Assignment 3 Flashcards
what is the role of antigen presenting cells?
they deliver antigen to CD4+ T cells
Name 3 antigen presenting cells?
dendritic cells
macrophages
B cells
explain the term antigen presentation
the process when antigen presenting cells deliver antigen to CD4+ T cells.
what is the major histocompatibility complex (MHC)?
encodes proteins that define antigen presenting molecules
a gene complex originally identified because of its role in graft rejection
The major histocompatibility complex (MHC) is a set of cell surface molecules encoded by a large gene family in all vertebrates. MHC molecules mediate interactions of leukocytes, also called white blood cells (WBCs), which are immune cells, with other leukocytes or body cells. MHC determines compatibility of donors for organ transplant as well as one’s susceptibility to an autoimmune disease via crossreacting immunization. In humans, MHC is also called human leukocyte antigen (HLA).
what do all antigen presenting cells express and require for T cell stimulatory function?
- cell surface class II MHC
- costimulatory molecules (CD80 and CD 86 and CD 40).
what are CD8+ T cells? Why?
not antigen presenting cells, they are target cells
the antigen displayed in their cell surface (with class I MHC) targets them for CD8+ T cell mediated death
why are all nucleated cells a potential target cell?
all nucleated cells express class I MHC - potentially be destroyed!
where are immature dendritic cells present?
in all lymphoid and non lymphoid tissue except the brain - including mucosal epithelium of the oral cavity, anus and vagina
skin = aka Langerhans cells
what is the function of dendritic cells?
sentinel cells (or gatekeepers) in peripheral tissues where they capture antigens and carry them to secondary lymphoid tissues (to the T cells)
some are also resident in secondary lymphoid tissue where they capture antigens that have invaded that site!
phenotypically, what do immature dendritic cells express high concentrations of?
FcϒR
also express CD 4
phenotypically, what do immature dendritic cells express low concentrations of?
- class II MHC
- co stimulatory molecules (B7-1, B7-2)
what is CD4?
one receptor for HIV, type 1 (HIV-1)
infection with HIV-1 is initiated by interaction of
viral envelope proteins with (at least) 2 receptors
- CD 4
- chemokine receptor = CCR5 and/or CXCR4
why can dendritic cells be targets for HIV infection?
because they express CD 4
HIV-1 uses CD4 to gain entry into host T-cells and achieves this by binding to the viral envelope protein
HIV infection leads to a progressive reduction in the number of T cells expressing CD4.
why are macrophages not particularly effective as antigen presenting cells during a primary immune response?
macrophages cannot capture antigen in the periphery and transport it to the appropriate lymphoid tissue - dendritic cells can.
where do primary immune responses occur
in secondary lymphoid tissues (where T cells hang out)
where do secondary immune responses occur?
site of infection
why are B cells able to function as well as an antigen presenting cell in secondary immune responses?
- use antigen specific receptors (membrane antibody)
- the receptors are so specific that B cells can bind antigen even when the antigen is in low concentration
- binding of B cell and antigen is followed by internalization of the receptor and the antigen into an endosomal vesicle = processing is the same as in APCs
what is the difference between the terms HLA, H2 and MHC?
MHC proteins - class I and class 2 (generalized)
Humans have HLA (human leukocyte antigen)
Mouse has H-2 system (murine system)
list the names of the class II MHC molecules in the human
HLA-DP
HLA-DQ
HLA-DR
list the names of the class II MHC molecules in the mouse
murine –
H2-IA
H2-IE
what are the major structural features of class II MHC
dimer alpha chain binds (restricted to binding proteins 15-30 aa)
what is the role of class II MHC?
they present the antigen to CD4+ T cells
recognized by CD4+ T cells
what is class II MHC restricted?
CD4+ T cells are RESTRICTED to “see” antigen only in associated with class II MHC
what is the role of the invariant chain?
prevents binding of endogenous peptides to class II MHC receptor in ER
what is MHC polymorphism?
the distinguishing characteristics of class I and class II MHC molecules
polymorphic (more than one type) in population = survival advantage!
what are the molecular interactions of APC — T cell?
APC------TCell class II MHC peptide ---TCR Class II MHC ---- CD4 CD80/CD86 (*costim) ---CD28 LFA-3 (*adh)----CD2 ICAM (1,2,3)(*Adh) --LFA-1 CD40---CD40L (CD 154)
LFA - lymphocyte function associated antigen
ICAM - intercellular adhesion molecule
list the names of the class I MHC molecules in the human
HLA-A
HLA-B
HLA-C
list the names of the class I MHC molecules in the mouse
H2-K
H2-D
H2-L
what is the minimum number of different class II and class I MHC molecules in unrelated parents?
minimum of 6 different class II molecules
where are class I MHC present?
on all nucleated cells
what are the major structural features of class I MHC?
- heavy chain (trnasmembrane polymorphic polypeptide)
- Beta2-microglobulin (smaller polypeptide)
*non covalently bound together
what is the function of B2 macroglobulin
class I MHC 45 kd chain does not fold properly when its not around?
non-polymorphic
no transmembrane domain
encoded on chromosome 15
does not bind antigen fragments
what is the role of class I MHC?
infected cells express class I MHC –> destruction by CD8+ Tcell
define class I MHC restricted?
CD8+ Tcells are restricted to seeing antigen in association with class I MHC (antigen/MHC class I complex)
what is cross presentation?
process by which exogenous antigens normally processed in phagolysosomes and presented on the cell surface are instead presented by class I MHC molecules
what cells primarily mediates cross presentation?
dendritic cells
what is cross priming?
class I MHC present antigens to CD8+ T cells - activation of CD8+ Tcells
define determinant selection
a phenomenon in which the MHC molecules present on the cell do not bind a particular peptide and so that peptide cannot be presented to T cells
Nonresponsiveness: peptide can’t be presented to T cells so no immune
response generated against it
explain the phrase “hole in the repertoire”
states that and individual may not have T cells with receptors that can recognize particular peptide-MHC complexes. This is entirely likely due to the phenomenon of negative selection which occurs during thymic education.
how does the role of CD1 molecules differ from that of Class I and class II MHc?
CD1 - similar to MHC class 1 –> form complex with Beta2 macroglobulin
CD-1 antigen complex - similar to MHC class II –> processing and cell surface presentation
Class I MHCs bind peptides only from ____sources
ENDOGENOUS
identify the steps of antigen processing that are negatively affected by various herpes viruses - HSV
neurons express small amount of class I MHC = safe haven for virus HSV produces immediate early protein hat binds to cytosolic portion of TAP transporter-> inhibits transport of peptides from cytosol to ER with no trnasport to ER -- MHC class I/peptide complexes don't form! - virus is undetected by body!
identify the steps of antigen processing that are negatively affected by various herpes viruses - EBV
inhibits the activity of proteosome - virus prevents hydrolysis of viral proteins into peptide size fragments
MHC/peptide complex won’t bind in groove maybe because they are too big - EBV stays sequestered in B cell
