Diebel-T Cell receptors and MHC Complex Flashcards
What are Th1 cells induced by?
DC1
IL-12
IFN alpha
What cytokines to Th1 cells make?
IL-2
IFNy
(TNFB)
What are the main functions of a Th1 cell?
IFNy polarizes macrophages into M1, activates and attracts them.
IL-2 helps CTLs get activated by antigen.
What cytokines do M1 macrophages release to intensify inflammation?
TNF alpha
IL-1
What causes contact sensitivity?
Normally T cell recognizes antigens and a macrophage removes them but this system can also damage local tissues. Over stimulation of Th1 cells (poison ivy)–> contact sensitivity.
What induces Th2 cells?
DC2
IL-4
What cytokines do Th2 cells make?
IL-4 IL-5 IL-6 IL-10 IL-13
What are the main functions IL-4?
IL-4 polarize macrophages into M2, activates and attracts them.
IL-4 also attracts eosinophils specialized for killing parasites like protozoans and worms.
What are the main functions of Th2 cells?
Th2 cells often act AFTER Th1. They are involved in healing (debris removal, scar formation, and walling off pathogens that M1 macrophages couldn’t kill).
Explain the ying and yang of T cell immunity.
Th1- active urgent destruction of invaders
Th2- later stages of inflammation, repair and healing
What are the 2 ways that Th2 mediates parasitic immunity?
Th2 secretes IL-4 which attracts eosinophils which are specialized for killing parasties.
Th2 gives rise to Th2fh cells that migrate to lymphoid follicles and secrete IL-4. High amts of IL-4 switch IgM/IgD to IgE–> parasite resistance.
What induces Th17 cells?
TGFB + IL-6
IL-21
IL-23
What are the main functions of IL-17 and 22?
Attract and activate inflammatory cells.
What helper cell is often implicated in autoimmune disorders?
Th17
What Th are Th17 most similar to?
Th1
Both lead to the accumulation of angry M1 macrophages.
Also plays a role in maintaining integrity of mucosal surfaces.
What cytokines does Tfh make?
Many of the ones that Th1 and Th2 make
What are the functions of IL-2, IL-4 and IFNy secreted by Tfh cells?
Help B cells switch isotypes
What induces Treg cells?
Natural TGFB
What cytokines are made by Treg cells?
TGFB
IL-10
What are the main functions of TGFB and IL-10?
Supress Th1,2,17,Tfh by contact and soluble factors
Most Treg cells ahve what phenotype?
CD4/CD25
What happens if Treg doesn’t work?
You can get overactive immune responses and self reactivity.
All Th cells have what surface marker?
CD4
What are the two ways that a CTL can initiate apoptosis?
- Fas (CD95) receptor cross linked to the Fas ligand (CD95L) activates apoptotic pathway
- secretion of lytic granules that lead to apoptosis:
granzymes
perforins
How and where are CTLs activated?
Lymph node after contact with an antigen bearing DC
What IL is required for activation of CTLs?
IL-2 from Th1
What IL is required for conversion of CTL into memory cells?
IL-21
What percent of T cells are left after a couple weeks of infection and what cells are these?
5%
Memory cells–they can replace themselves and quickly differentiate into effector cells when re-exposed to low antigen concs.
Could my T cells work in your body?
NO!
T cells are antigen specific and MHC restricted to cells of your own body
What cell is the BEST APC?
Dendritic cells
T cells ONLY see antigen when….
it’s complexed w/ cell surface MHC molecules
**B cells focus on free antigen by making antibodies
Class I products are found on…
nucleated cells (essentially found on all your cells except RBCs)
Class II products are found on…
the surfaces of dendritic and macrophage type cells and B cells
What is an important quality of DCs?
They CONSTITUTIVELY express high levels of MHC and B7
What is the difference between DCs and macrophages?
Macrophages aren’t always on–they have to be activated!
They’re activated by phagocytosis of Class II molecules.
What do B cells constitutively express and how are they activated?
MHC II
Antigen binding to Ab before they express costimulatory molecules
Describe a characteristic T cell receptor.
