Immunology chapter 5, sections 5-6 through 5-21, and 5-23

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bare lymphocyte syndrome type I or MHC I deficiency

rare genetically determined immunodeficiency disease in which MHC class I molecules are not present on cell surfaces, as a result of non functional TAP proteins. The result is a deficiency of CD8 T cell function.

professional antigen presenting cells

refers primarily to dendritic cells, but also to macrophages and B cells, all of which take up, process and present antigens from the environment, and once activated, are able to activate naive or partly activated T cells

HLA-E

relatively invariant human MHC class I molecules that form ligands for NK cell receptors

HLA-G

relatively invariant human MHC class I molecules that form ligands for NK cell receptors

present

MHC molecule does this to the peptide antigen to the T cell receptor

gene families

set of genes encoding proteins of similar structure, and often of similar function, such as the MHC class I genes

calreticulin

soluble chaperone protein in the endoplasmic reticulum that is part of the peptide-loading complex that loads peptides onto MHC class I molecules in the endoplasmic reticulum

alloreactive T cells

T cell in one member of a species that responds to an allogenic antigen from another member of the same species

tapasin

TAP associated protein, a chaperone protein involved in the assembly of peptide: MHC class I molecule complexes in the endoplasmic reticulum

promiscuous binding specificity (promiscuous specificity)

the ability of a protein to bind a number of different ligands; an example of this is the MHC molecules, which can each bind numerous peptides of different sequences

isotypes

the class of an immunoglobulin-that is, IgM, IgG, IgD, IgA, or IgE-each of which has a distinct heavy chain constant region encoded by a different constant region gene. The heavy chain constant region determines the effector properties of each antibody class.

HLA type

the combination of HLA class I and class II allotypes that person expresses

peptide-binding motif

the combination of anchor residues in an MHC protein that correspond to the amino acid sequences of peptides that can bind to that protein

antigen presentation

the display of antigen as peptide fragments bound to MHC molecules on the surface of cells. This is the form in which antigen is recognized by α:β T cells

antigen processing

the intracellular degradation of proteins into peptides that bind to MHC molecules for presentation to α:β T cells

HLA class I molecules

the name for the human version of an MHC class I molecule

HLA class II molecules

the name for the human version of an MHC class II molecule

human leukocyte antigen complex (HLA complex)

the name for the major histocompatibility complex in humans. It is loacted on the short arm of chromosome 6 and encodes the polymorphic HLA class I and class II molecules, as well as other proteins involved in immune system function. Individual genes are designated by capital letters, such as HLA-A, and alleles are designated by numbers, such as HLA-A*0201.

class I region

the part of the major histocompatibility complex that contains the MHC class I heavy chain genes

class II region

the part of the major histocompatibility complex that contains the MHC class II alpha and beta chain genes

MHC restriction

the property that a given T cell receptor recognizes its peptide antigen only when the peptide is bound to a particular form of MHC molecule

class III region or central MHC

the region of the major histocompatibility complex between the class I and II regions. It contains no genes for class I or II MHC molecules

peptide editing

the selection of peptides by the peptide loading complex that bind strongly to MHC class I molecules, together with the trimming of bound peptides to the correct length by the endoplasmic reticulum aminopeptidase

constitutive proteasome

the version of the proteasome present in normal uninfected cells

MHC class II

a family of molecules normally found only on antigen-presenting cells such as dendritic cells, mononuclear phagocytes, some endothelial cells, thymic epithelial cells, and B cells. The antigens presented by these peptides are derived from extracellular proteins ; hence, the (this)-dependent pathway of antigen presentation is called the endocytic or exogenous pathway

antigen-presenting cell

a heterogeneous group of immune cells that mediate the cellular immune response by processing and presenting antigens for recognition by certain lymphocytes such as T cells. Classical APCs include dendritic cells, macrophages, Langerhans cells and B cells.

HLA-A

a highly polymorphic human MHC class I gene

HLA-B

a highly polymorphic human MHC class I gene

HLA-C

a highly polymorphic human MHC class I gene

HLA-F

a monomorphic human MHC class I molecule that is a chaperone for HLA class I molecules that lose their bound peptide at the cell surface

allotypes

a naturally occurring variant of a protein. These are encoded by different alleles of the same gene.

peptide-loading complex

a protein complex in the endoplasmic reticulum membrane that loads peptides from the TAP transporter onto MHC class I molecules

HLA-DO

a relatively invariant human MHC class II molecule. The function of this is to counteract that of HLA-DM

MHC class II transactivator (CIITA)

a transcriptional activator of MHC class II genes. If defective, it results in the absence of MHC class II molecules on all cells, causing a severe immunodeficiency characterized by a lack of CD4-T cell function

CD8

a transmembrane glycoprotein that serves as a co-receptor for the T cell receptor (TCR).

