Test 1-2 Flashcards
B and T cells
addaptive immunity
NK cells
innate
B-lymphocyte origin
-plasma cell precursors from bone marrow stem cells
B-lymphoc characteristics
- antigen unstimulated B-lymphs have membrane anchored IgM and IgD which bind THE SAME antigen
- each B-cell has ONE antigen specificity
- B-cell clones reactive to >10^9 antigens without the need for exposure to these antigens
IgD helps with
activation of B-cells
not really meant to be secreted
priamry immune response
antibody response first time see something
- 7-10 days
- mostly IgM
secondary immune response
- from memory cells
- takes 2-3 days
- Most IgG
- antibody level is higher
- affinity maturation - longer immune response goes on the better the antibodies will bind
immature b-cells only have ______ when compared to mature which have______. When immatuer b-cells come in contact with antigen they ______.
immature have IgM
mature have IgM and IgD
appoptize - protects us from autoimmune diseases - held in check by regulatory t-cells
development into mature b-cell
- stem cells (bone marrow precursor and produce no mmunoglobulin)
- pre-b-cell-cytoplasmic mu-heavy chains (heavy chain of IgM) … not responsive to antigen
- -immature B-cell: expresses antigen-specific membrane IgM; immature b-cells tolerized if encounter antigen; present in the bone marrow*
- mature b-cell: membrane IgM and IgM specific for the SAME antigen - RESPOND to their antigen
- activated b-cell = lymphoblast: small amount of low affinity immunoglobulin; heavy chain isotope switching; differentiate into plasma cells or memory b-cells
- plasma cells - secrete one antibody isotype; found in lymph organ and bone marrow; live for a few days; secrete one antibody (evidence of LONG LIVED plasma cells too)
plasma cell morphology
elongated cell, eccentric nucleus, abundant cytoplasm, perinuclear halo
interaction b/w B and T-cells is …
- class II MHC restricted
- Bcell B7 interacts with T-cell CD28
- bcell CD40 binds t-cell CD40L
b-cell antigen presentation
- b-cell binds antigen — internalizes it (endocytosis) Once it is processed the b-cell has fewer lysosomes and is less efficient at processing— displays it on membrane on CLASS II and activates t-cell
- usually t-cells and b-cellsbind different epitopes on an antigen
- NONPROTEINS ARE NOT REOGNIZED
waht do secreted antibodies do when released?
- NEUTRALIZE ANTIGEN so it cant bind to anything
- OPSONIZE antigen so it can be phagocytosed (antibodies promote phagocytosis)
- COMPLEMENT ACTIVATION to enhance opsonization and lyse some bacteria
protein antigens=
thymus dependent antigens bc (require T-cells) of T_h cell dependence
non-prtein antigens=
- thymus independent bc TI dont need T-h cells
- polysaccharides, nucleic acids, lipids
- provide all necessary b-cell siganls
TI-1 antigens:
- bind non-immunoglobulin receptors and promote polyclonal expansion
- best example:lipopolysaccharide (LPS)-acts as a b cell mitogen
- does not utilize antibody on surface of b-cell
- NO memory cells, NO isotype switching, NO affinity maturation
TI-2 antigens:
bind through B-cell surface immunoglobulin (only activate antigen specific b-cells)
- ex) polysaccharide antigens with erpeated epitopes
- NO memory cells, NO isotype switching, NO affinity maturation
Get memory cells, isotype switching, & affinity maturation by involving…
t-helper cells
signal transduction in b-cells
bound antibody tails not long enough to transmit signal into cell
signalling through Igalpha and Igbeta
-same function as CD3 in tcells
antibodies made up of (chains)
2 heavy chains and 2 kappa or 2 lambda light chains
genes for antibodies organization on DNA
5’ —V-region gene segment —— D-region gene segment —– J-region gene segment —- C-constant region —– 3’
variable region of heavy chain made by…
V,D,and J gene segemnts —> antigen binding site
variable region of light chain made by…
V and J gene segments –_>antigen binding site
ways to generate diversity in antibodies…
1) pairing of heavy and light chains
2) combinatorial diversity - different gene segments rearranged
3) junctional diversity - nucleotide addition/removal occurs at joints bw gene segments (TDT enzyme during DNA split it randomly inserts nucleotides in DNA=more diversity)
4) somatic mutation - point mutations in variable regions of heavy and light chain gene segments that have been rearranged
TDT enzyme
enzyme that inserts nucleotides at random during DNA split of introduce diversity in antibody genes.
