Comprehensive Immunology and Immunohematology Review

Acute phase reactants

Proteins that ↑due to infection, injury, trauma (e.g., C-reactive protein, alpha-1 antitrypsin, haptoglobin, fibrinogen, ceruloplasmin, alpha-1 acid glycoprotein, complement).

Alloantibody

Antibody formed in response to antigens from individuals of same species.

Antigen (ag)

Foreign substance that stimulates antibody production. Large, complex molecules (MW >10,000), usually protein or polysaccharide.

Antibody (ab)

Immunoglobulin produced by plasma cells in response to ag.

Autoantibody

Ab against self.

Avidity

Strength of bond between ag & ab.

Chemokines

Cytokines that attract cells to a particular site. Important in inflammatory response.

Chemotaxis

Migration of cells toward chemokine.

Clusters of differentiation (CD)

Antigenic features of leukocytes.

Cytokines

Chemicals produced by activated immune cells that affect function of other cells. Includes interferons, chemokines, tumor necrosis factors, transforming growth factors, colony stimulating factors, interleukins.

Epitope

Determinant site on ag.

Hapten

Low molecular weight substance that can bind to ab once it's formed, but is incapable of stimulating ab production unless bound to larger carrier molecule.

Histamine

Vasoactive amine released from mast cells & basophils during allergic rxn.

Hypersensitivity

Heightened state of immune responsiveness that causes tissue damage in host.

Immunity

Resistance to infection.

Immunogen

Any substance capable of inducing immune response.

Immunoglobulin (Ig)

Antibody.

Immunology

Study of reactions of host when exposed to foreign substances.

Inflammation

Cellular & humoral mechanisms involved in reaction to injury or infection.

Interferons

Cytokines with antiviral properties. Also active against certain tumors & inflammatory processes.

Interleukins

Cytokines produced by leukocytes that affect inflammatory response through ↑in soluble factors or cells.

Ligand

Molecule that binds to another molecule of complementary configuration; the substance being measured in an immunoassay.

Lysozyme

Enzyme found in tears & saliva that attacks cell walls of microorganisms.

Major histocompatibility complex (MHC)

System of genes that control expression of MHC molecules found on all nucleated cells; originally referred to as human leukocyte antigens (HLA).

Monoclonal antibody

Ab derived from a single B-cell clone.

Opsonin

Serum proteins that attach to foreign substance & enhance phagocytosis.

Phagocytosis

Engulfment of cells or particulate matter by neutrophils & macrophages.

Plasma cells

Transformed B cells that secrete ab.

Polyclonal antibody

Ab produced by many B-cell clones.

Postzone

Reduced ag/ab complexes due to ag excess. Can cause false neg in serological test for ab. Repeat test in 1-2 wk.

Prozone

Reduced ag/ab complexes due to ab excess. Can cause false neg in serological test for ab. Dilute serum & retest.

Seroconversion

Change of serological test from neg to pos due to development of detectable ab.

Serum sickness

Type III hypersensitivity reaction that results from buildup of abs to animal serum used in some passive immunizations.

Thymus

Small, flat bilobed organ found in thorax; site of T-lymph development. One of the primary lymphoid organs.

Titer

Means of expressing ab concentration; reciprocal of highest dilution with pos rxn.

Vaccination

Injection of immunogenic material to induce immunity.

Zone of equivalence

When # of multivalent sites of ag & ab are approximately equal. Results in optimal precipitation.

Cell mediated

Defense against viruses, fungi, mycobacteria, other intracellular pathogens, tumor cells; involves T lymphs and macrophages.

Humoral

Antibody mediated defense against bacteria (extracellular); involves B lymphs and plasma cells.

Natural or innate immunity

Defense mechanisms present at birth. Not ag specific. Includes external defense system and internal defense system.

Acquired or adaptive immunity

Defense mechanisms that are antigen specific.

Naturally acquired active immunity

Individual infected with microorganism produces ab; example: clinical or subclinical infection.

Artificially acquired active immunity

Individual exposed to ag through vaccine develops immunity without having infection; examples: DTaP, MMR, polio, tetanus, Hib vaccine.

Naturally acquired passive immunity

Individual protected by abs produced by another person; example: maternal abs that cross placenta & are present in breast milk.

Artificially acquired passive immunity

Individual receives immune globulin containing abs produced by another person; examples: Rh immune globulin, HBIG, antitoxins.

Granulocytes

Include neutrophils, eosinophils, and basophils; involved in phagocytosis and inflammatory response.

Neutrophils

Phagocytosis, inflammatory response; respond to chemotaxins and contain bactericidal enzymes.

Eosinophils

Some phagocytic ability; neutralization of basophil & mast cell products; destruction of some helminths.

Basophils

Involved in hypersensitivity rxn; granules contain histamine, heparin, eosinophil chemotactic factor A.

