Immunology- antibodies, receptors, presenting, antigen recognition

clonal selection and clonal expansion

allow adaptive response to be specific and effective

surface bound receptors

bind antigen and initiate signaling pathways that activate the B cell

secreted antibodies

target bound antigens to other immune system components

light chain isotopes

kappa and lambda

• one variable and one constant region

heavy chain isotypes

immunoglobulins M, G, A, D, E

• 1 variable and 3-4 constant regions (that determine class and function of antibody)

antigen specificity

determined by variable regions of light and heavy chains

complementarity determining region

hypervariable, contains amino acids that make direct contact with antigen epitope

B cell receptor

requires membrane bound antibody and association of 2 signaling proteins

• each B cell has one unique BCR to recognize epitope

  • antibody produces by B cell identical to BCR on cell surface

numbers of genes

B cells- 10^11

T cells- 10^16

variable region made by

splicing of VJ or VDJ gene segments, also called somatic region

somatic recombination of gene requires

RAG1 and RAG2, Tdt, recombination signal sequences

RAG enzymes

select which V, J, D and loop out DNA

TdT

add random nucleotides into gene

D region

needed by heavy chain only

every cell starts with ___ but can switch to ___ after activation

IgM; IgG

one B cell expresses one antibody class except

during development

what immunoglobulins are expressed together on one B cell due to antigen specificity

M and D (transcribed together bc no off switch)

what makes the difference between IgM and IgD

mRNA splicing- VDJ does not change

what determines if antibody is secreted or membrane bound

RNA splicing; this allows B cells to express IgM and IgD to be expressed at same time with alternative splicing

what gives variable region

DNA splicing

polymeric structures of IgA and IgM require association of heavy chains with ___?

J chain protein- joining

T cell receptors

alpha and beta chain subunits, or less common gamma and delta

• gene segments V, D, J rearranged to make variable epitope binding region of a chain (chain determined by C region)

TCR constant region alpha and gamma

VJC

TCR constant region beta and delta

VDJC

TCR gene recombination requirements

RAG1 and RAG2 (recombinase enzymes), TdT, and RSS (recombination signal sequence)

CD8

MHC I

CD4

MHC II

MHC I

all cells express; alpha chain non-covalently linked to beta2 microglobulin

MHC II

dendritic cells, macrophages, and B cells express; presents peptides to CD4; made up of alpha and beta chain

exogenous pathway

degrades extracellular enzymes after loading peptides on MHC II to present to CD4

• requires endosomes, phagosomes, lysosomes

endogenous pathway

degrades intracellular antigens by loading peptides on MHC I and presenting to CD8 cells

• requires proteosome

TAP and proteosome

required for loading on to MHC I

endosome/phagosome, invariant chain, CLIP, HLA-DM

required for peptide loading on MHC II

HLA complex

collection of genes on chromosome 6, MHC region

MHC genes

multiple genes produce proteins with identical structures

• class I- HLA-A, B, C

• class II- HLA-DP, DQ, DR

polymorphic

MHC genes have multiple alleles at given locus

• variability by different AA in binding groove

MHC expression

co-dominance; different gene expression means greater variety of epitopes presented

• haplotype- set of MHC alleles an individual possesses and expresses on a cell

TCR

only surface bound, single antigen binding site, simple constant region

BCR

can be secreted as antibodies, can have 2 antigen binding sites, gene segments for multiple constant regions