lecture 3 exam 2 Flashcards
innate immunity
physical & chemical barriers phagocytes complement system NK cells works for IMMEDIATE but GENERAL recognition of conserved pathogen signals
adaptive immunity
works against pathogens that have eluded innate immunity
machrophages and DC BRIDGE innate & adaptive by secreting cytokines and presenting antigens to T cells
LONGER onset but more SPECIFIC recognition
two types: jumoral (antibody mediated) & cellular (Tcell mediated)
MHC is essential to trigger adaptive immunity
antigens must be processed into peptides to trigger adaptive immunity
-broken up inside cells and bound to antigen-presenting receptors
antigen presenting receptors are encoded by genes clustered together to form the MHC
all vertebrates have different variation of MHC
MHC 1
receptors for endogenous antigen found on most nucleated cells (except RBC)
dont eat me signal on non APC
TCR of CD8+
a1, a2, a3, b2m
a - 43kDa
b2microglobulin is 12kDa - nonMHC encoded, non transmembrane, noncovalently bound to a chain
present intracellular origin derived antigens
MHC 2
receptors for exogenous antigen predominantly found on APC (B cells)
professional antigen presenting cells, T cells
TCR of CD4+
2a 2b
a - 34 kDa
b - 29 kDa
no b2microglobulin
can accomodate peptides w more than 13 aa
present extracellular derived origin antigens
MHC 3
mixed group of proteins including some complement components, TNF
polygenism
multiple genes encoding different types of MHC molecules w a range of peptide binding specificities
polymorphism
variations at a single genetic locus in a population level
different versions of each gene among individuals in a pop
pop survival depends on expression of a sufficient number of diff MHC genes to enable at least some individuals to overcome infection by a new pathogen
affects peptide antigen binding
changes in pockets, walls and floor of peptide binding cleft
codominance
gene copies expressed from both parents
inheritance of MHC is codominant
heterozygous state increases the diversity of antigens that can be recognized
haplotype
complete set of alleles found within an individual animal’s MHC
properties that result in heterogeneity of MHC molecules across population
polygenism
polymorphism
codominance
haplotype
T cells must encoutner their antigen presented in context of MHC
APC processes antigen that T cells recognize
APC generate fragments of antigens that associate w MHC 1 or 2 that are displayed on the plasma membrane
cells that activate an immune response by presenting antigen to T cells are called professional APC
professional APC
DC
macrophages
B cells
activate immune response by presenting antigen to T cells
characteristics of MHC molecules
- MHC can present one peptide at a time
- an MHC molecule is capable of presenting different peptides at different times
- anchor residues are critical amino acids and must fit into binding pockets (limited variability)
- broad specificity = an MHC molecule can bind an array of different peptides (est. <10,000 diff peptides/MHC molecule
can bind peptides of differnet length
motif
common sequence in a peptide antigen that binds to an MHC molecule
anchor residues
amino acids common to many peptides tether the peptide to structural features of the MHC molecule
need not be idental but must be related - Y & F = aromatic, V, L & I are hydrophobic
MHC presentation of antigen induces innate immunity by activating T cells
TCR accessory molecules (CD8 & CD4) determine w which MHC class T cell will interact = class restriction
MHC 1 - 8
MHC 2 - 4
occurs in light zone of lymph nodes
MHC are targets for immune evasion by pathogens
T cells are required for an effective adaptive immune response
ag-specific t cells must be activated by peptide MHC complexes
there is a strong selective pressure for pathogens to mutate genes encoding antigens so that they can evade formation of peptide/MHC complexes
in order to prevent this pathogen evasion we have more than one type of MHC molecule in each individual and there are extensive differneces between individuals
