ACAAI Review Book Ch 1: Immune Mechanisms Flashcards
see ACAAI pre-made flashcards for additional cards. these fill in blanks from thoseNKT
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Superantigens bind what region of TCRs?
Vbeta (variable portion of the beta chain, outside the peptide binding groove of the MHC molecule). capable of activating a much larger polyclonal T-cell response than a typical antigen
All but which 2 of the following are conjugated vaccines
A. meningococcal (MSPV4) B. DTap C. Pneumococcal vaccine 23-valent D. Haemophilus influenza type B (Hib) E. Pneumococcal vaccine 13-valent
B. DTap
C. Pneumococcal vaccine 23-valent
What are conjugated vaccines?
T-independent antigens linked to a carrier protein, which can trigger a T-dependent response and memory
What does an MHC molecule being “co-dominant” mean?
an individual expresses one haplotype from each parent
Genes encoding MHC Class II include all but which of the following?
A. HLA-DP
B. HLA-DM
C. HLA-DQ
D. HLA-DR
B. HLA-DM
MHC class I encoded by HLA-A, B, C
HLA-DM is an intracellular protein involved in MHC-class II antigen processing. it does NOT present antigenic peptides and is not a component of MHC-class II
MHC I and MHC II are encoded by what polypeptide chains on what part of the genome, and antigenic sampling comes from where?
MHC I = alpha chain (a1, a2, a3), b2-microglobulin - intracellular
MHC II = alpha chain (a1, a2), beta chain (b1, b2) - extracellular
MHC molecules encoded on short arm of chromosome 6 (3 regions in order: class II, III, I)
b2-microglobulin chain encoded on chromosome 15
Which MHC is expressed on most nucleated cells?
MHC I
Which MHC is found on APCs, DCs, macros, B cells, thymic epithelia, and activated T lymphocytes?
MHC II
T cells can recognize which of these antigens presented as part of the MHC complex, leading to what is known as “MHC restriction”?
A. lipids
B. nucleic acids
C. peptides
D. polysaccharies
C. peptides
others are not presented on MHC molecules, which is why they are “T-independent” antigens
The MHC I antigen processing pathway involves what protein, and what MHC locus is it encoded on?
TAP (transporter of antigenic-processing proteins), encoded on MHC class II locus
- cytoplasmic proteins are degraded into antigenic peptides via proteasome processing
- transported into the ER by TAP
- remain sequestered in the ER by interacting with calnexin, calreticulin, Erp57, and tapasin (chaperone proteins)
Put the following steps of MHC II antigenic processing pathway in order:
A. phagosomes fuse with lysosomes forming phagolysosome, which uses endosomal/lysosomal proteases (cathepsins) to degrade microbe into antigenic peptides B. MHC class II and peptide are transported to cell surface C. newly synthesized MHC class II transported from the ER to the phagolysosome, forms MHC class II vehicle- where MHC class II-binding cleft is still occupied by invariant chain (Ii) prior to peptide loading D. HLA-DM removes CLIP (class II associated invariant chain peptide) and allows antigenic peptides to be loaded onto MHC-binding cleft E. extracellular antigen is endocytosed and compartmentalized into cytosolic phagosomes F. the invariant chain (Ii) is degraded by proteolytic enzymes in the MHC class II vehicle, leaving behind short peptide called CLIP (class II associated invariant chain peptide)
E A C F D B
Mutations in all but which of the following genes leads to MHC class II deficiency?
A. MHC2TA B. RFX5 C. FRXAP D. TAP E. FRXANK
D. TAP
- TAP is essential for MHC class I expression (even though it is encoded on the MHC class II locus) and leads to MHC class I deficiency when mutated.
