Block 2 Flashcards
IL-__ and IL-__ lead to T cells
2
7
IL-__ leads to B cells
4
do B or T cells perform somatic mutation during generation of antibody binding diversity
B
is VDJ associated with light or heavy chain of an antibody
heavy
is VJ associated with light or heavy chain of an antibody
light
what is junctional diversity during antibody generation
nucleotides are added or deleted during V(D)J recombination by Tdt enzyme to produce hypervariable regions
what is somatic hypermutation
mutations in V genes of heavy or light chains in the germinal center for B cells, with the goal to produce high affinity antibodies
*B cells only, occurs in dark zone of germinal center
what 3 enzymes are needed for
V(D) J recombination
RAG-1
RAG-2
TdT
what is the main V(D)J recombination gene
RAG
what happens if there is a decrease in TdT for V(D)J recombination
decrease in antibody diversity
what is another name for hypervariable region
complementarity determining region
what is the result of agammaglobinulinemia
inability to make antibodies
with x linked mutation causing agammaglobinemia, what gene is mutated
BTK
where is the first checkpoint in B cell receptor development
between pre-BCR and immature B
what gene segment do light chains of antibodies not have
D
what is receptor editing during B cell receptor development
if the rearranged kappa chain fails to bind, try the kappa on the chromosome from the other parent
if recombination still fails, it is tried `on the lambda chain
at the immature B cell level, if the receptor binds, signals are delivered that promote survival and there is a shutdown of what gene activity
RAG
when B cells just come out of bone marrow, they express both Ig__ and Ig__
M
D
where does isotype switch occur
germinal center light zone
what is the difference in structure between membrane bound Ig and secreted Ig
membrane bound has a hydrophobic tail that anchors it to the membrane
what enzyme associated with CD4 and CD8 mediates phosphorylation to transmit a signal
LCK
the alpha chain of T cells is similar to the __ chain of B cells, as they both are involved in VJ recombination
light
the complementarity determining region (hypervariable region) of a TCR variable region interacts with __ of an MHC molecule
peptide
in T cells, VDJ recombination occurs between __ and __
double - —> double +
weak recognition of MHC by T cells is positive or negative selection
positive
strong recognition of MHC by T cells is positive or negative selection
negative
what is Omenn syndrome caused by
RAG mutation= messed up T cells, no B cells
*diversity of proteins on the surface of B cells and T cells is severely limited, impairing the cells’ ability to recognize foreign invaders and fight infections
what is the question asked with T cell positive selection
will the cell become CD4+ or CD8+
what is the question asked with T cell negative selection
does the cell react with self
yes (strong recognition of MHC)= apoptosis
what is the difference between alphabeta and gammadelta T cells
gammadelta don’t go through selection so they aren’t as restricted
*still go through VDJ recombination
what are the 3 functions of gammadelta T cells
cytokine/chemokine production
dendritic cell maturation
antigen presenting
what accounts for no B or T cell recognizing the same antigen
variability in V region at hypervariable region (complementarity determining region)
cellular immunity is mediated by what cells
T cells
what are 2 ways in which naive T cells can enter a draining lymph node
blood
afferent lymph from an upstream lymph node
what does expression of CCR7 on dendritic cells or T cells means
can be trafficked to lymph node paracortical region
what are the 3 steps to T cell activation
- antigen presentation on class I or II MHC at antigen presenting cell surface
- co-stimulation (1 molecule on antigen presenting cell interacts with one molecule on T cell)
- production of cytokines
what is the co-stimulation molecule on naive T cells during T cell activation
CD28
what are the 2 possible co-stimulation molecule present on antigen presenting cells during T cell activation
CD80/86
B7.1/B7.2
what is the importance of Zap-70 in antigen recognition
it’s needed to get a T cell response to T cell stimulation
what is the effect of no Zap-70 in antigen recognition
abnormal T cell receptors result in low to normal CD4, and low CD8
T cells don’t respond to T cell stimulation, resulting in repeated viral infection due to lack of mature T cells
what is the function of the immune synapse
to activate protein kinase C for T cell response
an influx in what ion occurs during T cell activation
calcium
what is the result of calcium release activated channels deficiency in T cell activation
immunodeficiency due to limited T cell activation
for co-stimulation for T cell activation, what is the signal present on the antigen presenting cell
B7.1/B7.2 (CD80/CD86)
for co-stimulation for T cell activation, what is the signal present on the naive T cell
CD28
what does the presence of CD40L on T cells indicate
