Immunology 16L Flashcards
Plasma cells are derived from _____
B cells
Effector T cells are derived from _____
T cells
Macrophages are derived from _____
monocytes
Neutrophils, Eosinophils and Basophils are all derived from ______
Granulocyte Macrophage Progenitor
Platelets are derived from ____
Megakaryocytes
Erythrocytes are derived from _____
Erythroblasts
A high affinity bridge formation on a forign body that enhances phagocytosis
opsonization
Any molecule that enhances phagocytosis by marking an antigen for an immune response
Opsonin
Antibodies can either do ______ by binding Bacterial toxins or _____ by binding the bacterial surface
Neutralization
Opsonization
The ______ system is used to classify antigens
CD
Cluster of Differentiation
These make up 60-70% of circulating white cells
Neutrophiles
These three types of cells are called lymphocytes
T cells
B cells
NK cells
These cells have some type of CD cell surface marker
T cells
These are large granular lymphocytes that that kill tumor cells and some virally infected cells
NK cells
Proteins that will alter the response of the immune system
Cytokines
Antiviral and anti-tumor activity. These molecules stimulate macrophages, T cells, B cells and NK cells
Interferons
These interferons are synthesized by macrophages, fibroblasts and others
Alpha and Beta interferons (also type I)
Produced by stimulated T cells, stimulates macrophages, and leads to differentiation of T cells and B cells
Gamma interferon (INF-γ)
This is the primary mediator of septic shock in humans and is responsible for vascular damage and fever
TNF-α
TNF-β is also called ______
lymphotoxin (LT)
the part of an antigen molecule to which an antibody attaches itself (a binding location)
Epitope
_____ form the antigen-binding site and are found on both light and heavy chains and contribute to the specificity of each antibody
Highly Variable Regions
This antibody is attached to B cells and is first to be used in an immune response
IgM
This antibody is on Mast cells and when triggered, causes the release of histamine
IgE
When B lymphocytes encounter a pathogen they differentiate into ______
plasma cells
The largest immunoglobulin is _____
IgM
Which type of immunoglobulin diffuse into extravascular sites?
IgG
Which type of immunoglobulin sensitizes mast cells?
IgE
Which type of immunoglobulin plays the largest role in neutralization?
IgG
These immunoglobulin are toxin neutralizing, agglutinating, opsonizing and bacteriolytic with the aid of the complement system
IgG
These immunoglobulin are the predominant class in serum
IgG
These immunoglobulin are the predominant class in secretions such as mother’s milk
IgA
These immunoglobulin are transported across epithelium
IgA
These immunoglobulin are responsible for immediate hypersensitivity
IgE
These immunoglobulin are fixed to mast cells and mediate changes in vascular permeability
IgE
These immunoglobulin are involved in host defense against parasitic infectoin
IgE
These immunoglobulin are transported across the placenta
IgG
The _______ region contains of the immunoglobulin contains the amino acid sequence that does antigen binding
variable region
Between the light chain and heavy chain of an immunoglobulin there is a (continuous surface/large gap) capable of providing complementarity with a specific antigen
continuous surface
K = [Ab Ag] / ([Ab] * [Ag]) is called the _____
Antibody affinity
Most antigens have (one/many) epitopes
many
The strength of binding of multivalent antiserum to multivalent antigen is called ______
avidity
The affinity for antigen binding of a population of antibodies is (heterogeneous/homogeneous)
There is a heterogeneity of affinity
Monospecific antibodies that are made by identical immune cells that are all clones of a unique parent cell
Monoclonal Antibodies
All drugs from monoclonal antibodies end with the suffix -_____
-mab
To make monoclonal antibodies, you must fuze the desired B-cells with ______ cells to grow them in vitro
plasmacytoma (myeloma) tumor cells
Cell sorting can be automated by ______
FACS: Fluorescence activated cell sorter (flow cytometry)
Western Blots are used for ______
seperating protiens
Describe the 6 steps for producing a monoclonal antibody
1) Immunize animal
2) isolate spleen
3) fuse spleen cells to plasmacytoma
4) Select for hybrid tumor-B-cells
5) Clone Hybridomas
6) Select clones you are interested in
What can you tell about an antigen by western blot but not by ELISA?