- MHC class I def: sinopulmonary infections, granulomatous skin lesions, CD8 lymphopenia, PBMC lack MHC class I on flow. Tx treat infections like CF
- MHC class II def: diarrhea, HSM, transaminitis, SC/Crypto, Pulm infections (PJP, HSV, RSV), meningitis. CD4 lymphopenia (reversed CD4:CD8), lack HLA DR/DP/DQ on lymphocytes, hypogam, absent GCs. Tx HSCT
- both AR
The two main factors determining T-lymphocyte central tolerance or negative selection are antigen concentration and affinity to the TCR. High or low of these factors will promote negative selection?
high concentration and high affinity to the TCR (lead to negative selection or apoptosis)
The autoimmune regulatory gene promotes the expression of what type of antigens in the thymus?
AIRE promotes expression of non-thymic tissue antigens
In B-lymphocyte central tolerance, what is the phenomenon known as “failure of editing” that leads to an immature B lymphocyte being deleted by apoptosis?
when a high-affinity self-antigen is recognized by a BCR, RAG 1 & RAG 2 are reactivated to delete the previously rearranged VkJk exon, and give the BCR a new light chain leading to the self-reactive B cell having a new specificity.
“failure of editing” is when both recombinations recognize a self-antigen and the immature B lymphocyte is apoptosed
Which light chains of the BCR are rearranged first?
K
if receptor editing is needed, a lambda light chain is used
True or false: peripheral tolerance has the same outcomes as central tolerance in regards to T-lymphocytes
true. anergy, deletion, or regulation (become a Treg that confers suppression)
anergy is maintained by a blockade of: TCR-signaling, ubiquitin ligases (which target proteins for degradation), and inhibition of costimulatory molecules (CTLA-4 and PD-1). so T cells will recognize the antigen, but lack costimulation and receive no support to activate.
Treg cells express what markers, survival depends on what factors, and secrete/tolerance maintained by what factors?
EXPRESS: CD4, CD25 (IL-2R alpha chain), FoxP3
SURVIVAL: IL-2 and TGF-beta
SECRETE: IL-10 and TGF-beta
What protein is activated when self-antigen is repeatedly recognized by a T-lymphocyte without costimulation, that leads to cell apoptosis through the mitochondrial pathway?
Bim
mutations in FoxP3 lead to what disease?
IPEX
immune polyendocrinopathy with enteropathy X-linked
immune dysreg, watery diarrhea, eczema, endocrinopathy
What receptors can interact to signal through the caspase system to cause the death of a self-reactive T-lymphocyte and downregulate the immune response?
Fas ligand (CD95L) and Fas (CD95) interactions
Mutations in CD95 or caspase 10 manifest as what disease?
ALPS autoimmune lymphoproliferative syndrome
lymphocytes dont know when to die .they accumulate in lymph organs. lack of tolerance, leading to autoimmune problems
Chronic antigen recognition leads to downregulation of what, that results in inhibition of B-lymphocyte homing and interaction with T-cells -> cell death?
CXCR5
Which of the following single nucelotide polymophisms is associated with decreased albuterol response?
A. ADAM33 B. ADRB2 C. 5q31 D. Xp22 E. 17q12-21
B. ADRB2
B2-adrenergic receptor
Arg/Arg phenotype < albuterol response compared to Gly/Gly phenotype at residue 16
(see table 1-10 on pg 15 for others)
Which of the following single nucelotide polymorphisms is associated with decreased albuterol response?
A. ADAM33 B. ADRB2 C. 5q31 D. Xp22 E. 17q12-21
B. ADRB2
B2-adrenergic receptor
Arg/Arg phenotype < albuterol response compared to Gly/Gly phenotype at residue 16
(see table 1-10 on pg 15 for others)
What is the earliest cell in B-lymphocyte lineage that produces immunoglobulins?
pre-B lymphocyte
omalizumab binds to what part of the Ig molecule
Ce3 (C epsilon 3)
which enzymes cleave above and below the Ig molecule hinge region?
Papain- cleaves above
Pepsin- cleaves below
What is the most variable part of the Ig molecule?
CDR3
Which constant region mediates effector functions by binding to Fc receptors or binding complement?
Ch
What is the one conserved glycosylation site in human IgG?
Cy2 domain (asparagine-297)
Which of the following can be secreted in pentamers?
IgM
IgG in monomers, IgA in dimers
