Fundamentals of Immunology Flashcards
What are the cellular sources of C1 inhibitor?
Hepatocytes
Monocytes / macrophages
Fibroblasts
How does secretory IgA modulate the GI tract?
- Prevent binding of microbes to intestinal epithelium
- Trapping antigens in the mucus, preventing antigen presentation
- Facilitating biofilm of normal flora, preventing pathogenic overgrowth
- Transporting microbes back into GI lumen via IgA Fc receptor
What is MDA5?
RIG-I-like receptor, resides in cytosol and binds dsRNA to initiate NFkB and IRF3 transcription.
Abs associated with clinically amyopathic dermatomyositis with rapid ILD.
What are Langerhans cells?
Epidermal dendritic cells
What is a Type I hypersensitivity reaction?
Wheals, IgE mediated receptor aggregation causes degranulation of mast cells and basophils releasing histamine
What is a Type II hypersensitivity reaction?
Antibody-mediated (IgG or IgM) destruction via complement pathways and ADCC
What is a Type III hypersensitivity reaction?
-Immune-Complex Reaction
-Local or systemic
-Immediate or delayed
-Eg. Systemic lupus erythematosus, acute glomerulonephritis, and rheumatoid arthritis.
What is a Type IVa Hypersensitivity reaction?
Th1-mediated reactions inducing production of IFNg,l
E.g. tuberculin reaction
What is Type IVb hypersensitivity?
Mediated by Th2 cells –> IL-5, IL-4, IL-13
Influx of eosinophils –> cytokines, inflammatory mediators
ex. chronic asthma, chronic allergic rhinitis, maculopapular exanthema
What is Type IVc hypersensitivity?
Mediated by cytotoxic T cells –> perforin, granzymes
Cell associated antigen or direct T cell stimulation
Directly kill cells through apoptosis
E.g. Contact dermatitis, T1DM, Hashimoto’s thyroiditis
What is Type IVd hypersensitivity?
Neutrophils recruited by CXCL8, GM-CSF from T cells
IL-17 released from Th17 cells –> also recruit neutrophils
eg. AGEP - acute generalized exanthematous pustulosis (neutrophils enter lesion via GM-CSF secretion)
What is Type V hypersensitivity?
Antibody stimulates hormone receptor
e.g. Graves disease
Describe the Th1 phenotype
Induced by: IL-12 and IFNg
Requires: T-bet, STAT1, and STAT4
Secretes: IFNg
Function: enhance activation of macrophages for intracellular pathogens
Defect: MSMD (IL12RB1 def)
Describe the Th2 phenotype
Induced by: IL-4 and IL-6
Requires: GATA-3 and STAT6
Secretes: IL-4, IL-5, IL-13
Function: promote class-switching to IgE, recruit eosinophils, enhance anti-helminth immunity
Defect: STAT6 GOF
Describe the Th17 phenotype
Induced by: IL-6 and TGFb
Requires: RORgt and STAT3
Secretes: IL-17 and IL-22
Function: Recruit neutrophils to extracellular infections
Defect: STAT3 deficiency, STAT1 GOF
Describe the Treg phenotype
Induced by: IL-2 and TGFb
Requires: Foxp3
Secretes: IL-10 and TGFb
Function: Secrete suppressive cytokines and block co-stimulation
Defect: IPEX (Foxp3 def)
What’s occuring in early pro-B cell?
Heavy chain D-J rearrangement
What’s occuring in late pro-B cell?
Heavy chain V-DJ rearranging
What’s occuring in large pre-B cell?
Successful VDJ and subsequent pairing with surrogate light chains (VpreB and λ5).
Requires BLNK signalling.
What’s occuring in small pre-B cell?
Light chain V-D rearrangement, starting with kappa. Requires BTK signalling for progression.
What’s occuring in immature B cell?
Successful H- and L-chain gene rearrangement, IgM expression on surface (low IgD)
What are transitional B cells?
Cells that survive negative selection and migrate to spleen to receive BAFF survival signals -> CD21 and IgD upregulation
What are marginal zone B cells?
A subset of B lymphocytes, found exclusively in the marginal zone of the spleen, that respond rapidly to blood-borne microbial antigens by producing IgM antibodies with limited diversity.
What ligands do TLR1:2 and TLR2:6 recognise?
Lipoteichoic acid
Zymosan
Lipomannans
B-glucans
What PRRs are associated with recognising viral antigens?
TLR3
TLR7
TLR8
TLR9
RIG-1
MDA5
What transcription factors are acivated upon stimulation of a TLR?
NFkB, AP-1, IRF3, IRF7
What immunodeficiencies can affect NFkB activation?
MyD88 (AR)
IRAK-4 (AR)
NEMO (XL)
Name 2 triggers of NLRP3 inflammasome and 2 outcomes.
K+ efflux and ATP
Cleavage/activation of IL-1b/IL-18 and pyroptosis
What are the steps involved in endogenous antigen presentation?
Cytosolic proteins degraded in proteasome
Peptide antigens transported via TAP1 and TAP2 into ER
Antigens loaded onto MHC I
What are the steps involved in exogenous antigen presentation?
Antigens taken up into cell and degraded in endosomes
MHC II held stable by invariant chain > CLIP
Fusion of both endosomes, peptides load to MHC II
What cytokines are considered endogenous pyrogens?
TNFa, IL-1b, and IL-6
What molecules are involved in the reversible first steps of neutrophil extravasation?
Endothelium: e-selectin
Neutrophil: Sialyl-Lewis X
What molecules are involved in the second step of neutrophil extravasation?
Endothelium: IL-8 and ICAM-1
Neutrophil: CXCL8R and LFA-1 (integrin)
What inflammatory cytokine upregulates expression of endothelial adhesion molecules?
TNFa
