Immuno Quizzes
List the 4 levels of immune barriers
1. Anatomic barriers 2. Complement/antimicrobial proteins 3. Innate immunity 4. Adaptive immunity
Name the 3 complement pathways
1. Complement 2. Lectin 3. Alternative
What are 4 TREG methods of regulation?
1. Cytokine deprivation 2. Cytotoxicity 3. Inhibiting APCs 4. Inhibitory cytokines Using FOXP3 There is feedback inhibition between the T-cell subtypes
What are the 2 ways cytotoxic T-cells (CD8+) kill target cells?
1. FAS pathway (caspase apoptosome) 2. Perforin/granzyme pathway
What are the 3 effector mechanisms of the complement system?
1. Membrane attack complex formation (MAC) 2. Recruitment of inflammatory cells (inflammation) 3. Opsonization
What 2 types of white blood cells are the most abundant? How long do they live
1. Neutrophils (short) 2. Lymphocytes (long)
Name the 3 effector functions of antibodies
1. Opsonization 2. Neutralization 3. Complement activation
What are the 4 stages of Leukocyte trafficking?
1. Rolling (L-selectin) 2. Activation (CCL21) 3. Adhesion (LFA-1) 4. Diapedesis (CCL21/CXL12)
What occurs during pre-TCR signaling (beta selection)
1. Survival signaling- TCR alpha chain locus rearrangement begins 2. Stimulates CD4 and CD8 expression 3. Stimulates proliferation 4. Stops additional TCR beta-chain locus rearrangements (allelic exclusion) -Turns off pre-T alpha expression -Turn off RAG1&2
What are the 3 ways to prime T-cells
1. TCR signaling w/ MHC + antigen 2. Co-stimulatory interaction (B7 w/ CD28) 3. Cytokine signaling between APC and naive T-cell
Name the 5 classes of infectious agents
1. Viruses 2. Bacteria (intracellular and extracellular 3. Archaea, Protozoa 4. Fungi 5. Parasites - helminths/worms
Which one of the following mechanisms that generate variation in B cell receptor specificity DOES NOT rely on changes to the DNA within the B cell receptor heavy and light chain genes? A. The contributions of amino acids from both the heavy chain and the light chain to form the antigen-binding site. B. The activity of Tdt to add random nucleotides at the junctions between the V, D, and J region sequences C. Heavy chain V regions contain an extra gene segment encoded by the D region compared to light chain V regions D. The random rearrangement of V, D, and J gene segments to form the heavy chain variable region sequence
A (I think b/c it is about DNA not amino acids)
cGAS can act as what?
A dsDNA sensor during viral infection (eventually turns on IRFs)
An individual with a defect in which of the following cells/genes would have an absence of T-cells but have the normal amount of mature B cells? A. Thymic stromal epithelial cells B. Terminal deoxynucleotidyl transferase (TdT) gene C. Hematopoietic stem cells D. RAG1 and RAG2 genes
A.
MAC can form on the surface of bacteria as a result of complement activation. Which one of the following about the MAC is true: A. C9 is the complement factor that forms pores on the bacterial membrane B. The C5 convertase cleaves C3 to produce C5a and C5b which will initiate the MAC formation C. All are true D. MAC uses defensin proteins to form a pore on the bacterial membrane.
A.
Part of the requirement for B cell proliferation and differentiation in the germinal center is the periodic interactions with Follicular T helper cells. At which one of the following locations does this interaction between the germinal center B cells and Tfh cells occur? A. When B cells cycle between the dark zone and the light zone of the germinal center B. When B cells upregulate B7 and migrate towards the bone marrow C. When B cells leave the germinal center and migrate through the T-cell zone on their way to the blood D. When B cells up-regulate CXCR4 and migrate into the dark zone of the germinal center
A.
Pathogens that infect mammalian organisms have several advantages against their hosts. Which of the following describes one of these advantages? A. Pathogens divide and evolve faster than their hosts B. Pathogens strengthen the host immune system C. Pathogens evolve and divide slower than their hosts. D. Pathogens have been previously encountered as a result of vaccination
A.
