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IMMUNOLOGY

GLOSSARY

Accessory cell. Cell which aids, but docs not directly mediate an adaptive immune response.

Includes antigen presenting cells,NK, and mast cells.

Acute phase proteins. Serum proteins primarily produced by the liver whose levels increase

during acute inflammation or infection. They are an indicator of inflammation and are needed

during early phases of acute inflammation.

Adaptive acuired i!!une response. Clonally selected antigen-specific lymphocytes thai

respond to an antigen and develop immunological memory.

A"## $anti%ody&dependent cell&!ediated cytoto'icity(. Kill ing of antibody-coated target

cells by effector cells with c receptors that recogni!e the c region of the bound antibody.

"ffectors are NK cells or phagocytic cells which have C# $% or the c-y&lII type of c receptor.

Adhesion !olecules. Integrins, selectins, members of the immunoglobulin gene superfamily,

which mediate binding of lymphoid cells to one another or to the e'tracellular matri'.

Ad)uvant. ( substance when mi'ed with an antigen enhances an immune response.

A**inity !aturation. (n increase in the affinity of specific antibody for antigen. The antibody is

e'pressed on the cell surface of ) cell centrocytes in the basal light !one of germinal centers during

a humoral immune response.

Allele. *ariant forms of a particular gene at a single locus. +ultiple alleles result in

polymorphism.

Allelic e'clusion. "'pression of only one allele of a gene. ) and T cells e'press an antigen-

binding receptor that recogni!es one specific antigen with high affinity.

Allergy. &esponse to environmental antigen allergen due to pre-e'isting Ig" antibody attached

to mast cells. (n immediate hypersensitivity reaction is produced by mast cell products histamine,

etc. causing asthma, hay fever, serum sicness, systemic anaphyla'is, or contact dermatitis.

Allogeneic. Two individuals of same species that differ at the +/C see also Syngeneic and

+enogeneic(.

Allogra*t. ( tissue or cellular transplant between allogeneic individuals. The reccipient0s T cells

will normally react to foreign +/C antigens in the graft unless they are suppressed or are

genetically unable.

Allotypes. The different forms of a gene for a particular locus which determines the amino acid

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composition of the constant regions of Ig / and 1 chains for each individual.

Alternate pathay. Complement protein C2b binds to the surface of a pathogen and activates

C2 convertase -3 C4. actors ), #, and properdin are involved to generate the +(C. It is a

component of innate immunity which can amplify the classical complement pathway.

Anaphylato'ins. C5, C2a, and C6a complement proteins that recruit fluid and inflammatory

cells to sites of antigen location. These proteins mediate de-granulation of mast cells and basophils.

Anaphyla'is. ( systemic allergic reaction caused by the binding of an antigen to Ig" on mast

cells causing the release of inflammatory mediators histamine, etc.., which cause circulatory

vasodilation, smooth muscle contraction, and suffocation due to tracheal swelling.

Anergy $clonal(. Inability of T and ) cells to respond to their specific antigen under optimal

conditions.

Anti%ody $i!!unoglo%ulin(. 7lasma proteins produced by plasma cells in response to a specific

antigen. Consists of two identical light and heavy chains with specific binding sites on their N-

terminal end for a specific site $epitope( on the antigen that elicited thei r production. Surface

membrane-bound Ig+ and Ig# antibody is e'pressed on newly-formed ) cells even before they

have encountered the specific antigen.

Antigen. +olecule that binds to an antibody or a T cell receptor. I!!uno&gens are antigens

that induce an antigen-specific immune response.

Antigen&%inding site $paratope(. Site in the variable * domain of an antibody or T cell

receptor thai binds the epitope of an antigen. The complementary determining regions C#&s $-2

within the hypervarible loops of both heavy and light chains of antibody molecules are important

in determining the structure of the paratope.

Antigen presentation. 8hole antigen is degraded into peptide fragments and displayed to a T

cell receptor within the groove of a +/C I and9or II molecule.

Antigen presenting cell. Cells which can either process antigen or present already processed

antigenic peptides in association with their +/C class II molecules and which possess co&

sti!ulatory !olecules necessary for lymphocyte activation. 7rimarily macrophages, dendritic

cells, and ) cells.

