Immunity And Clinical Medicine
Clinical immunology is a specialty in its own right and there are many excellent textbooks devoted to it. Here we can only summarize the most common conditions encountered by the clinical immunologist, arranged by organs and/or systems rather than, as elsewhere in this book, by mechanism. Obviously there are frequent overlaps with other disciplines, which is why the clinical immunologist is expected to be familiar with all branches of pathology and medicine. For example, a case of myeloma could present to the accident and emergency department (A&E) with a fracture or be referred to the rheumatology department because of bone pain, to urology because of renal failure, to haematology because of anaemia, to immunology because of immunodeficiency, or even to the neurology or eye clinic. Abnormalities may be picked up by the radiologist, by the haematologist in a marrow biopsy, or simply from serum electrophoresis or a urine test. In the same way any patient with liver, kidney, lung, joint or skin disease, or with an unusual infection, should be looked at with the immunological possibilities in mind. The figure can be used as a checklist; brief details are provided on the opposite page. Remember that immune status is critical when considering vaccination, transplantation and in monitoring the course of AIDS.
CNS Blood–brain barrier keeps out most infections.
1 Meningitis: usually bacterial; encephalitis more often viral (NB prions: Creutzfeldt–Jakob disease [CJD]).
2 Multiple sclerosis: plaques of demyelination in brain, with Ig in cerebrospinal fluid (CSF); progressive with remissions, IFNβ delays progression.
3 Guillain–Barré syndrome: demyelination in peripheral nerve post infection; normally complete recovery.
4 Myasthenia gravis: autoimmune destruction of acetylcholine recep- tors at nerve–muscle junction; muscle fatigue; maternal antibody can affect neonate; plasmapheresis to remove antibody.
Eye The eye, open to the air, is protected from infection by tears, lysozyme and IgA.
5 Common infections: adenovirus, Streptococcus pneumoniae (con- junctiva), trachoma (eyelid), CMV, Toxoplasma spp. (retina), congeni- tal rubella (lens).
6 Uveitis: common in rheumatic and other systemic autoimmune diseases.
7 Sympathetic ophthalmia after unilateral damage.
8 Corneal grafts: 65% non-rejection.
• Hepatitis B and C: damage to liver cells by chronic cytotoxic T-cell activation, not by virus; 10% (B) and 50% (C) become carriers. Persistent ‘chronic active’ disease, may lead to cirrhosis, carcinoma. Congenital adrenal hyperplasia (CAH) may also be autoimmune, Wilson’s disease (copper), haemochromatosis (iron). Hepatitis A and B vaccines available.
• Primary biliary cirrhosis: autoimmune, with antimitochondrial anti- bodies; probably bacterial cross-reaction.
• Possibility of transplant for liver failure.
• Sjögren’s syndrome: salivary gland autoimmunity; dry mouth.
• Pernicious anaemia: autoimmune gastritis plus antibody to intrinsic factor; vitamin B12 not absorbed.
• Coeliac disease: α-gliadin hypersensitivity leading to jejunal malabsorption. Controlled by gluten-free diet.
• Crohn’s disease: constricting granulomas in small intestine. May result from granulocyte functional deficit.
• Ulcerative colitis: ulcers may bleed. Both ulcerative colitis and Crohn’s disease show lymphocytic infiltration.
Connective tissue and joints
• Rheumatoid arthritis: IgM antibodies to IgG (rheumatoid factor [RF]) in 70%, suggestive but not diagnostic. No infectious cause identified. May be changes in lung, skin, blood vessels, etc. T cells, plasma cells, macro- phages, cytokines in joints. Blocking TNF effective.
• Seronegative arthritis (i.e. no RF): includes ankylosing spondylitis (90 times greater risk if HLA-B27) and Reiter’s disease (post bowel or genitourinary infection – ‘reactive’ arthritis).
• Systemic lupus erythematosus: multiorgan pathology (lung, kidney, skin rash, brain); antibodies to nuclei (ANA), dsDNA, 25% have RF. High circulating interferon levels. Some cases due to drugs.
• Systemic sclerosis: multiorgan, may have RF, ANA, CREST syndrome (calcinosis, Raynaud’s, oesophageal dysmotility, sclerodactyly, telangiectasia).
• Polymyositis: muscle and joint lesions.
• Dermatomyositis: muscle, joints, skin.