Immunology Exam 3 Flashcards
(143 cards)
1
Q
What happens when B cells are activated?
A
They proliferate, expansion of antigen specific clones and differentiation into plasma cells
2
Q
Do plasma cells secrete antibodies?
A
YES
3
Q
Do memory cells secrete antibodies?
A
NO
4
Q
Heavy chain/isotope switching
A
When during differentiation B cells produce antibodies of different heavy chain classes that mediate different effector functions and combat different types of microbes
5
Q
Affinity maturation
A
Affinity of antibodies specific for microbial proteins increases during the response to microbes
Have an increase in antibodies with the improved capacity to bind to and neutralize microbes and their toxins
6
Q
Why can T cells only help B cell responses to protein antigens?
A
T cells can only recognize peptides derived from proteins and displayed by MHC molecules
7
Q
T-dependent antigens
A
Most protein antigens show no or weak antibody response
Therefore the B cells need T helper cell help
8
Q
T-independent antigens
A
Polysaccharides, NA, lipids, and other multivalent antigens can stimulate antibody production without helper T cells
Responses are short lived and require direct activation of B cells by antigens as well as signals via the innate immune system without the role of helper T cells
9
Q
What happens to antibodies made from helper T cells and protein antigens?
A
Have class switching and affinity maturation because helper T cells stimulate these processes
Generate plasma cells and memory B cells
Most specialized and long lived responses are from protein antigens with helper T cells
10
Q
Follicular B cells
A
Majority of B cells
Reside in and recirculate through follicles of the lymphoid organs
Are majority of T dependent B cells with class switching and plasma cell creation and high affinity antibody responses
11
Q
Marginal-zone B cells
A
Peripheral region of splenic white pulp and in outer rim of follicles of lymph nodes
Respond to polysaccharide and lipid antigens mostly
Express antigen receptors of limited diversity and make T independent IgM responses
12
Q
B-1 cells
A
Mucosal tissues and peritoneum
Respond to multivalent polysaccharide and lipid antigens
Express antigen receptors of limited diversity and make T independent IgM responses
IgM can be produced spontaneously without immunization
13
Q
Natural antibodies
A
IgM can be produced spontaneously without immunization via B-1 cells
Help clear dead cells that underwent apoptosis and provide protection against some bacterial pathogens
14
Q
Secondary response
A
Increased heavy class chain switching and affinity maturation
Repeated stimulation by protein antigen leads to an increase in the number and activity of antigen-specific helper T cells
15
Q
B cell antigen receptor mediated signaling requires…
A
Crosslinking of two or more Ig molecules
Two or more antigen molecules in an aggregate, or repeating epitopes of one antigen molecule, bind to adjacent membrane Ig molecules of a B cell
After the crosslinking, signals are transduced by receptor-associated proteins
16
Q
IgM and IgD on naive B lymphs
A
Highly variable antigen-binding regions
These membrane receptors have short cytoplasmic tails so they do NOT transduce signals themselves
The proteins associated with them (Ig-alpha and Ig-beta) transduce signals to form BCR complex
17
Q
Ig-alpha and Ig-beta
A
Part of BCR which have ITAMs (immunoreceptor tyrosine motifs)
When two or more antigen receptors of B cell are brought together by crosslinking, the tyrosine’s on the ITAMs are P’ed by tyrosine kinases
SYK tyrosine kinase is recruited and P’s tyrosine residues on adaptor proteins
Adaptor proteins activate downstream molecules (like enzymes) to activate signaling cascades
Txn. factors are activated and then there is expression of genes responsible for B cell proliferation and differentiation
18
Q
The complement system
A
A collection of plasma proteins that are activated by microbes and by antibodies attached to microbes and function as effector mechanisms of host defense
19
Q
What happens when the complement system is activated by the innate immune system?