can be used to track in leukemias and lymphomas as to ho developed the cells are
recombinases
loop out, excise DNA and then ligate
heavy chain rearrangement:
- happens first
1) Random D and J segments are brought together .. intervening DNA deleted
2) V gene segemnt randomly selected and placed 5’ to the DJ segment to form VDJ segment
3) intron separates VDJ segment from c-region gene C-miu and C-delta(which remain in the primary RNA transcript
4) processing of primary RNA—> splice out introns, remove C-delta, add poly A tail
5) mRNA —> cytoplasmic miu-heavy chain (pre-b-cell stage) - 4 shots to make a good one
light chain rearrangement:
- happens second
- random J with random V-segment to makr primary RNA and make mRNA…
- kappa and lamda gene segments rearranged until a good one made… if cant kappa then lamda - kappa is preference
- 2 shots to make a good one
allelic exclusion
cell decides to rearrange one parents genes and not the other allele
-this makes sure that each b-cell has one specificity
how do b-cells express Igm and IgD for the same antigen?
both antibodies use to same VDJ region but the tail end is different.
C-miu for IgM and Cdelta region for IgD
secreted igMs are missing…
a transcript code for membrane anchoring protin
primary RnA transcript codes for….
membrane anchored and secreted form antibodies
isotype swithcing:
immune response starts with IgM… how do we switch to IgG and retain specificity?
keeps VDJ region but splice out any other constant regions that you dont want
waht class (isotype swithcing) of antibody bcell or plsma cell is not random and which is completely random?
directed by cytokines!
IL-4 cytokine…
calls for the production of IgG1 and IgE
IL-5 cytokine
calls for the production of IgA (mucosal)
affinity maturation of antibodies…
- happens by the accumulation of point mutations in VDJ region.
- mutations accumulate in the descendents of an indiv b-cell
- these b-cells with higher affinity are selected for and stim by t-helper cells
- low affinity b-cells die
primary lymphoid tissues
- generation of mature but naive T and B cells
- development of antigen recognition
- involves rearrangement of antigen receptor genes
- bone marrow and thymus
secondary lymphoid tissues
- where naive lymphocytes go to wait for activation
- funnel antigen to antigen-specific B and T lymphocytes to drive antigen dependent activation to effector and memory cells
- lymph nodes, tonsils, peyers patches, spleen
tertiary lymphoid tissues
- where the elimination of antigen occurs
- “battlefield where immune system defends tissues from microbes
- tissues have direct contact with the external environment
- skin, GI, lungs, vagina
bone marrow
- pluripoetent stem cells –> dev into RBC, lymphoc, granulocy, erythrocytes, platelets, monocytes
- ~5% of total body mass primarily in long bones, sternum, pelvis
- stroma - reticular stromal cells, macrophages, adipocytes
- stromal cells provide cell to cell contact + soluble factors
B-lymphocyte dev
- earliest B-cell precursors located near inner surface of the bone… more mature cells reside in central axis of marrow cavity
- immature to mature B cells can take place in secondary lymphoid organs
- autoreactive B-cells deleted at immature B-cell stage
thymus stuff
- t-lymph orig in bone marrow but mature in thymus
- stem cells –> promothymocytes —> to thymus = thymocytes —> dif into mature t-cells
- autoreactive cells are deleted
- mature t-cells released into periphery to populate 2ndary lymphoid tissue
mature t-lymphs express:
TCR, CD3, and EITHER CD4 or CD8 proteins
hassals corpuscles are
dead thymocyte graveyards
cortical epithelium i nhte thymus acts as
nurse cell providing cell to cell contact, cytokines, and peptide hromones
lymphatic vessels are primary responders to
tissue borne antigens
lymph node locations
axillary, inuinal, cervical, intestinal messentery