Exam I Definitions

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Humoral Immunity

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is mediated by proteins called antibodies, which neutralize microorganisms and toxins and remove antigens in the body fluids by amplifying phagocytosis or lysis

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Cellular (cell-mediated) immunity

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is mediated by cytotoxic T cells, NK cells, polymorphonuclear (PMN) cells, and macrophages, and is responsible for readicating microorganisms residing within body cells, as well as killing aberrant host cells

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Aquired Immunity is Actively aquired by:

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- infection
- vaccination

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Aquired Immunity is Passively aquired by:

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- placental transfer of antibody
- injection of specific antibody or cells

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Clusters of differentiation (CD)

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these phenotypic markers appear on the T cell membrane as proteins at different stages of differentiation in the thymus and periphery

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CD2 and CD3

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are major markers that appear in the thymus and are retained on ALL peripheral T cells

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CD4

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defines a T helper cell (Th) subset

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T helper cell (Th) subset

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differentiates in the periphery into Th0, Th1, and Th2 cells based on differences in the molecules they secrete (known as cytokines)

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Th1 cells

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secrete mainly IL-2, IFN-gamme, and TNF-alpha

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Th2 cells

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secrete mainly IL-4, IL-5, IL-6, IL-10, and IL-13

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CD8 T cell

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defines a cytotoxic T cell

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T cell receptor (TCR)

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is epitope specific and exists on the T cell membrane as two types, designated: alpha:beta TCR, and gamma:delta TCR

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IgM

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membrane-boud, epitope-specific, antigenic receptor distinguishes the B cell receptor from that of the T cell

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alpha:beta TCR

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CD2+, CD3+, CD4+, CD8+

responds to peptide antigens bound to MHC

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gamma:delta TCR

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CD3+, CD8-, CD4-

Responds to nonpeptide antigens, lacks MHC restrictions
Antibacterial properties
Increased CMI against viruses

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Th1 functions

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- activation of B cells, cytotoxic T cells, Th cells, and APCs
Downregulation of Th2 cell fcns
Increased CMI

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Th2 functions

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B cell differentiation and proliferation
activation of eosinophils
Downregulation of Th1 cell fcns
class switching
increased antibody

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Antigens

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a foreign substance that induces antibody and/or CMI after binding to its specific antigen receptor on T and B cell clones

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Epitope (antigenic determinant, ligand)

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an epitope is the short sequence of amino acids or sugars in an antigen molecule that combines with a hypervariable reactive site on the antibody molecule. The sequence is usually repeated several times, and the number of repeats is referred to as the valence

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Hapten

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a hapten is a portion of an Ag molecule that contains the epitope, it reacts specifically with its Ab but is incapable of inducing Ab synthesis without a carrier molecule

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Pro-B Cell

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addition of CD19, CD22
mu chain D-J gene rearrangments

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Pre-B Cell

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Additiion of CD9, CD10
V-DJ-C gene rearrangements mu chains appear

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Immature B cell

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addition of CD20, CD21, CD37
loss of CD9, CD10
appearance of membrane and IgM and IgD receptors

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superantigen

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certain retroviral proteins and bacterial toxins (e.g. staphylococcal enterotoxins, toxic shock syndrome toxin 1) can link multiple T cells - at the TCR variable beta regions to the MHC II of APCs
b/c the linking occurs at regions independent of the specific peptide-binding sites, many T cell clones and APCs are activated, secreting excessive amounts if cytokines (e.g. IL-2, IL-1), potentially resulting in toxic shock syndrome

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Thymus-Independent Antigens

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activate B cells without T helper cell involvement
most possess multiple branched polysaccharide repeating units and activate B cells polyclonally, without regard to B cell specificity

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Defensins

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anti-microbial peptide
small group of catonic peptides that damage bacterial membranes
found in cytoplasmic granules of phagocytic and secretory cells

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Alternate complement pathway

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1. Independent of Ab or mannan-binding lectin pathways
2. Spontaneously hydrolyzes C3 in the plasma and forms a multiprotein complex, C3 convertase, that can randomly bind to any pathogen or host memb surface possessing thioester linkages
3. factor P binds to bacterial surfaces and augments C3 convertase activity
4. Host cells express surface regulatory proteins that suppress C3 convertase to prevent inadvertant complement action
5. complement pathways lead to opsonization or lysis of pathogen