2 chains that are alpha and beta or gamma and delta. Both alpha and beta domains have transmembrane domains.
Constant and variable portion
What molecule is associated w/ the TCR complex and is involved in downstream signaling?
CD3
What molecule has:
4 Ig like domains
binds to a conserved region on Class II
CD4
What signal transduction molecule does CD4 bind to?
p56 which then forms a bridge and also binds a chain of CD3
What molecule has:
aB heterodimer or aa homodimer
ONE Ig domain held together by a disulfide bond
Binds Class I
CD8
What co-receptors add to CD4/8 binding affinity?
CD2- LFA-3
LAF-1- ICAM-1
CD28- B7
CD45R- CD22
Rearrangement of the alpha chain (V, J and C segments) leads to…
selection of a VJ combination attached to a single C segment
*alpha chain has a cytoplasmic tail making the TCR alpha receptor membrane bound
The alpha chain is most similar to the….
Light chain
The beta chain is most similar to the….
Heavy chain
Rearrangement of the beta chain leads to…
A selection of a VDJ combination attached to one of two C gene segmenents
Does somatic hypermutation play a role in generating TCR diversity?
NOOOO
Can’t happen because there’s no way to change it once the T cell leaves the thymus.
Describe the process of TCR gene rearrangement…
- Pre-T cells express Rag1/2
- Enzymes recognize conserved recombination signal sequences flanking the regions of the VDJ coding sequences in the DNA
- RAG1/2 complex joins the various DNA segments and throws away DNA info in between
- Each rearranged DNA sequence encodes a single type of TCR
How do you increase diversity in TCR gene rearrangement?
- Alternating joining of the D seq to VJ, VDJ, or VDDJ
2. Somatic mutation can be added btwn v and D and D and J domains
What is TCR allelic exclusion?
Each T cell will produce ONE beta chain from just ONE chromosomal loci.
Where does T cell selection occur and what are the three things T cells must do?
Thymus
- Not recognize SELF
- Not recognize free antigen (Ab’s job)
- Recognize antigenic peptide plus self MHC
What are MHC molecules also known as?
HLA
How many class I gene loci are there and what are they?
3
HLA-a
HLA-b
HLA-c
What is B2 microglubluin?
A gene product that associates w/ the other MHI peptides.
How many peptides does the MHC II gene locus encode?
2!
Alpha subunit and a beta subunit are expressed together on the cell surface
What are the three major class II gene loci?
DP
DQ
DR
How does polymorphism relate to the gene loci of MHC I and II?
Polymorphism give you:
a unique identity
allows you to distinguish btwn self and non self
What are medically significant MHC polymorphisms?
HLA: B27 DR2 A3/B14 DQ2/GQ8 DR3 DR4
HLA-B27
Ankylosing spondylitiis
Individuals are 90% more likely to develop disease (destruction of vertebral cartilage)
Also linked to psoriasis, inflammatory bowel disease, reiter’s syndrome.
HLA-DR2
Narcolepsy
Linked to: MS, hay fever, SLE
HLA-A3-B14
hemochromatosis
too much Fe absorption which can lead to internal organ damage
HLA-DQ2/GQ8
Celiac disease
HLA-DR3
Type I diabetes
Graves Disease
HLA-DR4
rheumatoid arthritis
type I diabetes
How many different class I and class II molecules can a cell potentially express?
MHC I- 6
MHC II- 12
Why are there 6 different class I subtypes?
There are three genes one the loci (A,B,C) that you can inherit from either your M/D generating 6 options. One of these alleles will always be combined with the B2 chain leading to 6 different types.
Why are there 12 different class II subtypes?
There are three loci w/ two alleles for each loci.
DQ, DR, DP. Each allele can be inherited from mom or dad. This means that for each locus there are 4 different possibilities leading to 4x3=12.
What are lectins?
Lectins are proteins that function as immune molecules that can gum up the surfaces of foreign invaders, they can also bind to and stimulate T and B cells.
What is pokeweed mitogen (PWM)?
PWM is a lectin that stimulates both T and B cells to divide.