Unlike antibodies, TCRs don't recognize free antigens by themselves. This recognition system has evolved so that the small piece of degraded proteins (peptides) displayed on MHC molecules are displayed on the cell surface. These peptides can be derived from intracellular proteins. Which of the following types of infections can this form of the adaptive immune system detect? A. Intracellular infectious agents like viruses B. Extracellular bacterial infections in the lungs C. Infections by large parasites like helminths that colonize the GI tract D. Fungal infections under the skin
A.
Upon binding to their PRRs TLRs that reside in the plasma membrane induce a different pathway leading to the production of different cytokines by the cell. Which one of the following molecules is produced as a result of the stimulation of nucleic acid sensing TLRs? A. The antiviral cytokine, type 1 interferon B. Antimicrobial peptides by macrophages C. C3a and C5a D. TNR-alpha which induces increased vascular permeability E. chemokines that recruit neutrophils
A.
Which of the following processes that describe Ig light chain gene rearrangement can happen after reactivity to self-antigen in the bone marrow during the development of B-cells? A. Receptor editing B. Somatic hypermutation C. Clonal energy D. Chromosomal translocation
A.
Which one of the following accurately describes events that allow allelic exclusion to happen at the immunoglobulin heavy chain? A. RAG1 and RAG2 expression is down-regulated and TdT activity is lost to prevent additional heavy-chain rearrangements B. RAG1 expression is up-regulated while RAG2 and TdT expression is down regulated to prevent heavy-chain recombination on the second set of chromosomes C. TdT expression is upregulated to start light-chain rearrangement D. TdT expression leads to release of a cytokine that triggers apoptosis in the pre-B cell
A.
Which one of the following mechanisms that generate variation in the B-cell receptor specificity DOESN'T rely on changes to the DNA within the BCR heavy and light chain genes? A. The contributions of amino acids from both the heavy chain and the light chain to form the antigen-binding site. B. The activity of TdT to add random nucleotides at the junctions between the V, D, and J region sequences C. Heavy chain V regions contain an extra gene segment encoded by the D region compared to light chain V regions D. The random rearrangement of V, D, and J gene segments to form the heavy chain variable region sequence
A.
Which one of the following statements about T cells is correct? A. IL-2 triggers T-cell proliferation B. CD28 binding to B7 generates double positive T-cells in the lymph nodes C. TNF-a increases the production of IgM by activated T-cells D. CD8 triggers apoptosis in T-cells that recognize self-antigens
A.
Which one of the following statements best describes the functional purpose of somatic hypermutation in B cells? A. Increasing the affinity of immunoglobulins for their antigen B. Irreversibly changing the immunoglobulin isotype C. Increasing junctional diversity in heavy and ight chain variable regions D. Promoting alternative splicing of a B cell receptor heavy chain transcript to produce different isotypes on the B cell surface
A.
You are following the development of a T-cell in the thymus. This T cell is now at the double negative stage and you found out that it completed the rearrangement of the beta chain, which of the following describes what happens right after? A. A pre-T-cell receptor is assembled B. The linked gamma-chain genes are eliminated via recombination C. This cell will inevitably differentiate into a committed gamma delta T-cell D. Expression levels of RAG1 and RAG2 are increased
A.
You isolated a specific form of naïve T cell from a transgenic mouse that has a T cell receptor that is specific for a peptide: MHC complex from the influenza virus. You can stimulate these naïve T-cells with peptide: MHC tetramers that are specific for their TCRs, they show the appropriate activation responses such as the up-regulation of genes that are typically induced after TCR stimulation. However, these activated T cells fail to undergo robust proliferation, and the majority of them die within 3-4 days in culture. You can increase the proliferation and survival of these by adding: A. B7 ligands for CD28 B. Antibodies to the T-cell receptor C. Anti-inflammatory cytokines D. Toll-like receptor ligands E. The integrin LFA-1
A.
