NIELL Key Concepts in Immunology and Serology

Emil von Behring

Serum antitoxins

Robert Koch

Cellular immunity in TB

Elie Metchnikoff

Phagocytosis

Charles Richet

Anaphylaxis

Paul Ehrlich

Immunity

Jules Bordet

Complement

Karl Landsteiner

Human blood group antigens

Macfarlane Bumet, Peter Medawar

Discovery of immunologic tolerance

Gerald Edelman, Rodney Porter

Structure of antibodies

Rosalyn Yalow

Radioimmunoassay

George Snell, Jean Dausset, Baruj Benaceraf

Major histocompatibility complex

Niels Jeme Georges Koehler, Cesar Milstein

Immunoregulation

Susumu Tonegawa

Antibody diversity

Edward Donnall Thomas, Joseph Murray

Transplantation

Peter Doherty, Rolf Zinkernagel

Cytotoxic T cell recognition of virally infected cells

Francoise Barré-Sinoussi, Luc Montagnier

Human immunodeficiency virus

Cross-immunity

(cowpox, smallpox)

Edward Jenner

Father of Immunology, attenuated vaccines

Louis Pasteur

Discovery of the T cell receptor gene 1984

Neutrophil

First responder to infection, phagocytosis

Eosinophil

Kill parasites, neutralize basophils and mast cell products, regulate mast cells

Basophil

Induce and maintain allergic reactions, stimulate production of IgE

Mast Cell

Antigen presentation to T and B cells; enhancement and suppression of the adaptive immune response

Monocyte

Phagocytosis; kill intracellular parasites; tumoricidal activity; antigen presentation to T and B cells

Spleen

Filters blood

Lymph Nodes

Places where contact between T cells, antigens and B cells occur

Mucosal-associated lymphoid tissue (MALT)

Cutaneous-associated lymphoid tissue (CALT)

Plasma cells

Abundant cytoplasmic immunoglobulin and little to no surface immunoglobulin; represent the most fully differentiated lymphocyte.

CLASS I MHC MOLECULES

All nucleated cells.

CLASS II MHC MOLECULES

B cells, monocytes, macrophages, dendritic cells, thymic epithelial cells.

STRUCTURE of CLASS I MHC

One a chain and β2-microglobulin.

STRUCTURE of CLASS II MHC

An a chain and β chain.

CHARACTERISTICS OF ACUTE-PHASE REACTANTS

Proteins that increase in concentration during inflammation.

CRP

Increases 1000x in 4-6 hours; functions in opsonization and complement activation.

SERUM AMYLOID A

Increases 1000x in 24 hours; activates monocytes and macrophages.

ALPHA1-ANTITRYPSIN

Increases 2-5x in 24 hours; functions as a protease inhibitor.

FIBRINOGEN

Increases 2-5x in 24 hours; involved in clot formation.

HAPTOGLOBIN

Increases 2-10x in 24 hours; binds hemoglobin.

CERULOPLASMIN

Increases 2x in 48-72 hours; binds copper and oxidizes iron.

COMPLEMENT C3

Increases 2x in 48-72 hours; functions in opsonization and lysis.

IL-6

A cytokine that induces secretion of immunoglobulin and is a major factor in induction of the acute phase reaction.

EPITOPE

Single antigenic determinant; functionally the portion of an antigen that combines with an antibody paratope.

PARATOPE

Part of the antibody molecule that makes contact with the antigenic determinant.

ISOTYPE

Unique amino acid sequence that is common to all immunoglobulin molecules of a given class in a given species.

ALLOTYPE

Minor variation in amino acid sequence in a particular class of immunoglobulin molecule that is inherited in Mendelian fashion.

IDIOTYPE

Variable portion of light and heavy immunoglobulin chains that is unique to a particular immunoglobulin molecule; this region constitutes the antigen-binding site.

CLASSICAL PATHWAY

Initiated by immune complexes, apoptotic cells, certain viruses and gram-negative bacteria, C-reactive protein bound to ligand.

ALTERNATIVE PATHWAY

Initiated by various bacteria, fungi, viruses, or tumor cells.

MANNOSE-BINDING LECTIN

Initiated by microbes with terminal mannose groups.

C1q

Binds to Fc of IgM and IgG in the classical pathway.

C3

Key intermediate in all pathways of the complement system.

C5

Initiates membrane attack complex.

C1INH

Dissociates C1r and C1s from C1q.

C2

Most common deficiency associated with lupus-like syndrome and recurrent infections.

TYPE I HYPERSENSITIVITY

Immediate immune reaction mediated by IgE.

TYPE II HYPERSENSITIVITY

Cytotoxic immune reaction mediated by IgG or IgM.

TYPE III HYPERSENSITIVITY

Immune complex-mediated reaction.

TYPE IV HYPERSENSITIVITY

Delayed cell-mediated immune reaction.

GRAFT-VERSUS-HOST DISEASE

Occurs 100 days or more after transplant.

Immune complex disorder

A condition characterized by the formation of immune complexes that can lead to tissue damage.

Immunopathologic damage

Tissue injury caused by immune responses, often seen in transplantation scenarios.