the T cell is an effector T cell which can boost macrophage killing or induce class switch on T cells
what is IL-2 secretion needed for
T cell proliferation
what is clonal expansion in T cells
increase then contraction of T cells in response to the number of days since infection and T cell activation
non-classical antigen presentation involves what 2 types of molecules
lipids
glycolipids
what is non-classical antigen presentation
CD1 is a surface glycoprotein that can present lipids/glycolipids to T cells instead of peptides
what T cells do CD1 glycoproteins express their glycolipid/lipid to
alphabeta T cells
gammadelta T cells
NKT cells
what type of cells are NKT cells
antigen presenting
what does it mean to say NKT cells are semi-variant
they only have one Valpha and limited Vbeta genes
NKT cells only bind with __
CD1d
NKT cells only bind with __
CD1d (recognize glycolipids and lipids)
how is the binding of a superantigen different than that of an antigen
the superantigen binds to the side of the MHC class II and beta chain of CD4+T cell leading to non-specific T cell activation and an increased immune response
what are the 4 types of effector T cells naive CD4+ T cells can become
Th1
Th2
Th17
Tfh (follicular helper)
what are the 3 possible roles of effector T cells
help B cells proliferate/differentiate to plasma cells
help promote innate activity (make macrophages kill more)
help T cells proliferate/differentiate to effector CD8+ cells
what 2 cytokines are released in response to large intracellular microbes
IL-12
IFNgamma
what class of T helper cells clear intracellular larger microbes
Th1
what cytokine is released in response to a helminths (worm) infection
IL-4
what class of T helper cells clears worm infections
Th2
what cytokines are released in response to extracellular fungi and bacteria (smaller stuff)
IL-1
IL-6
TGF-beta
IL-23
what class of T helper cells clears extracellular fungi and bacteria
Th17
what is the main cytokine that signals Th17 pathway
IL-23
what 3 cells do Th1 cells activate
macrophages
killer T cells
B cells
what 4 cells do Th2 cells activate
eosinophils
mast cells
basophils
macrophages (M2)
what cell does Th17 recruit
neutrophils
what 3 cytokines do Th1 cells secrete
IFN-gamma
TNF-alpha
IL-2
what 3 cytokines do Th2 cells secrete
IL-4
IL-5
IL-13
what is the function of IL-17 release from Th17 cells
increase neutrophil response
push inflammatory response
improve epithelial cells
Th23+IL-6+IL-1+TGF-beta–>Th__
–>continued __ response
17
inflammatory
what STAT protein is needed for Th17 response
STAT3
what is involved in hyper IgE syndrome
loss of STAT so no Th17= increased susceptibility to bacterial and fungal infections
CD8+ killer T cells are upregulated by Th__ activity
1
how does perforin/granzyme mediated cell killing work
target cell and CD8+ T cell interact and form a synapse
CD8+ cell releases perforin granules into synapse
uptake of perforin and granzyme into target cell cytosol, creating an endosome
perforin pokes hole in endosome and granzymes flow out into cell, activating caspase and apoptosis in target cell
how does Fas/Fas-L mediated cell killing work
Fas-L on CD8+ T cell interacts with Fas on target cell, triggering caspase activity and apoptosis of target cell
how can CD4+ T cells provide help to CD8+ T cells
CD4+ T cells secrete IFN-gamma, increasing activity of CD8+
once T cells are effector cells, how do they get to their destination
effector T cells upregulate different selectins/integrins depending on where they go to
what 2 cytokines are requires for memory T cell development
IL-7
IL-15
what is the difference between central and effector memory T cells
central- stay in lymph node
effector- localize where they encounter the antigen so will be quick to respond to future antigen at same site
what is familial hemophagocytic lymphohistiocytosis
out of control macrophages secreting a lot of cytokines and eating everything due to a defect in lymphocyte cytotoxicity
where are marginal zone B cells located
peripheral region of splenic white pulp
most B cells are called __ because they reside in and circulate through the follicles of lymphoid organs
follicular
for T dependent responses, what 3 steps are required
activation of T cell
activation of B cell
2 interaction of B and T cells (1 interaction to proliferate, 1 signal to class-switch)
where does the first interaction between T and B cells occur in T dependent B cell activation
outside the lymph follicle
what is involved in the first interaction between B and T cells for thymus dependent antigen response
T cell instructs B cell to proliferate in dark zone and perform somatic hypermutation to increase binding affinity
what protein is required for somatic hypermutation
AID
what is involved in the second interaction between B and T cells for thymus dependent antigen response
B cell with best BCR interacts with T follicular helper cells (ICOS on T cell interacts with ICOS-L on B cell) and follicular dendritic cells (CD40 on B cell interacts with CD40-L on T cell) that instruct B cell to class switch in light zone
