Immuno Revision Notes

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Immunology Notes
Immune System
 Innate Immune System
o Phagocytes
o Complement
Immunodeficiency
Primary
 T cell
 B cell (antibodies)

Acquired Immune System
o B lymphocytes
o T lymphocytes


Phagocytes
Complement
General features
 Recurrent infections (number, organisms, sites, sensiIvity to antibioIcs)
 Unexplainable symptoms
o Failure to thrive
o Chronic diarrhoea, chronic mouth ulceraIon/thrush
 Specific features to each group/condition
Secondary/Acquired
 Age
 Malnutrition
 Pathology
o Haem. Malignancies/InfecIons/Organ failure
 Drugs
o Steroids, DMARDs, chemotherapy
B Cell Deficiencies
Disease
X-linked
aggammaglobulinaemia
Mutation/Problem
Failure of B cell maturation (DefectIve
tyrosine kinase)
Clinical Features/Result
No mature B cells
No antibodies (after 6 months)
IgA deficiency
Unknown cause
Hyper IgM syndrome
Most are X‐linked
MutatIon in CD40 ligand gene on T cells
Disrupted interacIon between T cell and
B cell
Results in:
– Failure of class switching
– Elevated IgM
– Reduced IgG, IgA, IgE
Common (1:600)
Most asymptomaIc
– General
– Specific: respiratory tract
infecIons
Males in first few years of life
with general B cell features +
specific PCP infection
CVID
Acquired hypogammaglobulinaemia
Set of 20‐30 condiIons of unknown
aeIology
Variable reducIon in IgG, IgA and IgE
General features
Investigations
 Lymphocyte counts + serum immunoglobulins
 Flow cytometry
 Measure antibody response to known pathogens (tetanus, H.influenza, Strep. Pneumoniae)
Management
 Ig replacement – i.v. every 3‐4 weeks
 Immunisation is not effective (except IgA)
T cell deficiencies
General PresentaIon
 Infections
o Viral, fungal, mycobacterial
Disease
DiGeorgeʼs Syndrome
Bare L syndrome
Wiskott-Aldrich syndrome


Malignancy
Autoimmunity
Mutation/Problem
Chromosomal deleIon – 22q11
Pathology
– Failure of thymic development
– Immunodeficiency
• Reduced T cells
• Normal/increased B cells
• Reduced anIbody response
• Immunodeficiency can improve with
age
Deficiency of CD4 cells
– Lack of expression of MHC Class II
– Normal B cells, reduced IgG/IgA
MutaIon in WASP gene
X‐linked
Ataxic telangiectasia
MutaIon in ATM gene
Autosomal recessive
SCID
T cell +/‐ B cell problem
2 important types:
X‐linked
• Mutation of IL‐2 receptor (gamma
chain)
• Reduced T cells/Normal B cells
Autosomal recessive
• Adenosine deaminase deficiency
• Reduced T and B cells
Phagocyte Deficiencies
General Presentation
 Recurrent deep bacterial + fungal infecIons
o Staph. Aureus
o Candida albicans
o Aspergillus fumigatus
Clinical Features/Result
Cardiac anomalies (Fallot’s)
Abnormal facies (low set ears/
fish mouth/high forehead)
Thymic hypoplasia (T cell
lymphopaenia)
Cleft Palate
Hypoparathyroidism
(hypocalcaemia)
General features in infancy
AssociaIon with primary
sclerosing cholangitis
Immunodeficiency +
Thrombocytopenia & Eczema
Lymphoma at a young age
Immunodeficiency + Ataxia,
Nystagmus & Telangiectasia
Lymphomaa/leukaemia at a
young age
Infants present by 3 months
- Persistent infections
- Failure to thrive
Graft vs. host disease
– Funny rashes
– Colonisation of bone marrow
with maternal lymphocytes

Poor response to antibiotics
Disease
Leukocyte Adhesion
Deficiency (LAD)
Mutation/Problem
Chronic Granulomatous
Disease (CGD)
Granuloma formation
Kostmannʼs syndrome
(KS)
Severe congenital neutropenia
Cyclic neutropenia
Episodic neutropenia
Investigations
 Neutrophil count
 Presence of leukocyte adhesion markers
Treatment
 Conservative
o Manage infections aggressively
o Vaccination + septrin/itraconazole
o Surgical drainage of abscess
Clinical Features/Result
Delayed separation of the umbilical
cord
No adhesion of phagocytes
High neutrophils
Treat with IFN‐gamma
No oxidative killing
Normal or high neutrophil count
No granulocyte precursors
No neutrophils, abnormal NBT