Antinuclear antibodies (ANA)

Autoantibodies that target substances within the nucleus of cells, used in the diagnosis of autoimmune diseases.

Homogenous ANA pattern

Characterizes anti-deoxyribonucleoprotein antibodies, typically seen in rheumatoid disorders and suggestive of systemic lupus erythematosus (SLE).

Peripheral ANA pattern

Associated with active SLE and Sjögren's syndrome, occurring in the presence of antibodies to extractable nuclear antigens.

Speckled ANA pattern

A mottled pattern associated with various rheumatic diseases, including SLE and Sjögren's syndrome.

Nucleolar ANA pattern

Reflects an antibody to nucleolar RNA, present in about 50% of patients with scleroderma and SLE.

Anti-centromere antibody (ACA)

Antibody that reacts with centromeric chromatin, highly selective for the CREST variant of progressive systemic sclerosis.

Anti-ds DNA antibodies

Most specific for SLE, primarily seen in patients with lupus.

CREST syndrome

A subset of scleroderma characterized by calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia.

Anti-CCP antibodies

Highly specific indicator for rheumatoid arthritis (RA).

Myasthenia gravis

An autoimmune disorder characterized by acetylcholine-receptor blocking antibodies.

Multiple sclerosis

An autoimmune disease characterized by anti-myelin antibodies.

Goodpasture's syndrome

An autoimmune disorder characterized by anti-glomerular basement membrane antibodies.

Primary biliary cirrhosis

An autoimmune disease characterized by anti-mitochondrial antibodies.

Chronic active hepatitis

An autoimmune condition characterized by anti-smooth muscle antibodies.

Hashimoto's thyroiditis

An autoimmune disorder characterized by anti-thyroglobulin antibodies.

Graves' disease

An autoimmune disorder characterized by anti-TSH receptor antibodies.

Sensitivity

The proportion of people who have a specific disease and have a positive test for that disease, calculated as TP/(TP+FN)x100.

Specificity

The proportion of people who do not have the disease and have a negative test for that condition, calculated as TN/(TN+FP)x100.

Positive predictive value

The probability that a person with a positive screening test actually has the disease, calculated as TP/(TP+FP)x100.

Negative predictive value

The probability that a person with a negative screening test does not have the disease, calculated as TN/(TN+FN)x100.

Nephelometry

A technique that measures light scattered at an angle to indicate the amount of antigen or antibody present.

Radial immunodiffusion

A technique where antigen diffuses out into gel infused with antibody, with measurement of the radius indicating concentration of the antigen.

Ouchterlony double diffusion

A technique where both antigen and antibody diffuse from wells in a gel, with precipitate indicating the relationship of antigens.

Immunoelectrophoresis

A technique for differentiating serum proteins by electrophoresis followed by direct application of antibody to the gel.

Immunofixation electrophoresis

A technique used to detect over- or underproduction of antibody.

Indirect (passive) agglutination

A technique where particles coated with antigens indicate the presence of patient antibody.

Reverse-passive agglutination

A technique where particles coated with reagent antibody indicate the presence of patient antigen.

AGGLUTINATION INHIBITION

Lack of agglutination is a positive test, indicating the presence of patient antigen.

HEMAGGLUTINATION INHIBITION

Lack of agglutination is a positive test, indicating the presence of patient's antibody.

COMPETITIVE ASSAY

Patient antigen competes with labeled antigen for limited antibody-binding sites. The more patient antigen is present, the less the label detected.

NONCOMPETITIVE OR INDIRECT ELISA

Excess solid-phase antigen binds patient antibody and a second labeled antibody is added. Amount of label is directly proportional to the amount of patient antibody present.

CAPTURE OR SANDWICH ASSAY

Excess solid-phase antibody binds patient antigen and a second labeled antibody is added. Amount of label is directly proportional to the amount of antigen present.

HOMOGENOUS ASSAY

NO SEPARATION STEP. Patient antigen and enzyme-labeled antigen react with reagent antibody in solution. Inverse ratio between patient antigen and amount of label detected.

DIRECT FLUORESCENT ASSAY

Patient antigen is attached to a slide. Specific fluorescent-labeled antibody is added. If fluorescence is detected, patient antigen is present and the test is positive.

INDIRECT FLUORESCENT ASSAY

Reagent antigen is attached to a slide. Patient antibody is allowed to react. A second fluorescent-labeled antibody is added. If fluorescence is detected, patient antibody is present and the test is positive.

FLUORESCENT POLARIZATION

Fluorescent-labeled antigen competes with patient antigen for a limited number of soluble antibody-binding sites. Inverse ratio between patient antigen and amount of polarization.

IMMUNOCHROMATOGRAPHIC TEST

Patient sample is added to a test strip and migrates through the strip. Labeled antigen or antibody binds and is captured by a second reagent in the detection zone.

DIRECT MICROSCOPIC TEST

Uses darkfield microscopy to detect T.pallidum from patient. Requires active lesion and good specimen; inexpensive.

FLUORESCENT ANTIBODY TEST

Uses antitreponemal antibody with fluorescent tag to detect T.pallidum from patient. Requires active lesion; more specific than darkfield.