A
The microbe is coated with the proteolytic fragments of C3. One of the fragments is C3d. B lymphocytes have a receptor for C3d (CR2, or CD21)
20
Q
What happens when CR2 is engaged on B cells
A
C3d has been bound and the antigen dependent B cell activation is enhanced via activating ITAMs
21
Q
How do microbial products directly activate B cells
A
Engage in innate pattern recognition receptors
Pathogen-associated molecular patterns of microbes bind to TLRs on PM or endosomes of B cells which causes signaling pathways that work with signals from the antigen receptor
These two signals causes B cell proliferation, Ig secretion, and differentiation
22
Q
What do protein antigens do to B cells then?
A
They do not stimulate high levels of B cell proliferation, they induce changes in B cells that enhance their ability to interact with helper T lymphocytes
23
Q
What happens when protein antigen finds B cell?
A
It binds to BCR and the antigen is endocytosed then it is degraded and displayed by class II MHC to helper T cells
Therefore response to cytokines is enhanced
Migration from follicle of the secondary lymphoid organ to T-cell zone
24
Q
Interactions of helper T cells and B lymphocytes in antibody responses to T-dependent protein antigens
A
Recognition of different epitopes of the same protein antigen by the two cell types
1. CD4 cells are activated by presentation of antigen by class II MHC by dendritic cells and then CD4 cells differentiate into cytokine producing, CD40 ligand having helper T cells
2. Naive B cells are activated in the follicle by exposed epitope on the same protein
3. The activated B and T cells migrate to one another and interact at edges of the follicles where initial antibody response develops
4. Some B and T cells go back into the follicles and form germinal centers where more specialized antibody responses are induced
25
How do B cells present antigens to helper T cells?
Bind protein antigens by their Ig and endocytose the antigens, process them in endosomal vesicles and then display them on class II MHC
26
Why do B cells present multiple peptides?
So helper T cells can recognize multiple epitopes of the same protein antigen later
27
What ensures B cell and T cell interactions are antigen specific?
B cells internalize the antigen they have receptors for and then helper T cells recognize peptides derived from the same antigen
28
Can B cells activate previously differentiated effector T cells?
Yes
They cannot initiate a response from naive T cells tho
29
Hapten-carrier conjugates
B cell binds hapten portion, ingests the conjugate and then displays the peptides to helper T cells
Antibody response is specific to the epitope recognized
The peptides derived from the carrier protein bring the T cell into this situation
30
B cell epitopes
Recognizes one epitope of an antigen and then displays different epitopes of the antigen for helper T cells
31
What is a hapten?
Small chemical recognized by B cells and stimulates strong antibody responses if it is attached to a carrier protein
32
Conjugate vaccine
Way to get antibody response against microbial polysaccharides
Polysaccharide is coupled to a protein. Then the B cells recognizes the polysaccharide and ingests it, displays it for T cells
This stimulates polysaccharide specific B cells
High affinity T dependent antibody responses are induced against the polysaccharide because helper T cells specific for the carrier are engaged
33
What is induced in a response to polysaccharides?
Isotope switching, affinity maturation, long lived plasma cells and memory cells
34
Results of conjugate vaccines
T cells recognize peptides from the attached protein
B cells recognize polysaccharide
Antibody response is specific for the polysaccharide
Is much stronger than T independent responses because helper T cells are able to participate
35
What do conjugate vaccines protect against?
Bacteria
Haemophilus influenzae, meningococci, pneumococci, and typhoid
36
How do helper T cells activate antigen-specific B cells?
When the helper T cells are activated by recognizing an antigen from B cells, they use CD40 ligand and secreted cytokines to activate antigen-specific B cells
37
Two ways helper T cells activate B cells
1. CD40L ligand from T cells bind to CD40 on B cells
2. Cytokines secreted by T cells bind to cytokine receptors on B cells
Both of these induce B cell proliferation and differentiation
38
Cells made from initial T-B cell interactions
Low levels of antibodies with switched isotopes and short-lived plasma cells that secrete antibodies for a few weeks
39
Where do fully developed antibody responses occur?
