<p> Immunology Notes</p><p>Immune System  Innate Immune System  Acquired Immune System o Phagocytes o B lymphocytes o Complement o T lymphocytes   Immunodeficiency  Primary  T cell  Phagocytes  B cell (antibodies)  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  Mutation/Problem  Clinical Features/Result  X-linked  Failure of B cell maturation  No mature B cells aggammaglobulinae (DefectIve tyrosine kinase)  No antibodies (after 6 mia  months)  IgA deficiency  Unknown cause  Common (1:600)   Most asymptomaIc  – General  – Specific: respiratory tract infecIons  Hyper IgM  Most are X‐linked  Males in first few years of syndrome  MutatIon in CD40 ligand gene on life with general B cell T cells features + specific PCP  Disrupted interacIon between T infection cell and B cell  Results in:  – Failure of class switching  – Elevated IgM  – Reduced IgG, IgA, IgE   CVID  Acquired  General features hypogammaglobulinaemia  Set of 20‐30 condiIons of unknown aeIology  Variable reducIon in IgG, IgA and IgE   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  Malignancy o Viral, fungal, mycobacterial  Autoimmunity   Disease  Mutation/Problem  Clinical Features/Result  DiGeorgeʼs  Chromosomal deleIon – 22q11  Cardiac anomalies Syndrome  Pathology (Fallot’s)  – Failure of thymic development  Abnormal facies (low set  – Immunodeficiency ears/  • Reduced T cells  fish mouth/high forehead)  Thymic hypoplasia (T cell  • Normal/increased B cells  lymphopaenia)  • Reduced anIbody response  Cleft Palate •  Immunodeficiency can improve  Hypoparathyroidism with age (hypocalcaemia)  Bare L syndrome  Deficiency of CD4 cells  General features in  – Lack of expression of MHC infancy Class II  AssociaIon with primary  – Normal B cells, reduced sclerosing cholangitis IgG/IgA  Wiskott-Aldrich  MutaIon in WASP gene  Immunodeficiency + syndrome  X‐linked Thrombocytopenia &  Eczema  Lymphoma at a young age  Ataxic  MutaIon in ATM gene  Immunodeficiency + telangiectasia  Autosomal recessive Ataxia, Nystagmus &  Telangiectasia  Lymphomaa/leukaemia at a  young age  SCID  T cell +/‐ B cell problem  Infants present by 3  2 important types: months  X‐linked  - Persistent infections  • Mutation of IL‐2 receptor  - Failure to thrive (gamma chain)   • Reduced T cells/Normal B cells  Graft vs. host disease Autosomal recessive  – Funny rashes  • Adenosine deaminase  – Colonisation of bone deficiency marrow with maternal  • Reduced T and B cells lymphocytes   Phagocyte Deficiencies  General Presentation  Recurrent deep bacterial + fungal infecIons o Staph. Aureus o Candida albicans o Aspergillus fumigatus  Poor response to antibiotics   Disease  Mutation/Problem  Clinical Features/Result  Leukocyte   Delayed separation of the Adhesion umbilical cord Deficiency (LAD)  No adhesion of phagocytes  High neutrophils  Chronic  Granuloma formation  Treat with IFN‐gamma Granulomatous   No oxidative killing Disease (CGD)  Normal or high neutrophil  count  Kostmannʼs  Severe congenital neutropenia  No granulocyte precursors syndrome (KS)  No neutrophils, abnormal NBT   Cyclic  Episodic neutropenia  neutropenia    Investigations  Neutrophil count  Nitric‐blue test of oxidaIve killing (NBT  Presence of leukocyte adhesion markers test)  FormaIon of pus   Treatment  Conservative  Definitive o Manage infections aggressively o BMT o Vaccination + septrin/itraconazole o IFN therapy in chronic o Surgical drainage of abscess granulmatous disease   Complement deficiencies   Allergy  Type  Mechanisms  Examples  Type I  IgE-mediated  Allergies, Asthma hypersensitivity  Type II  IgG/IgM reactive with self  Grave’s disease, antigen Goodpastures Syndrome, Autoimmune haemolytic anaemia  Type III  Immune  Lupus, Polyarteritis complexmediated damage Nodosa  Type IV  T-cell mediated  Rheumatoid, IDDM, MS, damage/delayed Transplant rejection hypersensitivity   Clinical Features  Primary  Delayed o Skin changes o Onset 2‐24 hours after exposure, o Smooth muscle contraction o Lasts many days (lungs/gut) o Inflammatory cell infiltration o Mucus secretion (lungs) (associated tissue damage) o Vascular permeability (shock)   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                 ANA’s              Autoimmune Disease’s  Disease  Auto-antibodies  Features  SLE  Anti-sm  F:M = 9:1  Anti Ro  Serositis, Oral ulcers, Arthritis,  Anti-LA Photosensitivity, Blood changes, Renal  