thymus independent antigens are what type of molecules
polysaccharides
do thymus independent or dependent antigens perform class switching
dependent
do thymus independent or dependent antigens have high affinity
thymus dependent
do thymus independent or dependent antigens produce memory B cells
thymus dependent
thymus independent-1 antigens make IgM antibodies through use of what 3 stimulations
BCR
CD21 (C3d)
TLR
how do thymus independent-2 antigens make IgM antibodies
stimulating a bunch of B cell receptors at once
how can a T cell epitope convert from a thymus independent response to a thymus dependent response
conjugate the polysaccharide of the independent response to a carrier
what is immunologic tolerance
elimination/inactivation of lymphocytes that express high affinity for self
what do medullary thymic epithelial cells (MTEC) do
develop self antigens under the control of AIRE
what causes autoimmune polyendocrinopathy-candidiasis ectodermal dystrophy (APECED)
lack of AIRE protein leads to autoreactive T cells with failure of central T tolerance
what is anergy
the down regulation of receptors on B/T cells so they no longer show high affinity for self, downregulating the immune response to self antigens
how does CTLA-4 work as an inhibitory receptor for T cells
it competitively binds to CD28 and blocks CD28-B7 interaction to ensure the T cell doesn’t get out of control
how does PD-1 work an inhibitory receptor
it blocks signaling through the TCR leading to death of the T cell
what is the function of regulatory T cells (Tregs)
inhibit T cell response
what 3 cytokines do T regulatory cells (Tregs) express
CD4
CD25
FoxP3
what is the main cytokine that is required for survival and function of Treg cells, and determines the number of activated T cells
IL-2
what causes IPEX syndrome
deficiency in FoxP3 leading to no central or periphery Treg response
what are 3 types of B cell tolerance
receptor editing
deletion
anergy
how do the inhibitor receptors for peripheral B cell tolerance, FcgammaRIIb and CD22, act through feedback inhibition
if there is already a lot of antibody, they dephosphorylate the B cell, making them inactive
what are the 2 main feature that favors tolerance to an antigen
antigens without adjuvants
high doses of antigen
autoimmunity is caused by an error in __ which is triggered due to an environmental stimulus, leading to a break in __
MHC
tolerance
what is immunity self-tolerance
the ability to recognize self-produced antigens as a nonthreat and respond properly to foreign antigens
what is hyper IgM syndrome X linked
CD40L signal is messed up so no B cell class switching occurs
what is hyper IgM syndrome autosomal recessive
CD40 or AID mutation occurs so there is no B cell class switching
hypersensitivities start with a __ phase then a __ phase
sensitivity
elicitation
what are the 4 types of hypersensitivity reactions
I- allergy
II- cytotoxicity
III- immune complex formation
IV- delayed
type I hypersensitivity involved what type of reactions
allergy
allergic reactions involve production of Ig__
E
what is involved in antigen sensitization
dendritic cell activates T cell to become Th2
Th2 makes IgE
IgE binds to mast cell and causes degranulation
what makes a good allergen
repeated exposure to antigen
is IgE level higher in plasma or tissue
tissue
__ cells express IgE of a single specificity
__ and __ bind different IgE molecules specific for different antigens
B cells
mast cells and basophils
what occurs during a sensitization phase for type I hypersensitivity
Th2 cell activated, caused B cell class switch to IgE, IgE binds to mast cell
what occurs during elicitation during a type I hypersensitivity
antigen protein is crosslinked on IgE on mast cell, causing mast cell degranulation
what is one of the pathways activated with mast cell degranulation
arachidonic acid
what is the purpose of the arachidonic acid pathway in type I hypersensitivity
make prostaglandins and leukotrienes
for type I hypersensitivity to occur, there must be __, __ exposure of B cells to that antigen presented on the MHC of a Th2 cell
recurrent. low-dose
the immediate phase of allergen exposure involved release of __, while the late phase involved release of __
mast cell degranulation
eosinophils
In type I hypersensitivity, a wheal and flare reaction occurs
wheal=__
flare=__
swelling
redness
during late phase of an allergic reaction, after __ hours there is maximum inflammation before inflammation subsides
24
in asthma and rhinitis, there is an increase in mucous due to in increase in what cytokine
IL-13
in bronchial asthma during type I hypersensitivity, there is standard inflammation as well as __
spasm contraction of smooth muscle surrounding bronchi
in an asthma late response, what happens to the airway
remodeling that can lead to scarring due to activity of eosinophils and neutrophils
chronic responses to asthma involve the entry of __ and __
eosinophils
neutrophils
how does extrinsic asthma differ from intrinsic asthma
extrinsic- hypersensitivity type I reaction