Which of the following statements about T-cell development is false? A. If alpha-chain rearrangement is successful, it is still possible to produce a committed gamma: delta T-cell B. Neither gamma nor delta chains associate with pre-T-alpha C. T-cell development is biased in favor of alpha: beta lineage commitment D. gamma and delta rearrangements may occur at 2 different stages, once the committed double negative stage and again at the uncommitted double positive stage
A. False b/c the delta locus is eliminated after alpha-chain rearrangement
TFH cells do what?
Activate B-cells for maturation of antibody response Causes B-cells to differentiate to plasma cells and release IgG that targets all types of microbes
RIG-1 Like Receptors (RLRs)
Activate IRFs and NFkB
TH1 cells do what?
Activate macrophages by enhancing phagocytosis Good for intracellular bacteria & protozoa
TH2 cells do what?
Activate responses against parasites (ex: helminths) B/c macrophages cannot eat big parasites so toxic molecules need to be used to kill them, along with increased mucus and peristalsis
The APC-T-cell interaction kinase cascade does what
Activates genes that regulate survival, proliferation, and effector function (differentiation) TFs: AP-1, NFAT, NF-B
What does IgE do?
Activates mast cells to release histamines via cross-linking of multivalent antigen Lowest concentration in blood
What is IgM very important for?
Activation of the complement system b/c it binds to C1q
When does T-cell selection begin?
After alpha chain rearrangement
When does CD4/CD8 induction begin?
After beta chain rearrangement
When do pre-cursors commit to the T-cell lineage?
After notch signaling in the thymus via thymic stromal cell This initiates antigen receptor gene rearrangement Same self antigen testing & self-reactive removal as B-cells
Discuss T-cell receptor loci diversity in the context of alpha and beta chains
Alpha chain- has VJ and C Beta chain- has VDJ and C
What is AIRE
An autoimmune regulator (transcriptional factor) that allows for the expression of tissue-specific proteins in the thymus (i.e retina or ovaries) Allows for the deletion of tissue-reactive T-cells in the thymus Absence of AIRE causes autoimmune disorder b/c tissue-specific antigen exposure is absent in mature T-cells
T-cells that bind to Non-APC MHC become?
Anergic due to the absence of other signals (co-stimulatory and cytokines)
What is a secreted form of the BCR?
Antibody
How do B-cells come in contact w/ foreign antigens?
Antigens are delivered to lymph nodes via afferent lymphatics, transferred to macrophages, given to FDCs and presented to B-cells
Apoptosis vs. Necrosis
Apoptosis is natural and does not cause inflammation Necrosis is always pathological and causes inflammation
Receptor editing of the light chain
B-cell development is arrested and light chain is rearranged until a new specificity is produced If the new receptor is still self-reactive the cell undergoes apoptosis If the new receptor is no longer-self reactive the immature B-cell migrates to periphery to mature *HC does not undergo RE
B and T-cells find each other via various cytokines and receptors, what 2 important receptors are on the respective cells.
B-cells have CXCR5 T-cells have CCR7
APECED is an autoimmune disease that presents with multi-organ damage and recurrent fungal infections. Which one of the following describes the mechanism that leads to the development of APECED? A. AIRE is mutated so self-antigens were NOT expressed in the bone marrow B. AIRE is mutated so self-antigens were NOT expressed in the thymus C. AIRE is mutated so self-antigens were expressed in the bone marrow D. AIRE is mutated so self-antigens were expressed in the thymus
B.
Antibodies can exert all of the following effector functions except: A. acting as opsonins that mediate phagocytosis B. Exerting cytotoxic effects on infected cells through the release of cytotoxins C. Neutralizing viruses by binding to their surface D. Activating complement fixation
B.
Bonds formed between the T-cell and dendritic cell are relatively weak. So, which of the following help to strengthen this association? A. CD28/LFA-5 B. ICAM-1/LFA-1 C. IL-2R D. Pattern Recognition Receptors (PRRs)
B.