Germinal centers formed by lymphoid follicles and require helper T cells
Some helper T cells express chemokine receptor CXCR5 which pulls the cells into adjacent follicles
40
Follicular helper T cells (Tfh)
CD4+ cells that migrate into B cell rich follicles
Generation and function of them depend on the receptor of CD28 family called inducible costimulator which binds to its ligand on B cells
41
What do Tfh cells are their precursors secrete?
Cytokines such as IL-4 and IL-13
They determine which antibody isotope is produced by class switching
42
Germinal center
Few activated B cells and Tfh cells migrate to the lymphoid follicle to divide rapidly in response to Tfh signals
B cells undergo further class switching and somatic mutations of Ig genes
43
B cells made in early germinal center
B cells of moderate affinity develop into memory cells and exit germinal layer
44
B cells made in later germinal center
High affinity B cells are produced by repeated Ig mutation and selection
Eventually differentiate into long-lived plasma cells and memory cells
45
Where are proliferating B cells in germinal center?
Dark zone
46
Where does selection of B cells occur in germinal center?
Less dense light zone
47
How the immune system protects the body from bacteria and viruses
They coat (opsonize) them with antibodies so then they can by phagocytosed by macrophages and neutrophils
Best done by IgG molecules
48
What do IgG molecules do to antigen
Bind high affinity phagocyte Fc receptors for specific Fc portion of the gamma heavy chains
49
What stimulates the production of IgE antibodies?
Helminths
IgE binds and activates mast cells (have high affinity Fc receptors for epsilon heavy chain
50
IgA
mucosal immunity
51
How do IgG antibodies have a longer half life than IgM?
IgG is able to bind to a specialized Fc receptor (neonatal Fc receptor (FcRn))
52
FcRn
Expressed on the placenta and mediates the transfer of maternal IgG to the fetus
When it is expressed on endothelial cells and phagocytes it plays a role in protecting IgG from intracellular catabolism
53
What induces heavy chain class switching?
A combination of CD40L mediated signals and cytokines
54
What happens when CD40 or CD40L is absent?
B cells only secrete IgM
and fail to switch to other isotopes
55
Switch recombination
molecular mechanics of class switching
Taking former VDJ exon encoding the V domain and of an Ig micro heavy chain and moving it adjacent to a different C region downstream of the Ig heavy chain
56
Cytokines produced by Tfh cells do what?
Determine which heavy chain isotope is produced
57
Switching to IgE heavy class
Stimulated by IL-4 and IL-13 made by Tfh cells
Associated with helminth infections
Induce Th2 cells and related Tfh responses
58
Affinity maturation
The affinity of antibodies produced in response to a protein antigen increases with prolonged or repeated exposure to that antigen
59
Where does affinity maturation occur?
Happens in the germinal centers of lymphoid follicles and is the result of somatic hypermutation of Ig genes in dividing B cells, followed by the selection of high-affinity B cells by antigen
60
What happens in dark zones of germinal centers?
Where B cells are proliferating
Numerous point mutations are introduced into Ig genes
61
What does enzyme AID do?
In dark zone
Is required for class switching
Converts cytosines to uracil
The C to T mutations are either removed or repaired by mechanisms that lead to the addition of new nucleotides in the vicinity of the original mutated cytosine
62
Role of FDCs in antigen-antibody complexes
Displays the complexes
Are found only in lymphoid follicles
Most antigen in germinal centers carriers attached antibody or complement proteins which bind receptors on FDCs and are therefore displayed by FDCs
63
Antigen-antibody complexes
When residual antigen from original infection binds antigen
Activates complement
Complexes are displayed by FDCs
64
B cells interacting with FDCs
They recognize the antigen, internalize it, process it and then present it to Tfh cells which provide survival signals
Therefore high affinity B cells are more effective when it comes to competing for an antigen than a low affinity B cell.
More likely to bind to antigen and survive
65
What happens with B cells that have been selected?
They return to the dark zone and the process starts all over again
66
Properties of selected B cells
Must be able to bind antigen at increasingly lower concentrations and therefore are cells whose antigen receptors are of a higher affinity
Ex. Vaccine boosters
67
What can activated B cells in the germinal centers turn into?
