Immunology Flashcards
A 35 year old woman presents with persistent itchy wheels for the last 2 months. She noticed that when this is at its worst, she also has a fever and feels generally unwell. After an acute attack, she has bruising and post-inflammatory residual pigmentation at the site of the itching.
Chronic Urticaria
Type II (IgG) note acute uritcaria is Type I
Persitent Itchy wheels
Angiodema can occue
Increased ESR
TX: Responds well to histamine. If it does not respond it is not Chronic Urticaria.
Q) WHy not acute? Acute urticaria lasts less than 6 weeks.
This 45 year old woman presents to A&E with tongue swelling and acute respiratory tract obstruction.
She has longstanding hypertension and received a renal transplant two years previously. She has no history of a_llergic disease_. On examination her blood pressure is stable, and examination of her lung fields reveal normal breath sounds. Her current medication includes cyclosporine, azathioprine, captopril and nifedipine.
What is the condition?
Acute angioedema
This 45 year old woman presents to A&E with tongue swelling and acute respiratory tract obstruction. She has longstanding hypertension and received a renal transplant two years previously. She has no history of allergic disease. On examination her blood pressure is stable, and examination of her lung fields reveal normal breath sounds. Her current medication includes cyclosporine, azathioprine, captopril and nifedipine.
What is the condition?
Acute angioedema. This woman has angioedema of the tongue, without symptoms suggestive of a generalised allergic reaction. Isolated angioedema may be allergic in origin, but 94% of cases angioedema presenting to A&E are drug induced and the majority of these are associated with ACE inhibitors (eg captopril).
A 19 year old male presents to A&E with increasing breathlessness. On examination his BP is 90/55 mmHg and his respiratory rate is 28/min. He shows you a generalised red itchy skin rash, and examination of his chest reveals bilateral inspiratory and expiratory wheezes throughout.
IM adrenaline 1 mL of 1:1000
A 35 year old woman presents with a two day history of a red itchy skin rash which started soon after her first scuba-diving lesson. She is otherwise well.
What is it? How would you treat it?
PO antihistamines -acute urticaria type I
A 22 year old woman is presents with this intermittently itchy and desquamating skin rash which is unresponsive to antihistamines
None of the above
A 40 year old man complains of loss of smell with nasal itching and discharge over 4 weeks. He also describes morning sneezing. He is otherwise in good health. On examination his nasal mucosa are swollen and hyperaemic.
PO antihistamines
Allergic
Rhinitis
This 45 year old woman presents to A&E with tongue swelling and acute respiratory tract obstruction. She has longstanding hypertension and received a renal transplant two years previously. She has no history of allergic disease. On examination her blood pressure is stable, and examination of her lung fields reveal normal breath sounds. Her current medication includes cyclosporine, azathioprine, captopril and nifedipine.
IM adrenaline 0.5 mL of 1:1000
Elevate Legs
100% Oyxgen
- IM Adrenaline 500 mcg
- Inhaled bronchodilators
- Hydrocortisone 100mg IV,
- Chlorphenamine 10mg IV,
- IV Fluids, Seek Help
Cytokines exerting an anti-viral effect
infereron
Immunoglobulin dimer
What other types of IgG do you knw?
IgA:
IgA: mucosal areas, saliva, tears, breast milk
IgE: allergy – histamine release from mast cells
IgG: can cross from placenta to foetus
IgM: on surface of B cells
Immature B cells express only IgM.
Human normal Ig has a half life of 18 days
MHC associated with Th1 cells
Major histocompatibility complex class 2
Reminder – Immune Recognition
T-Cells (TCs) recognise antigen with
MHCs on APCs
B-Cells (BCs) can recognise just
antigen
Acts on hepatocytes to induce synthesis of acute phase proteins in response to bacterial infection (complement activation)
IL6
Arise in the first few days after infection and are important in defence against viruses and tumors
Natural Killer cells
MHC associated with Th2 cells
Major histocompatability complex class I
MHC associated with cytotoxic T cells
Major histocompatability complex class 1
Along with IgD, is one of the first immunoglobulins expressed on B cells before they undergo antibody class switching
IgM
The most abundant (in terms of g/L) immunoglobulin in normal plasma
IgG
Deficiencies in this predispose to SLE
Classical complement pathway: C2 and C4 measured by CH 50
Kostmanns syndrome is a congenital deficiency of which component of the immune system?
Kostmann Syndrome-no pus
- Severe congenital neutropenia
- Mainly Autosomal Recessive (HAX-1)
- 1-2 cases per million
Patients have infections shortly after birth
Diagnosis based on chronicallLlow Neutrophil count and bone marrow test showing an arrest of neutrophil precursor maturation
- Treatment includes G-CSF, prophylactic antibiotics and BMT if G-CSF is ineffective
Which infection is most common as a consequence of B cell deficiency?