ERp57

thiol reductase protein that is part of the peptide loading complex that loads peptides onto MHC class I molecules in the endoplasmic reticulum

MIIC (MHC Class II compartment)

acronym for MHC class II compartment and pronounced 'em two see". an endosomal compartment in professional antigen presenting cells where MHC class II molecules load with peptides derived from pathogens and antigens that have been taken up from the extracellular environment

alloreaction

adaptive immune response made by one member of a species to an allogeneic antigen from another member of the same species

anchor residues

amino acid residues in MHC binding peptides that interact with pockets in the peptide binding groove of the MHC molecule. Peptides that bind to a given MHC allotype have the same or similar of these

HLA-DM

an invariant MHC class II molecule in humans that is involved in the intracellular loading of MHC class II molecules with peptides

alloantibody

antibody that is made by immunization of one member of a vertebrate species with antigen derived from another member of the same species. Alloantibodies recognize antigens that are the result of allelic variation of polymorphic genes. Common types of alloantibody are those recognizing blood group antigens, and MHC class I and class II molecules

self peptides

any peptide produced from the body's own proteins. in the absence of infection, these peptides occupy the peptide binding sites of MHC molecules on cell surfaces and are usually not recognized as antigenic by that person's immune system

non-self peptides

any peptide that derives from a protein not present in a person's own body. It can refer to a peptide derived from a pathogen protein or from a protein from a genetically unrelated person. such peptides are recognized as foreign and provoke an immune response

self proteins

any protein of a person's own body. these proteins are usually not recognized as antigenic by that person's immune system

non-self proteins

any protein that is not present in a person's own body. It can refer to a pathogen protein or to a protein from a genetically unrelated person that is recognized as foreign. Such proteins are recognized as foreign and provoke an immune response.

homozygous

describes an individual who has inherited the same form (allele) of a given gene from both parents

autologous

describes cells, HLA molecules, and other components, that derive from the individual or person in question

highly polymorphic

describes genes that have many alleles and for which most individuals in a population are heterozygous

oligomorphic

describes genes that have only a small number of different alleles in the population

heterozygous

describes individuals who have inherited different forms (alleles) of a given gene from their two parents

allogenic

describes two members of the same species who are genetically different

T-cell co-receptors

either of the cell surface glycoproteins CD4 or CD8, which cooperate with the T cell receptor to determine which target cells a given T cell will interact with

endoplasmic reticulum aminopeptidase (ERAP)

enzyme in the endoplasmic reticulum that removes amino acids from the amino-terminal end of peptides bound to MHC class I molecules to improve their fit, a process known as peptide editing

helper T cell

general name for effector CD4 T cells that function to help other immune system cells perform their roles, such as to help B cells produce antibody

isoform

general term for a particular MHC protein

monomorphic

having only one form. the term is used, for example, for genes that have only one allele

haplotype

in reference to a linked cluster of polymorphic genes, the set of alleles carried on a single chromosome. Every person inherits two (usually different) haplotypes for such genes, one from each parent. The term was first used in connection with the genes of the major histocompatibility complex

cross-priming

initiation of an adaptive immune response by cross presentation of antigen

β2-microglobulin

invariant polypetide that is common to all MHC class I molecules. Also called the light chain of MHC class I molecules

major histocompatibility complex molecules (MHC molecules)

large cluster of mainly immune-system genes present in all vertebrates that encodes, among other proteins, the highly polymorphic MHC class I and class II molecules, which present peptide antigens to T cells and are the basis of an individual's tissue type

proteasome

large multisubunit protease present in the cytoplasm of all cells that degrades cytoplasmic proteins. It generates the peptides presented by MHC class I molecules

cytotoxic T cell

type of effector T cell that kills its target cells. It expresses the CD8 co receptor and recognizes peptide antigens presented by MHC I molecules. It is important in host defense against viruses and other cytosolic pathogens because it can recognize and kill the infected cells

genetic polymorphism

variation in a population owing to the existence of two or more alleles of a given gene

calnexin

membrane protein of the endoplasmic reticulum that facilitates the folding of newly synthesized MHC molecules and other glycoproteins

self-MHC

A person's own MHC class I and class II molecules

immunoproteasome

A proteasome assembled using alternative β form subunits in response to pro-inflammatory signals.

transporter associated with antigen processing (TAP)

ATP binding protein in the endoplasmic reticulum membrane that transports peptides from the cytosol to the lumen of the ER. It is composed of two subunits, TAP-1 and TAP-2. It supplies MHC class I molecules with peptides

HLA-DP

one of the highly polymorphic human MHC class II molecules. Each class II molecule is made from alpha and beta chains encoded by A and B genes, respectively.

HLA-DQ

one of the highly polymorphic human MHC class II molecules. Each class II molecule is made from alpha and beta chains encoded by A and B genes, respectively.

HLA-DR

one of the highly polymorphic human MHC class II molecules. Each class II molecule is made from alpha and beta chains encoded by A and B genes, respectively.

MHC class I

one of two primary classes of major histocompatibility complex (MHC) molecules and are found on the cell surface of all nucleated cells in the body. Their function is to display peptide fragments of non-self proteins from within the cell to cytotoxic T cells; this will trigger an immediate response from the immune system against a particular non-self antigen displayed with the help of an MHC class I protein. Because these molecules present peptides derived from cytosolic proteins, the pathway of its presentation is often called cytosolic or endogenous pathway

class II associated invariant chain peptide (CLIP)

peptide of variable length cleaved from the invariant chain protein by proteases in the endosomal pathway. CLIP remains unstably bound in the peptide binding cleft of an MHC class II molecule until it is removed by the HLA DM protein and replaced by an antigen peptide

invariant chain (Ii)

polypeptide that associates with major histocompatibility complex (MHC) class II proteins in the endoplasmic reticulum and prevents them from binding peptides there. Ii is degraded in endosomes, enabling MHC class II molecules to bind endosomal peptides

cross presentation

process that occurs within dendritic cells whereby antigen of extracellular origin is presented by MHC class I molecules


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