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188 Cards in this Set

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What are the components of innate immunity?
epithelial barrier; NK cells; alternative and lectin pathways of complement; direct phagocytosis by PMNs, neutrophils, and macrophages
what is a strong immunogen? weak?
high molecular-wt protein; low molecular-wt protein
what is the definition of an antigen?
substance bound by receptors of immune system
immunodominant epitope
portion of antigen that binds to receptors of immunoglobulin or T cell receptor; can be linear or conformational
how does innate phagocytosis influence adaptive immune response?
the phagocytic cell presents processed antigen on MHC molecules to B or T lymphocytes
what is a way to make a non-immunogenic substance immunogenic?
bind it to a protein carrier
what is a T-independent immune response?
IgM on B lymphocyte recognizes non-protein antigen (carbohydrate; nucleic acids; lipopolysaccharides) e.g. pneumococcal
what genes encode MHC II molecules?
what size antigens can MHC II molecules present?
what is the structure of MHC II molecules?
HLA-DP, DQ, DR
14-20 a.a.s
1 alpha chain and 1 beta chain; each has 2 domains
what are examples of APCs?
macrophages; dendritic cells; B lymphocytes
what are mechanisms of microbial activity used by APCs?
oxygen radicals; lysosomal enzymes
IL-12
produced by APC when it recognizes microbe
stimulates naive T helper cells to beome Th1 cells
upregulates MHC II expression
induces NK and T cells to make more IFN-gamma
IFN-gamma
main cytokine of Th1 cells
also produced by NK cells in innate immunity
feeds back on APCs to activate them
increases MHC expression
stimulates IgG production
IL-4
produced by naive T helper cells in the absence of APC producing IL-12
makes naive T helper cells become Th2 cells
main cytokine produced by Th2 cells; results in IgE production
CD40L
expressed on activated T cells
binds CD40 on APCs and B cells
activates B cells and macrophages; allows class-switching
CD40
expressed on APCs and B cells
binds CD40L on T cells
adhesion molecules
hold immunologic synapse between APCs and T cells long enough for T cell to be activated
invariant chain
protects MHC II molecules from binding antigenic peptides in the ER - they bind antigenic peptides only when the vesicle from the ER has fused with the endosomal vesicle containing the antigens
CLIP
class II associated protein. remains on MHC II molecules after the rest of the invariant chain has been degraded. protects premature binding of antigenic peptides to MHC II in the ER. removed by HLA-DM
processing of antigen protein in APCs (MHC II)
1. engulfed by phagocytosis into endosomal vesicle
2. pH decreases
3. cathepsins cleave protein into peptides
4. endosomal vesicle fuses with exocytic vesicle from ER that contains MHC II molecules
5. CLIP removed from MHC II
6. MHC II + peptide brought to membrane of APC
what is the structure of MHC I?
what genes encode MHC I?
which cells express MHC I?
how long is the peptide that MHC I binds?
alpha 1 alpha 2 alpha 3 + beta 2 microglobulin
HLA-A, B, C
all nucleated cells
9 a.a.s
cathepsins
acid proteases that cleave antigenic protein into peptide in late endosomal pathway for presentation by MHC II
signal 1
antigen in the context of MHC molecule
B7
co-stimulatory molecule presented by B lymphocytes and APCs. binds CD28 expressed by T cells. interaction allows full activation of Th cell
CD28
co-stimulatory molecule expressed by Th cells. binds B7 expressed by B cell or APCs. allows full activation of Th cell
CD3
expressed on all mature T lymphocytes. allows signal transduction so that T cell becomes activated. goes together with T cell receptor to cell surface. phosphorylated via ITAMS; adaptor proteins recruited; gene expression of T cell regulated (IL-2 Receptor)
ITAMs
site of phosphorylation of CD3 molecule that allows T cell activation and Ig-alpha / Ig-beta molecules that allow B cell activation
IL-2 receptor
presented on T cell. changes from low-affinity to high affiinity for IL-2 when T cell is activated via phosphorylation of ITAMs on CD3
IL-2
first cytokine secreted by activated T cells
growth factor for T cells
also mediates sensitivity of T cells to Fas-FasL induced apoptosis
CD4
expressed on T helper cells
stabilizes interaction between Th cell and APCS, allowing T cell to be activated
binds to beta-2 domain (non-polymorphic domain) of MHC II presented by APC
CD8
expressed on T cytolytic cells
stabilizes interaction between Tc cell and APC
immunologic synapse
region of contact between APC and T cell
how do Tc cells kill target cells?
apoptosis - 2 pathways:
(1) T cell granules contain perforin and granzyme. perforin creates pores in membrane of target cell. granzyme enters through pores and induces apoptosis
(2) T cell express Fas Ligand, which binds to Fas expressed on target cell and induces apoptosis
what is a target cell?
any cell infected by intracellular microbe (e.g. virus)
what are the components of humoral immunity?
secreted antibodies; membrane-bound immunoglobulins on B cell surface; classical pathway of complement
extracellular pathogens
what are components of cell-mediated immunity?