Memory B cells: DO NOT SECRETE ANTIBODIES!!! Are in tissues and secondary lymph organs
survive months to years and cycle around waiting to see the antigen again
Plasma cells: SECRETE ANTIBODIES!!!!
Go to circulation and migrate to bone marrow and mucosal tissues
68
T-independent protein antigens
Differ from responses to proteins
Most of these differences come from the role of helper T cells in antibody responses to proteins
Engage TLRs providing activating signals to the B cells that enhance B cell activation in the absence of T help
Polysaccharides activate complement system
Crosslinking of BCRs by multivalent antigens may activate B cells strong enough in order to stimulate their proliferation and differentiation without T cell help
69
What can elicit antibody responses without the help of helper T cells?
Polysaccharides, lipids and other nonprotein antigens
These non-protein antigens cannot bind to MHC molecules and therefore cannot be seen by T cells
70
How are bacteria killed?
They contain polysaccharide rich capsules which can be bound by antibodies which target the bacteria for phagocytosis
71
What are B cell responses regulated by?
Products of B cells: antibodies, cell-intrinsic mechanisms (inhibitory receptors and signaling pathways)
72
What happens to activated B cells that do not differentiate into plasma cells or memory cells?
Apoptosis
73
Antibody feedback
When antibody bound to antigen inhibits further antibody production
Terminates further B cell activation
74
Mechanism of antibody feedback
IgG that circulates through blood binds antigen to forming immune complexes
B cells specific for an antigen may bind antigen part of the immune complex by their Ig receptors
Fc tail of attached IgG antibody may be recognized by Fc receptor Fc-gamma-RIIB which is an inhibitory receptor that contains immunoreceptor tyrosine-based inhibitory motif (ITIM) which is P'ed by LYN tyrosine kinase and phosphatase is recruited to ITIM
The phosphatase shuts off antigen receptor-induced kinase-dependent signals. Terminating B cell responses
Terminates further B cell activation once enough IgG are produced
75
Other inhibitory receptors to shut off B cell activation other than Fc-gamma-RIIB?
CD22 and CD72 which have ITIMs that are P'ed after the BCR is engaged
P'ed ITIMs recruit tyrosine phosphatase SHP-1 which dampens signaling
76
IgG
Neutralization of microbes and toxins
Opsonization of antigens for phagocytosis by macrophages and neutrophils
Activation of the classical pathway of complement
Antibody-dependent cellular cytotoxicity mediated by NK cells
Neonatal immunity: transfer of maternal antibody across placenta and gut
Feedback inhibition of B cell activation
77
IgM
Activation of the classical pathway of complement
78
IgA
Mucosal immunity: secretion of IgA into lumens of gastrointestinal and respiratory tracts, neutralization of microbes and toxins
79
IgE
Mast cell activation
Defense against helminths
80
Antibody Fab (antigen-binding) and Fc regions role
Fab region bind to and block harmful affects of microbes and toxins
Fc (made up of heavy chain constant regions) regions are used to activate diverse effector mechanisms that eliminate the microbes and toxins
81
Binding of Fc region
Fc region contains binding sites for Fc receptors on phagocytes and for complement proteins
Binding of Fc receptors and complement proteins happens only after Ig molecules recognize and become attached to a microbe or a microbial antigen
Therefore Fc dependent functions require antigen recognition by Fab regions
82
What is affinity maturation induced by?
Repeated stimulation with protein antigens
Leads to production of antibodies with a higher and higher affinities for an antigen
83
Benefits of switching to IgG
It prolongs the protective functions of the humoral immune response
IgG isotopes survive longer duration in the blood than IgM and other isotopes
IgG has a half-life of three to four weeks because of neonatal Fc receptor (FcRn)
84
Where is FcRn expressed?