Nitric‐blue test of oxidaIve killing (NBT
test)
FormaIon of pus
Definitive
o BMT
o IFN therapy in chronic
granulmatous disease
Complement deficiencies
Allergy
Type
Type I
Type II
Type III
Type IV
Mechanisms
IgE-mediated hypersensitivity
IgG/IgM reactive with self antigen
Immune complexmediated
damage
T-cell mediated damage/delayed
hypersensitivity
Examples
Allergies, Asthma
Grave’s disease, Goodpastures
Syndrome, Autoimmune
haemolytic anaemia
Lupus, Polyarteritis Nodosa
Rheumatoid, IDDM, MS,
Transplant rejection
Clinical Features
 Primary
o Skin changes
o Smooth muscle contraction
(lungs/gut)
o Mucus secretion (lungs)
o Vascular permeability (shock)

Delayed
o Onset 2‐24 hours after exposure,
o Lasts many days
o Inflammatory cell infiltration
(associated tissue damage)
Investigations
 RAST
o Quantity of IgE to proposed antigen
o Less sensitive and specific cf. skin prick
o Useful for dermatographism; Hx of anaphylaxis; cannot stop antihistamine
 Mast Cell Tryptase
o During an acute episode (1‐6 hours after)
 Skin Prick Testing
o Gold standard test
o Rapid; cheap; sensitive; specific
o Safe (relatively)
o Anti‐histamines stopper prior to testing
o Ineffective in food allergies
Management
 Avoidance of allergen
 Supportive (bronchodilators/adrenaline/fluids)
 Drugs
o Block MC activation – sodium chromoglycate
o H1‐receptor antagonists – antihistamines
o Anti‐inflammatory – corticosteroids
o Leukotriene receptor antagonist ‐montelukast
 Allergen specific immunotherapy
Autoimmunity
Hypersensitivity
 Inappropriate immune reaction that produces Issue damage on exposure to an antigen
Autoimmune Disease
 Immune reaction produces Issue damage due to a reaction against self‐protein
 Breakdown in self‐tolerance
Central tolerance – failure to delete autoreactive T cells in thymus/ B cells in bone marrow
Peripheral tolerance – reactivation of weakly autoreactive T/B cells, Inflammation, infection, tissue
damage
Autoimmune Disease
Organ Specific
Non-Organ Specific
Hashimoto’s
Graves’
Pernicious anaemia
Addison’s disease
Lupus
Scleroderma
Rheumatoid
ANA’s
ANA
dsDNA
SLE
Autoimmune Disease’s
Disease
SLE
ENA
Ro, La SLE, Sjogrens (Cross placenta)
Sm SLE (v. Specific)
RNP MCTD, SLE
Jo-1 Myositis
Anti-centromere CREST
Anti-SCL70 Diffuse Scleroderma
Anti-CCP Rh. Arthritis
Auto-antibodies
Anti-sm
Anti Ro
Anti-LA
Anti-dsDNA
Drug-induced lupus
Anti-Histone
Sjogrenʼs Syndrome
Ant-LA
Anti-Ro
Anti-CCP
Anti-SCL 70
RA
Diffuse Scleroderma
Limited
Scleroderma/CREST
Anti-centromere
Dermatomyositis/
polymyositis
Wegnerʼs
granulomatosis
Pernicious anaemia
Anti-Jo-1
Features
F:M = 9:1
Serositis, Oral ulcers, Arthritis,
Photosensitivity, Blood changes, Renal
involvement, ANA, Immunological changes,
Neuro stuff, Malar rash, Discoid rash
– Procainamide
– Hydralazine
– Isoniazid
– Clindamycin
CREST + Pulmonary fibrosis, Renal disease,
Polyarthritis, Myopathy/muscle atrophy
Calcinosis, Raynauds Phenomenon,
Osephageal dismotility, Sclerodactyly,
Telangectasia
C-ANCA
90% anti‐parietal cell
antibodies
Autoimmune attack on parietal cells - atrophic
gastritis & lack of intrinsic factor
50% anti‐IF antibodies
Graveʼs disease
Hashimotoʼs thyroiditis
Anti‐TSH receptor antibodies
Anti‐thyroid eroxidase/
anti‐thyroglobulin AB
Anti‐microsomal
Anti‐thyroglobulin
Anti‐peroxidase
Mixed Connective tissue Anti-RNP
disease
Anti-phospholipid
Anti-Cardiolipin
syndrome
Autoimmune Haemolytic
Anaemia
Addisons Disease