Tc cells and NK cells eliminate target cells
intracellular pathogens
how does NK cell kill target cells?
apoptosis - 2 pathways:
(1) perforin granzyme
(2) NK expresses Fas Ligand; target cell expresses Fas
what is the main difference in recognition of cells by NK cells and B/T lymphocytes?
NK cells don't need to see MHC molecules to recognize antigen; B and T lymphocytes do
Fas ligand
expressed by Tc cell or by NK cell
binds to Fas on target cell to induce apoptosis
Fas-FasL interaction
between either target cells and T cells / NK cells or between two T cells to reduce T cell number
lymphoproliferative disorders
result from failure of T cells to eliminate themselves by Fas-FasL induced apoptosis. lymphocytes accumulate and lymph nodes swell
class switching
form different Ig classes at the DNA level. antigen-dependent b/c B cells are stimulated to become plasma cells that secrete different Ig classes by Th cells
IgM
secreted in pentameric form; complement activator; membrane-bound
IgD
membrane-bound only
IgG
complement activator; opsonin; crosses placental to provide fetal immunity
IgE
binds to epsilon receptor on mast cells and basophils, sensitizing them to allergens (antigens). functions in parasitic infections
IgA
mucosal
how are Ig heavy chains synthesized?
VDJ gene recombination - V gene encodes HV1 and HV2 regions
need DJ recombination followed by V-DJ recombination to get HV3 region
what is the structure of Ig?
2 heavy chains and 2 light chains. each heavy chain has 1 variable domain and 3 or 4 constant domains. each light chain has 1 variable and 1 constant domain. each variable domain has 3 hypervariable regions.
HV3
where the antigen binds to the Ig
how are Ig light chains synthesized?
either lambda or kappa, no class switching
VJ gene rearrangement to form variable region; downstream regions code for constant region
class switching
to create different Ig isotype. specificity of the Ig remains the same, but Fc portion differs. antigen dependent.
what are the methods of creating diversity in Ig molecules?
1. variability in V gene segments
2. V[D]J gene recombination
3. variability in which light chain associates with which heavy chain
4. junctional diversity: variability in nucleotides added to or deleted from heavy chain breakpoints
a) random insertion by TDT
b) template-driven insertion (P nt insertion)
5. somatic hypermutation (antigen dependent)
Ig-alpha and Ig-beta
similar to CD3, go along with Ig to cell surface to accomplish signal transduction and allow B cell activation. have ITAMs that get phosphorylated
functions of B lymphocytes
engage antigen with membrane-bound Igs
secrete Igs to eliminate circulating antigen
present antigen to Th cells in context of MHC II molecules
functions of Th cells
help activate B cells and macrophages for class switching, somatic hypermutation, and memory; help phagocytes -- increased microbial activity
what are the steps of the classical pathway of the complement system?
1. secreted IgM (later IgG) binds antigen - antigen must be cross-linked (?)
2. C1q binds to the Fc portion of the Ig
3. C1r (has serine protease activity) cleaves itself, then cleaves C1s
4. C1s cleaves C4 to produce C4a and C4b; C4b binds to antigen surface
5. C1s cleaves C2 to produce C2a and C2b
5. C2b binds to C4b to produce C4b2b which is the C3 convertase
6. C3 convertase converts C3 to C3b and C3a
7. C3b opsonizes bacteria
8. C3b binds to C4b2b to produce C4b2b3b, which is the C5 convertase
9. C5 convertase produces C5a and C5b
10. C5b binds C6, C7, C8, and C9 to form C5b6789, which is the membrane attack complex
what is the C3 convertase of the classical pathway of complement?
C4b2b
AICD
activation-induced cytodine deaminase. converts B cells to plasma cells
how are antigenic proteins processed for presentation by MHC I molecules?
