Immunology

Unit 22 Clinical laboratory immunology The body against others and itself.

Objectives, to know the tests in Immune disease  Autoimmune disease  Infectious disease  Allergies  Inflammatory diseases  Complement diseases  Arthritis. 

Immunoglobulins: Produced by B lymphocytes in response to foreign or self antigens.  Two light chains: kappa or lambda.  Two heavy chains: alpha, gamma, delta, epsilon or mu.  Immunoglobulins: IgA, IgG, IgD, IgE and IgM. 

Immunoglobulins: Form

Found in

Function

IgM Penta ECF,membrane 1st response. IgG Mono

ECF

Toxin, activates complement. IgA Dimer ECF, secretions Antimicrobial. IgE Mono

ECF

IgD Mono

Anti allergic/ anti parasites. ECF,membrane Unknown.

Immunoglobulin deficiency: Normal: IgM and IgA are low at birth and for months after.  Inherited agammaglobulinaemia: the “boy in the bubble”.  Acquired: malnutrition, malignancy, infections, drugs, overstress. 

Immunoglobulin excess  Paraproteins

in cancers – monoclonal. Unit 13.  Autoimmune disease – polyclonal. Units 15, 21, 22, 24,25  Infections –polyclonal. Unit 22.

Some autoimmune diseases and laboratory tests: Systemic lupus erythematosus Arthritis

Anti nuclear antibodies ANA ANA,Rheumatoid factor

Sjogren’s,scleroderma Extractable Nuclear Ag Vasculitis Anti self

Antineutrophil cytoplasmic antibodies Human leukocyte Antig

Thyroiditis

Antithyroid antibody

Infections, symptoms:  





Pain, heat, redness, swelling. Toxic reactions: rashes , muscle pains, cardio respiratory, gastrointestinal. Acute: fever, chills, flushing, increased pulse. Chronic: fatigue, lassitude, weight loss.

Infective organisms:        

Viruses Bacteriophage, plasmids, transposons. Bacteria Chlamydia, rickettsia, mycoplasma. Fungi, Protozoa Helminths Ectoparasites.

Infections, laboratory work: Erythrocyte sedimentation rate, ESR  Complete blood count, CBC  Serum C-reactive protein, CRP  Serum IgG, IgM.  Serology – specific tests for organisms.  DNA and RNA based tests. 

Laboratory work in infectious diseases:  

3. 4. 5. 6.

Most bacteria found by culture. Serological test for antibodies against bacteria are used for: Population studies post infection. Current or recent infection where culture is negative. Fever of unknown origin > 2-3 weeks. Unique applications.

Immunology issues:  Is

there an antibody?  Can it be measured?  Is it increasing or decreasing in amount?

Infections, serology and other NPLEx tests: 1.

Antistreptolysin O: streptococcus pyogenes.

Note: this is by titration. Increases a week after infections Peaks at 3-5 weeks. 6-12 months to normal.

NPLEx infectious serology: 2. Chlamydia. Note: may be STD or from parrots. 50% men 70% women have no symptoms.

NPLEx infectious serology: 3. Cytomegalovirus IgG and IgM. 4. Epstein Barr virus: Monospot IgG. 5. Escherichia coli:

NPLEx infectious serology: 6. Helicobacter pylori. IgG and IgA seen in 80-100% with infection. Elderly 60% positive.

NPLEx infectious serology: 7. Hepatitis viruses A, B, C, D, E. 8. Herpes simplex: HSV1, HSV2. Most adults have had this.

Infectious disease testing (continued) 9. Human Immunodeficiency virus: HIV-IgG, HIV load, CD4, CD8. P24 soon after infections but fades away. HIV-1 Ab 4-12 weeks after infection. No Ab just before death and p24 etc antigens increase. CD4 and CD8 response to treatment.

NPLEx serology 10. Human papilloma virus. 16 type causes cancer. A success! 11. Rubella. Very serious to foetus in pregnant women. 12. Syphilis: VDRL, RPR (screening test). Tests positive 2-3 weeks after infection.

NPLEx infectious serology: 13. Tuberculosis: BCG, Bovine TB given. Skin test 1-3 days later see reaction 14. Lyme disease.

Allergy testing: 1.

2.

RAST: serum IgE, general and specific tests. Skin prick test.

Inflammation markers:    

Erythrocyte sedimentation rate (ESR). Plasma viscosity. Serum C-reactive protein- acute phase reactant. Other serum acute phase reactants: complement, ceruloplasmin, haptoglobulin, fibrinogen, alpha-1antitrypsin, alpha-1-acid glycoprotein (orosomucoid).

Acute phase reactants:  Illness  Infection  Trauma  Tissue

necrosis.

Serum C-reactive protein 





Always: rheumatic fever, rheumatoid arthritis, acute bacterial infections, viral hepatitis, myocardial infarction – high sensitivity version Frequent: active tuberculosis TB, gout, advanced malignancy, leprosy, active cirrhosis, burns, peritonitis. Sometimes: multiple sclerosis, GuillainBarre, scarlet fever, varicella, post surgery, intrauterine contraception.

Serum complement Classical – triggered by antigen/antibody.  Alternate – triggered by foreign and cell surfaces.  Recognition: C1q, C1r, C1s,  Activation: C2, C3, C4.  Membrane attack: C5, C6, C7, C8, C9. 

Serum complement, clinical  Systemic

lupus erythematosusdeficiency in serum C1q, C1r, C1s, C2 or C4.  Rheumatoid arthritis - some have decreased serum C1.  Most have decreased serum C2 and C4.

Complement, laboratory measurements:  Whole

system: serum CH50.  Assay of individual components; serum C3 and C4.  Activation: serum C1q, C2, C3 and C4.

7 elite Swedish orienteers aged 25-29 years from Dala Sudden unexplained deaths (really 20) Possible explanations:  Viral infection TWAR  Coronary disease  Lyme disease  Inbreeding  Dope: amphetamines, cocaine, steroids. EPO… 

Official explanation 

Virus infection.

But  Why is this not seen in parallel sports and activities.  The consequence of official action….

SUD, what the Swedes did No orienteering competition allowed for 6 months (1992).  National team disbanded.  No foreign visitors for training or competition. 



No further cases reported.