Bacterial
Meningococcal infections are quite common as a result of which deficiency of the component of the immune system?
Complement
Produced by the liver, when triggered, enzymatically activate other proteins in a biological cascade and are important in innate and antibody mediated immune response?
Which interleukin acts on the liver to activate complement?
Complement
Answer: IL-6
A complete deficiency in this molecule is associated with recurrent respiratory and gastrointestinal infections.
Selective IgA Deficiency
Most common defiency
Reccurent gastro and resp infections
Affects 1 in 600 Caucasians
70% are asymptomatic
Leukocyte Adhesion Deficiency is characterised by a very high count in which of the white cells? What other findings would be?
Whcih molecule is dysfunctional in this syndrome?
What would be the presentation?
Neutrophils
B2-integrin
A) Deleyed umbilical cord separation, and high neutrophil count.
Which crucial enzyme is vital for the oxidative killing of intracellular micro-organisms?
NADPH oxidoase
Which complement factor is an important chemotaxic agent?
C3a
What is the functional complement test used to investigate the classical pathway?
CH50
Graves Disease
antibodies
treatment
type of hypersentivity reaction
Type II – Antibody mediated
anti-TSH
carbimazole
SLE
Type Hypersnsitivity
antibodies present (6)
D.
- Type III – Immune complex mediated
- ANA
- antiSM
- anti dsDNA
- Beta-2-glycoprotein
- Anti-cardiolipin
- Lupus anti-coagucalant.
Rheumathoid artheritis
type of reaction
- Type III and Type IV
- type IV - delayed hypsensitivity T-cell mediated
- Type III - IgM antibodies vs Fc region of IgG.
RF (+)
- Anti-CCP (95% specific)
- Increased ESR
Asthma
type of reaction
pathology involved
- non-immune mediated
- SM cell hyperplasia
- excess mucus
- inflammation=Group of immune-mediated lung disorders caused by intense/prolonged exposure to inhaled ORGANIC antigens → widespread ALVEOLAR inflammation (cf asthma = airway inflammation).
Type 1 diabetes
Type IV – T-cell mediated
Pancreatic Beta Cell proteins. (Glutamate Decarboxylase GAD)
Insulitis
Beta Cell Destruction
Immune thrombocytopaenic purpura
How does it present?
What sort of reaction it is?
Where antibodies bind to?
- Type II - abnomral IgG** and IgA
- Generally asymptomatic illnes following viral infection or immunisation in children less than <10 years and adults>65
- Petchial Rash
- Low platelets is the only finding. In adults you need to do bone marrow biopsy to exclude myoplastic syndrome.
- Glycoprotein IIb/IIIa on platelets
- Bruising/ Bleeding (Purpura)
- Anti-Platelet Antibody
- Steroids, IVIG, Anti-D Antibody, splenectomy
/ABO hemolytic transfusion reaction. What type of reaction is it?
Type II – Antibody mediated
Hepatitis C associated membranoproliferative glomerulonephritis type I
Q) Type of immune reaction it is
Q)
- Type III – Immune complex mediated
- Mixed Essential Cryoglobuinaemia
- gM against IgG +/- hepatitis C antigens
Joint pain, splenomegaly, skin, nerve and kidney involvement. Associated with Hep C.
A mixture of clinical and biopsies
NSAIDs, Corticosteroids and plasmaphoresis
GOOdpasture’s syndrome?
1) What type of reaction is it?
2) How does it present?
3)
Type II – Antibody mediated
a) of pulmonary renal syndrome: pulmonary haemorrhage with rapidly progressive glomerulonephritis. so hemoptysis and blood in the pee.
b) Remeber always two things in GOODPASTURE
c) Linear smooth IF staining og IgG deposit in BM.
A 32yr old woman complains of fatiguability in many muscles and double vision. She is thought to be at risk of other autoimmune diseases as she has a family history of various autoimmune diseases and herself has autoimmune hypothyroidism. Her thyroid function is normal because she is well replaced with thyroxine. What might be causing her muscle weakness?
What type of reaction it is?
Myaesthenia gravis
Type II – Antibody mediated
Recurent bacteria infections 3 months after birth.
What is the model of inheritance?
What is lacking?
Which gene is mutated?
Bruton’s Agammaglobulinemia
- X-Linked Tyrosine Kinase Defect
- Mutation in BTK gene
- Failed production of mature B-Cells and antibodies. T cells would be present
- No antibodies
- Symptoms after 3-6 months
DiGeorge’s Syndrome
1) how does ir present?