1. ubiquinated
2. degraded by proteolytic enzymes in proteasome
3. transported from cytosol to ER by TAP
4. combine with MHC I in ER (beta-2 microglobulin promotes proper folding)
5. transported to surface of APC
clonal selection
when a lymphocyte interacts with a specific antigen, that lymphocyte and its clones are induced to proliferate
what are classes of structures shared by microbes that distinguish them from host?
1. mannose
2. N-formyl methionine
3. various molecules that bind to Toll-like Receptors of phagocytes
phagocytes recognize these structures in the innate immune response
receptors of innate immune response
germline encoded, so limited diversity
each one recognizes a class of microbes, not an individual, specific microbe
PAMPs
pathogen-associated molecular patterns
Receptors have broad specificity, i.e., recognize many related molecular structures called PAMPs (pathogen-associated molecular patterns)
PAMPs are essential polysaccharides and polynucleotides that differ little from one pathogen to another but are not found in the host.
functions of epithelia in innate immunity
1. physical barrier
2. locally produced antibiotics = defensins
3. intraepithelial lymphocytes (have gamma-delta receptors)
4. cilia moves mucus
alpha-defensins
broad-range epithelial antibiotic found in small intestine
beta-defensins
broad-range epithelial antibiotic found in skin and resp. tract
1st cell of innate immune response
neutrophil
2nd cell of innate immune response
macrophage (from monocyte)
components of inflammation
1. leukocyte recruitment
2. plasma protein extravasation
3. leukocyte activation
4. increased vascular permeability and dilation
TNF-alpha
secreted by macrophages upon microbe recognition (innate immunity)
acts on endothelium of post-capillary venules to bring leukocytes to infection site
IL-1beta
secreted by macrophages on microbe recognition (innate immunity)
acts on endothelium of post-capillary venules to bring leukocytes to infection site
ICAM-1
expressed by endothelial cells; binds to LFA-1 of leukocytes for cell adhesion in leukocyte recruitment
VCAM-1
expressed by endothelial cells; binds to VFA-1 of leukocytes for cell adhesion in leukocyte recruitment
LFA-1, VFA-1
leukocyte integrins that bind to ICAM-1 and VCAM-1 expressed by endothelial cells in leukocyte recruitment and adhesion
toll-like receptors
expressed by macrophages, dendritic cells, neutrophils, mast cells, B cells
act as microbial pattern recognition receptors
how do phagocytic cells kill microbes?
1. reactive oxygen intermediates
2. nitric oxide
3. lysosomal enzymes that break down microbial proteins
how do MHC I molecules inhibit NK cells?
MHC I molecules bind to inhibitory receptor of NK cell
NK inhibitory receptor engaged
NK cell blocked from cell killing by MHC I molecule
C3d
complement system protein that coats microbes
recognized by antigen receptors of B cells, specifically CR2 (type 2 complement receptor)
CR2
type 2 complement receptor
recognizes C3d that coats microbes
recognizes breakdown products of C3b
expressed on B cells and important for B cell activation
which cells always express MHC II molecules?
macrophages; dendritic cells; B lymphocytes
what are Langerhans' cells?
dendritic cells of the skin
polyclonal response
many different antigens are presented on APC surface (each bound to different MHC molecule), so many lymphocytes are activated
anchor residues
invariant residues of the antigenic peptide that allow it to bind to the MHC molecule. any peptide can bind, as long as it has the correct anchor residues and is the correct length
how is specificity of the immune response determined?
specific T cell receptors bind to specific antigens that are bound to MHC molecules
MHC-restriction of T cell activation
T cell must see both antigen and MHC molecule together in order to be activated
calnexin, calreticulin
accessory molecules in the ER that help viral antigens bind to MHC I molecules
FAB
fragment antigen binding
portion of the Ig that binds antigen
consists of heavy and light chains, variable regions and first constant region
Fc
fragment crystallizable
the effector portion of the Ig - where the C1q portion binds if the Ig is bound to antigen
contains 2 (or 3) constant domains of the heavy chains
hinge segment
allows flexibility so that epitopic determinants can bind
papain
cleave Ig to produce 2 separate FAB fragments + intact Fc fragment
pepsin
cleave Ig to produce 2 FAB fragments linked together but no Fc fragment (gets degraded)
J chain
holds together the 5 monomers of pentameric IgM and the 2 monomers of dimeric IgA
what are the functions of the complement system?