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neutrophils

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polymorphonuclear leukocytes (PMNs)
the earliest and most abundent respondent cell to pathogen invasion

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Macrophages

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derived from their monocytic precursor following stim by GM-CSF
highly phagocytic, utilizing their Fc receptor or complement receptors to capture Ab or complement associated pathogens
capaple of killing IC pathogens with ROS and lysosome enzymatic digestion

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Immature dendritic cells

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higly phagocytic, expressing low MHC levels that capture and process pathogens into antigenic fragment
exposure to pathogen molecules activates toll like receptors (TLR) to stim differentiation into mature dendritic cells

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mature dendritic cells

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they are sessile, non-phagocytic and express abundent MHC in secondary lymphoid organs, this results in a display of antigenic peptides to naive T cells

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NK cells

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lymphoid derived, granular secretory cells
cells expressing both Fc receptors and CD56 and producing IFN-gamma
deficient in expressing antigen-specific memb receptors or memory, and are not MHC restricted
capaple of IDing cells expressing low levels of MHC I and are indiscriminate in binding to all host cells
capable of initiating a killing response to any docked cells using a killer-activating enzyme (KAR), apoptosis is induced in the target cell using perforins and granzymes
capable of halting inadvertent host cell death by recognizing the presence of MHC complexes on the target cell through killer inhibitory receptors (KIR)

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Antibody Structure: Amino acid sequences: H Chains

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a specific, short amino acid sequence on the H chains differentiates the classes (i.e. IgG, IgA, IgM, IgE, IgD), these H-chain differences are called isotypes and are designated by the greek letters gamma, alpha, mu, epsilon, and delta

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Antibody Structure: Amino acid sequences: L Chains

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all 5 classes have an amino acid sequence in common on the L chain, thus they can be classified together as Igs
In addition, two L-chain isotypes, kappa and lambda exist for all 5 classes

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Hypervariable region

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amino acids that show marked differences b/w Abs of different specificities within each variable region

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Epitope-binding region

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the hypervariable regions of both the H and L chains associate to form this,

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Hinge Region

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exists b/w the CH1 and CH2 domains permiting flexibilty in the movement of the 2 antigen-binding sites

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monoclonal antibodies

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most antigenic preparations give rise to a mixture of Abs, however, Abs of a single specificity are highly desirable for many purposes

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Papain

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splits IgG into 3 fragments
- 2 of these fragments (Fab; fragment, antigen binding) are similar with each containing only one of the reactive sites for the epitope, b/c Fab is monovalent, it can bind to but not enter into lattice formation and ppt or agglutinate Ag
- a third fragment (Fc; crystallizable) activates complement, controls the catabolism of IgG

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Pepsin

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splits behind the disulfide bonds joining the 2 H chains, permitting the 2 Fab fragments to remain joined

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Joining Segment

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an additional gene sequence is required during the formation of the L chain
it joins the VL region gene to the CL region gene

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Diversity segment

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an additional gene sequence is required during the formation of the H chain
links the VH gene to the J gene, these genes are then fused with the CH gene

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H-Chain class swithcing

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from mu and delta to gamma3, gamma1, alpha1, gamma2, gamma4, epsilon, and alpha2 is dictated by a later rearrangement of the class genes in the CH region and is mediated by T cell cytokines (IL-4, IL-3, IFN-gamma, TGF-beta)

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randome selection of Ig chains

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by each B cell from the variety of V, D, and J germ line genes available results in a large number of structural possibilities for the VL and VH epitope-binding regions of the Ig

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Allelic exclusion

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only one of the two parental alleles is expressed by a single B cells, resulting in a single H-chain isotype and L-chain subtype receptor capable of reacting with only one antigenic epitope

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Functions of HLAs (human leukocyte antigens)

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1. discrimination b/w self and nonself
2. antigen presentation to T cells, but only of the same HLA type (self-MHC restriction)
3. susceptibility to immunologic disorders and infectious angents

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Class I HLAs

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glycoproteins found on the memb of most nucleated cels
encoded by 3 gene regions: A, B, C
they are linked to cytotoxic T cells through the CD8 molecule and present peptide epitopes to spefic TCRs
2 chains form the class I molecule:
-the alpha chain has three external domains, a transmemb segment, cytoplasmic tail
-beta 2 - microglobulin is an invarient protein
- peptide binding site b/w domains alpha 1 and alpha 2 binds peptides containing 8-10 amino acids