1) weight
2) amount of antigen
3) possible different forms of antigen
The period of time after initial exposure to an immunogen before a specific antibody can be detected
Lag or inductive phase
The 4 phases of the antibody production curve are:
1) lag phase
2) logarithmic (or exponential) growth
3) Steady State
4) Decline pahse
A protein that will kill you is called a ______
Toxin
Antigenically the same as a toxin, but biologically inactive
Toxiod
After initial exposure to an antigen, the resulting immune response is called the ____ response
secondary / memory
The secondary response has more (IgM/IgE/IgG)
IgG
The switch from IgM to IgG is called the _____ switch
Class Switch
Selection for the best antibody is based on _______
Binding affinity
The process of selecting the Antibody with the highest binding affinity is called _______
Affinity maturation
By the end of an infective process, the antibody _____ has developed the highest binding affinity
IgG
B cells can differentiate into ______ cells or _____ cells under stimulation by T-cells
plasma cells
memory cells
The unique set of antigenic determinants (epitopes) of the variable portion of an antibody is called the ______
idiotope
When a B-cell has an antibody that matches an infective antigen, it undergoes _____ _____ to make up to 1000 daughter cells to help clear the infection
clonal expantion
These cells are distinguished by the surface antigen CD4
T helper cells
These cells do endocytosis or phagocytosis to capture antigens and show them to B-cell
APCs, Antigen Presenting Cells
Two common APCs are _____ and ____
Macrophages
Dendritic cells
(and langerhans cells)
Antigen is presented by cells that bear _____ antigens
MHC
T-cells can help stimulate B-cells to turn into ______
Plasma cells
T-cells can stimulate B-cells to switch from producing _____ to producting ____
IgM to IgG
In addition to antigen processing, antigen presenting cells must also provide ______
a second, co-stimulating factor
Any agent capable of producing an immune response is an _____
Immunogen
Any agent that binds to components of the immune system is an _____
Antigen
The small molecule Hapten is (immunogenic/antigenic) but not (immunogenic/antigenic)
Hapten is antigenic but not immunogenic
The enzyme responsible for both class switching and somatic hypermutation is _______
AID
Activation-induced cytidine deaminase
RAG 1 deficiency leads to a lack of ___ cells and ___ cells
T cells and B cells
like bubble boy, severe combined immunodeficiency
These genes encode enzymes that are important for rearrangement and recombination of the genes of immunoglobulin and T cell receptor molecules during VDJ recombination
RAG
Recombination-activation gene
The sole purpose of a B-cell is to make an ______
immunoglobulin
For an early pro-B cell to rearrange the immunoglobulin heavy-chain genes it must express the recombination-activating genes ______ and ______
RAG-1 and RAG-2
The V, D and J segments of DNA are brought together by the recombinase genes _____ and _____
RAG-1 and RAG-2
Each immunoglobulin gene segment has ____ ______ which determine which segments can be joined to each other
signal sequences
Immunoglobulin can bind (linear/discontinuous/both) epitopes
Both linear and discontinuous
During the development of B cells, the arrays of V, D, and J segments are cut and re-spliced by DNA recombination. This is called _____
Somatic Recombination
The recombination of V, J, and D gene segments is directed by sequences called ________
Recombination Signal Sequences (RSSs)
The main differences between different V gene segments are in the sequences that encode _____ and _____ of the V domain
CDR1 and CDR2
____, _____ and ____ are the contact residues of the antigen that are selected for alteration
CDR1, CDR2 and CDR3
Most mechanisms of formation of the T-cell receptor are the same as the B-cell except the _____ ______
somatic hypermutation
Which immunoglobulin gene rearrangement happens first, D-J or V-DJ?