Apoptosis. Cell death resulting from activation of an internal lethal caspase en!yme cascade

resulting in nuclear membrane damage. #N( fragmentation, and condensation, culminating in

apoptolic body formation. ound in high levels during development of T cells in the thymus and

during antibody formation by centrocytes in germinal centers.

Autogra*t. Tissue graft from one site to another in the same individual.

Autoreactivity. (n immune response to self-antigens.

- !olecules $-./0#"123 -.40#"15(. The main co-stimulatory molecules for C#:; and

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CT1(-6 on T cells. &elated to members of the immunoglobulin gene superfamily.

-asophils.Nonphagocytic granulocyte with cereceptors. Contain large granules with heparin

and histamine. (ntigen binding to Ig" monomer attached to ce receptor triggers degranulation

and immediate hypersensitivity response.

- cells. #evelop in the bone marrow under the influence of I1-< and contact-mediated signals

delivered by stromal cells. =ne of three classes of lymphocytes other than T and NK cells. Their

antigen-binding receptor is cell surface Ig+.

8hen stimulated, ) cells differentiate into plasma cells producing antibody with the same

specificity as the original cell surface Ig+. (s ) cells become memory cells, they e'press Ig>

antibody on their cell surface.

-cl&4. (n oncogenic protein that prevents apoplosis by inhibiting the conversion of caspase-$ to

caspase-2 in the apoptotic pathway. ound on the outer mitochondrial membrane, the endoplasmic

reticulum, and nuclear envelope. (lso, functions as an ion channel and an adapter or docing

protein.

-one !arro. Site where hematopoietic cells develop in the newborn, as well as white and red

blood cells in the adult. ) cells develop in the bone marrow and this compartment gives rise to pre-

T cells which go to the thymus for selection and maturation.

-one !arro chi!era. ormed by transferring bone marrow from one individual to an

irradiated recipient resulting in all hematopoietic elements of donor origin.

#alcineurin. ( calmodulin-dependent cytosolic serine9threonine phosphatase that is important

in activation of N-(T nuclear factor of activated T cells during T cell activation. Inhibited by the

immunosuppressive drugs cyclosporin A and K-5?%, which form comple'es with

i!!unophilins en!ymes with pep-tidyl-prolyl cis-trans isomerase activity which then binds to

and inactivates calcineurin.

#aspases. 7art of a series of specific intracellular serine proteases important in the apoptotic

pathway. (ll caspases have cysteine at their active site, re@uire aspartic acid at their cleavage site,

and are synthesi!ed as proen!ymes.

#" #lusters o* "i**erentiation see (ppendi' I.

#ell adhesion !olecules $#AMs(. ( class of cell-surface proteins necessary in intercellular

adhesion. Include integrins, selectins, and immunoglobulin super-family.

#ellular i!!unity. (n immune response mediated by antigen specific T cells and other non-

specific accessory cells of the immune system. "volved to protect against intracellular bacteria,

viruses, and some cancers, causes graft reAection, and causes graft-versus-host disease.

#entrohlasts. 7roliferating ) blasts found in the dar !one of germinal centers. Somatic

hypermutation taes place in them. They give rise to centrocytes in the basal light !one.

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#entrocytes. Non-proliferating progeny of centrohlasts that are located in the light !one of

germinal centers. #epending on their interaction with antigen on the surface of follicular dendritic

cells, they may mature into plasmablasts, memory ) cells, or die via apoptosis.

#he!o6ine. 1ow molecular weight polypeptides involved in the directed migration

chemota'is and activation of phagocytes and lymphocytes. *ery important in inflammation.

#lassical co!ple!ent pathay. (ctivated by antigen-antibody comple'es and involves CI,

C6, and C: in generating C29C5 convertase.

#lonal selection theory. (daptive immunity occurs when antigen binds to membrane antibody

on ) cells or the antigen specific T cell receptor to stimulate these cells to enlarge and divide.

These proliferating cells develop into a clone of cells with the same specificity as he original

responding cells. This clone also gives rise to memory cells. If antigen causes the cells to be

illed, it is said to cause clonal deletion.

