Assignment 3

Question 1

what is the role of antigen presenting cells?

Answer 1

they deliver antigen to CD4+ T cells

Question 2

Name 3 antigen presenting cells?

Answer 2

dendritic cells
macrophages
B cells

Question 3

explain the term antigen presentation

Answer 3

the process when antigen presenting cells deliver antigen to CD4+ T cells.

Question 4

what is the major histocompatibility complex (MHC)?

Answer 4

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).

Question 5

what do all antigen presenting cells express and require for T cell stimulatory function?

Answer 5

• cell surface class II MHC

- costimulatory molecules (CD80 and CD 86 and CD 40).

Question 6

what are CD8+ T cells? Why?

Answer 6

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

Question 7

why are all nucleated cells a potential target cell?

Answer 7

all nucleated cells express class I MHC - potentially be destroyed!

Question 8

where are immature dendritic cells present?

Answer 8

in all lymphoid and non lymphoid tissue except the brain - including mucosal epithelium of the oral cavity, anus and vagina

skin = aka Langerhans cells

Question 9

what is the function of dendritic cells?

Answer 9

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!

Question 10

phenotypically, what do immature dendritic cells express high concentrations of?

Answer 10

FcϒR

also express CD 4

Question 11

phenotypically, what do immature dendritic cells express low concentrations of?

Answer 11

• class II MHC

- co stimulatory molecules (B7-1, B7-2)

Question 12

what is CD4?

Answer 12

one receptor for HIV, type 1 (HIV-1)

Question 13

infection with HIV-1 is initiated by interaction of

Answer 13

viral envelope proteins with (at least) 2 receptors

• CD 4
• chemokine receptor = CCR5 and/or CXCR4

Question 14

why can dendritic cells be targets for HIV infection?

Answer 14

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.

Question 15

why are macrophages not particularly effective as antigen presenting cells during a primary immune response?

Answer 15

macrophages cannot capture antigen in the periphery and transport it to the appropriate lymphoid tissue - dendritic cells can.

Question 16

where do primary immune responses occur

Answer 16

in secondary lymphoid tissues (where T cells hang out)

Question 17

where do secondary immune responses occur?

Answer 17

site of infection

Question 18

why are B cells able to function as well as an antigen presenting cell in secondary immune responses?

Answer 18

• 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

Question 19

what is the difference between the terms HLA, H2 and MHC?

Answer 19

MHC proteins - class I and class 2 (generalized)
Humans have HLA (human leukocyte antigen)
Mouse has H-2 system (murine system)

Question 20

list the names of the class II MHC molecules in the human

Answer 20

HLA-DP
HLA-DQ
HLA-DR

Question 21

list the names of the class II MHC molecules in the mouse

Answer 21

murine –
H2-IA
H2-IE

Question 22

what are the major structural features of class II MHC

Answer 22

dimer alpha chain binds (restricted to binding proteins 15-30 aa)

Question 23

what is the role of class II MHC?

Answer 23

they present the antigen to CD4+ T cells

recognized by CD4+ T cells

Question 24

what is class II MHC restricted?

Answer 24

CD4+ T cells are RESTRICTED to “see” antigen only in associated with class II MHC

Question 25

what is the role of the invariant chain?

Answer 25

prevents binding of endogenous peptides to class II MHC receptor in ER

Question 26

what is MHC polymorphism?

Answer 26

the distinguishing characteristics of class I and class II MHC molecules polymorphic (more than one type) in population = survival advantage!

Question 27

what are the molecular interactions of APC --- T cell?

Answer 27

``` 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

Question 28

list the names of the class I MHC molecules in the human

Answer 28

HLA-A HLA-B HLA-C

Question 29

list the names of the class I MHC molecules in the mouse

Answer 29

H2-K H2-D H2-L

Question 30

what is the minimum number of different class II and class I MHC molecules in unrelated parents?

Answer 30

minimum of 6 different class II molecules

Question 31

where are class I MHC present?

Answer 31

on all nucleated cells

Question 32

what are the major structural features of class I MHC?

Answer 32

- heavy chain (trnasmembrane polymorphic polypeptide) - Beta2-microglobulin (smaller polypeptide) *non covalently bound together

Question 33

what is the function of B2 macroglobulin

Answer 33

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

Question 34

what is the role of class I MHC?

Answer 34

infected cells express class I MHC --> destruction by CD8+ Tcell

Question 35

define class I MHC restricted?

Answer 35

CD8+ Tcells are restricted to seeing antigen in association with class I MHC (antigen/MHC class I complex)

Question 36

what is cross presentation?

Answer 36

process by which exogenous antigens normally processed in phagolysosomes and presented on the cell surface are instead presented by class I MHC molecules

Question 37

what cells primarily mediates cross presentation?

Answer 37

dendritic cells

Question 38

what is cross priming?

Answer 38

class I MHC present antigens to CD8+ T cells - activation of CD8+ Tcells

Question 39

define determinant selection

Answer 39

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

Question 40

explain the phrase "hole in the repertoire"

Answer 40

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.

Question 41

how does the role of CD1 molecules differ from that of Class I and class II MHc?

Answer 41

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

Question 42

Class I MHCs bind peptides only from ____sources

Answer 42

ENDOGENOUS

Question 43

identify the steps of antigen processing that are negatively affected by various herpes viruses - HSV

Answer 43

``` 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! ```

Question 44

identify the steps of antigen processing that are negatively affected by various herpes viruses - EBV

Answer 44

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