First D-J
(Second V-DJ
Then κ
Then λ)
Engagement of the ______ receptor in macrophages lead to transcription of inflammatory cytokines
toll-receptor
Circulating precursors to macrophages are called ______
Monocytes
These cells control the immune response to parasites
Basophiles
These lymphocytes are important in defense against viral infections
NK cells
This class of cells has different version, one that kills infected cells, a second that secretes cytokines and that activates macrophages and a third that controls activity of cytotoxic cells
T cells
Immunity due to antibodies and their actions is often known as ______ immunity
humoral
In the spleen, the ____ pulp is where RBCs are are monitored and removed, the ____ pulp is where WBCsgather to provide adaptive immunity
Red pulp
White Pulp
An IgG’s Fc region and Fab regions can be cleaved apart by an enzyme called a ______
protease
The V region of a heavy chain is encoded by the combination of one ___, one ___, and one ___ segment.
one V, one D, and one J segment
mutations occur with greater frequency in the (V/J) regions of the variable region
V
Light chains are composed of only two segments. which two? (V/D/J)
V + J
N nucleotides are added randomly to the end of a single strand by the enzyme _____
TdT
Terminal deoxynucleotidyl transferase
In Naive B cells, simultaneous expression of both μ and δ chains from the same heavy-chain locus is accomplished by ______ of the same primary RNA transcript and no rearrangement of genomic DNA
differential splicing
B cells rearrange their immunoglobulin genes in the bone marrow, the precursors of T cells leave the bone marrow and enter the lymphoid organ, _____, before they rearrange their T-cell receptor genes
the thymus
A molecule found on the surface of T lymphocytes that is responsible for recognizing antigens bound to major histocompatibility complex (MHC) molecules
TCR
T Cell Receptor
Helper CD4+ T cells will only recognize MHC class (I/II) and become activated
Class II
Cytotoxic “killer T” CD8+ T cells only recognize MHC class (I/II).
Class I
DiGeorge syndrome (22q11.2 deletion) leads to congenital heart disease, defects in the palate, are athymic and effects which immune cells?
T cells
The ____ transcription factor expressed in the medulla of the thymus regulates the expression of tissue specific antigens. Prevents the immune system from attacking itself
AIRE
autoimmune regulator
The sum of all the T cell specificities produced in the thymus is known as the T cell _____
Repertoire
N regions are found in (light chains, heavy chains, both)
Heavy chains only
ALL joining junctions have (P nucleotides/ N nucleotides/ Both)
All joining junction have P nucleotides
Only developing B-cells have N nucleotides
Heavy chains are selected from the gene at the level of (DNA/RNA)
RNA
Progenitor B cells exclusively make Ig____
IgM
The most variable part of the variable region, the part that does the antigen binding is called the _____
CDR
Complementarity Determining Region
The enzyme that brings specific switching regions together to create looping out is called _____
AID
Activation-Induced cytidine Deaminase
O antigen is an endotoxin found on gram negative bacteria and is the outermost part of the molecule _____
LPS
Lipopolysaccharides
The endotoxic part of LPS is the ______ region, made up of a disaccharide of glucosamine
Lipid A
Septic shock is associated with gram (negative/positive) infection
gram negative
An assay that can be used to check for circulating levels of endotoxin is _____
LAL
Limulus Amebocyte Lysate
The most important mediators of the inflammatory response are _____ and _____
Interleukin (IL-1)
and Tumor Necrosis Factors (TNF-α)
LPS stimulates ________ cell type to produce IL-1 and TNF-α, which produce an inflammatory response
macrophages
The primary mediator of septic shock is the molecule ______
TNF-α
The inflammatory molecule ____ has been implicated in arthritis and Crohn’s disease
TNF-α
Mature double positive T cell has both the ___ and ___ markers
CD4 and CD8
A double positive T cell with CD4 and CD8 is type (α:β/γ:δ)
αβ
Each Toll Receptor has (unique/the same) signaling transduction pathway
The same
When a Toll Like Receptor (TLR) engages a target (like LPS) it an intracellular cascade releases the molecule ______, that activates transcription of genes for inflammatory cytokines
NFκB
The TLR4 homodimer on macrophages is great at binding the endotoxin _____ produced by gram ______ bacteria
LPS produced by gram negative bacteria
Cell Apoptosis –> release of ATP into ECM –> High ATP activates ______ –> cleavage of pro-IL-1β –> release of IL-1
capsase 1
Cleavage of the pro-cytokine pro-IL-1β is done by _____ which causes the release of IL-1
capsase 1
The two Super-Antigenic Toxins that mediate toxic shock are _____ and _____
TNF-α and IL-1
The end result of both the classical and alternative pathways is the cleavage of C____
C3
In the complement system, the “b” fragment is bigger except for the molecule C____
C2
C3a, C4a and C5a are all ______, meaning that they cause release of histamine from mast cells and increase vascular permeability
Anaphlytoxins
C5a does ____, meaning that it attracts polymorphonuclear leukocytes and macrophages
Chemotaxis
C3b does _____, meaning that it increases phagocytosis of particles by granulocytes and macrophages
Opsinization
A deficiency in C1, C2, or C4 will lead to ______
immune complex disease
A deficiency in C3 will make you susceptible to ______
encapsulated bacteria
A deficiency in C5 through C9 will leave you susceptible to _______
Neisseria
Deficiency in Factor I leads to similar effects as a deficiency in ____
C3
The C1 complex binds to a single _______ bound on the surface of a bacterium. C1q binds to multiple.