↓serum vit. B12
Associations: other autoimmune disease,
gastric adenocarcinoma
Low TSH
Elevated free T4 (if T4 normal – consider T3)
Autoimmunne destruction of thyroid
Diffuse lymphocyte infiltraIon
High TSH
Firm goitre → atrophy
Autoantibodies →RBC haemolysis
Features of haemolysis
Raised unconjugated bilirubin
↓ haptoglobin
↑LDH
↑ urinary urobilinogen
Reticulocytes
Positive DAT test
↑Potassium
↓Sodium
Vasculitides
 Inflammation of blood vessels, cause is largely unknown
Disease
Temporal arteritis (Giant cell
arteritis)
Vessels Affected
Large
Takayasu’s
Large
Polyarteritis nodosum
Medium
Kawasaki’s
Medium
Wegener’s
Small
Features
Affects carotids and temporal arteries
2:1 (F:M), > 50yrs
Headache and tender over scalp “combing”
Risk of blindness
Affects aorta and vessels coming off it
Asian women
20s – 30s
Difference in blood pressure between arms
Affects many organ system
Symptoms are often nonspecific
Classically affects renal vessels and coronary arteries
Affects Children
? secondary to infection
- Fever for more than 5 days
-Erythema/desquamation of palms and soles
- Cervical lymphadenopathy
- Conjunctivitis
- Changes to lips/oral cavity = dry, swollen,
strawberry tongue
- Erythematous rash
Midline structures
cANCA +ve
Churg‐Strauss
Small
Microscopic polyangitis
Small
Epistaxis, Pulmonary pain, saddle nose nodules,
haemoptysis, Glomerulonephritis
Late onset asthma, eosinophilia
Primarily the lung
Gut, kidney or nerve involvement
cANCA or pANCA +ve
Huge number of systems affected
pANCA +ve
Mononeuritis Multiplex, Haemoptysis, Renal failure,
Skin rash
Transplantation
Hyperacute rejection
Acute cellular rejection
Acute vascular rejection
Chronic allograft
rejection
Timeframe
Minutes to
hours
Pathophysiology
Pre‐existing anti‐donor
antibodies
Massive inflammatory
vasculitis→ graft thrombosis
Days to 1 month Recognition of CD4 cells →
activation of CD4 cells →
type IV hypersensitivity
response
Unwell, reduction in graft
function, pain/tenderness
1‐2 weeks
Mediated by antibodies
post‐transplant Results in vasculitis +
thrombosis
> 30 days
Major cause of graft loss
post‐transplant affects all types of solid
organ transplant
Risk factors:
- Repeated acute rejection
episodes
- Pro‐atherogenic factors
- Drug toxicity
- Non‐compliance with
medication
Therapeutics in Immunology
Class
Examples
Steroids
Prednisolone
Hydrocortisone
Dexamethasone
Antiproliferative agents
Inhibitors of cell
signalling
Azathioprine
Cyclophosphamide
Mycophenylate
mofetil
Ciclosporin
Tacrolimus
Treatment
None once it occurs
Blood groups and HLA to
detect pre‐existing
antibodies
Partially treated with
immunosuppressive therapy
Immunosuppresion
Manage atherogenic risk
Drugs with low toxicity
Effects
Side effects
↓ Phagocyte recruitment
↑WCC (neutrophils)
Lmyphocyte SequestraIon,
cytotoxicity, reduced cytokine
gene expression
Block Purine synthesis (T>B)
Blocks DNA replication (B>T)
Cushingoid sx
Danger of marrow
suppression
Haemorrhagic cystitis
NephriIs
Diabetes
Gingival hypertrophy
Antibodies to cell
surface
antigens
OKT3 (anti-CD3
antibody)
Anti-IL2 antibody
(CD25)
Anti-cytokine agents
Infliximab
Etanercept
Adalimumab
OKT3 - prevention and
treatment of solid organ
transplant rejection
CD25 - rejecIon
prophylaxis in transplantaIon
Infliximab - murine anti‐TNF
antibody
Etanercept - human soluble
TNF receptor
Adalimumab - human anti‐TNF
antibody
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