#o!ple!entary deter!ining regions $#"Rs(. Three loops in the terminal end of the

variable region of the ) cell surface immunoglobulin and Tcell receptor that maes contact with

the specific ligand. (lso called hypervaria%le region because their e'treme variability among

immunoglobulins and T cell receptors give them their diversity.

#o!ple!ent syste!. ( group of over :? serum proteins that act in concert to attac

e'tracellular pathogens. (ctivated via antigen-antibody binding classical pathway or

spontaneously by C2b binding directly to the surface of a pathogen $alternate pathway.

Complement coats the pathogen and if CI-4 are bound, it is illed. (lso, C2b acts as an opsonin

facilitating pagocytosis.

#orte'. The outer layer or periphery of an organ.

#o&sti!ulatory !olecules. +olecules on the surface of antigen presenting cells (7C that

may be necessary for lymphocyte activation in addition to antigen binding. T cells re@uire -./

$#"12( and9or -.4 $#"15( on (7Cs which bind to #"41 and #7LA&8 on the surface of T

cells. ) cells re@uire #"82 ligand on C#6 cells to bind to their #"82.

#yclosporin A see #alcineurin(.

#yto6ines . 7roteins produced by cells that have autocrine, paracrine, or endocrine actions on

themselves or other cells. +ost target cells have specific receptors. Interleu6ins $IL( are

cytoines primarily produced by lymphocytes.

" $diversity( gene seg!ent. #N( se@uences that Aoin * and B segments in immunoglobulin

heavy-chain genes and between the and D chain genes in the T cell receptor. They are

important in Aoining these segments during somatic generation of * regions during ontogeny.

"iapedesis. 1euocyte movement between endothelial cells of blood vessels into the tissues.

Important in movement of lymphocytes across high endothelial cells lining post-capillary

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venules in the lymph node deep corte'.

9osinophils. 1euocytes important in defense against parasites. /igh levels in immediate

hypersensitivity reaction because of their content of histaminase. (ctivated by I1-5 from Th:

cells.

9pitope see Anti%ody(.

(S. ( member of the TN family which is e'pressed on target cells maing them targets for

illing by (S-ligand e'pressing cells.

:ollicular dendritic cells. Cells with long dendritic processes which mae contact with

centrocytes in the germinal center. Contain c receptors to hold antigen-antibody comple'es for

many years.

Ger!inal centers $4; *ollicles(. In the corte' of lymph nodes, the peripheral white pulp of the

spleen, and beneath the epithelial lining in gut-associated lymphoid tissue. They are formed when

activated ) cells enter pri!ary *ollicles. Consists of a basal dar !one containing both

centroblasts and Th cells, and a light !one containing centrocytes, follicular dendritic cells,

macrophages, and Th cells. Sites for ) cell proliferation, selection, death, and maturation.

Gra*t&versus&host disease $Gy!es A, -. Serine proteases with specificity for aspartic acid. Stored in the granules of

cyto'ic cells along with perforin. Transferred into target cells through $?-:? nm poly-perforin

pores. (ctivate caspase-2 and thus induces )cl-: independent apopotosis.

Gut&associated ly!phoid tissue $GAL7(. 1ymphoid tissue associated with the gastrointestinal

tract. Includes the palatine, pharyngeal, and lingual tonsils, 7eyers patches, appendi', and

intraepithelial lymphocytes.

=aplotype. 1ined set of alleles of genes present on one parental heploid chromosome. =ne

haplotype of +/C genes are inherited from each parent.

=apten. 1ow molecular weight molecules that bind antibody, but must be chemically lined to a

carrier in order to elicit T cell or antibody responses.

=eavy chain. "ach Ig> immunoglobulin has : identical heavy / and light 1 chains. "ach /

chain has a variable domain */ at the N-terminal end and 2-6 constant C/ domains at the C-

terminal end. There are 5 maAor classes $iso&types( of heavy chains that each denote a specific

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function of the antibody molecule.

=elper 7 cells $7h(. ( functional class of C#6 ET cells which secrete cytoines necessary in

the generation of cell-mediated Thl and humoral Th: adaptive immune responses. /owever, not

all C#6Ecells are Th cells, as some have been reported to be cytoto'ic.

