lecture 2 exam 2 Flashcards
function of secondary lymphoid tissue
develops late in fetal life and persists life long
facilitate antigen trapping
collects antigen presenting cells (DC) and lymphocytes
support clonal expansion of antigen specific T and B lymphocytes
antigen specific T and B cell effectors move to target tissues
retain any antigen specific memory cells
encapsulated secondary lymphoid tissue
lymph nodes
spleen
hemalnodes
unencapsulated secondary lymphoid tissue
mucosal lymphoid tissue (MALT)
gut associated lymphoid tissue (GALT)
bronchial associated lymphiod tissue (BALT)
tonsils
lymph node schematic
T cell clonal proliferation in paracortex w CD3
B cell clonal proliferation in germinal center of follicle
Ag and APC drainage from inflamed tissue through lymph flow from cortex to medulla
blood flows opposite direction
naive cells enter the lymph node thorugh high endothelial venules
how does antigen get to lymp node to stimulate an immune response
DC take up bacterial antigens in skin and then move to enter draining lymphatic vessel
DC bearing the antigen enter the draining lymph node (cortex-medulla) where they settle in T cell areas (paracortex)
T and B effector cells & antibodies leave via
efferent lymphatics to thoracic duct and systemic circulation
chemotaxis
movement of cell in response to chemical stimulus
chemokine
a family of cytokines w ability to induce directed chemotaxis
tell cells where to go!!
migration to ln through HEV is regulated by chemokines and adhesion molecules
integrins
transmembrane cell adhesion proteins and signaling receptor
migration to ln through HEV is regulated by chemokines and adhesion molecules
high endothelial venules
HEV are sticky for naive lymphocytes
in paracortex of ln
L selectin on lymphocytes (CD62L) bind vascular addressins (CD34) on endothelium of HEV
rolling to diapedesis process
CD62L + CD34/glyCAM1 = loose
ICAM + LFA = tight
how do DC arrive in paracortex
CCR7 - on T cell and DC attracted to CCL19 & CCL21 expressed in paracortex
CXCR4 - on DC attracted to CXCL12 in paracortex
how do B cells get to LN follicle
CXCR5 - on b cell attracted to CXCL13 in follicle
CCR7 - on be cells comes through HEVS to CCL19, CCL21 paracortex
loop through lymphoid system for up to 100 days for antigen
present their antigen they encounter in T cell w MHC 2 to T cells
cognate interaction
T & B recognize same antigen’s differnet epitopes
B cell activation and differentiation
- b cell activation in paracortex of lymph node (find antigen and BCR rearrangement)
- somatic hypermutation (in follicle) in the germinal dark zone of germinal center
- affinity maturation in germinal light zone by follicular DC
- isotype (class) switch) in germinal light zone - either apoptosis or survivie and call Tfh cells through cytokines then become plasma or memory b cell
phase 1: B cell activation
in paracortex complete activation of B cells requires multiple signals from other sources helper t cell co stimulation: 1. antigen specific 2. costimulation 3. cytokines
signal 1 for B cell activation
antigen specific
antigen binding to BCR + CR2/CD21
-ag processed to peptide and presented to Th on MHC 2 from b cell
signal 2 for B cell activation
costimulation
of CD40 on B cell + CD154 (CD40L) on T cell
signal 3 for B cell activation
cytokines
IL4 made by T cell engages IL4 on B cell to signal proliferation & differentiaion
phase 2: clonal expansion & somatic hypermutation
Th activated B cells move to dark zone of germinal center and proliferate
somatic hypermutation: mutational hotspots in rearranged DNA that encodes CDR1, CDR2, CDR3
-AID: activation induced cytidine deaminase ONLY made in B cells
AID in B cells
activation induced cytidine deaminase
deaminates cytosines and leaves uracils during ssDNA transcription
DNA repair enzymes replace all uracils w other nucleotides randomly
activity results in altering aa sequence, protein structure, antigen affinity
phase 3: affinity maturation
B cells enter light zone of germinal follicle and encounter the antigen present on FDC
newly mutated BCRs that bind to antigen w high affinity receive survival signals
BCRs that bind w low affinity do not receive survival signals so the apoptosis
phase 4: isotype (class) switching
B cells w high affinity BCRs move to margin of germinal center and interact w Tfollicular helper cells for cytokines signals to cause class switching on B cell
IGNgamma cuases IgM -> IgG
IL4 causes IgM -> IgE
TGF beta causes IgM -> IgA
IL21 is essential for TFH and plasma cell differeniation
IFNgamma cytokine signaled to B cell causes
IgM -> IgG
IL4 cytokine signaled to B cell causes
IgM -> IgE
TGFbeta cytokine signaled to B cell causes
IgM -> IgA
how many lymphocytes are in pig lymph
NONE - lymph nodes are inside out
hemolymph
dark red or brown
most prominent in ruminants
scattered among blood vessels - filter blood and substances in circulation
contain B cells in cortex and T cells at center
have gamma delta T cells
spleen structure
red pulp
white pulp
encapsulated
red pulp of spleen
filters blood rather than lymph
removes aged blood cells and immune complex coated cells by macrophages in sinus of red pulp
salvage iron and bilirubin from red cells
white pulp of spleen
marginal zone - macrophages surround (APC) outer region of follicle
follicles - b cell home
periarteriolar sheath (PALS) - T cells
NO HEV
sinusoidal type of spleen
abundant venous sinuses
store large amounts of blood for quick release (horses, dogs, humans)
splenic contraction during physical exercise
smooth muscle around ellipsoid capillary (most prominent in horses)
nonsinusoidal type of spleen
poorly developed sinuses
cats and ruminant
bone marrow as secondary lymphoid tissue
memory cells and plasma cells colonize
second dose of aantigen causes bone marrow to release large quantities of antibodies in rodents and other species