1. opsonization
2. chemotaxis
3. anaphylotaxis
4. membrane attack complex yields lytic hydrolysis of target cell
isotype
Ig class (determined by class-switching, which is T cell dependent)
differences in the Fc
idiotype
specific, unique portion of the Ig (variable region)
how do antigens bind to antibodies?
non-covalently: H-bonds; hydrophobic forces; electrostatic forces; Van der Waals forces
affinity
strength of single antigen-antibody binding interaction
avidity
includes affinities of all monomers of the antibody
affinity maturation
upon repeated exposure to an antigen, the antibody binds the antigen more effeciently (so can have increased antigen elimination even as antigen concentration decreases). facilitated by somatic hypermutation
why does transfusion with the wrong blood type result in an immediate hemolytic response?
because the blood group structures are very similar to those seen in the bacteria of the gut
what are the different possible Ig light chains?
kappa and lambda; differ in constant domain
what are the primary lymphoid organs in the adult? in the fetus?
thymus and bone marrow; yolk sac; fetal liver and spleen; bone marrow and thymus
what are the secondary (peripheral) lymphoid organs?
spleen; lymph nodes; mucosal and cutaneous immune system
what happens in the peripheral lymphoid organs?
antigens interact with APCs and lymphocytes
positive selection
in thymus, of T lymphocytes that recognize self antigens bound to MHC
negative selection
elimination of developing lymphocytes that express antigen receptors specific for self antigens
allelic exclusion
in synthesis of Ig
once a functional heavy chain has been synthesized, the pre-B cell receptor triggers the cell to stop heavy chain synthesis and begin light chain synthesis
the second chromosome is restricted from recombining - only 1 type of heavy chain is produced
pre-B cell receptor
heavy chain for IgM (cytoplasmic mu) + surrogate light chain
can't bind antigen, but triggers allelic exclusion
12-23 spacer rule
there must be set number of residues between V, D, and J gene segments to allow recombination to occur
immature B cell
expresses IgM only
mature B cell
expresses IgM and IgD
membrane-bound IgM vs. secreted IgM
determined by alternative splicing
hydrophobic residues vs. hydrophilic residues
RAG-1 and RAG-2
portions of VDJ recombinases that are expressed only in lymphocytes, only during the time that recombination occurs
recombinase activating genes
switch site
allows class switching from IgM/IgD to IgG, IgA, or IgE at the DNA level
stimulated by CD40L-CD40 interaction
alternative splicing
determines IgM/IgD/both
determines membrane-bound or secreted IgM
happens at mRNA level
junctional diversity
one method of diversity in Ig synthesis. involves both random and template-driven addition / deletion of nucleotides at heavy chain breakpoints
TDT
terminal deoxyribonucleotidyl transferase
adds/deletes nts to breakpoints of HV3 region (N-region insertion)
P nt insertion
add/delete nts to overhanging ends of DNA in template-driven fashion. one component of juctional diversity. insertions need to be in frame or cell will die
somatic hypermuation
mutation of V gene segments of HV regions to produce antibodies that have higher antigen affinity
leads to more efficient antigen elimination
antigen (T cell)-dependent
causes affinity maturation
AICD
activation induced cytodine deaminase
mediates somatic hypermutation
mediates class switching
allows B cell to become plasma cell
cross-linking
of Igs on B cell surface by epitope. at least 2 Igs must be cross-linked in order for ITAMS of Ig-alpha and Ig-beta to be phosphorylated and B cell to be activated
hyper IgM syndrome
B cells can make only IgM b/c they can't class switch
caused by absence of the CD40L-CD40 interaction
how does adjuvant create more immunogenic response?
1. antigen persists longer / is released more slowly
2. adjuvant promotes phagoyctosis by forming particulates
3. adjuvant increases production of co-stimulatory molecules, e.g. B7
monoclonal antibodies
this technology is available only b/c each B cell makes a single, specific antigen receptor.
fuse mouse cells that produce antibodies with immortal tumor cells; culture hybridoma cells; each cell supernatant contains unique antibody that can be tested against original antigen
what is the C5 convertase of the classical pathway?
C4b2b3b
what is the membrane attack complex of the complement system? how does it work?
C5b6789
creates holes in target cell membrane, leading to loss of cell volume control and direct colloid osmotic lysis
what are the steps of the lectin complement pathway?