Monocytes

Phagocytosis; migrate to tissues and become macrophages.

Mast cells

Involved in hypersensitivity rxn; resemble basophils but larger with more granules.

Macrophages

Activated by contact with microorganisms or cytokines from T lymphs; involved in phagocytosis and ag presentation.

Dendritic cells

Initiate acquired immune response; involved in phagocytosis and presentation of ag to helper T lymphs.

Natural killer (NK) cells

1st line of defense against tumor cells & cells infected with viruses; lack specificity.

T lymphs

Cell-mediated immunity; derived from cells in bone marrow.

Helper/inducer T cells

CD4+; orchestrate cell-mediated immunity and activate B cells, cytotoxic cells, & NK cells.

Cytotoxic/suppressor T cells

CD8+; suppressor cells inhibit helper T cells, cytotoxic cells kill other cells.

T regulatory cells

Suppress immune response to self.

B lymphs

Transform into blasts that give rise to plasma cells & memory cells after antigenic challenge.

Memory cells

Respond to ag when encountered again with ↑speed & intensity.

Lymphocyte

A type of white blood cell involved in the immune response.

T Cells

60-80% of lymphocytes.

B Cells

10-20% of lymphocytes.

NK Lymphocytes

< 20% of lymphocytes.

Lymphoid Organs

Organs involved in the production and maturation of lymphocytes.

Primary Lymphoid Organs

Bone marrow and Thymus.

Secondary Lymphoid Organs

Spleen, Lymph nodes, Tonsils, Appendix, Cutaneous-associated lymphoid tissue, Mucosal-associated lymphoid tissue (MALT).

Isolation of Lymphocytes

Density gradient centrifugation with Ficoll-Hypaque.

Identification of Lymphocytes

Flow cytometry with fluorescent-labeled monoclonal antibodies against specific surface antigens.

Immunoglobulin (Ig) Structure

2 heavy (H) chains & 2 light (L) chains held together by disulfide (S-S) bonds.

Heavy (H) chains

Determine Ig class (IgG, IgA, IgM, IgD, IgE).

Light (L) chains

κ or λ. Only 1 type per molecule.

Fab fragment

Fragment antigen binding consisting of 1 L chain & 1/2 H chain held together by S-S bonds.

Fc fragment

Fragment crystallizable, role in opsonization & complement fixation.

Constant region

Carboxy-terminal ends of H & L chains where amino acid sequence is the same for all chains of that type.

Variable region

Amino-terminal ends of H & L chains where amino acid sequence varies.

Hinge region

Flexible portion of H chain between 1st & 2nd constant regions.

Joining chain

Glycoprotein that links Ig monomers in IgM & secretory IgA.

Immunoglobulin Types

IgG, IgM, IgA, IgD, IgE.

IgG Molecular weight

150,000 daltons.

IgM Molecular weight

900,000 daltons.

IgA Molecular weight

160,000 or 400,000 daltons.

IgD Molecular weight

180,000 daltons.

IgE Molecular weight

190,000 daltons.

IgG Serum concentration

800-1,600 mg/dL.

IgM Serum concentration

120-150 mg/dL.

IgA Serum concentration

70-350 mg/dL.

IgM

Produced by newborn. Most efficient Ig at initiating complement cascade. More efficient at agglutination than IgG. Destroyed by sulfhydryl compounds.

Complement

Group of >30 proteins involved in phagocytosis & clearance of foreign antigens. Most are inactive enzyme precursors that are converted to active enzymes in precise order (cascade).

Functions of Complement

Inflammation, opsonization, chemotaxis, cell lysis.

Classical pathway

Triggered by ag/ab rxn. IgM is most efficient activator. Single molecule attached to 2 adjacent ags can initiate cascade. IgG1, 2, & 3 can activate complement but at least 2 molecules required. Recognition unit: C1 (first to bind). Activation unit: C4, C2, C3. Membrane attack complex: C5, C6, C7, C8, C9 (cell lysis).

Alternative pathway

Ab independent. Activated by bacteria, fungi, viruses, tumor cells, some parasites.

Lectin pathway

Ab independent. Initiated by mannose-binding lectin (MBL). Nonspecific recognition of sugars on microorganisms. Important defense mechanism in infancy.

C3

Present in highest concentration in plasma. Key component of all pathways.

Ions required for Complement

Ca2+, Mg2+

Complement deficiencies

↑susceptibility to infection. Accumulation of immune complexes, which can lead to glomerulonephritis.

Inactivation of Complement

56°C for 30 min.

Hypersensitivity Reactions

Classified into four types: TYPE I: Anaphylactic, TYPE II: Cytotoxic, TYPE III: Immune Complex, TYPE IV: T-Cell dependent.

Type I Hypersensitivity

Immediate reaction mediated by IgE.

Type II Hypersensitivity

Immediate reaction mediated by IgG, IgM, complement, and soluble antigens.