2) what sort of infections is he predisposed to?
DiGeorge’s Syndrome (CATCH 22)
Impaired development of the 3rd and 4th pharyngeal pouches (oesophagus, thymus, heart)
22q11.2 deletion – 75% sporadic
Low set ears, cleft lip and palate
Low calcium > seizures
Susceptibility to viral infection
V. low numbers of mature T cells
(absent thymus)
Treated by thymus transplant
Treatment of T cell deficiencies: infection prophylaxis, Ig replacement if necessary, specific other treatments.
Infants present with recurrent infections, failure to thrive, and chronic diarrhoea.
1) what is it?
2) what is lacking?
3) what is model of inheritance?
4)
IL-2
- Severe Combined Immune Deficiency (SCID)
- lymphoid tissue precursors IL-2 receptor
- pattern of inheritence
- Failure to thrive and persistent diarrhoea & early infant death
- Low or normal B cell numbers, reduced T cells, low antibodies
BMT only established treatment
45% are X-linked
Small platelet size is the one consistent feature. Eczema and reccurent infections are common.
Q) What is it?
Q) What is the model of inheritence?
Q) What does it increases the risk of?
Wiskott-Aldrich Syndrome
X-linked condition characterised by thrombocytopenia.
Small platelet size is the one consistent feature.
Eczema and recurrent infections are common.
There is an increased risk of haematological malignancies.
1) Failure to thrive by the age of three months
2) The child presents with jaundice and hepatosplenomegaly
2) Which Immunoglubins will be low?
3) Which Immunoglobulin will be normal?
Bare Lymphocyte Syndrome:
Bare lymphocyte syndrome
Absent expression of HLA molecules within thymus
lymphocytes fail to develop
Type 1: MHC I absent - ↓CD8 cells
Type 2: MHC II absent - ↓CD4 cells
BLS type 2 more common:
B-cell class switch needs CD4 therefore less I_gA_ and IgG made.
IgM would be normal
- Associated with Sclerosing Cholangitis
Unwell by 3 months of age
Boys present first years of life with
recurrent bacterial infections esp.
Pneumocystis carinii & failure to thrive
What is the mechanism?
Hyper IgM
Activated T-cells cannot interact with B-cells to class switch
Therefore B-Cells cannot make IgA and IgG, but elevated IgM
A 25 year old woman comes to her GP about family planning. She is worried because she had an older brother who died before she was born and her grandmother lost two children which she things were both boys. Her GO thinks there may be a genetic disorder in her family affecting the IL-2 receptor. If correct she has a 50% of inheriting the trait from her mother and being a carrier herself. And there would be a 50% chance of passing it to her children. If inherited, her daughters would be carriers and her sons would require treatment which is usually a bone marrow transplant but gene therapy is sometimes used.
Severe Combined Immune Deficiency (SCID)
- Defects in lymphoid precursors e.g. Adenosine Deaminase Gene; IL-2 receptor
- Recurrent infections
- Failure to thrive and persistent diarrhoea & early infant death
- Low or normal B cell numbers, reduced T cells, low antibodies
- BMT only established treatment
- 45% are X-linked
A jaundiced 8 month old child presents with failure to thrive, and a history of recurrent infections (viral, bacterial and fungal). On examination there is hepatomegally and blood tests show a raised alk phos and low CD4 count. A defect is found in the proteins that regulate MHC Class II transcription.
BARE LYMPHOCYTE SYNDROME
Patient X’s GP writes inquiring about whether to vaccinate. The patient suffers from recurrent respiratory tract infections and has been diagnosed with one of the B-cell maturation defects. For which one is immunisation still effective?
Selective IgA Deficiency
Most common defiency
Reccurent gastro and resp infections
Affects 1 in 600 Caucasians
70% are asymptomatic
For which disorder would a bone marrow transplant be unhelpful but a thymic transplant may provide a cure?
DIGEORGE CATCH-22
A difference in this between host and recipient is the main cause of transplant rejection
HLA
Along with anti-HLA antibodies, the most important screen to ensure a match before transplantation
ABO blood type
Risk factor for chronic allograft rejection
Hypertension
Hyperlipidaemia
Transplanting an ABO incompatible kidney will result in ___ rejection
1) Why
2) what would be the consequence?
3) How it could be prevented?
Hyperacute
Preformed Ab which activates complement
Thrombosis and Necrosis
Prevention: Crossmatch (ABO groups) HLA-matching
You are about to see a gentelman following kidney transplant developng vascullitis following 2 weeks of his transplant.
1) What is it?
2) Wha is the mechanism?
2) What is the treatment?