Expressed in the placenta, endothelium, phagocytes and a few other cell types
Transports antibodies from the mothers circulation to the fetus
FcRn also protects IgG antibodies from intracellular catabolism
85
FcRn and IgG mechanism
Way to recycle IgG. Proteins attached to IgG are degraded in the lysosomes and the IgG are taken out of the endosomes
FcRn binds to IgG that is in the cells in the endosome and it recirculates it back into blood or tissue fluids to avoid lysosomal degradation
The IgG-FcRn complexes are sorted to recycling endosomes to be released from the cell
This is why IgG half-life is unusually long
86
What antibodies do at epithelial barrier?
Antibody blocks penetration of microbe through epithelial barrier by binding microbe
Without antibody the microbe would enter through epithelial barrier
87
What antibodies do when microbe tries to infect cell?
Antibody blocks binding of microbe and infection of cell by binding to microbe
Without antibodies the cell is infected by the microbe
88
What antibodies do when a toxin tries to bind to cell surface receptor?
Antibody blocks binding of toxin (caused by endotoxins or exotoxins) to cellular receptor by binding to toxin
Without antibody the toxin binds to cell surface receptor and there is a pathologic effect of the toxin
89
Fc-gamma-RI (CD64) and Fc region of IgG
When a microbe is bound by IgG, Fc regions face away from microbe allowing the Fc region to bind to high affinity receptor of Fc regions called Fc-gamma-RI (CD64)
Fc-gamma-RI is expressed on neutrophils and macrophages
Phagocyte extends its PM to endocytose microbe into a phagosome which fuses with lysosomes
Binding of Fc-gamma-RI also activates phagocytes because it contains a signaling chain that triggers biochemical pathways in the phagocytes
Signals lead to creation of ROS, NO, and proteolytic enzymes in the lysosomes of activated neutrophils and macrophages
90
What does the spleen do to encapsulated bacteria?
The spleen has large amounts of macrophages and is a major site for phagocytic clearance of opsonized bacteria
91
Fc-gamma-RII
Does not mediate effector functions
Shuts down antibody production
Reduces inflammation
Feedback inhibition of B cell activation
Inhibits activation of dendritic cells and are therefore anti-inflammatory
92
Intravenous immune globulin (IVIG)
Pooled IgG from healthy donors is given to the sick to treat inflammatory diseases
Is effective because it binds to Fc receptor Fc-gamma-RII
93
Can natural killer cells bind to opsonized cells and kill them?
Yes
They express Fc-gamma receptor called Fc-gamma-RIII (CD16) which is an activating receptor for NK cells
Fc-gamma-RIII (CD16) binds an array of IgG antibodies
Signals made by the binding of Fc cause NK cells to release their granule proteins which kill antibody coated cell
94
Antibody-dependent cellular cytotoxicity
Process by which Fc-gamma receptor on NK cells is activated by signals produced by receptor which Fc-gamma binds to cell that has been opsonized
Cells with an enveloped virus can express viral glycoproteins on their surface which can be recognized by antibodies which can cause ADCC-mediated destruction of the infected cell
ADCC is one of the ways therapeutic antibodies can be used to treat cancers to eliminate tumor cells
95
What are heminthic parasites dominated by?
T helper 2 (Th2) cell activation, IgE antibody production, eosinophilia
96
How are eosinophils activated?
Fc-epsilon-RI is not expressed at high levels and lacks its signaling chain in eosinophils so IgE does not activate eosinophils
The cells are recruited by chemokines to sites of infection
May bind to IgG coated parasites by Fc-gamma-RI
They can also be activated by Th2 cytokine IL-5 independent of antibody and release their granule contents which destroys the thick integuments of helminths
97
How complement stimulates inflammatory responses?