=e!atopoiesis. >eneration of white and red blood cells, as well as platelets from

he!atopoietic ste! cells /SC. +ost /SC reside in the bone marrow and their differentiation

re@uires various growth factors.

=igh endothelial venules $=9

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molecules, )< molecules, and some cell adhesion molecules.

I!!unophilins see #alcineurin(.

I!!unoreceptor tyrosine&%ased activation !oti*s $I7AMs(. Transmembrane molecules on T

and ) cells with FGG1 motifs in their cytoplasmic domains. Involved in receptor signal

transduction pathways after tyrosine phos-phyorylation.

I!!unosuppressive drugs. #rugs which inhibit any adaptive immune response.

In*la!!atory response. ( response to either inAury or infection which is often local. It is

characteri!ed by increased blood flow and capillary permeability, as well as diapedesis of

neutrophils and macrophages out of the circulation into the inflammatory site. Acute

inflammation can occur within minutes and usually is resorbed. but differs from chronic

inflammation, which occurs altera persistent infection.

Innate i!!unity. Nonspecific cellular and humoral first line defense. #oes not increase in

intensity after repeated e'posure to the same or different pathogens.

Integrins. ( group of heterodimeric cell-surface molecules important in cell-cell lymphocytes

and antigen presenting cells and cell-matri' leuocyte migration interactions. or e'ample, 1(-

I, *1(-6, C# I lb on leuocytes bind the immunoglobulin superfamily proteins, IC(+s, *C(+-

$ on endothelium.

Inter*erons $I:N(. Cytoines which help cells resist viral replication and regulate the immune

response. INot and IN) Type I are produced primarily by leuocytes and fibroblasts and are

anti-viral. IN< Type II produced by Thl and NK cells, which can activate macrophages,

upregulate +/C molecules, and promote ) cells to produce lg>:a

Interleu6in. ( cytoine produced by leuocytes.

Intraepithelial ly!phocytes $I9L(. ound between epithelial cells lining mucosal surfaces. 7art

of the mucosal-associated lymphoid tissue defense system. +ainly C#; ET cells, $?-6?H of which

are TC&D. 7roduce IN and I15. unction in immune surveillance with reactivity to bacterial %?-

%5#a heat shoc proteins.

Intron. The intervening se@uences of nucleotides between e'ons that encode protein.

Invariant chain. )inds to +/C II molecules in the endoplasmic retriculum to bloc their

ability to bind peptides. #egraded in vessicles, resulting in +/C II molecules able to bind

endocytosed degraded peptides.

Isogra*t. Tissue transplanted between two genetically identical individuals.

Isotypes see =eavy chain(.

Isotype sitching. #uring antibody production, Ig+ is produced first. 1ater, through site-

specific recombination with deletion of intervening #N( in immunoglobulin heavy chain genes,

Ig>, Ig(, and Ig" are produced and secreted.

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Langerhans cell. #endritic cell with c receptors and found primarily in the stratum spinosum

area of the epidermis. They transport antigen from the epidermis to the regional lymph node where

they become interdigitating dendritic cells.

Large granular ly!phocytes $LGLs(. ( group of morphologically defined lymphocytes which

include NK cells.

Leu6ocyte. (ll white blood cells, including lymphocytes, polymorphonuclear leuocytes, and

monocytes.

Leu6otrienes. +etabolic products of arachidonic acid that serve as lipid mediators of

inflammation. (lso called slow reacting substance of anaphyla'is S&S-(.

Light chain. Smaller of the two chains of an antibody molecule. /as a variable domain *1

and a constant domain J . Two types, Kand G.

L&selectin. (dhesion molecule on lymphocytes that binds C#26 and >ly-C(+-$ on high

endothelial venules to initiate lymphocyte diapedesis.

Ly!ph nodes. Important secondary lymphoid organs with a blood supply and receiving afferent

lymphatic vessels. Cells that leave the parenchyma e'it via efferent lymphatics to the thoracic duct.

Ly!phopoiesis. #ifferentiation and generation of lymphocytes from hematopoietic stem ceils.

Ly!photo'in $7N:-, L7ot(. Cytoine produced by leuocytes, primarily C#6Ecells, which

can cause necrosis. Important in normal secondary lymphoid tissue development, particularly in

inducing follicular dendritic cell clusters.

