Exam 2 Immune Ontogeny and MHC Flashcards
Waldeyer’s ring consists of:
- pharyngeal tonsil (adenoid)
- tubal tonsils
- palatine tonsils
- lingual tonsils
Primary and secondary follicles - describe the difference
Secondary follicle has darker staining (more cells) and surrounds germinal center
Germinal center is active site of:
- B cell profileration and differentiation
- Class switching
- Affinity maturation
Affinity maturation
Highest affinity B cells are selected by binding to antigen on follicular dendritic cells
Class I MHC is expressed by:
most somatic cells (except erythrocytes and platelets)
What antigens are presented on MHC I, and they are recognized by:
Endogenous; CD8 T-cells
Class II MHC is expressed by:
APC only
MHC II presents ____ and recognized by ____
Exogenous/found antigens; CD4 T-cells
Which part of CD3 specifically is responsible for signal transduction?
Zeta component
MHC I is expressed on most somatic cells except:
Erythrocytes
HLA stands for
Human leukocyte antigens
HLA/MHC genes are on:
Chromosome 6
MHC I genes
A, B, C
MHC II genes
DM, DP, DQ, DR
Which MHC gene has the most/least allelic variations?
Most - DP
Least - DR
MHC is inherited via:
Mendelian inheritance
Most transplant rejections are due to:
mismatched HLA-A (solid tumors), HLA-DR (BMT)
Mismatched MHC molecules can mediate:
transplant rejection or Graft vs host disease (GVHD)
- look for HLA-A (most common reason for solid tumor rejection) - must all be the same for a transplant to have less likelihood of being rejected
For a bone marrow transplant, look at:
HLA-DR
For a solid transplant, look at:
HLA-A
In MHC I, the peptide-binding groove is found between:
Alpha-1 and alpha-2
Some tumors over-express ____, which inhibits the NK response
HLA-E
Non-classical MHC 1B genes
HLA-E, HLA-G, HLA-F
In MHC II, peptide-binding groove is found between:
Alpha-1 and beta-1
Most T cells are within which TCR subset?
TCR2 (have alpha/beta subunits)
TCR subset intraepithelial cells have what subunits?
gamma, delta
T cell antigen receptor components
Variable domain (antigen binding domain)
Constant domain (transmembrane)
There are variable genes for alpha/beta chains of TCRs, which allow for:
somatic recombination
In TCR gene rearrangement, gene segments are flanked by conserved ____
Recombination signal sequences (RSS)
TCR gene rearrangement segments are recognized by what enzyme?
VDJ recombinase (same as BCR)
TCR gene rearrangement occurs where?
In the thymus
Somatic recombination occurs at:
Hypervariable regions of BCR and TCR
Thymus is the site for:
T cell processing and differentiation
Why is the thymus so large when you’re young?
Because you should be responding to many new antigens
T-cells originate in the ____ and move to the _____. They enter as immature _____ and emerge as ______
bone marrow; thymus; thymocytes; mature T cells
When thymocytes enter the thymus, they are termed:
Double negative cells
Early thymocytes lack:
TCR, CD4, CD8
Thymic development begins when thymocytes contact ______ and dendritic cells to create a microenvironment
Epithelial reticular cells
ERC provides majority of:
Cytokines
Besides ERC, what is another important cell type that participates in T cell selection?
Interdigitating reticular cells (IDC)
Hassall’s corpuscle is associated with ERC type:
Type 6; DC maturation
Medullary and cortical ERC produce thymic hormones such as:
Thymosin, thymulin, thymopoietin
In precursor T-lymphocytes, the TCR locus is:
Methylated –> DNA inaccessible
Thymic cytokine ____ triggers DNA remodeling
IL-7
IL-7 is expressed as a result of:
thymic hormones (microenvironment)
- thymosin
- thymopoietin
- thymulin
IL-7 is required for development of
T-cells
During chromosomal DNA remodeling, what happens to the TCR locus?
It is moved into a central/active transcriptional position, methylation marks are removed to induce conformational change to euchromatin
What is positive selection?
- Double positive T cells have both CD4 and CD8
- TCR binds to MHC I or II
- Specific T cells are retained if they can recognize MHC without antigen
- lose either CD4 or CD8 depending on what they come into contact with first (become single positive)
Negative selection
removes T-cells reacting to MHC+ “self” peptides (self reactive) via apoptosis
Difference between positive and negative selection
- positive selection retains T cells that recognize self-MHC
- negative selection destroys cells that react with self MHC and self peptide (apoptosis)
Final result of mature, single positive T cells
- immunocompetent
- self-restricted (can bind MHC)
- self-tolerant (does not bind endogenous host antigens)
Next generation sequencing for HLA 1
HLA-A*02:101 - many people show different disease predilection/risk
High risk oncogenic HPV strains
HPV 16, HPV 18
If you have HLA-DR-B1*04:01 and HPV 16:
Cells don’t show HPV16 very well so can’t make antibodies to HPV16. Increases risk of reinfection
Highly increased risk of HPV16 infection is highly concentrated in what population?
Swedish - Scandinavian populations
In addition to HPV16, HLA-DR-B1*04:01 also implies highly increased risk of:
wt COVID-19 infection. Can’t present antigen well to be able to make antibodies
Distribution of HLA-DR-B1*04:01
- highest concentration in Sweden (Scandinavia) – 6x more deaths than in Germany
- densely concentrated in Northern europe
Those with HLA-DP-B1*04:01:
- In Chile and Uruguay, highly increased risk of COVID-19 L84S variant
- highly increased risk of H1N1 morbidity and mortality
HLA-A02:06 and HLA-A11:01
HLA-B07:02 and HLA-B54:01
Highly decreased risk of wt COVID-19 infection
Highest concentrations in Asia (Japan and Korea)