C3a and C5a both bind to receptor of leukocytes (neutrophils and other leukocytes) and cause inflammatory reactions which can lead to destruction of microbes by leukocytes
98
How complement phagocytose microbes
Opsonization of microbe with C3b/C4b
C3b is recognized by phagocytes CR1 receptor
Leads to phagocytosis and killing of microbe
99
Fc-gamma-RI (CD64)
High affinity for Ig, binds to IgG
Are on macrophages, neutrophils
Causes to activation of phagocytosis
100
Fc-gamma-RIIB (CD32)
Low affinity for Ig
Are on B cells, DCs, mast cells, neutrophils, macrophages
Cause feedback inhibition of B cells
Attenuation of inflammation
101
Fc-gamma-RIIIA (CD16)
Low affinity for Ig
On NK cells
Antibody-dependet cellular cytotoxicity (ADCC)
102
Fc-epsilon-RI
High affinity for Ig, binds IgE
On mast cells and basophils
Activation (degranulation) of mast cells and basophils
103
Way complement system promotes antibody production
breakdown product C3d from C3 is recognized by complement receptor 2 (CR2) on B cells
Enhances B cells response against microbes
With this antigen-antibody complex DCs can recognize these complexes and antigens can then be displayed for more B cell activation
104
Ways complement system is regulated
Regulatory proteins which prevent complement-mediated damage to host cells
105
decay accelerating factor (DAF)
Hydrolyze C3b and inactivate it
Microbe cell membranes lack DAF
Prevents the binding of Bb in the alternative pathway and C2a in the classical pathway
106
membrane cofactor protein (MCP)
Hydrolyzes C3b and inactivates it
Microbe cell membrane lacks MCP
107
C1 inhibitor (C1 INH)
Prevents assembly of C1 complex
Therefore blocks initiation of classical pathway
108
Complement receptor (CR1)
Interferes with formation of C3 convertase by blocking the binding of Bb in the alternative pathway and C2a in the classical pathway
109
Factor I
Cleaves C3b into inactive fragments
110
Why is complement activated for microbes and not host cells?
Complement regulatory proteins are made by vertebrae cells but not by microbes
Microbes therefore lack the regulatory proteins
111
Mucosal immunity
IgA binds and neutralizes toxins in the lumens of the mucosa-lined organs
Also called secretory immunity
IgA is produced in plasma cells in mucosal tissues and then are transported across epithelia to the lumens of mucosa-lined organs
112
Why is IgA for mucosal immunity?
The cytokines that induce switching to this isotope are present in the B cells there
Includes transforming growth factor beta (TGF-beta)
113
How is IgA transported across epithelia to lumen?
With special Fc receptor (poly-Ig receptor) which is expressed on basal surface of epithelial cells
Binds IgA, endocytoses into vesicles, transports it to luminal surface
Receptor is cleaved by a protease and then IgA is released into lumen
114
What protects IgA from degradation by proteases in the gut?
After the poly-Ig receptor is cleaves by a protease, some of the bound receptor (secretory component) protects the antibody from degradation
115
What antibody is in breast milk?
IgA
They are secreted across mammary gland epithelia via poly-Ig receptor
116
How long is baby protected with mom's antibodies?
Six months for IgG since it has a long half-life
At that time the baby will begin to make its own antibodies
117
How do bacteria and viruses evade humoral immunity?
Mutate their surface molecules that are needed for entry into host cells so they can no longer be recognized by antibodies
118
Why are gp120 vaccines not affective?
There are many variant forms of the gp120 glycoprotein for HIV that one subtype may not protect against other virus subtypes that appear in infected individuals
119
How has COVID-19 evaded vaccine-induced immunity?