Macrophage. 1arge bone marrow-derived phagocytic cells of the monocytic series, which are

very important in innate immunity, and early phases of host defense. unctions also as the maAor

antigen processing and presenting cell in adaptive immunity. ound throughout the body as the

mononuclear phagocytic system. In addition, secretes I1-$, %, ;, $?, $:, TN, T>, >+-CS, >-

CS, +-CS, and functions in (#CC.

Ma)or histoco!pati%ility co!ple' $M=#(. >roup of very polymorphic genes found on

chromosome % in humans that encode +/C or /1( molecules. M=# I molecules present cytosolic

peptides to C#S T cells, M=# II molecules present endocytosed and lysosomal degraded peptides

to C#6 T cells. oreign surface +/C molecules function as cellular antigens and are the targets

for T cells in graft reAection or >*/#.

Mantle >one. &im of primarily resting ) cells surrounding germinal centers. (lso may be an

e'it point for cells from germinal centers.

Marginal >one and sinus. &egion of spleen between red and white pulp. The !one contains )

ceils, memory cells and macrophages. The sinus receives cells which migrate into the white pulp.

Mast cells. )one marrow derived cells residing in connective tissue areas similar to but

different from basophils. 1arge granules with histamine, heparin, serotonin, chondroitin sulfate ",

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etc. "'press cereceptors similar to basophils. Secrete many immunoregulatory cytoines which

can effect modulation of C#6 cell polari!ation into Thl or Th: subsets.

Medulla. The central or innermost aspect of an organ with the corte' being the periphery. It is

usually the collecting or e'it point in an organ such as the thymus and lymph node.

Me!%rane attac6 co!ple' $MA#(. ormed at the end of the classical or alternate complement

pathway and thus contain C5b-4. +ediates cell lysis by forming a transmembrane channel in the

target similar to perforin.

M=# restriction. T cells will only recogni!e peptide if it is presented to them in the conte't of

the +/C molecules of their maturing environment.

Micro*old $M( cells. Speciali!ed cnterocytes found in primarily the ileum of the small intestine

and rectum. They line the surface of 7eyers patches 77 in the ileum and are speciali!ed in their

abil ity to endocytose and transport antigen including viruses from the gut lumen to the underlying

lymphoid tissue in the lamina propria and submucosa.

Monocytes. )one marrow derived peripheral blood cells that are the pn sors of tissue and

organ macrophages and thus represent the mononuclear ph cytic system.

Mucosal associated ly!phoid tissue $MAL7(. (ll intraepithelial I phocytes as well as

lamina propria and submucosal lymphoid tissue bi mucosal lined areas. >ut associated lymphoid

tissue $GAL7( and bronchialL ciated lymphoid tissue $-AL7( are components of the +(1T.

Natural 6iller $N?( cells. ( subset of large granular lymphocytes whicl not T or ) cells. They

ill some tumor cells and virally-infected cells, as wc those cells lacing +/C I molecules but

e'hibit no memory. (re C#$%E C#5%E. &epresent 5-$5H of lymphocytes found in peripheral

blood and sp but as much as :5H of those found in the sinusoids of the liver where the called pit

cells. #o not recirculate and they arc not found in the thoracic duct, of the innate immune system

and can produce IN, TN, and >+-CS.

Necrosis. "'tensive cell inAury and death leading to debris and inflan lion. In apoptosis there is

no inflammation.

Neutrophils $neutrophilic poly!orphonuclear leu6ocytes(. The / abundant white cell in

peripheral blood. +ultilobed nucleus with granules don0t stain with most peripheral blood

tctrachrome stains. irst circulating ph cytic cell to be involved in an inflammatory response.

Nude mice. +ice which are not only hairless, but also have no thymus to a defect in their

thymic stroma and, thus, do not produce normal T cells.

Opsoni>ation. #eposition of antibody and complement on bacteria proi ing contact and

destruction by phagocytic cells.

@aratope. (rea in the * domain of an antibody or T cell receptor bindinA epitope of an antigen.

@er*orin. 7rotein, stored in the granules of cytoto'ic T cells and NK $ along with gran>y!es

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that are released on contact with the target cell. Ir presence of Ca E E, polymeri!es to form

transmembrane pores on target cells ilar to those produced by the +(C.

