Antigen presentation

Question 1

pathogen entrers the skin. What is the first immune response cell to encounter? How does this cell respond?

Answer 1

Pathogens have entered the wound.

1. dedritic cells respond
   
   1. in the skin - langerhan cells
2. take the A and head for draining lymphnode
3. immature dendritic cells mature into classical dendritic cells as they traffic to the draining lymphs node, presenting the antigen to T lymphocytes

Question 2

describe the three state the dendritic cell can be in

1. before Ag interaction
   
   1. state of cell
   2. protein expression signicifance
2. just encountered Ag interaction
   
   1. special process
3. post Ag interaction
   
   1. funciton
   2. protein expression

Answer 2

1. dendritic cells
   
   1. encounter the Ag immature
      
      1. immature DC
         
         1. highly phagocytic
         2. express low levels of
            
            1. MHC2
            2. CCR7-specific for chemoattracting cytokines generated by the lymphnodes
   2. after they encounter the Ag, they head for the lymphnode
      
      1. Ag is processed by DC enroute to the lymph node.
      2. mature from cells designed to capture antigens to cells capable of presenting the antingens.
         
         1. increased synthesis and steady expression of MHC molecules
   3. when the DC is completly mature
      
      1. lose their phagocytic abilit,
      2. express high levels
         
         1. MHC2
         2. CCR7
         3. B7
         4. CD40
            
            1. costimulatory molecules interact with CD28 &CD40L- on naive Tcells
      3. secrete
         
         1. CCL18
            
            1. attracts naive T cells

Question 3

discuss the relationship as you fill in the blank

Answer 3

Question 4

what is the relationship emphasized in this photo?

Answer 4

dendritic cells enable the innate and adaptive immunit to work in concert

1. plasmacytoid
   
   1. ​immature
   2. major source of type 1 IFN in response to viral infection
2. skin and elsewhere is the conventional/classic
   
   1. mature

Question 5

Discuss the possible outcomes for the two signals a DC can receive

Answer 5

Question 6

Answer 6

Question 7

Why would the APC’s go to a draining lymph node?

Answer 7

naive T lymphocytes continuously recirculate through lymph nodes and also express CCR7, which promotes their entry into the T cell zones of lymph nodes.

Hence, the reason for and APC to express the chemokine receptor CCR7

Question 8

Describe MHC with respect to the terms autologus and allogenic.

what does it mean to have

Answer 8

1. autology= self
2. allogenic=non-self

MHC molecules are defined as autologous or allogeneic.

with 1-10% of the circulatory Tcells are alloreactive.

• this means at any point in time 10% of your MHCs are ready to detect foreign molecules.
• major cause of organ and tissue transplant rejection.
  
  • with in 30 mins

Question 9

Draw the strucure of the MHC molecules and describe they functions

Answer 9

1. MHC1
   
   1. structures
      
      1. alpha
         
         1. 1 and 2
            
            1. peptide groove allowing for amino acids of 8-9 in length to bind
            2. floor contains aa that bind the antigen
               
               1. location in most of the variation of MHC molecules
         2. 3
            
            1. site that binds the CD8 cofactor
            2. extends throught the plasma membrane
      2. beta2-microglobulin
         
         1. encoded by gene outside of MHC
      3. alpha noncoavalenty bound to B2-microglobulin
2. MHC2
   
   1. two transmembrane chains
      
      1. alpha
      2. beta
   2. amino terminal region give rise to A1/B1
      
      1. polymorphic region for antigen presentation
      2. accomodates a single peptide 11-30
   3. A2/B2

Question 10

Describe the exogenous process ending with plasma cell presenting moiety on the plasma membrane.

Answer 10

1. phagocytosis or ADCC antigen
2. endosome merges with lysosome
3. ER
   
   1. generates MHC2 molecules
      
      1. MHC2 is made with invariant chan and CLIP
         
         1. clip is added between a and v moieties to prevent MHC2 from accepting any random peptide
4. MHC2-CLIP migrates from ER->golgi
5. leaves the golgi and CLIP has a cytosolic tail atracted to the acidic vesicles
6. lysosome and MHC2-CLIP vesicle merge.
   
   1. inside the lysosome
      
      1. invariant chain is degraded and HLA-DM exchanges CLIP for peptides available in the compartment. The one with the highest affinity sticks
7. if the MHC2 gets a peptide with enough of an affinity to stay, it is then transported to the plasma membrane
   
   1. if it does not have enough of an affinity, it is degraded

Question 11

describe the endogenous process ending with the moiety displayed on the plasma membrane

Answer 11

1. the endogenous protein is tagged for proteolysis with ubiquitin.
2. preteosome degrades the protein
3. the ER contains TAP, which binds peptides and escorts the peptide to the
4. the MHC alpha chain is fitted with the peptide
5. the MHC 1 moiety is transported from the ER to the Golgi
6. Then from the golgi to the plasma membrane

Question 12

because all of the MHC alleles are on the same gene, what is the consequence of their expression?

Answer 12

primarily DR are expressed

1. HLA-single letter= MHC1
2. HLA-two letters=MHC2
3. alleles of a given isotype are designated as HLA-isotype*allelenumber
   
   1. HLA-B*2701-HLA-B

>100 diseases have been associated with different HLA gene alleles

Question 13

what is the theory on why we have a select amount of HLA expressions?

Answer 13

MHC diversity is due to natrual selection

1. balancing selesction
   
   1. tends to maintain a given polymorphism
2. directional selection
   
   1. tends to introduce new haplotypes

polymorphism

polygeny

Question 14

how is the MHC allele inherited and expressed

Answer 14

co-dominant-

1. alleles refer to two different alleles at a locus which are responsible for different phenotypes and both alleles affect the phenotype of the heterozygote.
2. products of all alleles are found on all expressing cells

Question 15

Which cells/cytokine leads to expression of MHC1/2

Answer 15

NK cells generate INF-gamma

INF-gamma turns on NLR and C2TA

1. NLR turns on MHC1
2. C2TA turns on MHC2

Question 16

explain both the pathways and list strutures/functions.

Answer 16

Question 17

explain a scatter histogram and how flow cytometry works.

Answer 17

fluid with cells passed through a laser. The light is scattered and picked up

1. hydrodynamic focusing
   
   1. column has solution ran with it into column to get cells in single file line
2. interigation point -collects information on three dimensions
   
   1. the magnitude of the scatter is used to determine the cell
      
      1. more scatter = larger cell
   2. scatter plot-2d representation of the following
      
      1. allows the organization of cells based on size and cellular complecxity
         
         1. forward scatter-the scattered light is converted to a voltage pulse and read on a histogram
            
            1. the cell counts are converted to a graphical representation on how many cells of a size are present
         2. side scatter- pick up light scattered by granule content
         3. fluorscence
            
            1. fluorescent molecules are attached to antibodies. the Ag Fc region attaches the the cell of high affinity and fluoresces when passes the laser
               
               1. more fluorescent component=larger signal
   3. observing data
      
      1. threshholds are established to only look at cells of interest

Question 18

How can an infected cell or cancerous cell be recognized by the immune system while it is not in the linear path of the exposure?

Answer 18

cross presentation

1. subset of classical dendritic cell have the ability to ingest infected host cells, dead tumor cell, microbes and microbial antigens andtransport the peptides into the MHC1 pathway.
2. this allows the activation of CD8+ cells for targeting infected cells and/tumor cells

Question 19

describe how to read a 2d scatter plot.

Answer 19

Question 20

generate a scatter plot of a sample containing neutrophils, t lymphocytes and monocytes.

granularity(side scatter) x cell size (forward scatter)

Answer 20