Causative agent is a spike protein that gain entry into host cells
Variants of spike protein exist which allows proteins to evade the vaccine
120
Ways antigens can evade immune system
Antigenic variation (many viruses (influenza, HIV, SARS-CoV-2), some bacteria, Protozoa) Inhibition of complement activation, and blocking phagocytosis (many bacteria) by hyaluronic acid capsule (Strep)
121
Live attenuated viruses
Lack of pathogenicity while retaining their infectivity and antigenicity
Production of neutralizing antibodies
Killed viruses such as hepatitis A, polio and rabies
122
Subunit vaccines
Composed of microbial proteins and polysaccharides
Can also be produced using recombinant DNA technology like in hepatitis B and human papilloma virus vaccines
123
Conjugate vaccines
Microbial polysaccharides that are unable to stimulate T cells are coupled with proteins so T cells are activated and high-affinity antibodies are produced
T cell-B cell interactions
Inactivated microbial toxins with microbial proteins
Stimulates antibodies to bind to and neutralize native toxins and the microbes
124
Nucleic acids as vaccines
Advantage is that microbial proteins may be produced in host cells and secreted which would cause a humoral and cell-mediated responses
Nucleic acids engage TLRs and therefore have adjuvant activity
Plasmid DNA vaccines have not been successful
125
Issues with mRNA vaccines
Extracellular RNA is unstable
When RNA enters cytosol, innate immune system recognizes it and causes type I interferon response that can cause harmful inflammation
Therefore putting RNA in lipid nanoparticles has helped these issues
Vaccine was successful for COVID-19
126
Hybrid viral vaccines
Now used for SASRS-CoV-2 and have been approved for the Ebola virus
When the DNA encoding a microbial antigen can be incorporated into the genome of a replication defective viral vector
Virus is harmless for humans
When it enters the host cell the microbial proteins are produced.
127
Immunologic tolerance
Unresponsiveness to self antigens
Lack of response to antigens that is induced by exposure of lymphocytes to these antigens
128
autoimmunity
The immune system attacks the individuals own cells
129
Immunogenic antigens
lymphocytes are activated to proliferate and to differentiate into effector and memory cells
aka...affective immune response
Microbes are immunogenic antigens normally
130
Tolerogenic antigens
When lymphocytes may be functionally inactivated or killed, resulting in tolerance
Self antigens are tolerogenic normally
131
Immunologic tolerance to different self antigens
Induced when developing lymphocytes encounter these antigens in the generative (central) lymphoid organs called central tolerance
132
Primary mechanism of central tolerance in T cells
Death of immature T cells that recognize self antigens in the thymus
133
Peripheral tolerance
Mature lymphocytes that recognize self antigens may be suppressed by Tregs, inactivated (anergy) or deleted (apoptosis)
134
Medullary thymic epithelial cells (MTECs)
Transcribe and express genes encoding antigens that are otherwise only expressed by the cells in one or another peripheral tissue type
Expression is induced by AIRE expression
135
Autoimmune regulator (AIRE)
Protein that promotes expression of antigens characteristic of the various tissue cell types
136
What happens when there are mutations in the AIRE gene?
Autoimmune polyglandular syndrome
Tissue antigens are not expressed in MTECs from lack of AIRE protein
Antigens are expressed normally in peripheral tissues
Immature T cells specific for these antigens are not eliminated and do not develop into to Tregs. They mature into functioning T cells
Enter periphery and attack tissues. The T cells promote production of autoantibodies by B cells since the B cells recognize the T cell cytokines
137
FOXP3
required for development and function of T regs
Depends on IL-2
Factor beta (TGF-beta) plays a role in expression of FOXP3
138
IL-2
Promotes immune responses by stimulating T cell proliferation
Inhibits immune responses by maintaining functional T regs
139
CTLA-4
Inhibitory receptor expressed by Tregs that blocks B7 costimulators from APCs and blocks T cell activation
140
Central B lymphocyte tolerance
Occurs in bone marrow
Receptor editing: Change receptor specificity by re-expressing genes to express a new Ig light chain
Deletion: When editing fails, cells receive death signals and die by apoptosis
141
Peripheral B cell tolerance
Mature B lymphs that encounter self antigen in peripheral tissues (become functionally unresponsive (anergic))
Transitional B cells (just left bone marrow) that are triggered by self antigen are eliminated by apoptosis
142
Immune privilege
Occurs in central nervous system, brain, eyes, testes
Immune responses do not occur in these regions due to suppressive factors released by various cells
143
Infections and Environmental triggers of autoimmunity
Molecular mimicry
Tissue injury releases self antigens not normally seen by immune system