@eriarteriolar ly!phoid sheath $@ALS(. 1ymphocytes, primarily T c that surround the central

arterioles which branch from trabecular arteries ol spleen. (ttached to the 7(1S are the primary

and secondary lymphoid follic

@hagocytosis. Internali!ation of a foreign particle or another cell by a ph cytic cell. Ingested

material is contained in a phagoso!e which fuses with $ somes to become a phagolysoso!e.

1ysosomal en!ymes degrade the mat into small peptides which can occupy the +/C II groove for

presentation to ) cells.

@latelets. Small membrane bound cytoplasmic product of megaaryocyti the bone marrow. /as

granules which contain clotting factors, vasoactive stances, and growth factors $platelet derived

groth *actor(.

@oly!orphis!. *ariability at a specific gene locus. The +/C is the r polymorphic gene locus

in humans.

@ri!ary *ollicles. ound in all secondary lymphoid tissue. Contain resting ) cells and some

follicular dendritic cells. 8hen activated ) cells centroblasts and Th cells enter, they become

secondary *ollicles with ger!inal centers.

@ri!ary ly!phoid organs. The bone marrow and thymus where lymphocyte precursors

mature into immunocompetent antigen reactive T and ) cells without having ever seen the antigen

previously. These immunocompetent cells seed secondary ly!phoid organs.

@rogra!!ed cell death see Apoptosis(.

@roteoso!e. ( large cytosolic catalytic multisubunit protease comple' that degrades cytosolic

proteins to peptides for presentation by +/C I molecules.

@roto&oncogens. >enes that encode growth-controlling proteins in normal cells.

Receptor editing. &eplacing a potentially self-reactive light chain of an antigen receptor on a

developing ) cell with a non-self-reactive light chain.

&ecombination activating genes $RAG&/, RAG&4(. "ncoding &(>-$ and &(>-: proteins

critical for variable region gene rearrangement in developing lymphocyte receptors such as the T

cell receptor and ) cell immunoglobulin.

Red pulp o* spleen. (n area of spleen around the white pulp which contains red cells,

sinusoidal macrophages, and NK cells. Site where old red cells are destroyed.

Secondary i!!une response. =ccurs after another e'posure to antigen and involves memory

cells that arc activated to produce a more rapid and more pronounced response than in the pri!ary

response.

Selectins. +onomeric cell-surface adhesion molecules on leuocytes 1-selectin and

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endothelial cells "- and 7-selectin that bind mucin-lie C(+s on specific glycoproteins to

initiate leuocyte binding to endothial interactions.

Sepsis. )acterial infection of the bloodstream that can trigger massive release of TN- and

septic shoc6.

Serotonin $&hydro'ytrypta!ine(. 7rincipal vasoactive amine found in basophil, mast cell,

and platelet granules. &eceptors on local endothelium and vascular smooth muscle.

So!atic cell hyper!utation. 7oint mutations introduced into rearranged imunoglobulin *-

region genes during ) cell activation, proliferation, and maturation. >enerates variant antibodies,

some of which have a higher binding affinity. 7ermits refinement of antibody specificity

contributing to antibody diversity.

Ste! cells. Cells found in the blood islands of the yol sac and paraaortic splanchnopleura

mesenchyme of the day

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musosal epithelial surfaces.

7er!inal deo'ynucleotidyl trans*erase $7d7(. "n!yme responsible for inserting nontemplated

or N-nucleotides into Aunctions between gene segments in the T cell receptor or the

immunoglobulin heavy chain *-region genes. These N-nucleotides contribute e'tensively to he

diversity of *-region genes of T and ) cell receptors.

7ransgenic ani!al. (nimals developed with genes placed into their original genome with

specific promoters controlling their site and duration of their e'pression.

7u!or i!!unology. The immune response to tumors. Syngeneic tumors are accepted as grafts

unless their +/C groove contains proteins which the host can perceive as foreign. Some tumor

antigens are found on heat shoc proteins.

7yrosine 6inase. "n!yme that phosphorylates the tyrosine residues of proteins, which are

important in T, ). and NK cell activation. T cell has 1c, yn, and (7-