Overview and antibodies Flashcards
Role of Immune system
host defense Discriminate self form non self (tolerance) Loss of tolerance leads to autoimmunity
Chemical barriers
lysozyome in secretions (splits cell walls of the Gm+ bacteria) Spermine in semen( prevents growth of Gm+ bacteria) Acid pH of the stomach(prevents colonization of bacteria
physical barriers to prevent pathogen entry
intact skin mucosal linings
Properties of antigens
-are foreign(NON-SELF) -chemically complex -molecular weight of 6Kd - has a particular sequence that is recognized by receptors on cells of the immune system called a Epitope/antigenic determinante/Determinant
Characteristics of adaptive immunity
-specific -memory- (you save cells so that your body will know how to deal with it) -lag time (for first encounter due to time for T Cell and B cell to change) -adaptivity(faster response with more exposure
Characteristics of innate immunity
not exquisitely specific -no memory -no lag time -no adaptivity
Cells of innate immunity
basophils, dendritic cells, eosinophils, mast cells, monocytes, macrophages, NKC, Neutrophils
Cells of adaptive immunity
B cells CD8+ T cells, CD4+ tcells and its subsets (Thp, 0,1,2,3,17, nTreg, a/iTreg
Primary immune tissue
Bone marrow- hematopoiesis of both myeloid and lymphod cells, ome cells emerge from bone marrow as precursors and differentiate in other tissue Thymus- progenitor t cells from bone marrow differentiate into naive mature cells in thymus ( nTregs, Thp, and pCTL)
Secondary Immune tissue
Lymph nodes, tonsils, adenoids, spleen, mucosa associated tissues MALT, GALT
MALT
unencapsulated tissues underlying mucosal areas -follicle associated lymphoid epithelium is a region without mucus -M cells located in the FAE -Mcells transport microbes to the lamina propria via vesicles - Lamina propria: phagocytes, dendritic cells lymphocytes are located here - organized aggregates in GALT are called Peyer’s patches GALT and BALT ( Broncus)
Intial site of primary immune response
depends on the route of pathogen Blood- spleen lymph- lymph nodes Mucosa- MALT GI tract- GALT
Cytokines
small peptides secreted mainly by activated leukocytes - critical for all aspects of immnity
Chemokines
smal peptides that induce leukocyte accumulation in tussues that have unique disulphide bonds
chemoattractant molecules
attract cells to a particular region without unique disulphide bonds
complement components
family of proteins that facilitate elimination of microorganisms particularly extracellular bacteria, proteins, activated by cleavage
antibodies
antibody isotypes Ig M, D, G, E , A which correpsond to Mu, Delta, Gamma, Epsilon, and Alpha are polypeptides, that are bifunctonal molelcues that bind antigen.
monomeric antibody
two identical light chains covelently linked to two identical heavy chains with each chain witha varible region and a constant region
dimeric, trimeric and pentameric forms
two three or five monomeric units
light chain constant regions
kappa or lambda
isotypes
IgA, IgD, IgE, IgG, and IgM with 5 different heavy chain constant regions named alpha, delta, epsilon, gamma, or mu
subclasses
antibodies have small differences in amino acid sequences in heavy chian constant region, unique properties ( IgG1, IgG2 , IgG3, IgG4, and IgA1, IgA2
allotypes
polymorphisms within an IgG or IgA constnat regions (Gm or Am)
bifunctional molecules
antigen binding site in variable region confers specificity, biological activity in the constnat region confers different roles for isotypes
antigen binding site(FAB)
hypervariable region, complementary determining region, paratope, refer to sites within varible region that contact antigen
antigen-antibody interaction
hydrophobic and ionic
affinity
interaction strength between 1 antigen binding site and its monovalent Antivent
antibody avidity
overall binding energy of all binding sites with antigen
Properties and role of IgG
-75% of total circulating Ig -150 kD monomer - four subclasses with differnet bio activities (IgG1,2,3,4) -Half life ~three weeks(IgG3-1 week) -Receptor for Fc gama R on monocytes, macrophages, neutrophils, B cells - Different cell types exrpess FcgammaR that have differenty avidity for Fcgamma) -down regulation of B cells following binding of antigent and FcGammaR -Major role in elimination of microbes by opsonization of phagocytes, antiobody dependent cell mediated cytotoxicity by NK cells, Neutralization of viruses and toxins, Complement activaiton (not IgG4)
Properties and Role of IgM
-exists as a monomer on B cells -exists as a pentamer when secreted form plasma cells -15% of total circulating immunoglobins -half life is 1 week -pentameric form- five covalently attached monomeric units and a single short J chain -only antibody isotype present on immature B Cells -main role in immune repsone is activate the classical pathway of complement -only one IgM antigen/antigen complex required to activate classical pathway
Properties and role of IgD
-Exist primarily as a membrane bound monomeric form -expressed on naive B cells along with IgM
Iso-hemagglutinins
IgM antibodies against the ABO blood group antigens
Properties and role of IgE
-monomeric antibody -normal barely detectable in serum -most is bound to FcepsilonR on mast cells and basopihls -crosslinking Fcepsilon by multivalent antigens results in crosslinking of Fcepsilon Rs -Cross linking=release of inflammatory mediators from perfromed granules present in mast cells and basophils -eiosinopihls also express FcEpsilon R which binds IgE helminth complexes
Properties and role of IgA
-Exists as a monomer, dimer, or trimer with J chain on Dimers and trimers -IgA half life ~one week -subclasses: IgA1 and IgA2 and allotypes Am -in mucosa associated lymphoid tissue; primarily gastrointestinal tract and secretions. Also in breast milk and colostrum -traces in circulation
B cells activated in lamina propria turn into
plasma cells
plasma cells secrete
dimeric IgA (D-IgA_
D-IgA binds
secretory component on epithelial cells
D-IgA attached to SC is
transported in vesicle through the epithelial cell
at luminated side of epithelial cells,
SC is cleaved and D-IgA retains a piece of the SC and becomed D-IgA-SC
SC protects D-IgA-SC from
degradation
D-IgA-SC is referred to as
secretory IgA
Role of Secretory IgA
binds to and neutralizes pathogens, binds to microbes before they bind to M Cells
monoclonal antibodies
arise from a single clone of plasma cells the speciicity for one epitope
crosslinking
one antigen is bound to two antibodies
cross reactivity
antibody generated to one epitope can bind with lower affinity to similar epitope on a different antigen
polyclonal collection
collection of several monoclonal antibodies to an antigen that has several different epitopes
idiotope
antigenti determinants in hypervariable rgions
antio-idotypic antibodies
antibodies generated to idiotopes on a single antibody molecule
anti-isotypic antibodies
antibodies generated to epitopes present on constant region of a heavy chain antibody molecule.