During the class switch recombination process, there are 2 key features that direct AID to the specific switch region. One of these is the stalling of RNA polymerase during transcription. Which one of the following correctly describes the other key feature that allows AID to be directed to the switch region? A. The binding of AID to the RNA polymerase that is transcribing the switch region B. The processed RNA from the switch region forms a quadruplex and guides AID to this site in the DNA C. The presence of double-stranded breaks in the DNA in this region D. The excessive amounts of G-C base pairs in the switch sequence
B.
Toll Like Receptors (TLRs) are a family of Pattern Recognition Receptors (PRRs). Which of the following statements is TRUE about the TLRs A. TLRs genes can be rearranged to make multiple variants B. TLRs can be found on the plasma membrane or endosome in the cells C. TLRs are key molecules of the adaptive immune system D. TLRs are restricted to NK cells and are not found in mother other immune cells
B.
Which of the following best describes what happens to immature B-cells that are self-reactive in the bone marrow? A. They will leave the bone marrow and change the autoreactive BCR in the lymph node B. They are prevented from leaving the bone marrow and have the ability to change the autoreactive receptor C. They can leave the bone marrow but killed via apoptosis in the blood stream D. They will kill the cells in the bone marrow
B.
Which of the following cells is NOT descended from the common lymphoid progenitor: A. B-cells B. Macrophages C. T-cells D. NK cells E. All originate from CLP
B.
Which of the following is FALSE about inflammation at an infection site? A. Gaps will form between endothelial cells to allow for the movement of fluid and cells B. There will be decreased adhesiveness of immune cells to endothelial cells C. Immune cells will extravasate into connective tissue D. Vasodilation will lead to increase in the volume of blood at the infection site
B.
Which of the following statements about T cell development is correct? A. None of these statements are correct B. In adult humans the mature T-cell repertoire is self-renewing and long-lived and does not require a thymus for the production of new T cells C. Both T and B cells are short-lived cells and require continual replenishment from primary lymphoid organs D. The human thymus is not fully functional until age 30, at which it begins to shrink and atrophy
B.
Which of the following statements is FALSE about the anatomical barriers of the innate immune system? A. Mucus is a thick fluid layer that contains glycoproteins and enzymes that is involved in the prevention of infection B. Genetic changes are a type of anatomical barrier defense that ensures bacteria are eliminated from the body before establishing an infection C. Skin can act as both a chemical and physical barrier against pathogens D. Pathogens enter the body via multiple places covered by the skin
B.
Which one of the following pair of antibody isotypes are the best at complement activation? A. IgD and IgG B. IgM and IgG C. IgG and IgE D. IgM and IgA
B.
Which one of the following statements is correct regarding how B and T-cells recognize antigen A. T-cell receptors can bind antigen only after secretion of the TCR from the surface of the T-cell B. T-cells recognize peptides bound to MHC molecules C. TCRs can bind to carbohydrate groups of clusters of amino acids D. Antibodies can only bind to denatured proteins
B.
Why do B-cells mature in the bone marrow?
B/c they need constant survival signals from things like epithelial stromal cells and IL-7
What are the 2 important co-stimulatory molecules for TCR activation and inhibition?
B7 --> (+) CTLA-4 --> (-) Both bind to CD28
Why is there no V to J joining in the heavy chain?
Because of the 12-23 rule (?)
Where is the immunological synapse?
Between the T-cell and the dendritic cell (APCs)
The invariant chain does what?
Binds to MHC 2 and leaves behind a CLIP molecule post cleavage to block binding of peptides and misfolded proteins HLA-DM released CLIP and allows other peptides to bind
During positive selection of T cells, if the double positive T-cell successfully interacts with MHC class 1 molecule presenting self-antigen, which of the following is most likely to occur? A. Gene expression of CD4 is enhanced B. This T cell differentiates into a CD4 T cell C. The thymocyte (T-cell) is committed to the CD8 lineage D. Gene expression of CD8 is halted
C.
Junctional diversity during antibody and T-cell receptor gene rearrangement results from the addition of A. mRNA splicing B. Mutations in the hypervariable loops C. P and N nucleotides D. VDJ recombination
C.