intrinsic-mast cell degranulation without type I hypersensitivity reaction
what causes atopic urticaria
IgE response to allergens that enter the skin from outside or travel through circulation, causing an allergic response on the skin
what is a more severe version of atopic urticaria
atopic dermatitis
what is atopic dermititis
thickening of the skin following scratching
what is the pathway involved in atopic dermatitis
- Th2 activation and release of IL-4, IL-5, and IL-13
- scratching
- cytokine release
- Th1 activation and macrophage/neutrophil increase
- thickening of skin
what is the primary way of diagnosing type I hypersensitivity
skin test to determine wheal and flare reactions
why is the RAST test gradually being replaced
it tests IgE in serum but IgE is seen more in tissue than serum
what is the cause of a penicillin allergy
haptenization (penicillin forms a larger molecule which is recognized by our immune system)
why do most people not develop a penicillin allergy
most people’s MHC class II will not present the haptenized penicillin to T cells
what causes red man syndrome
IV infusion of vancomycin that causes degranulation of mast cells but not IgE response
how does allergy desensitization work
the patient received increases dosage of allergen, increasing IL-10 and serum IgG and decreasing IgE
type 2 HSR involves ___, while type 3 HSR involves __
antibody binding to protein on the cell
immune complex formation and deposition
what antibody is involved in type 2 and 3 HSR
IgG
what is the difference between warm antibody mediated HSR and cold antibody mediated HSR
warm- IgG binds protein antigens at core body temp
cold- IgM binds polysaccharide antigens in peripheral circulation
what causes erythroblastosis fetalis
Rh- mother is sensitized during birth of first Rh+ child
anti-Rh IgG can cross placenta and bind to Rh antigens of the next Rh+ child RBC
results in lysis of fetal RBC
what does the direct Coomb’s test test
if IgG is bound to the RBC
pemphigus vulgaris is a type __ HSR
2
what occurs with pemphigus vulgaris
IgG is produced against desmoglein proteins in desmosomes, leading to blisters and tissue destruction
myasthenia gravis is an example of a type __ HSR
2
what occurs with myasthenia gravis
antibody against a receptor at the neuromuscular junction causes loss of cell function
goodpasture syndrome is an example of a type __ HSR
2
what occurs with goodpasture syndrome
antibodies bind to glomerular basement membrane in kidneys/lungs causing destruction through phagocytosis granule release
what is an Arthus reaction
the result of a localized inflammation of the small vessels (i.e., vasculitis) near the injection of antigen due to the interaction between the injected antigens and the circulating antibodies IgG which are created after repeated exposure to a specific antigen.
As a result, immune complexes are formed around and within the blood vessels of the skin. Subsequently, activation of the complement cascade, which is part of the innate immune system, enhances the local inflammation.
type 3 HSR
how are immune complexes normally cleared
complexes are carried to the spleen/liver to be phagocytosed
what causes serum sickness
injection of non-human serum into a human causes IgG made against the non-human serum
complement is activated and immune complex formation is formed, which is not cleared by the liver/spleen quick enough
what are the 4 symptoms of serum sickness
fever
arthralgia (achy joints)
lymphadenopathy
skin eruption (rashes)
is serum sickness a fast or slow response
slow due to production of IgG and complement activation
what is extrinsic allergic alveolitis
repeated inhalation of an antigen causes IgG production
results in complement activation and inflammation
what is the cause of lupus symptoms
autoantibody and immune complex deposition
lupus is a type __ HSR
3
in lupus, anti-dsDNA antibodies will be present where, causing the most evident symptoms
in cells with rapid turnover
hyperacute graft rejection is __ immunity while acute is __ immunity
hyperacute= humoral (B cell antibody)
acute= cellular/adaptive (T cell) or humoral (if complement is deposited)
what is involved in the prescreening before a graft transplant
prescreen recipient for existing antibody reaction to different HLA proteins to determine how reactive the patient is to different proteins
what are some reasons for ischemia/reperfusion injury during graft transplant
death of donor brainstem induces hemodynamic and neuroendocrine responses
there may be a period of warm ischemia after cardiac death
cell swelling and toxic metabolite buildup during cold storage
further injury due to rapid warming following revascularization
what is a consequence of tissue damage caused by ischemia/reperfusion injury
activation of autoreactive T and B cells, leading to further inflammation and graft damage
what is clinical operational tolerance
a solid organ transplant recipient exhibits a well functioning graft and lacks histological signs of rejection after receiving no immunosuppression for at least 1 year
