Jones criteria to diagnose
Aspirin, penicillin and steroids
Antigen for pernicious anaemia
IF or gastric parietal cells
Symptoms and Diagnosis of pernicious anaemia
Low B12 and anaemia
Schilling test
Anti IF AB
Anti gastric parietal cell ab
Diagnosis of churg Strauss syndrome eGPA
P-ANCA against myeloperoxidase
Also see granulomas and eosinophilia granulocytes
Wegeners granulomatosis [GPA]
C-ANCA against proteinase 3
Granulomas
Symptoms of wegeners granulomatosis
Small vessel vasculitis
Cresenteric glomerulonephritis
Lung cavitations and pulmonary haemmorage
Sinus problems
Churg Strauss syndrome symptoms
Type 2 hypersensitivity
Triad of asthma, eosinophilia and vasculitis
Diagnosis of micropolyangiitis
P-ANCA against myeloperoxidase
Treatment of micropolyangiitis
Steroids
Cyclophosphamide
Azothioprine
Plasmapheresis
Symptoms of micropolyangiitis
Livido
Purpura
Antigen for chronic urticaria
Cold Exercise NSAID Food Pressure Insect bites Sun Idiopathic
Pathology for chronic urticaria
Anti IgE
IgG against FC§R1
Diagnosis of chronic urticaria
Skin prick test
ESR (raised in urticarial vasculitis)
Challenge test
Treatment of chronic urticaria
Avoid précipitants Screen for thyroid disease IM adrenaline for angiooedema ( associated with 50% of case) 1% menthol in aqueous cream for pruritis Doxepin and cyclosporine May help
Type II hypersensitivityndisorders (13)
Goodpastures Graves
Churgstrauss. Pemphigus vulgaris
Wegeners. Chronic urticaria
Micropolyangiitis
AIHA. Myasthenia gravis
HDN
EVANS SYNDROME. Rheumatic fever
AITP. Pernicious anaemia
Type 3 hypersensitivity syndromes (4)
Mixed essential cryoglobulinaemia
Serum sickness
SLE
polyarteritis nodosa
Human immunoglobulin
Give IV OR SC every 3-4 weeks
Hl is 18days
From 1000 donors
PREFORMED IGG AGAINST LOADS OF ORGANISMS
Give in pri wry and adaptive immunodeficiencies
Specific immuniglobulin
Post exposure prophylaxis against rabies, tetanus, VZV and hep B
Interferon alpha
Recombinant cytokine
Hairy celll leukoplakia Hep b and c Kaposi sarcoma CML Malignant myeloma
Interferon beta as recombinant cytokine
Relapsing MS
Interferon gamma (recombinant cytokine)
Chronic granulotomous disease
Ipilimumab
Antibody for CTLA4
Indicated for advanced melanoma
Blocks the immune checkpoint and so enables Tcell activation
Pembrolizumab
Nivolumab
ANTIBODY
Indicated for advanced melanoma
Enables T cell activation
Blocks immune checkpoint PD1
Injection site reaction
Peaks at 48 hours
Usually CD8 cell infiltrate (NOT IGE)
Antigens that cause transplant rejection
HLA DR>B>A
ABO
Two stages of transplant rejection
- Recognition of foreign antigens
- Activation of antigen specific lymphocytes, proliferation of B cells and antibody production
- Effector phase (
A.graft infiltration by all alloactive CD4 cells
B.macrophages cause oxidative death and apoptosis
C. cytottoxic T cells cause apoptosis by toxin release
D. antibodies bind to graft endothelium,
How do you match transplant cases
- ABO
- HLA MATCH VIA PCR
- check preformed antibodies with cdc, facs and luminex
- Cross match and check if recipient serum will react with donor lymphocytes using facs and luminex
- check for antibodies to the graft after transplantation
What are cdc, facs and luminex
Cdc: complement dependent cytotoxicity
Facs: flow cytometry
Luminex: flow cytometry but for solids and picks up individual HLA reactivities
What are the pre transplant induction agents that suppress T cell responses
Anti CD25 basiliximab
ANTI CD52 alemtuzumab
OKT3
ATG
How to prevent transplant rejection
- CNI
- MMF/AZO
- STEROIDS
How to treat acute transplant rejection
CELLULAR
steroids, OKT3, ATG
Antibody
IVIG, plasma exchange, anti CD5, anti CD20
GVHD prophylaxis
Cyclophosphamide
Methotrexate
GVHD symptoms and treatment
