2.3 Flashcards
Binding of an protein antigen by an antibody. This
model of a protein antigen bound to an antibody molecule shows
how the antigen-binding site can accommodate
soluble
macromolecules in their native (folded) conformation.
Antibodies can also recognize (3)
lipids, nucleic acids,
and other types of molecules
Small molecules like — are
antigenic for antibody recognition
digoxigenin
dendritic cell response after antigen presentation
naive T cell activation: clonal expansion and differentiation into effector T cells
macrophage response after antigen presentation
effector T cell activation: activation of macrophages (cell-mediated immunity)
B cell response after antigen presentation
effector T cell activation: B cell activation and antibody production (humoral immunity)
infected cell with microbes in cytoplasm:
killing of infected cells
Role of Dendritic cells in antigen capture and presentation (2)
lymph node collects antigen from tissue
blood-borne antigens are captured by antigen presenting cells in the spleen
feature: surface markers
classical dendritic cells: (2)
plasmacytoid dendritic cells: (3)
CD11c high
CD11b high
CD11c low
CD11b negative
B220 high
feature: major location
classical dendritic cells:
plasmacytoid dendritic cells:
tissues
blood and tissues
feature: expression of toll-like receptors
classical dendritic cells: (3)
plasmacytoid dendritic cells: (2)
TLRs 4, 5, 8 high
TLRs 7, 9 high
feature: major cytokines produced
classical dendritic cells: (3)
plasmacytoid dendritic cells: (1)
TNF, IL6, IL12
type 1 interferons
feature: postulated major functions
classical dendritic cells:
plasmacytoid dendritic cells:
introduction of T cell responses against most antigens
antiviral innate immunity and induction of T cell responses against viruses
cell type: dendritic cells
expression of Class2 MHC:
ecpression of costimulators:
principal function:
constitutive, increases with maturation, increased by INFgamma
constitutive, increases with maturation, increased by TLR ligands, INFgamma, and T cells (CD40-CD40L interactions)
antigen presentation to naive T cells in the initiation of T cell responses to protein antigens (priming)
naive T cell activation:
clonal expansion and differentiation into effector T cells
Costimulators are important for antigen
presentation to by
dendritic cells
activate naïve T cells.
Macrophages and B lymphocytes are also important —-
APCs
class 1 MHC Polymorphic regions: (2)
a1 and a2
class 1 MHC: Peptide-binding cleft for peptides --- aa long
8-9
class 1 MHC: --- binds CD8 T cell co-receptor
a3
---- T cells can only respond to antigen presented by MHC class I molecules
CD8+
class 2 MHC Polymorphic regions: (2)
a1 and b1
class 2 MHC
class 2 MHC:
(2) binds CD4 T cell
co-receptor
a2 and b2
class 2 MHC: Peptide-binding cleft for peptides --- aa long
10-30
--- T cells can only respond to antigen presented by MHC class II molecules
CD4+
Class I and class II MHC genes are the most — genes in the genome.
polymorphic
The total number of HLA alleles in the human population is estimated to be about --- class I alleles and --- class II alleles.
10,000
3,000
— expression of alleles inherited from parents
Codominant
feature: polymorphic genes: many different alleles are present in the population
significance:
different individuals are able to present and respond to different microbial peptides
10,000 class 1 alleles 3,000 class 2 alleles
feature: codominant expression: both parental alleles of each MHC gene are expressed
significance:
increases number of different MHC molecules that can present peptides to T cells
feature: MHC expressing cell types: class 2 (dendritic cells, macrophages, B cells) significance:
CD4+ helper T lymphocytes interact with dendritic cells, B lymphocytes
feature: MHC expressing cell types: class 1 (all nucleated cells) significance:
CD8+ CTLs can kill any type of virus infected cell
feature: broad specificity
significance:
many different peptides can bind to the same MHC molecule
feature: each MHC molecule displays one peptide at a time
significance:
each T cell responds to a single peptide bound to an MHC molecule
feature: MHC molecules bind only peptides
significance:
MHC restricted T cells respond mainly to protein antigens
feature: peptides are acquired during intracellular assembly
significance:
class 1 and class 2 MHC molecules display peptides from different cellular compartments
feature: style surface expression of MHC molecule requires bound peptide
significance:
only peptide loaded mhc molecules are expressed on the cell surface for recognition by T cells
feature: very slow off rate
significance:
mhc molecule displays bound peptide for long enough to be located by t cell
CD8+ Cytotoxic T cells (CTLs) recognize
endogenous (cytosolic) antigen presented by MHC class I molecules on an infected cell
Class I MHC pathway of processing of cytosolic antigens (5 steps)
production of proteins in the cytosol
proteolytic degradation of proteins
transport of peptides from cytosol to ER
assembly of peptide class 1 complexes in ER
surface expression of peptide class 1 complexes
CD4+ Helper T cells recognize
exogenous antigen presented by MHC class II molecules on a professional antigen presenting cell (APC)
Class II MHC pathway of processing internalized vesicular antigens (5 steps)
uptake of extracellular proteins into vesicular compartments of APC processing of internalized proteins in endosomal/ lysosomal vesicles biosynthesis and transport of class 2 mhc molecules to endosomes association of processed peptides with class 2 MHC molecules in vesicles expression of peptide mhc complexes on cell surfaces
Class I MHC-restricted cross-presentation of microbial antigens from
infected cells by dendritic cells (3)
antigen capture
cross presentation
T cell response
T cell dependent effector functions (3)
macrophage activation: killing of phagocytosed microbe
b cell antibody secretion: antibody binding to antigen
killing of antigen expressing target cell