Acute organ transplant
B cell producion and antibody attacking the blood vessls leading to vasculitis
The treatment would be to remove the antibody = plasmapharesis and immunospuression
Treatment of acute cell mediated rejection
what is the pathology involved?
How does it work?
High dose corticosteroids
CD4 activating a Type IV
reaction
Cellular
Infiltrate
T-Cell
Immunosuppression
The 3 most important HLA types to screen for in renal transplantation when matching donor and recipient, in order of importance
HLA DR > B > A
The 3 most important HLA types to screen for in renal transplantation when matching donor and recipient, in order of importance
B.
HLA DR > B > A
Lymphocyte that responds to foreign HLA DR types
P.
CD4+ T cells
Lymphocyte that responds to foreign HLA A types
CD8+ T cells
Prevents DNA replication especially of T cells?
How it can prevent replication?
What is it used for?
Mycophenolate Myofeti
Prevents Guanine Synthesis
Transplantation
Autoiimune
Vascullitis
Causes a transient increase in neutrophil count
Prednisolone
Monoclonal antibodies inhibiting the actions of cytokines
Infliximab
Can cause gingival hypertrophy as a side effect
how does it work?
Ciclosporin
inhibits Calceurin
whihc normally activates the transcription of Il-2, thus reduces T cell proliferation
Administration of this may boost the immune system
Immunoglobulins
prevent lymphocyte proliferation by inhibiting DNA replication, affects B cells more than T cells.
Q) What is it used for?
Cycloophoshamide. Both mycophenolate mofetil and cyclophosphamide prevent lymphocyte proliferation by inhibiting DNA replication. However, mycophenolate mofetil is more selective for T cells, whereas cycophosphamide affects B cells more than T cells.
Note that cyclophosphamide at high doses will affect all cells with a high turnover.
b) connective tissue disease, vascullitis
Bone marrow suppresion, infection, malignancy
_Corticosteroids,_ as well as being directly lymphotoxic in high doses, icell via which other mechanism?
What else does it do?
- Blocking cytokine synthesis
- Inhibits PLA12, hence blocks archaidonic acids
- Reduces prostaglandin synthesis
- Inhibits phagocyte trafficing
- Phagocytocis and relase of proteolytic enzymes
The antiproliferative drug cyclophosphamide inhibits lymphocyte proliferation by which mechanism?
Inhibition of DNA synthesis
Plasmapheresis may be indicated in which conditions?
Goodpasture’s syndrome- removal of anti-GBM antibody
Myasthenia Gravis - nACHR antibodies
Vascular Transplant rejection - hyperacute but aapears 6 days afterwards
Example of a vaccine that should NOT be given to a severely immunocompromised patient.
POLIO
MMR BOY
A condition where antigen desensitization therapy may be indicated.
Bee/wasp venom allergy
The main side effect of this drug is diabetogenic drug
How does it work?
is also used in the treatment of other T cell-mediated diseases such as eczema (for which it is applied to the skin in a medicated ointment), severe refractory uveitis after bone marrow transplants, exacerbations of minimal change disease, and the skin condition vitiligo.
Tacrolimus
Inhibits calceurin, which normally inhibits synthsis of IL-2 thus T lymphocyte proliferation.
How does it work?
Main SE Predinolone
Transistent neutrophilia
Hypertension
Glaucoma
Antimetabolite agent
Metabolised by liver to 6 mercaptopurine,
blocks de novo purine (eg adenine, guanine)
synthesis – prevents replication of DNA,
preferentially inhibits T cell activation &
proliferation
What is its main side effetc?
Azathropine
Bone marrow supression
inhibits dihydrofolate reductase (DHFR), therefore decreases DNA synthesis
Methotrexate
Bone Marrow Supression
Pnemottis, Pulmonary Fibrosis, Cirhiosis
What is conjugate vaccine vaccine?
Pneumococcal vaccine
A conjugate vaccine is created by covalently attaching a poor antigen to a strong antigen thereby eliciting a stronger immunological response to the poor antigen. Most commonly, the poor antigen is a polysaccharide that is attached to strong protein antigen.
A live attenuated viral vaccine
Live attenuated: BCG, MMR,
typhoid
Inactivated preparations of the bacteria
Whole cell typhoid vaccine
- Yellow fever
- BCG
- Typhoid
Extracts of or detoxified exotoxin product by a micro-organism.
tetanus vaccine
Diphtheria, Tetanus
Vaccine that is made using recombinant DNA technology.
Hepatitis B virus vaccine
An antigen assembled in a multimeric form and saponin that provokes a strong serum antibody response.