Skin rash
Gut pain, N&V, bloody diarrhoea, jaundice
Treat with steroids
Haematopoeitic stem cell transplant steps
- Total body irradiation plus cyclophosphamide
- Repack BM with donor BM
- Reaction of DONOR LYMPHOCYTES against HOST TISSUE
Infection risk after transplant
CMV
BK VIRUS
PNEUMOCYSTITIS CARINII
Malignancy risk post transplant
Kaposi sarcoma due to HSV8
SKIN CANCER
LUNG CANCER
Atherosclerosis risk post transplant
Hypertension and hyperlipidaemia cause MI risk to increase 20 times compared to matched controls
HIV antigens
Glp120 for initial binding to CD4 cells
Glp41 which induces conformational change in CD4 cells
CCR5 and CXCR4 chemokine coreceptors to infect macrophages
Gag protein for HIV virus structural support
Innate immune response to HIV virus
Macrophages, NK cells and complement are activated
Dendritic cell stimulated via TLR
Cytokine and chemokine release
Adaptive immune response to HIV
Neutralising antibodies: anti gp120, anti
Non neutralising antibodies: anti p24, gag antibodies
Chemokine produce MIP1a and MIP1b plus RANTES which block coreceptors
How does HIV damage the immune hresponse
- Disables CD4 cells
Lifecycle of HIV
- Attachment and entry
- Reverse transcription
- Viral transcription
- Viral integration
- Synthesis of viral proteins
- Assembly of virus
- Maturation
What predicts HIV viral progression
Initial viral set point
What is the normal time course from HIV infection to AIDS
8-10 years
What percentage are long term non progresseds with a stable viral loadin HIV
Less than 5%
What are rapid progressors in HIV
The 10% of people who progress to AIDS in 2-3 years
What is the screening test for HIV
ELISA for anti-HIV antibodies
What is the confirmation test for HIV
Western blot for HIV ab
How long does it take for HIV seroconversion to happen
About 10 weeks
How is viral count calculated in HIV
PCR
How is CD4 count measured in HIV
FACS
Treatment of HIV
HAART
efavirenz, tenofivir, emtricitabine
Treatment of HIV in pregnancy
Ziduvidine
Limitations of HAART
Difficult adherence and high pull burden
Doesn’t restore specific HIV T cell response
Doesn’t eradicate latent HIV1
Toxicities
HAART
fusion inhibitors
Enfuviratide
Enfuvirtide SE
Local reaction
HAART
attachment inhibitors
Maraviroc
Nucleoside reverse transcriptase inhibitors
Abacivir Combivir Didanosine Emtricitabine Emzicom Lamivudine Stavudine Tramivir Zalcitabine Zidovudine
HAART therapies causing peripheral neuropathy
Zalcitabine and stavudine
reverse transcriptase inhibitors causing GI upset and fever
Zidovudine
Reverse transcriptase inhibitors causing allergic reaction
Abacavir
Nucleoside reverse transcriptase inhibitors causing mitochondrial toxicity
Stavudine
NucleoTide reverse transcriptase inhibitor
Tenofivir
NucleoTide reverse transcriptase inhibitors causing BM toxicity
Tenofivir
HAART therapy
Integration inhibitors
Raltegravir
Elvetegravir
HAART therapy
Protease inhibitors
Amprenavir
Fosamprenavir
Lopinavir Saquinavir Nelfinavir Ritonavor Indinavir
SE of protease inhibitors
Hyperlipidaemia
Fat redistribution
T2DM
Efavirenz nonNRTI SE
CNS effects
Nevirapine (non NRTI) SE
Hepatitis and rash
Delavirdine (nonNRTI) SE
rash
Where are central memory T cells found
Tonsils and lymph nodes
How do central memory cells travel
They roll along and extravasate in high endothelial venules (HEV)
What antigens are present on central memory cells and how do they help
CCR7
CD62L
These allow entry to HEV and then to peripheral lymph nodes
What cytokine do central memory cells produce
IL2
Central memory cells tend to be found in…
The CD4 population
Where are effector memory cells found
Lung liver and gut
What do effector memory cells produce
Perforin and IFN gamma
Effector memory cells tend to be found in the ….
