Signaling PRR: C-type lectins bind β-glucan and α-mannans, respectively; control some bacterial & fungal infections
NOD like receptor (NLR) that responds to multiple stimuli to form a multi-protein complex termed the NALP3 inflammasome which activates the IL-1β family of cytokines (powerful mediators of inflammation) (mutation causes cryopyrinopathies such as Mucle-Wells syndrome)
RIG-1 like receptors (RLRs)
RNA helicases that detect RNA derived from viruses in the cytoplasm
Inducible Nitric Acid Synthase (iNOS) Rxn
L-arginine + O2 ð L-citrulline + NO Nitric Oxide
The inflammatory cytokines
TNF-α, IL-1, IL-6
a bridge to induce active immunity” induces naive CD4+ T cells to differentiate into TH1 cells and Activates NK cells
Chemotactic Factor, used to be called IL-8, induces integrin conformational change to promote strong adhesion
Bacterial products in the bloodstream activate macrophages in the liver & spleen to produce high levels of TNF- α
Explain Neutrophil diapedesis
Selectin and ICAM on endothelial cells bind Siayl-Lewis and LFA-1 on neutrophils
Leukocyte Adherence Deficiency (LAD)
LAD1 a mutation in the common chain of the β2 integrin family (CD 18).
LAD2 a mutation in the sialyl-Lewis ligand for selectins
Leukocytes do not bind adhesion molecules (ICAMs / VCAMs) on endothelial cells
Patients have recurrent bacterial infections, impaired pus formation and impaired wound healing
Papain and Pepsin
Papain cuts the antibody into two Fab fragments and one Fc fragment
Pepsin cuts the antibody into a F(ab’)2 fragment and the Fc fragment dissolves
Cd79s and CD79b
Also known as Ig-alpha and Ig-beta, when membrane bound Ig crosslink, signal is started—Tyrosine Phosphorylation of ITAM and activation of transcription factors NFkB, NFAT and AP-1
What chromosomes are involved with Ig?
Lambda light chain = 22
Kappa light chain = 2
Heavy chain = 14
What CD markers are involved in the B cell co-receptor complex?
CD19, CD21 (CR2), and CD81
C3d binds to the CD21 (CR2) (CR = complement receptor)
X-Linked hyper-IgM syndrome
Defect in CD40/CD40L
Elevated IgM, but no other isotypes
No germinal centers, no tonsils
Enzyme that mediates class switching
What cytokine promotes the switch to IgE? IgA?
IL-4 promotes IgE and TGF-beta promotes IgA
What does Forward angle Light scatter measure? What does side scatter measure?
Forward angle light scatter measures size
Side scatter measures granularity
Natural killer cells recognize bound antibody with which receptor?
FcyRIII, also known as CD16
This happens during Antibody-Dependent cell mediated cytotoxicity
What is ficolin?
Lectin protein that binds N-acetylglucosamine to start the complement pathway
What do MASP1 and MASP2 bind to?
C1r and C1s respectively
Epstein-Barr virus complexes with which receptor?
What prevents complement mediated lysis?
CD35 (CR1), MCP, DAF, and Protectin (CD59)
Defects in these lead to paroxysmal nocturnal hemoglobinuria
Explain hereditary angioedema
Factor XII is activated (possibly due to lack of C1 inhibitor), which activates kallikrein. Bradykinin is generated which binds Bk-B2 receptor on endothelial cells leading to edema
What is the accessory molecule for the TCR?
CD3 and zeta: Zap70 interacts with CD3 starting Signaling cascade involves protein tyrosine phosphorylation and intracellular calcium nflux resulting in activation of transcription factors
Protein kinase C activates NF-kappaB
Calcineurin activates NFAT
Ras Kinase activates AP-1
What do NF-kB, NFAT, and AP-1 activate in T cells?
What are the differences in binding of alphaBeta T cells and gammaDelta T cells?
gammaDelta T cells recognize antigen directly, they do not require MHC presentation of peptide like alphaBeta T cells do, but gammaDelta T cells have a restricted repertoire
What chromosome is the MHC complex found on?
What genes encode proteosome subunits?
LMP 2 and LMP 7
What genes encode peptide transporters from cytosol to ER?
TAP 1 and TAP 2
What do the terms double positive and double negative refer to in relation to T cells?
before cell rearranges it is double negative (CD3- CD4- CD8-)
If cell rearrange alphabeta TCRs they become double positive, CD3+ CD4+ CD8+
If cell rearranges gammadelta it becomes CD3+ but CD4- and CD8-
Where does T cell alphabeta selection occur?
Positive selection in the cortex of thymus (to determine if cell becomes CD4+ or CD8+)
Negative selection in the medulla of thymus (removes T cells that react with self)
What is Bare lymphocyte syndrome I?
Tap-1/2 deficiency – can’t transport antigen associated peptides to the ER to combine with MHC class I
CD8 T cell numbers are very low
Increased susceptibility to viruses
What is the enzyme that catalyzes CLIP removal?
What is Bare lymphocyte syndrome II?
MHC class II deficiency – CD4 cells cannot be positively selected in Thymus and few develop
Ig levels are low due to no T cell help
Increased susceptibility to pyogenic and opportunistic pathogens such as Pneumocystis jiroveci
What do superantigens bind? What response is triggered?
MHC II and TCR Vbeta regions of CD 4 T cells
IL-1, IL-2, TNF-alpha
What functions does CD28 binding to B7 have on T cells?