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Class II HLAs

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glycoproteins found on the membs of dendritic cells, macrophages, and activated T and B cells
gene regions: DQ, DR, DP
are linked to Th cell through CD4 molecule and present peptide epitopes to specific Th cell receptors
two chains, alpha and beta, transmemb segment, and cytoplasmic tail
peptide-binding site formed by juxtaposition of alpha 1 and beta 1 domains binds peptides containing 13-18 amino acids

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TCR

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a dimer of either alpha:beta chains (95%) or gamma:delta chains (5%)
do not respond to soluble antigens
recognize antigenic epitopes only as peptide fragments boundto either class I or II HLA molecules on APCs
co-receptors CD4 or CD8 determine humoral or cell mediated immunity
union of the specifc TCR and co-receptor w/ the peptide-HLA memb complex is associated w/ signal transductio into the cytoplasm by a complex of proteins --> CD3

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Recombinase enzymes (RAG-1 and RAG-2)

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are required for both H chain and L chain rearrangments in both early B and T cell antigen receptor expression
part of an enzyme complex, the V(D)J recombinase in lymphocyes, which mediates the somatic recombination of V and J or V, D, J genes

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CD1

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DC
MHC class I like, presents lipid antigen

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CD2

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T cells, NK cells, Thymocytes
Adhesion molecule that binds CD58
controls Lck in T cell activation

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CD3

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T cells, Thymocytes
Signal transduction associated w/ TCR

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CD4

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Th1 and Th2 cells, Monocytes, Macrophages
Co-receptor that docks to MHC class II and controls Lck in T cell activation

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CD11d

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Leukocytes
alphaD subunit of integrin

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CD11c

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Myeloid cells
alphaX subunit of integrin

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CD11b

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Myeloid cells, NK cell
AlphaM subunit of integrin CR3 and binds fibrinogen

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CD11a

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Lymphocytes, Granulocytes, Monocytes, Macrophage
alphaL subunit to integrin LFA-1 binds to CD54, CD50, and CD102

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CD8

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Cytotoxic T cells
Co-receptor that docks to MHC class I and controls Lck in T cell activation

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CD14

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DC, Macrophage
TLR, binds LPS binding protein

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CD16

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Neutrophils, NK cells, Macrophages
Subunit of low-affinity Fc receptor and mediates endocytosis

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CD25

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Activated T cells and B cells, macrophage
Alpha subunit of IL-2 receptor

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CD23

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Eosinophils, B cells, macrophage
Low-affinity receptor for IgE

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CD21

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B cells
Subunit of co-receptor for BCR complex

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CD19

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B cells
Subunit of co-receptor BCR complex and binds protein tyrosine and PI-3 kinases

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CD18

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Leukocytes
Integrin beta2 subunit, associates with CD11 (a-d)

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CD28

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T cells, activated B cells
T cell activation and receptor for co-stimulatory signal by binding CD80 and CD86

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CD45

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All hematopoietic cells
Transmemb tyrosine phosphatase, regulates Src kinases and augments lymphocyte activation

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CD35

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B cells, Monocytes, Neutrophils, Eosinophils, DC
Complement receptor 1 and mediates phagocytosis

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CD34

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Hematopoietic stem and progenitor cells, endothelium
Receptor for CD62L, a selectin

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CD54

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Ubiquitous to all cells
Intracellular adhesion molecule (ICAM) binding CD11a and CD11b

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CD89

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Leukocytes
IgA receptor

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CD86

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Monocytes, Activated B cells, DC
Co-stimulated and ligand for CD28 and CTLA-4

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CD81

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Lymphocytes
Subunit of B cell co-receptor

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CD80

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B cells
Co-stimulator and ligand for CD28 and CTLA-4

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CD71

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Ubiquitous to all proliferating cells (i.e. activated cells)
Transferring receptor

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CD64

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Monocyte, Macrophages
High affinity receptor for IgG

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CD82L

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B cells, T cells, monocytes, NK cells
Leukocyte adhesion molecule, mediates rolling interaction with endothelium

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CD58

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Ubiquitous to all cells
Adhesion molecule, binds to CD2

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CD56

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NK cells
Adhesion molecule