CD8 population
What does CCR7 do
It binds to CCL19 & CCL21 on the luminal surface of endothelial cells of lymph nodes and causes firm arrest and starts the process of extravasion
It causes the homing of dendritic cells to lymph nodes
What does cd62l do
It interacts with a molecule on HEV to mediate attachment and rolling
Which cytokines are involved in Th2 response
IL 4,5,6
Which cytokines are involved in Th1 response
IL2, IFN GAMMA AND TNF
What are adjuvants in vaccines for
Slowing the release of antigen
What is ALUM (vaccine adjuvant)
Antigens are adsorbed to alum to ensure they are released slowly.
It activates gr1+ cells to produce IL4 to prime naive B cells
Adjuvants for vaccines
Alum Cpg Complete freund’s adjuvant ISCOMS IL2
What is ISCOMS
Expeiemental multimeric antigen+ adjuvant
When combined with saponin their is a strong serum response
How is IL2 used as an immune adjuvant
In individuals with Hep B surface antigen it is used tomforce seroconversion
What is Cpg (vaccine adjuvant)
It activates TLRs on APC to increase costimulatory activity
Immunostimulatory activity is linked to unmethylated DNA motif (where cytosine is next to guanine)
What is complete freund’s emulsion and is it used in humans
It is an oil in water solution containing mycobacterium cell wall
It is used only in animals
Which are the passive vaccines
Hep A Hep B Measles Rabies RSV
What is the Mantoux test
Intradermal injection of 0.1ml of 5 units of tuberculin.
If after 72 hours a swelling of greater than 10mm is felt then there has been previous TB exposure, either via mantoux or by infection
Antigen in mixed essential cryoglobulinaemia
IgM against IgG +/- hep C
Antigen in serum sickness
Reactions to proteins such as Penicillin in anti serum
Antigen in polyarteritis nodosa
Hep B, hep C
Pathology in SLE
Anti dis-DNA and anti sm
Antigen for T1DM
Pancreatic beta cell proteins such as GAD (glutamate decarboxylase)
Antigen and pathology of MS
Myelin proteins such as MBP and proteolipid protein
IgG oligoclonal bands on electrophoresis
Treatment of MS
Interferon beta
Steroids
Antigen and antibody in rheumatoid arthritis
Antigen is protein in synovial membrane
Anti CCP antibody
Rheumatoid factor used for diagnosis
Gene mutation in 30% of Crohn’s disease
NOD2
Chromes is Th1 mediated
HLA association for ankylosis spondylitis
HLA B27
HLA association for goodpastures syndrome
HLA DR2/15
HLA association for Graves’ disease
HLA DR3
HLA association for SLE
HLA DR3
HLA association for T1DM
HLA DR3/4
HLA association for rheumatoid arthritis
HLA DR4
What is genetic polymorphism PTPN22
A mutation in lymphocyte tyrosine phosphatase associated with RA, T1DM and SLE
What is polymorphism CTLA4
T cell receptor for CD80 and CD86 which transmits inhibitory signals for T cell activation. Associated with autoimmune thyroid disease, SLE and T1DM
Autoantibody in antiphospholipid syndrome (Hugh’s syndrome)
Antibodies against cardiolipin and beta 2 glycoproteins and lupus anticoagulant
Autoantibody in autoimmune hepatitis
Anti smooth muscle antibody
Anti liver kidney microsomal 1 antibody
Anti soluble liver antigen
Autoantibody of infants with complete heart lock from mothers with SLE
Anti ro
Dermatomyositis autoantibody
Anti Jo1
Autoantibody in Hashimoto’s thyroiditis
Anti thyroglobulin and anti thyroperoxidase
Autoantibody in mixed connective tissue disease
Anti U1RNP
Autoantibody in dermatomyositis
Anti Jo1
t RNA synthetase
Auto antibody for primary biliary cirrhosis