what are 4 mechanisms associated with tolerance following a graft transplant
deletion of alloreactive T cells
anergy
immunoregulation
clonal exhaustion (T cells get exhausted and give up)
bone marrow transplants involve CD __ cell transplant
CD34+ (stem cells)
in graft vs. host disease, what are the 3 main organs affected
skin
liver
gut
graft vs. host disease is believed to be mediated by what cells in the graft
mature donor T cells
what are neoantigens
tumor antigens
is an immune response made against cancer
yes, macrophages and lymphocytes (CD8+ T cells) infiltrate, however it doesn’t always work
how do cytotoxic T cells (CD8+ T cells) become sensitized to tumor antigens
antigen presenting cells present tumor antigen
what occurs to antigen presenting cells when there is tumor development
APC convert to being regulatory
*they calm T cell response instead of activating
____ antibodies are being used to attack cancer cells
monoclonal antibodies
what is involved with checkpoint blockade for immune evasion by tumor cells
Checkpoint proteins, such as PD-L1 on tumor cells and PD-1 on T cells, help keep immune responses in check. The binding of PD-L1 to PD-1 keeps T cells from killing tumor cells in the body. Blocking the binding of PD-L1 to PD-1 with an immune checkpoint inhibitor (anti-PD-L1 or anti-PD-1) allows the T cells to kill more, including to kill tumor cells. Suppression of the T cell response is relieved
Immune checkpoints are a normal part of the immune system. Their role is to prevent an immune response from being so strong that it destroys healthy cells in the body.
what are chimeric antigen receptor T cells (CAR T cells) for use in cancer (usually blood cell cancers)
A patient’s T cells are changed in the laboratory so they will bind to cancer cells and kill them
The gene for a special receptor called a chimeric antigen receptor (CAR) is inserted into the T cells in the laboratory. Millions of the CAR T cells are grown in the laboratory and then given to the patient by infusion. The CAR T cells are able to bind to an antigen on the cancer cells and kill them.
what is natural active immunity
direct exposure to the antigen (“in the wild”)
what is artificial active immunity
intentional exposure through vaccine
what is natural passive immunity
transfer of antibodies from mother to baby through placenta (IgG) or through breast milk (IgA)
what is artificial passive immunity
injection of purified antibody, antibody containing serum (pooled plasma/serum), or sensitized cells
what is involved in neutralization of virus with vaccines
antibody binds to protein on viral surface that would otherwise bind to proteins on host cells
what are AB exotoxins
toxins released from an antigen
contains A site and B site
B chain attached to binding side on host cell, allowing for entry through phagocytosis
what is involved with viral neutralization through AB exotoxin using a vaccine
antibody binds to the B subunit of an A/B endotoxin, preventing bind and phagocytosis of the exotoxin
what are the 2 classes of whole organism vaccines
live attenuated
whole killed
what are live attenuated vaccines
a selected for microbe has the same epitopes as the pathogenic strain, but is unable to cause disease
replication of virus in vaccine is possible
what are whole killed vaccines
a microbe that causes disease is killed but still has the same epitopes
no replication is possible
what are 3 subunit vaccine types in which the whole organism isn’t used
acellular
toxoid
anti-capsular
what are acellular subunit vaccines
proteins known to be important for pathogenicity are used
what are toxoid subunit vaccines
an inactivated version of an A/B exotoxin are used through modification of the B binding subunit
what are anti-capsular subunit vaccines
the carbohydrate used in capsules is used along with a complexed protein
what are live attenuated vaccines used for
protection requiring T cell immune response and/or a secreted IgA response
what is the most effective vaccine form
live attenuated
*they look like the actual antigen and replicate at the actual site of the antigen
what are whole killed vaccines used for
microbes that can’t be attenuated or microbes with oncogenic potential
what are adjuvants
material added to subunit/toxoid vaccines to increase immunogenocity
(prolongation of antigen persistence, enhancement of so-stimulation signals, induction of localized inflammation)
acellular boredtella pertussis vaccine and hepatitis B vaccine are examples of what type of vaccine
subunit
DTaP is an example of what type of vaccine
toxoid
what is sertotype replacement
vaccinating against one type of capsule doesn’t give the selected advantage against another type of capsule
how do RNA viruses work
the vaccine contains pieces of mRNA packed into a lipid that can slide into cell
once inside the cell, mRNA attached with ribosome to make protein against the virus
what is herd immunity
the idea that not everyone needs to be vaccinated to gain protection against a disease, as long as they’re surrounded by people who are immune to the disease