Immunostimulatory complexes (ISCOMS)
The general name for a compound which increases the immune response without altering its specificity.
Adjuvant
A vaccine given only to sero-negative women
Rubella vaccine
Management
- women normally have their immunity checked before becoming pregnant
- rubella immunity is routinely checked at the booking visit. If the no immunity is demonstrated pregnant women need to keep away from people who might have rubella
- non-immune mothers should be offered the MMR vaccination in the post-natal period
A central cytokine involved in immunological central memory
IL2
Which type of vaccine generally achieves immunisation with a single dose and is not suitable for pregnant and immunocompromised patients?
A.
Live attenuated
Which vaccine is usually given to children at 12-15 months?
MMR vaccine
Which vaccine is normally given to infants under the age of 13 months in the form of three doses at monthly intervals to protect against an infection that has symptoms similar to meningitis and predominantly occurs in children < 5 years?
Haemophilus influenzae type b vaccine
Conjugate vaccine routinely given to neonates in the UK.
H. influenzae B
Agent used in humans that promotes a predominantly antibody response through the release of Il-4 that primes naïve B-cells.
Alum
Diploid cell vaccine containing inactivated virus given before or after exposure to those considered at risk.
Rabies
Live attenuated vaccine that is no longer given as standard in the UK since the rates of reverse mutation are higher than those of active disease.
Polio (Sabin)
Subunit vaccine given to the elderly and immunocompromised
H.
Influenza
Which is recommended in all individuals over 65 years of age?
Influenza vaccine
Sterility in adult males may occur if a particular vaccine is not administered. Which one is it?
Mumps vaccine
Which vaccine is given to the mother to prevent congenital cardiac defects, eye lesions (particularly cataracts), microcephaly, mental handicap and deafness of her newborn baby?
Rubella vaccine
Which group of patients are at particularly high risk of pneumococcal disease, and are the major group that need Pneumovax revaccination after 5 years.
patients > 54
patients<65 with chronic conditions such as chronic lung disease
diabetes
Live, attenuated vaccines:
Measles, mumps, rubella (German measles), polio (Sabin vaccine), chicken pox, yellow fever, BCG
Adv: Produces a strong immune response so can provide life-long immunity with 1–2 doses.
Disadv: Not safe for people with compromised immune systems. Needs refrigeration to stay potent
2) Inactivated ‘killed’ vaccines
Cholera, Flu, hepatitis A, Rabies, Polio (Salk vaccine)
Remember SCAR (Salk vaccine, Cholera, Hep A, Rabies)
Adv: Safe for people with compromised immune systems. Easily stored and transported; does not require refrigeration.
Disadv: Usually requires booster shots every few years to remain effective.
Subunit Vaccines, example, adv and dis
This is a vaccine made of recombinant protein.
Adv:
Disadv:
Hepatitis B
Lower chance of adverse reaction.
Research can be time-consuming and difficult.
Conjugate Vaccines
Haemophilus influenzae B (or Hib) and pneumococcal vaccine
Adv:Safe for people with immune compromised systems
Disadv: Usually requires booster shots every few years to remain effective.
A water-in-oil emulsion containing mycobacterial cell wall components that could be used to increase the immune response of a vaccine.
Freund’s adjuvant
This type of vaccine activates all phases of the immune response, has the most durable immunity and is the most cross-reactive.
Live attenuated
This test measures the immune response to the BCG vaccine.
Mantoux
This form of immunity is induced by vaccination.
Active immunity
Monocytes and Macrophages
Monocytes are produced in bone marrow, circulate in blood and migrate to tissues where they differentiate to macrophages
Liver
Kidney
Bone
Spleen
Lung
Neural tissue
Connective tissue
Skin
Joints
Capable of presenting processed antigen to T cells
Kupffer cell
Mesangial cell
Osteoclast
Sinusoidal lining cell
Alveolar macrophage
Microglia
Histiocyte
Langerhans cell
Macrophage like synoviocytes
Thic cytokin deficiency may cause susceptibility to mycobacterial infections
IL12, IL12R, IFNg or IFNg R
Recurrent infections with high neutrophil count on FBC but no abscess formation
Leukocyte adhesion deficiency
Recurrent infections with hepatosplenomegaly** and **abnormal dihydrorhodamine test
Which infections are patietns predisposed to? >
Chronic granulomatous disease
PLACESS
Pseudomonas
Listeria
Aspergillius
Candidia
E.Coli
Staph Aureus
Serratia
•Recurrent infections shortly after birth with no neutrophils on FBC
•Kostmann syndrome
Infection with atypical mycobacterium. Normal FBC
IFN gamma receptor deficiency, IL-12 = cytokine deficency
•Membranoproliferative nephritis and bacterial infections
•C3 deficiency with presence of a nephritic factor
•Meningococcus meningitis with family history of sibling dying of same condition aged 6
•C9 deficiency
•Severe childhood onset SLE with normal levels of C3 and C4
•C1q deficiency
Recurrent infections when receiving chemotherapy but previously well. This pathway has two names
MBL pathway deficency
Leptin Pathway Deficency
Antibodies to Thyroglobulin and Thyroperoxidase
Hashimoto
Shared epitope in RA
P gingivalis
C. Expresses PADI enzymes capable of deiminating arginine to form citrullinated proteins
Anti-CCP antibody, where does it bind to? What is specific for?