antibodies
C____ is a product of C3 convertase and binds to the bacteria surface and induces bacteria phagocytosis
C3b
C5b, C6, C7, C8 and C9 all work together as part of the _____ pathway which pokes holes in a pathogen
Lytic pathway
A measurement of complement activity: the dilution of serum that lyses 50% of RBCs
CH50
Complement Hemolysis
This receptor on macrophages binds C3b on a bacterial surface as part of the signaling for phagocytosis
CR1
This molecule binds an antibody on a bacterial surface and begins the complement system cascade
C1q
MHC Class (I/II) can bind more residues outside (at either end) of the groove
Class II
MHC class (I/II) is expressed on ALL nucleated cells
Class I
MHC class (I/II) molecules are expressed on a subset of hematopoietic cells and thymic stromal cells
Class II
(αβ/γδ)TCR recognizes an antigen bound to an APC’s MHC
αβTCR
(αβ/γδ)TCR can recognizes a free (natural) antigen, similar to how a BCR works
γδTCR
More MHC diversity makes you (more/less) resistant to infections such as HIV
more
CLIP is Class (I/II)-associated invariant chain peptide that binds MHC class (I/II) groove to prevent the binding of self-peptide fragments
Class II
These can act as bridge between TCR and MHC and stimulate high percentage of T cells without additional co-stimulation.
Super Anitgens
The first immunoglobulin synthesized by a new born is _____
IgM
One of the most important cytokines in the non-specific activation of MACROPHAGES as effector cells of cell mediated immunity is ______
IFNγ
The primary function of the T cell is to monitor the ______ environment of the host cell
intracellular
Somatic mutations (does/does not) take place in T cells
does not
Somatic mutation (does/does not) take place in B cells
does
how antigens are randomized
There is a greater potential for diversity in (immunoglobulin/αβ TCRs)
αβ TCRs
Recognition of specific antigen alone leads unresponsiveness, called ____
Anergy
The major T-cell co-stimulatory molecules found on other immune cells that binds CD28
B7 molecules
The receptor on T cells for the B7 co-stimulatory molecules. Plays a key role in the activation and proliferation of T cells after they first encounter antigen
CD28
The high affinity receptor for B7 molecules on T cell. Role in shutting off the B cell response
CTLA-4
Serine proteases in cytotoxic T cells and NK cells that induce cell death of target cells
Granzymes
A cytokine made by naive T cells essential for their proliferation and differentiation by an autocrine response is _____
IL-2
Interlukin-2
A hematopoetic growth factor secreted by stomal cells in the bone marrow and thymus as well as keratinocytes, dendritic cells, hepatocytes, etc. Important for T-cell development
IL-7
interlukin-7
A protein made by the complement system lytic pathway (C-5 through C9) that drills holes in invading cells
perforin
Bacterial proteins picked up by a dendritic cell will be presented on MHC class (I/II)
Class II
Migration of naive T cells is modulated by mature T cells that express 3 types of molecules, ___, ___ and ___
Selectins, Integrins and Chemokine
To stimulate a T cell, the dendritic cells must present it with matching antigen and co-stimulation by B7 binding _____
CD28
Certain antigens, such as _____ antigens do not require a CD28 co-stimulation
super antigens
Stimulation through CD28 (is/is not) required for naive T cells to become activated
Is required
Production of cytokines IL-12 and INF-γ by macrophages induces this type of T cells to differentiate
Th1 cells
Production of cytokine IL-4 by basophiles induces this T cells to differentiate
Th2 cells
Production of cytokines IL-16 and IL-23 induces this T cells to differentiate
Tfh cells
Production of cytokine TGFβ induces this T cells to differentiate
Treg
T regulatory cells
After killing one cell, a killer T cell (can/cannot) disengage to kill new target
can
T cell activation can be regulated by ______, an inhibitory receptor for B7
CTLA-4
The MHC class I has __α chains and __β chains while class II has ___α and ___β
class I has 3α chains and 1β chain while class II has 2α and 2β
TH1 cells secrete cytokines that induce activation of ______
macrophages
With this diesase, patients do not generate mature B cells manifesting as a complete lack of antibodies in their bloodstream
XLA
X-linked agammaglobulinemia
B cells require stimulation from T__cells to Proliferate, Class switch and Differentiate to plasma cells
Th2 cells
Which type of T cells activate macrophages?
