Adaptive Immunity Flashcards
Principle defense against extracellular microbes
Humoral Immunity
Promotes destruction of intracellular microbes
Cell Mediated immunity
IL-7
Principle cytokine that stimulates the proliferation of B and T cell progenitors
Clonal selection hypothesis
Antigen receptors are produced by random DNA recombination events that are not dependent on or influenced by the presence of antigens
Somatic recombination
- VDJ combination
- Process of DNA recombination by which the functional genes encoding the variable regions of antigen receptors are formed during lymphocyte development
- Occurs only in immature B and T cells
Allelic exclusion
- Protein product of one productively recombined antigen receptor locus on one chromosome blocks rearrangement of the corresponding locus on the other chromosome
- Ensures that each lymphocyte will express a single antigen receptor and that all antigen receptors expressed by one clone of lymphs will have identical specificity
Which lymphs have allelic exclusion?
B cell light and heavy chains
TCR b chain
Self MHC restriction
T cells only recognize antigens displayed by MHC molecules that the T cell encountered during maturation in the thymus (and thus sees self)
CD1
- Class I like non classical MHC molecule
- Bind and display lipids (instead of peptides) to certain types of T cells, particularly NKT
MHC Class I
- Expressed on most nucleated cells
- Displays peptides to and recognized by CD8+ T cells
- Composed of 3 genes: HLA- A, HLA- B- HLA-C
- Increased expression can be induced by interferon A, B, G and TNF
- Composed of alpha chain (a3 is conserved among all class I MHC) with beta 2 microglobulin unit
- Accomodates peptides 8-11 residues long
- A3 binds CD8
MHC class II
- Normally expressed only on DCs, B cells, macrophages and a few other types
- 3 genes HLA DP, DQ, and DR
- Interferon gamma is principal cytokine
- Composed of alpha and beta chain
- B2 is invariant and binds CD4
Where are the mature T cells?
Thymic medulla
Most effective for activating naive T cells
DCs
Most effective at activating effector T cells
B cells and macrophages
Which uses proteosome and TAP?
MHC CLASS I (cytosolic and nuclear protein antigens)
What is the process for peptide MHC class II production?
Protein antigens are captured from the extracellular environment–> internalized into endosomes by specialized APCs–> Degradative enzymes in endosomes and lysosomes generate peptides–> MHC II are synthesized int he ER and transported to same endosomes with the invariant chain–> In the endosomal vesicle, invariant chain is degraded, leaving 24 amino acid remnant called CLIP–> CLIP is removed by HLA-DM–> MHC class II is stabilzed and bound to peptide
TCR components
- Variable domain
- Hydrophobic transmembrane region
- Constant domain
- Short cytoplasmic region
What area recognizes peptide MHC complexes?
V region, specifically concentrated
What do T cells require for transition to effector cells?
- First signal is response by the TCR to MHC and peptide on an APC (foreight signal)
- Second signal is costim ligand induced on APC by microbes (danger signal)
CD28
- Recognized and binds B7 proteins on activated APCs
CTLA-4
- Inhibitory receptor of the CD28 family
- Also bind B7
LFA-1
- Binds ICAM-1 on APCs and endothelium and functions to help cell adhesion
CD44
- Binds hyaluronan, involved in leukocyte adhesion to endothelial cells and ECM
CD45
- Tyrosine phosphatase that regulates T and B cell activation
L-Selectin
- Part of selectin family which mediates low affinity adherence of leukocytes as they roll through venules
Naive T cells
CD45 RA
Memory T cells
CD45 RO
Where is antigen binding?
- Hyper variable region of the VH and VL
Where does the antigen recognition take place?
FAB
Where does the effector function take place?
Fc region
Where are all Ig Heavy chain genes found?
Chromosome 14
What is the structure of Ig?
Two beta pleated sheets held together by disulfide bridge
What differentiaties antibodies into distinct classes?
Structure of their heavy chain C region
IgA
- Secreted form is dimer
IgD
- Circulates as a monomer
- Naive B cell antigen receptor
IgE
- Circulates as a monomer
- Mediates immediate hypersensitivity, defense against helminthes
IgG
- Circulates as a monomer
- Functions in opsonization, complement activation, antibody dependent cell mediated cytotoxicity, neonatal immunity and passive immunity, feedback inhibition of b cells
IgM
- Circulates as pentamer
- Functions in complement activation, naive B cell antigen receptor (monomeric form)
B cell maturation steps
- Stem cell
- Pro B cell
- Pre B cell
- Immature B cell (IgM)
- Mature B cell ( co -express IgM and IgD)
CD19
- Role in B cell activation
- Forms a co receptor complex with CD21 and Cd81 that delivers signals that synergize with signals from b cell antigen
CD21
- Receptor for complement fragment C3D
- Forms a co receptor complex with CD19 and CD81
that delivers activating signal in B cells, receptor for EBV
Phenotype markers of B cells
- MHC class II
- CD19
- CD21
- Fc receptors
Where does isotype switching happen?
- Germinal center and sometimes extrafollicular foci
- Constant regions of the heavy chains change but the specificity of the antibodies (which is determined by the variable regions) remains unaltered
Match cytokine to Ig
- IFN gamma–> IgG
- IL-4–> IgE
- TGF beta–> IgA
- B cells in mucosal tissues also switch to IgA
Fc gamma receptor 3 (CD16)
- binds IgG
- Found on NK cells
- Responsible for antibody dependent cell mediated cytotoxicity
Fc epsilon
- Binds IgE
- Expressed by mast cells, basophils, and eosinophils
Where do T cells reside in the spleen?
Periarteriolar lymphoid sheath
Where do B cells reside in the spleen?
- Follicles and germinal centers
Genes involved in class switch recombination and somatic hypermutation
activation induced cytosine deaminase
Uracil n glycosylase
Defects prevent B cells from switching from IGm to IGG.