Binds to citrullinated proteins and has ~95% specificity for development of rheumatoid arthritis
Anti-CCP antibody or ACPA
D. Binds to citrullinated proteins and has ~95% specificity for development of rheumatoid arthritis
Where does Rheumatoid factor bind to?
Binds to Fc region of IgG
Molecular Patterns. Where to they occur? ‘Lump-Bumby’ versus smooth linear pattern?
Antibodies may occur in SLE
- ANA(+)
- anti-SM
- dsDNA
- anti-Ro, anti-La, U1RNP (specled)
- anti-cardiolipin
- anti-phospholipid
How to differentiate between active and inactive SLE disease?
The activity of SLE is relaiting to the complement deficiencies.
In the active disease, the C4 will be reduced, wheres in severe active disease both C3 and C4 will be monitore
Two major types of anti-phospholipid antibodies
- cardiolipin
- B2 glycoprotein
- lupus anti-coagucalant
ANA staining is an important prognostic indicator in
XXXXX
Systemic Scleriosis
Which antibodies are ENA (+)?
anti-Ro, La, Sm, SNP
SCL70
CREST
A. Screening test for a connective tissue disease
ANA
Sometimes positive in patients with idopathic inflammatory myopathy particularly if they have interstitial lung disease
- Anti-Jo-1 (t-RNA synthetase)
- Also positive in dermatomyosistis and polymyositis
This is very important:
Which antibodies are a ) organ specific
b) ANA positive
c) ANCA associatted vascullitis
b) all starting with S
- Systemic scleriosis
- Sjorgen Syndrome
- SLE
- Dermatomyositis/polymyositis
What is human Immunoglobulin?
- Prepared from pools of >1000 donors
- Contains preformed IgG antibody to a wide range of unspecified organisms
What is Specific Immunoglobulin?
Human immunoglobulin used for post-exposure prophylaxis (passive immunisation)
Derived from plasma donors with high titres of
IgG antibodies to specific pathogens
•Hepatitis B immunoglobulin
•Tetanus immunoglobulin
•Rabies immunoglobulin
•Varicella Zoster immunoglobulin
What is the clincal use of cytokines?
- Interferon alpha -HEP C, HEP B, Kaposi Sarcoma
- Interferon beta - Relapsing MS
- Interferon gamma - Chronic granulamtous Disease
B. Part of treatment for Hepatitis C
IFN alpha
X-linked SCID treatment
Blood Marrow Transplant
Chronic Granulotamous Disease Treatment
IFN-gamma
EBV-specific CD8 T cells
A. Post-transplant lymphoproliferative disorder
Human normal immunoglobulin
C. X linked hyper IgM syndrome
G. What are two treatment options for Metastatic melanoma ?
- Blocking immune checkpoints
-
Ipilimumab – antibody specific for CTLA4 – blocks immune checkpoint and allows T
cell activation; indications: advanced melanoma
Pembrolizumab/Nivolumab – antibody specific for PD-1 - blocks immune checkpoint
and allows T cell activation; indications: advanced melanoma
When would you use the Varicella zoster immunoglobulin?
Immunosuppressed seronegative individual after chicken pox exposure
Indications for plasmapheresis
- Severe antibody-mediated disease
Goodpastures syndrome
•Anti-glomerular basement membrane antibodies
Severe acute myasthenia gravis
•Anti-acetyl choline receptor antibodies
Severe vascular rejection
•Antibodies directed at donor HLA molecules
Cyclophosphamide SE
Infertility
Azathropine SE
Neutropenia particularly if TPMT is low
Cyclosporin SE
Hypertension
Mycophenolate Mofetil SE
Progressive Multifocal Leukoencephalopathy
Antibody specific for CD25 which inhibits T cell activation and is used to prevent rejection
Basiliximab (Anti-IL2 receptor) CD25 is the alpha chain of IL-2
Inhibits T-cell activation and is effective at Rheumatoid Artheritis (CTLA4-Ig fusion protein)
Abatacept
Depletes Mature B cells and is effective in treatment of B cell lrheumatoid arthritisymphomas and
Rituximab (Anti-CD20)
Inhibtis T-cell migration (integrin and rollling prevention) but can be used in relapsing/remitting MS
Natalizumab (Anti-a4 integrin)
anti-IL-6 receptor. Inhibits function of lymphoid and myloid cells
and is used in management of RA and Castelman Disease
Tocilizumab (Anti-IL6 receptor)
B. Treatment options include inhibition
IL12/23:
TNF alpha:
IL17A:
For which conditions these medications can be used for?