Th1 cells
These T cells help eosinophils, basophils, mast cells, and B cells respond to parasite infections
Th2 cells
Who does this?
- repertoire assembly
- negative selection
- positive selection
- search for infection
- find infection
- attack infection
B cells
A “mature naive” B cells (has/has not) seen antigen
has not
The pre-B cell receptor signals that _____
a functional heavy chain has been made
The two light chain loci used for gene rearrangement are denoted ____ and ____
kappa and
lambda
The first checkpoint for B cells is the _____
pre-B cell receptor check
which checks the heavy chain
The second checkpoint for B cells is ____
light chain check
checks both heavy and light
What is the function of AID?
Involved in double stranded breaks to recombine DNA at switching regions
Produced mostly in the fetus (B1/B2) cells
B1
Secrete mostly IgM (B1/B2) cells
B1
Made in bone marrow (B1/B2) Self regenerating (B1/B2)
Bone marrow B2
Self regenerating B1
What does AIRE do?
causes expression of peripheral genes in thymus to reduce self-reactivity of T cells
B cells are educated about self antigen in the ____ ____
bone marrow
B cells that fail to recognize any self antigen in the bone marrow _____
exit as naive B cells
If a B cells does recognize self in the bone marrow, it can re-express the RAG genes and try again through a process called ______
receptor editing
Class switching for B cells occurs in the ____ of lymph nodes
germinal centers
Interaction with follicular _____ cells drives the final maturation of B cells
dendritic cells
Light chain rearrangement happens at which stag of B-cell development
Pre-B
CR2 (also CD 21) of a B cells recognizes which components of the complement system bound on a pathogen?
iC3b and C3d (derivatives of C3b fragment)
When CR2 recognizes C3b, CR1 comes along and uses _____ to cleave C3b to iC3b and C3d
factor 1
CR2 on B cells binds to ____ after C3b cleavage
C3d
Cognate pairs of T and B cells meet up at the ____ of lymph nodes
boundary regions
of the follicle
T and B cells see their targets differently
T cells see _____
B cells see _____
digested (processed) peptides
native (intact) antigen
Somatic hypermutation occurs in ______
germinal centers
Define Tolerance:
Lack of response to a specific antigen
Tolerance is only relevant for __ and __ cells
T cells and B cells
Anergy is a specific type of ____ where an immune cell does not respond anymore
tolerance
Selection in the thymus involve only the (α:β/γ:δ) T cells and not the (α:β/γ:δ) T cells
Selection in the thymus involve only the α:β T cells and not the γ:δ T cells
Education of T cells in the thymus to prevent auto-immune disease is done by _____
AIRE
Autoimmune regulator
T reg cells can be distinguished by the transcription factor ____
FoxP3
Mutation of FoxP3 can lead to _____
lack of Tregs: autoimmune disease
This T cell is FoxP3+, CD4+ and CD25+.