1. mannose-binding protein binds to terminal bacterial mannose
2. MASP-1 cleaves itself, then cleaves MASP-2
3. MASP-2 cleaves C4 to produce C4a and C4b; C4b binds to microbe surface
4. MASP-2 cleaves C2 to produce C2a and C2b
5. C2b binds to C4b on the microbe surface to produce C4b2b, which is the C3 convertase of the lectin pathway
6. C3 convertase converts C3 to C3a and C3b
7. C3b opsonizes bacteria
8. C3b binds to C4b2b to produce C4b2b3b, which is the C5 convertase of the lectin pathway
9. C5 convertase converts C5 to C5a and C5b
10. C5b binds C6-9 to generate C5b6789, which is the MAC
what is the C3 convertase of the lectin pathway?
C4b2b
what is the C5 convertase of the lectin pathway?
C4b2b3b
what are the steps of the alternative pathway for complement?
1. C3b is produced in different forms by continuous tickover. it also feeds in from the C3b produced in the classical pathway that opsonizes bacteria.
2. factor B binds to C3b to produce C3bB
3. factor D cleaves factor B to produce C3bBb, the C3 convertase of the alternative pathway
4. C3bBb converts C3 to C3b and C3a
5. C3b binds to C3bBb to produce C3bBb3b, which is the C5 convertase of the classical pathway
6. C5 convertase converts C5 to C5a and C5b
7. C5b binds to C6-9 to produce C5b6789, which is the MAC
what is the C3 convertase of the alternative pathway?
how does it get produced?
C3bBb
1. factor B binds to C3b on bacterial surface
2. factor D cleaves factor B to produce C3bBb
properidin
enzyme that increases the half-life of C3bBb
what is the C5 convertase of the alternative pathway? how does it get produced?
C3bBb3b
C3b binds to C3bBb
what is the cause of multiple pyogenic infections?
C3 deficiency
what is the cause of increased susceptiblity to Neisseria infections only?
MAC deficiency
CR1
complement receptor type 1
binds to C3b to promote phagocytosis
CR1 is expressed on macrophages, neutrophils, and RBCs
also a cofactor for factor I and a membrane-bound regulator of the complement system
what is the function of RBCs?
CR1 (receptor) on RBCs binds to C3b on antigen-antibody complex to facilitate removal in spleen and liver. if RBCs do not bind immune complex, the immune complex blocks the glomeruli and results in renal disease
role of C2a
induces inflammation
role of C5a, C3a, C4a
chemoattractants of neutrophils and monocytes
anaphylatoxins - induce smooth muscle contraction and vascular permeability
C1-inhibitor

what happens with increase?
what happense with decrease?
soluble regulator of the classical complement system
regulates 1st step of classical pathway by dissociating C1r and C1s from C1q. if you are deficient in C1-inhibitor, you will have constant activation of the pathway and constant inflammation and edema
hereditary angioedema
constant edema caused by continuous activation of classical complement pathway caused by deficiency of C1 inhibitor
C4 binding protein

what happens with increase?
what happens with decrease?
soluble regulator of the classical complement system
inhibits action of C3 convertase by dissociating C4b from C2b. if you have increased C4 binding protein you will have decreased C3 convertase activity and therefore increased C3/ decreased C3b. if you have decreased
C4 binding protein you will have increased C3 convertase activity and therefore decreased C3/increased C3b.
factor H
soluble regulator of the alternative complement pathway
inhibits C3 convertase activity by dissociating C3b from Bb
if you have increased factor H you will have decreased C3 convertase activity and therefore increased C3/decreased C3bBb
cofactor for factor I
factor I
soluble regulator of the alternative complement pathway
cleaves C3b and C4b to produce their breakdown products - so they can't persist indefinitely
factor H is a cofactor
what are the soluble regulators of the classical pathway of complement system?
1. C1-INH inhibits first step of pathway by dissociating C1s and C1r from C1q
2. C4 binding protein inhibits C3 convertase activity by dissociating C4b from C2b
what are the soluble regulators of the alternative pathway of the complement system?