Psoriasis
IL12/23: Ustekinumab
TNF alpha: Entarecept,
IL17A: Secunimab
C. Treatment options include inhibition of IL6, TNF alpha and depletion B cells
Rheumatoid arthritis:
- anti-IL (6) Toclizumab
- TNF-alpha (infliximab)
- B-cells Depletion: Rituximab
A. Treatment options include inhibition of RANK ligand
a) name the condition
2) name the medication
a) Osteoporosis
b) Densumab
•Severe recurrent infections from 3 months,CD4 and CD8 T cells absent, B cell present but immature phenotype, some IgM present, IgA and IgG absent. Normal facial features and cardiac echocardiogram
•X-linked SCID
•Young adult with chronic infection with Mycobacterium marinum
•IFN gamma receptor deficiency
•Recurrent infections in childhood, abnormal facial features, congenital heart disease, normal B cells, low T cells, normal IgM, borderline low IgA and IgG
•DiGeorge syndrome CATCH22
6 month baby with two recent serious bacterial infections. T cells present – but only CD8+ population. B cells present. IgM present bu_t IgG absent_
Bare Lymphocyte Syndrome
Adult with bronchiectasis, recurrent sinusitis and development of atypical SLE
•Common variable immunodeficiency
Recurrent bacterial infections in a child, episode of pneumocystis pneumonia, T and B cells present, high IgM, absent IgA and IgG
•X linked hyper IgM syndrome due to CD40ligand mutation
1 year old boy. Recurrent bacterial infections. CD4 and CD8 T cells present. B cells absent, IgG, IgA, IgM absent
•Bruton’s X linked hypogammaglobulinaemia
Recurrent respiratory tract infections, absent IgA, normal IgM and IgG
•IgA deficiency
A. Single gene mutation involving MEFV and affecting the inflammasome complex, resulting in recurrent episodes of serositis
B. +++ production of IL-1 → attacks of fever and inflammation of serosal
surfaces (pleura, peritoneum, synovium)
Familial Mediterranean Fever:
FAMILIAL AMYLOIDOSIS
● Several kinds, all rare
● Most common = Familial Mediterranean Fever (AR)
● +++ production of IL-1 → attacks of fever and inflammation of serosal
surfaces (pleura, peritoneum, synovium)
● Associated gene encodes pyrin
● AA amyloid, predominant renal deposition
Clinical features: caused by amyloid deposits in various organs:
(1) KIDNEY: nephrotic syndrome = most common presentation
(2) HEART: conduction defects, heart failure, cardiomegaly
(3) LIVER/SPLEEN: hepatosplenomegaly
(4) TONGUE: macroglossia in 10%
(5) NEUROPATHIES: incl carpal tunnel
C. Single gene mutation involving FOXp3 resulting in abnormality of T reg cells.
X- linked so affects boys only
IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X linked)
IPEX syndrome
- Immune dysregulation, Polyendocrinopathy, Enteropathy and X-linked inheritanc syndrome + autoimmune diseases
- Eczematous dermatitis, nail dystrophy and autoimmune skin conditions such as alopecia universalis and bullous pemphigoid
- Most affected children die within the first 2 years of life.
B. Mutation within the Fas pathway associated with lymphocytosis, lymphomas and auto-immune cytopenias
Auto-immune lymphoproliferative syndrome (ALPS)
B. Mixed pattern auto-inflammatory / auto-immune disease with >90% heritability that results in inflammation typically involving the sacro-iliac joints and responds to TNF alpha antagonists
Which allelle is it associated with?
Ankylosing spondylitis
Ankylosing spondylitis HLA B27
A. Polygenic auto-inflammatory disease. ~30% patients have a mutation of CARD15 which may affect response of myeloid cells to bacteria.
