Lymphocytes & Their Receptors

Question 1

Describe lymphocytes.

Answer 1

-imp for adaptive immune resp
-lg nucleus
-3 major types:
>T lymphocytes (T cells) = reg adaptive immunity & cell mediated immune resp
>B lymphocytes (B cells) = resp for antibody production
>NK = innate immunity ‘lg granular lymphocyte’

Question 2

Describe T cell development.

Answer 2

-before birth
-pre T cells leave bone marrow & migrate to thymus = ‘thymocytes’
-TCR forms:
>express B chain & become aB T cells
>express y or delta chains = ydelta T cells

Question 3

Describe specificity of a response to antigen.

Answer 3

-complement between antigen & TCR = specificity of resp
-1 TCR for one antigen (epitope)
-resp to many antigens

Question 4

Describe diversity in TCRs.

Answer 4

-random rearrangement of germ line gene seg encoding TCR
>unique to T & B cells
>takes place in thymus for T cells
-genes that encode a & B chains of TCR are not contiguous
>found in seg in diff regions of DNA
>seg: V, J, C, D regions

Question 5

Describe TCR gene rearrangement.

Answer 5

-rearrangement of B chain genes in pre T cells
>random joining of DB & JB gene seg
>random link of new DJB seg w VB seg
>form variable region of B chain
-a chain gene seg rearrangement after B chain
>Va & Ja gene seg join to make a chain variable region
>VJa seg joined w Ca region
*fully rearranged B chain cant be expresses before a chain has been rearranged
*rearrangement of seg via RAG1 & RAG2
>mutations/deficiency in RAG cause immunodeficiency

Question 6

Describe the DNA dependent protein kinase enzyme function.

Answer 6

excise the intervening DNA to increase diversity of TCR

Question 7

Describe the selection of T cells.

Answer 7

-T cells must express functional TCR that can recog & react w MHC-antigen complex on surface of APC
-pos/neg selection
>occurs in thymus

Question 8

Describe pos selection.

Answer 8

-test whether a TCR can bind to MHC I or II on thymic cortical epi cells (APCs)
-T cell bind to MHC = pass pos selection
-T cell doesnt bind to MHC = fails pos selection & dies via apoptosis (96%)
-eliminates thymocytes that
>fail to assemble TCR
>assemble useless TCR
-commitment of T cells to either CD4 or CD8

Question 9

Describe neg selection.

Answer 9

-T cells TCR binds w high affinity to MHC-antigen complex on APC = die via apoptosis
-eliminates thymocytes that react w self
-early stage thymocytes lack CD4 & CD8 = double neg
-CD4 & CD8 expressed once the aB TCR is expressed = double pos
-mature T cells = single pos (CD4 or CD8 only)
-CD4 & CD8 = coreceptor on T cells

Question 10

Describe the commitment to be a CD4 or CD8 T cell.

Answer 10

-if TCR has affinity for MHC I = thymocytes turns off CD4 gene & only expresses CD8 vice versa
-T cells that survive pos & neg selection leave thymus via blood
-CD8 = cytotoxic
-CD4 = helper T cells (differentiate into Th1, Th2 etc)
>some into regulatory T cells
-selection of non self reacting T cells easier bc thymus has representation of non thymus self antigens

Question 11

Describe AIRE.

Answer 11

-(AIRE) autoimmune regulator gene = allows thymic epi cells to express proteins found on other tissues of body
>ex. Eye, erythrocytes, testis, oocyte/zygote

Question 12

Describe the major groups of receptors on T cells.

Answer 12

Question 13

Describe T cell surface molecules.

Answer 13

TCR a/B & TCR y/delta

Question 14

Describe the development of B lymphocytes.

Answer 14

1. maturation = make mature immunocompetent B lymphocyte
2. activation = contact of B lymphocytes w specific antigens
3. differentiation = activated B cells become plasma cells that make antibodies or be memory B cells
   *in bone marrow

Question 15

Describe B lymphocyte maturation.

Answer 15

-fetal development = yolk sac, fetal liver, bone marrow
-after birth = only in bone marrow
-cells differentiate from lymphoid precursor into B lymphocyte = progenitor cells (pro-B)
-differentiate into B lymphoycte precursor cells in presence of IL7 & bone marrow stromal cells

Question 16

Describe the rearrangement of Ig genes.

Answer 16

-first to appear on pro-B cells = heavy chains (H) (DHJH) followed by VHDH rearrangement & further the a & B chains of poly-Ig
-light chains rearranged at pre-B cell stage
-alleleic exclusion one type of light chain expressed VLJL (κ or λ)
-after pre-B cell = immature B cells emerge w antigen specificity resulting from rearrangement of V,D,J regions of H chains and V,J regions of L chains
-immature B cells have membrane bound IgM & Iga/IgB chains = BCR complex
*chain rearrangement regulated by RAG1 & RAG2
-immature B lymphocytes not fully functional -> stimulation through BCR = cell death/anergy
-full maturity after IgD expressed
>requires change in RNA coding to allow coding of both heavy chains μ and δ (IgM & IgD)

Question 17

Describe neg selection/clonal deletion of B cells.

Answer 17

-10% reach circulation
-neg selection or clonal deletion to B cells that have high affinity for self antigens
-mature B cells leave bone marrow & arrive at periphery where they do activation & differentiation into plasma cells

Question 18

Describe the structure of the B cell receptor.

Answer 18

-4 polypeptide chains
-2 identical H & L chains
-L chains bound to H chain by disulfide bonds
-H chain bound to each other by disulfide bonds

Question 19

Describe the C & N terminal of the BCR.

Answer 19

1. C terminal = (H chain) span cell membrane & identical for each Ig isotype
2. N terminal = portions of H & L chain highly variable
   *Iga/IgB = signalling molecules