Anti-dsDNA involvement, ANA, Immunological changes, Neuro stuff, Malar rash, Discoid rash  Drug-induced  Anti-Histone  – Procainamide lupus  – Hydralazine  – Isoniazid  – Clindamycin  Sjogrenʼs  Ant-LA  Syndrome  Anti-Ro  RA  Anti-CCP   Diffuse  Anti-SCL 70  CREST + Pulmonary fibrosis, Renal Scleroderma disease, Polyarthritis, Myopathy/muscle atrophy  Limited  Anti-centromere  Calcinosis, Raynauds Phenomenon, Scleroderma/CRE Osephageal dismotility, Sclerodactyly, ST Telangectasia  Dermatomyositis  Anti-Jo-1  /  polymyositis  Wegnerʼs  C-ANCA  granulomatosis  Pernicious  90% anti‐parietal cell  Autoimmune attack on parietal cells - anaemia antibodies atrophic gastritis & lack of intrinsic  50% anti‐IF antibodies factor  ↓serum vit. B12  Associations: other autoimmune disease, gastric adenocarcinoma  Graveʼs disease  Anti‐TSH receptor  Low TSH antibodies  Elevated free T4 (if T4 normal –  Anti‐thyroid eroxidase/ consider T3)  anti‐thyroglobulin AB  Hashimotoʼs  Anti‐microsomal  Autoimmunne destruction of thyroid thyroiditis  Anti‐thyroglobulin  Diffuse lymphocyte infiltraIon  Anti‐peroxidase  High TSH  Firm goitre → atrophy  Mixed  Anti-RNP  Connective tissue disease  Anti-  Anti-Cardiolipin  phospholipid syndrome  Autoimmune   Autoantibodies →RBC haemolysis Haemolytic  Features of haemolysis Anaemia  Raised unconjugated bilirubin  ↓ haptoglobin  ↑LDH  ↑ urinary urobilinogen  Reticulocytes  Positive DAT test  Addisons Disease   ↑Potassium  ↓Sodium   Vasculitides  Inflammation of blood vessels, cause is largely unknown   Disease  Vessels  Features Affected  Temporal arteritis  Large  Affects carotids and temporal arteries (Giant cell arteritis)  2:1 (F:M), > 50yrs  Headache and tender over scalp “combing”  Risk of blindness  Takayasu’s  Large  Affects aorta and vessels coming off it  Asian women  20s – 30s  Difference in blood pressure between arms  Polyarteritis  Medium  Affects many organ system nodosum  Symptoms are often nonspecific  Classically affects renal vessels and coronary arteries  Kawasaki’s  Medium  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  Wegener’s  Small  Midline structures  cANCA +ve  Epistaxis, Pulmonary pain, saddle nose nodules, haemoptysis, Glomerulonephritis  Churg‐Strauss  Small  Late onset asthma, eosinophilia  Primarily the lung  Gut, kidney or nerve involvement  cANCA or pANCA +ve  Microscopic  Small  Huge number of systems affected polyangitis  pANCA +ve  Mononeuritis Multiplex, Haemoptysis, Renal failure, Skin rash   Transplantation   Timefra  Pathophysiology  Treatment me  Hyperacute  Minutes  Pre‐existing anti‐  None once it occurs rejection to hours donor antibodies  Blood groups and   Massive inflammatory HLA to detect pre‐ vasculitis→ graft existing antibodies thrombosis  Acute cellular  Days to  Recognition of CD4  Partially treated with rejection 1 month cells → activation of immunosuppressive  CD4 cells → type IV therapy hypersensitivity response  Unwell, reduction in graft function, pain/tenderness  Acute vascular  1‐2  Mediated by  Immunosuppresion rejection weeks antibodies Results in  post‐ vasculitis + transpla thrombosis nt  Chronic allograft  > 30  Major cause of graft  Manage atherogenic rejection days loss affects all types risk  post‐ of solid  Drugs with low transpla  organ transplant toxicity nt  Risk factors:  - Repeated acute rejection episodes  - Pro‐atherogenic factors  - Drug toxicity  - Non‐compliance with medication   Therapeutics in Immunology  Class  Examples  Effects  Side effects  Steroids  Prednisolon  ↓ Phagocyte  Cushingoid sx  e recruitment  Hydrocortis  ↑WCC (neutrophils) one  Lmyphocyte  Dexametha SequestraIon, sone cytotoxicity, reduced cytokine gene expression  Antiproliferative  Azathioprin  Block Purine synthesis  Danger of agents e (T>B) marrow   Cyclophosp  Blocks DNA replication suppression hamide (B>T)  Haemorrhagic  Mycopheny cystitis late  mofetil  Inhibitors of cell  Ciclosporin   NephriIs signalling  Tacrolimus  Diabetes   Gingival hypertrophy  Antibodies to cell  OKT3 (anti-  OKT3 - prevention and  surface CD3  treatment of solid  antigens  antibody) organ transplant   Anti-IL2 rejection antibody  CD25 - rejecIon  (CD25)  prophylaxis in transplantaIon  Anti-cytokine  Infliximab  Infliximab - murine  agents  Etanercept anti‐TNF antibody   Adalimuma  Etanercept - human b soluble TNF receptor  Adalimumab - human anti‐TNF antibody </p>