Crohn’s disease
Polygenic auto-inflammatory disease resulting in a large vessel vasculitis and requiring immediate treatment with high dose corticosteroids
Giant cell arteritis
–Involves IgE and mast cells
•Eg Anaphylaxis, Atopic asthma
•Type I Anaphylactic hypersensitivity
–Involves Ab binding to cells with complement mediated host cell destruction (or inhibition/activation or receptor signalling)
•Eg Goodpasture disease, Graves disease
•Type II Cytotoxic hypersensitivity
–Involves deposition of Ab/Ag complexes in tissue
•Eg SLE, Serum sickness
•Type III Immune complex hypersensitivity
Involves T cells and cytokines: Eg Diabetes, Contact dermatitis
Type IV: Delayed hypersensitivity
SLE
type III
Eczema
Type I hypersensitivity
Type IV hypersensitivity examples
Multiple sclerosis
Type I Diabetes
Rheumatoid Artheritis
Contact Dermitis
Mantoux Tes
Crohn’s
Goodpasture disease
Type II hypersensitivity
Managment of Anaphylaxis
•Oxygen by mask
–Improve oxygen delivery
•Adrenalin im (0.5mg for adult and may repeat)
–Acts on B2 adrenergic receptors to constrict arterial smooth muscle
- Increases blood pressure
- Llimits vascular leakage
- Bronchodilator
- Intravenous anti-histamines (10mg Chlorpheniramine)
–Acts to oppose the effects of mast-cell derived histamine
- Nebulised bronchodilators
- Improve oxygen delivery through bronchial dilatatio
- Intravenous corticosteroids (Hydrocortisone 200mgs
- Systemic anti-inflammatory agent.
- Effect takes about 30minutes to start, and does not peak for several hours.
- Important in preventing rebound anaphylaxi
- Intravenous fluids
- Increase circulating blood volume and therefore increase blood pressure
Latex has two types of sensitivity reactions
Type (I) Acute
Type (IV) Deleyed - Chronic Dermitis
What are the tests uused to describe the severity of SLE?
C4 and C3 (C4 first affected)
dsDNA
ESR
What is the name of this condition?
serum sicness
•Presenting complaint – recurrent infections
- 3 year old Caucasian Male
- Weight and height dropping from 50th centile to 10th centile
•First infection aged 3 months
–Cellulitis of gluteal region
–Responded to antibiotics
•64 year old lady is seen in A&E after slipping and injuring her left hip when getting out of the bath
•Other problems
- –Persistent back pain and generalised lethargy for 12 months
- –Three episodes of pneumococcal pneumonia in last 2 years
- –Post-menopausal – on HRT
- High IgG
- monoclonal band on the electroporesis
movement
–Clinically anaemic
Monoclonal band in gamma region, subsequently shown to be IgG lambda
Urine electophoresis: Free light chains detected - Bence Jones proteins
Q: What is the most common allergy in humans?
Allergic Rhinitis
Q1) What are the receptors required for the HIV entry?
Q2) What are the co-receptors required for the HIV entry to target cells.
- CD4 molecule/Ag is the Receptor for HIV-1.
- Most infecting strains of HIV-1 use co-receptor molecules (CCR5 and CXCR4) in addition to CD4 to enter target cells.
Indications for specific IgE testing
- Patients who can’t stop anti-histamine
- Patients with dermatographis
- Patients with extensive eczema
- History of anaphylaxis
- Borderline/equivocal skin prick test results
- Primary adjuvant utilized in humans. Antigens are adsorbed to alum so acts
as means of slowly releasing antigen. Activates Gr1+ cells to produce IL-4, helps
prime naïve B cells (mainly antibody mediated response). Generally safe and mild
- Activates TLRs on APCs stimulating expression of costimulatory molecules.
- Water-in-oil emulsion containing mycobacterial cell wall components. Mainly for animals, painful in humans (not used clinically)
- Cell-mediated immune response and humoral response. With saponin results in strong serum antibody response.
- In individuals with Hep-B-Sag in order to get them to seroconvert
- ALUMN
- CPG
- Complete Freund’s adjuvant:
- ISCOMS (Immune Stimulating Complex):
- Interleukin 2
Episodic neutropenia occuring every 3 weeks and lastiing several days.
Caused by mutation in the ELA1 gene (neutrophil elastase)
Treated with the mutations in the ELA1 gene
The most severe form of SCID
Results in absolute deficiency of neutrophils, lymphpcytes, macrophages, platlets
Reticular Dysgenesis
What is the atopic triad?
What type of reaction is it?
Eczema, asthma and hay fever
guanine synthesis
mycophenolate mofeyteil
Patients with SLE have a cross reactive antibody towards the platlets and red blood cells. Look for the signs of ITP or AIHA.
the first cytokine to be relased in response to allergen
IL-12
Pattern of antibodies in dermatomyositis
specled
what molecule is central to the pathogenesis of central systemic scleriosis? CREST
TGF-beta