Anti mitochondrial antibody
Prednisolone mechanism of action
Phospholipids A2 inhibition to block arachadonic acid and therefore prostaglandin production
Inhibits phagocyte trafficking, release of proteolytic enzymes and phagocytosis
Blocks cytokine gene expression
Decrease ab expression
Promotes cell apoptosis
SE of prednisolone
Cushingoid symptoms (adrenal suppression) Avascular necrosis Osteoporosis Transient neutropenia Peptic ulceration
Any proliferative agents
Cyclophosphamide:moa
Alkylate guanine of DNA, so damage DNA replication. Works better on B than T cells but at high doses affects all cells
SE of cyclophosphamide
Teratogenic BM suppression Hair loss Haemmoragic cystitis Infertility
Indications for cyclophosphamide
Anti cancer
Vasculitis
Connective tissue agent
Plasmapheresis mechanism
Aim: removal of a pathogenic stimulus
Blood removed and immunoglobulins removed and then reinfused. If replaced with albumin then it is plasma exchange
Plasmapheresis indications
Antibody mediated disease and reactions e.g. antibody mediated transplant rejection
SE include anaphylaxis and rebound low antibody
Methotrexate mechanism
Inhibits dihydrofolate reductase and so black,s DNA replication
Methotrexate Se
Infection, BM suppression, Teratogenic Pulmonary fibrosis Hepatotoxicity Folate deficiency- megaloblastic macrocytic anaemia
Azothioprine indications
Transplant
Autoinflammatory conditions
Autoimmune disease
Azothioprine mechanism
Metabolised by liver to 6 mercaptopurine and inhibits de novo purine synthesis.
Blocks T cell activation
Methotrexate indications
Crohn’s disease
RA
psoriasis
Abortifacients
Anti proliferative agent
Mycophenalate mofetil
Blocks de novo Nucleotide synthesis by preventing guanine sysnthesis
Does this by blocking IM PDH
Immune therapies
Inhibitors of cell signalling
Tacrolismus Cyclosporin Sirolimus Tofacitinib Apremilast
Apremilast
PDE4 INHIBITOR
For psoriasis
Tocafatinib
JAK inhibitor For RA
Sirolimus
Blocks clinal proliferation of T cells and is used as anti rejection meds
Inhibits Calineurin to prevent IL2 transcription and therefore block the T cell response
Tacrolismus
Cyclosporin
Anti rejection meds for transplant
SE of tacrolismus and cyclosporin
Nephrotoxic, hypertension,neurotoxicity
Cyclophosphamide also causes gingival hypertrophy
Basaliximab
Agent directed at cell surface antigens
block signalling, cell depletion
Anti CD25- alpha chain of IL2 receptor and inhibits T cell activation
Used in allograft rejection
SE
GI disturbance, infection, malignancy and local site reaction
Abatacept
Agent directed at cell surface antigens
block signalling, cell depletion
Anti CTLA4-ig
used for RA
SE cough, infection, malignancy, infusion reaction
Rituximab
Agent directed at cell surface antigens
block signalling, cell depletion
Anti CD20 so depletes B cells
SLE, RA, lymphoma
SE infection, exacerbates CVS disease
Natalixumab
Agent directed at cell surface antigens
block signalling, cell depletion
Anti alpha 4 integrin that binds to VCAM1 and MADCAM1 to mediate rolling and array of leukocytes
Used in RRMS, Crohn’s disease
SE hepatotoxic, infection, PML, malignancy and infusion reaction
Tocilizumab
Agent directed at cell surface antigens
block signalling, cell depletion
Anti IL6 so prevent macrophage, B, T cell and neutrophil activation
Used in castle and disease and RA
SE
Infusion reaction, hyperlipidaemia, hepatotoxic
Muromonab CD3
Agent directed at cell surface antigens
block signalling, cell depletion