1. factor H inhibits C3 convertase activity by dissociating Bb from C3b
2. factor I inhibits C5 convertase activity by cleaving C3b so it can't attach to to C3bBb
DAF
decay accelerating factor
membrane-bound regulator of the complement system
inhibits C3 convertase activity
MCP
membrane co-factor protein
cofactor for factor I
membrane-bound regulator of the complement system
binds to C3b and C4b, making them susceptible to degradation by factor I
CD59
membrane-bound regulator of the complement system
inhibits formation of the membrane attack complex
paroxysmal nocturnal hemoglobinuria
caused by deficiency of DAF and CD59
leads to destruction of RBC membranes and Hb release
Fc - gamma - R1
IgG receptor on phagocytic cells
Fc-gamma-R3a
IgG receptor expressed by NK cells
Fc-gamma-R2b
receptor for IgG that feedback inhibits B cells
Fc-epsilon-R1
IgE receptor expressed on eosinophils
double negative
cells destined to become T cells in the subcapsular space of the thymus
TcR-CD3-CD8-CD4-
double positive
in cortex of thymus, uncommitted T cells
TcR+CD3+CD8+CD4+
where are T cells double negative?
in the subcapsular space of the thymus
where are T cells double positive?
in the cortex of the thymus
where do T cells that engage MHC I or MHC II bound to self antigen become CD8 or CD4?
in the corticomedullary region of the thymus
how are the alpha chains of T cell receptors synthesized?
by VJ recombination
how are the beta chains of T cell receptors synthesized?
by VDJ recombination
what are autologous antigens?
self antigens
immunologic tolerance
unresponsiveness to self antigens
what is the cause of autoimmune disease?
failure of immunologic tolerance (failure of mechanisms that prevent activation of lymphocytes that react with self antigens)
activation
lymphocyte + immunogenic antigen = lymphocyte activation
tolerance
lymphocyte + tolerogenic antigen = killed / inactivated lymphocyte
ignorance
lymphocyte + non-immunogenic antigen = ignorance / no response
central tolerance
self tolerance induced by negative selection of immature lymphocytes that interact strongly with self antigens in bone marrow and thymus
peripheral tolerance
mature lymphocytes in peripheral organs are killed, become anergic, or are suppressed by regulatory T cells
anergy
lymphocyte does not react with antigen
how does anergy occur?
1. APC does not present co-stimulatory molecules such as B7 that are important for T cell activation
2. T cell expresses CTLA-4, which binds to B7 molecules that inhibit T cells instead of activating them
3. T cell sees signal 1 but not signal 2 (co-stimulation)
CTLA-4
expressed by T cells
binds to B7 that inhibits T cells instead of activating them
allows cells to become anergic
AIRE
autoimmune regulator
allows self antigens to be expressed in thymus so that T cells can be positively and negatively selected
mutation in AIRE gene leads to autoimmune disease APECED
APECED
autoimmune disease caused by mutation in AIRE
Tregs
T regulatory lymphocytes
develop from T lymphocytes that recognize self antigens too strongly in the thymus
go to peripheral tissues
regulate T cells that respond strongly to self antigen by producing IL-10 and TNF-beta
what are the possibilities for T cells that recognize self antigens too strongly in the thymus?
1. negative selection (apoptosis)
2. become Tregs and go to peripheral tissues
what are the possibilities for T cells that recognize self antigen in the peripheral tissues?
1. apoptosis
2. become anergic
3. suppressed by Tregs
what is co-stimulation for?
what are some important interactions of co-stimulation?
allows T cells to be fully activated by microbial antigens
B7 on APC and CD28 on T cell
ICAM-1 on APC and LFA-1 on T cell
how does administration of some foreign antigens "free" the immune response?
the antigen causes T cell to see signal 1 but not signal 2, resulting in T cell anergy
internal T cell death program
one T cell expresses Fas, the other FasL - apoptosis
IL-2 increases sensitivity of T cells to Fas-mediated apoptosis
IL-10
produced by Tregs to block activation of lymphocytes and macrophages
TGF-beta
produced by Tregs to block activation of lymphocytes and macrophages
how do Tregs suppress T lymphocytes that recognize self antigen too strongly?
1. direct contact inhibition
2. produce IL-10 and TGF-beta
what are the possibilities for B cells that recognize self antigen too strongly in the bone marrow?
1. negative selection
2. receptor editing of light chain
receptor editing
changes receptor specificity of B cells that recognize self antigen too strongly in the bone marrow - creates new light chain
what are the possibilities for B cells that recognize self antigen too strongly in proliferative tissue?
1. B cell becomes anergic (no T cell help to become activated)
2. B cell undergoes apoptosis (T cell help to become partially activated but deprived of certain stimuli)
how would oral administration of protein antigen without adjuvant result in tolerance / systemic supression of immune response?
no adjuvant means no production of co-stimulatory molecules
oral administration of antigen may stimulate TGF-beta production, which inhibits T cells and macrophages