T reg cells
T cells have (B7/CD28)
CD28
APC cells have (B7/CD28)
B7
CTLA-4 binds (B7/CD28)
B7
If a B cell reacts with self antigen in the bone marrow, it is allowed to try to ______ before it dies
receptor edit
A B cell that sees antigen, but doesn’t get T cell help becomes _____
anergic
The AIRE protein is only in the (thymus/bone marrow)
thymus
Activate cellular and antibody response to parasites (Th1/Th2)
Th2
Most antigens are T (dependent/independent)
depndent
Who is better educated about self and antigens (T/B) cells
T cells
due to AIRE
Feedback that there is too much antibody is mediated though a B cells ____ receptor
Fc
List the mechanisms for inducing immunological tolerance
- functional deletion
- clonal deletion
- clonal anergy
- regulatory T cells
If you blocked all the B7, what would happen?
no immune response could be elicited
Which bacteria can escape a phagosomes? (3)
Listeria
Mycobacter tuberculosis
Mycobacter leprae
(an gonorrhea)
With Mycobacter leprae a Th1 response leads to (tuberculoid/lepromatous) infection
tuberculoid
With Mycobacter leprae a Th2 response leads to (tuberculoid/lepromatous) infection
lepromatous
Without T cells, you are more susceptible to (bacteria/viruses)
viruses
The only way to cure SCID is _____
Bone marrow transplant
X-linked agammaglobulinemia is due to a deficiency in _____
BTK
Bruton’s Tyrosine Kinase
There are two types of NK cells _______ and _____
cytolytic and cytokine producing
NK cells can kill (one/multiple) cells at a time
one
IL___ and IL___ both activate NK cells
12 and 15
NK cells express TLR numbers __, __ and __
3, 7,and 8
the CD94:NKG2-A on NK cells interacts with _____ to prevent and NK cell from attacking a healthy cell
HLA-E
In order for HLA-E to get out of the ER and to the cell surface it must have a ____ attached to it
leader protien
Expression of MIC and CD48 on the surface of an infected cell tells the NK cell to ____
kill the infecetd cell
Education for NK cells happens in the _____
bone marrow
Killer Inhibitor Receptor (KIR) on NK cells allows them to recognize ______
HLA molecules (A, B or C)
A special role of NK cells is in controlling ____ virus infection
cytomegalovirus (CMV)
Class switch recombination is IL___
IL4
Peripheral T cell homeostasis is IL___
IL2
Abnormal embryonic development of the 3rd and 4th pharyngeal pouches is associated with _____ syndrome
DiGeorge
AIDS results in a loss of ____ T cells
CD4+
A compound that increases the immunogenicity of an antigen is called a _____
adjuvant
The use of immune serum to give an immediate resistance to infection is called _____
Passive imunization
A weakened virus that can replicate to a limited extent is called a _____vaccine
Live attenuated
The actofimmunizingwithantigenstoinduceanimmune response to a pathogen
Active immunization
CD94:NKG2-C is activating NK cell for control of _____ virus
cytomegalovirus (CMV)
A class of antigens that cause non-specific activation of T-cells, resulting in polyclonal T cell activation and massive cytokine release
Super Antigen
Which Th cells is associated with asthma (Th1/Th2)
Th2
Activated macrophages secrete IL__ and TNF__ to induce an inflammatory response
IL1 and TNF alpha
An uncommitted T cell progenitor expresses CD__
34
Cells that lack HLA-E are ____ ____
virally infected
Cells that are virally infected do not express HLA-E and express ____ instead
MIC
NK cells recognize HLA (A,B,C) via their ___
KIR
Killer inhibitory response
IL__ from macrophages Induces fat and muscle to increase metabolism, raise body temp
IL-6
IL___ from macrophages recruits activated NK cells
IL-12
the enzyme AID is only expressed in ___ cells
B cells
IL 4,5,6 are associated with (Th1/Th2)
Th2
CD2 is found on the surface of ____ cells and ____ cells
T cells and NK cells
Leader peptides from HLA A,B and C get stuck onto HLA-___
HLA-E
HLAs corresponding to MHC class ___
MHC class I
A Th1 response leads to activated _____
macrophages