Mouse ab (OKT)
Blocks CD3 on T cells
Active anti allograft rejection med
SE fever, leukopenia
Anti thyomite globulin (ATG)
Agent directed at cell surface antigens
block signalling, cell depletion
Allograft rejection med esp renal or heart transplant
It modulates T cell activation and proliferation. It causes leukocyte depletion
SE infusion reaction, infection, malignancy, leukopenia
Daclizumab
Agent directed at cell surface antigens
block signalling, cell depletion
Anti IL2 receptor antibody that targets CD25
Organ transplant rejection prophylaxis
Efalizumab
Agent directed at cell surface antigens
block signalling, cell depletion
Anti CDIIa which inhibits migration of T cells
Alemtazumab (campath)
Agent directed at cell surface antigens
block signalling, cell depletion
Mab that binds to CD52 on lymphocytes to cause depletion
Used in RRMS, CLL
SE risk of CMV infection
Anti TNF alpha agents
Infliximab
Adalimumab
Certolizumab
Golimumab
Indications and SE of anti TNFalpha therapy
RA, IBD, ANK SPOND, PSORIASIS
SE Infections eg hepatitis B/C/TB Demyelination Lupus like conditions Lymphoma
Etanercept
Blocks action of cytokines
TNF alpha/ beta p75 IgG fusion protein
Used in RA, ank spond and psoriasis
SE
Infections eg hepatitis B/C/TB
Demyelination
Lupus like conditions
Lymphoma
Ustekinumab
Anti cytokine
Blocks IL12 AND IL23( binds to p40 subunit)
Used for psoriasis
SE
cough, injection site reaction, malignancy, infection (TB)
Secukinumab
Anti cytokine
Anti IL17a
Used for psoriasis
SE TB infection
Denusumab
Anti RANK ligand antibody. It prevents RANK mediated osteoclasts differentiation and recruitment.
Used in osteoporosis, multiple myeloma, bony metastasis
SE
avascular necrosis of jaw and infection
Hyperacute transplant rejection
Complement mediated activated by preformed antibodies
Results in thrombosis and necrosis and occurs within hours
Treat by HLA cross matching
Acute transplant rejection (cellular)
A type 4 hypersensitivity reaction (cell mediated) occurring over weeks. Caused by CD4 cells
Treat with T cell suppression
Acute transplant reaction ( antibody mediated)
Occurs over months
Due to B cell activation where antibody attacks vessels causing vasculitis
Treat with Ab removal and B cell suppression
Chronic graft rejection
RF: HTN, previous rejectionS, hyperlipidaemia
Sx: bronchiolitis obliterans, glomerulopathy, vasculopthy, fibrosis
Tx: try and reduce end organ damage
GVHD
Donor cells attacking the host- occurs over days to weeks
Symptoms include rash, jaundice, D&V
Treat with steroids and immunosupression
features of chronic granulomatous disease
absent respiratory burst because of reduced NADPH and impaired oxidative killing
excessive inflammation and persisting neutrophils because antigens aren’t cleared
granuloma formation
lymphadenopathy and hepatosplenomegaly
what cytokines are deficient in cytokine deficiency
IL12/ IL12R
IFNg/ IFNgR
what infections are you predisposed to in cytokine deficiency
salmonella
mycobacteria
infections you are predisposed to in phagocyte deficiency
bacteria: staph aureus, enteric
mycoplasma: TB, atypical mycobacteria
fungi: candida, aspergillus flavus/ fumigatus
what is complement
proteins produced in liver that circulate as inactive molecules
when activated cause a cascade via enzyme action
SLE is associated with a defect in which complement pathway
classical
how does the classical complement pathway clear immune complexes
via erythrocytes
deficiencies cause skin/ joint inflammtion