What is the primary function of the complement proteins that act in the early stages of complement activation? A.Induce the secretion of complement proteins to extracellular locations B. Extend the serum half-life of complement proteins by stabilizing them C. Ensure that C3b is deposited on the pathogen surface D. Regulate the expression of complement proteins
C.
When a dendritic cell is activated upon PAMP binding which of the following does NOT happen? A. Migration to the T-cell regions of the lymph node B. Upregulation of MHC class 2 at the cell surface C. Loss of antigen processing functions D. Expression of T-cell co-stimulatory molecules such as B7
C.
When a naïve T cell recognizes its antigen on an MHC without co-stimulatory signals, this leads to: A. Upregulation of B7 receptor B. Expression of high affinity IL-2 receptor C. T cell anergy D. T cell death
C.
Which of the following is a characteristic of follicular dendritic cells? A. They are bone marrow-derived hematopoietic cells B. They produce cytokines that induce B-cells to proliferate and become centroblasts C. They provide a stable depository of intact antigens able to bind to B-cell receptors D. They act like APCs and express MHC 2 on their surface
C.
Which one of the following is the correct path of T cell development? A. Thymus --> Bone marrow --> spleen B. Bone marrow --> Lymph nodes --> Thymus C. Bone marrow --> Thymus --> Lymph nodes D. Thymus --> Bone marrow --> Thymus
C.
You generated a mouse deficient in all MHC class 1 genes. Which one of the following would correctly describe the T cell receptors of this mouse? A. Only double positive T cells would develop B. Only double negative T cells would develop C. CD4 positive T-cells would develop, CD8 positive T cells would not D. CD8 positive T cells would develop, CD4 positive T cells would not E. No T cells would develop
C.
Which of the following statements about antibodies is TRUE? A. Antibodies can only bind to linear epitopes B. There are 8 CDR (complementarity determining region) loops in a single light chain of an antibody C. Each chain of an antibody contains multiple immunoglobulin domains D. The antigen binding site of an antibody is composed of only 2 heavy chain variable regions
C. (I think)
Which one of the following immunodeficiencies would you expect to be the result of inactivating mutations in the gene encoding AID? A. MHC Class II deficiency B. X-linked agammaglobulinemia (lack of B-cells) C. Hyper IgM snydrome D. Hyper IgE syndrome
C. B/c of the lack of class switching
Which one of the following would best explain why IgM is particularly efficient at fixing complement? A. IgM is much larger than the other isotypes B. IgM has an extra CH domain C. IgM has 5 binding sites for C1 D. IgM is made first in an immune response and thus has first access to C1
C. I think
What are the co-receptors on the TCR?
CD3 that has ITAMs
CD4 Cells interact with MHC on what cells ? CD8?
CD4 interacts with MHC 2 on APCs to activate Th cells CD8 interacts with MHC 1 on target cells (that get killed)
What do CD8 T-cells do? What do CD4 T-cells do?
CD8 = cytotoxic T-cells, kills target cells via DNA fragmentation, activates macrophages CD4 = T-helper cells, recruits macrophages and other cells to help fight infection
Systematic inflammatory cytokines can do what?
Cause death by decreasing blood volume and the vessels collapsing This can cause wasting and organ failure
What happens when L-selectin and ICAM-1 interact?
Causes a conformational change to increase affinity and strengthen binding
What is the process of removing self-reactive lymphocytes?
Clonal deletion/selection
How does the complement distinguish self vs. non-self?
Complement inhibitors are expressed and block complement activation DAF and MCP --> disrupt C3 convertase CD59 prevents pore formation by the MAC complex before C9 binds
What cells positively select T-cells in the thymus and what cells negatively select?
Cortical epithelial cells --> (+) Tight binding good Weak binding bad (apoptosis) Other cells like APCs --> (-) Tight binding bad (apoptosis) Moderate binding good
How do B-cell receptors signal?
Cross-linking via foreign antigen binding to multiple BCRs and phosphorylation of each other using IgA + IgB ITAM bound kinases
Approximately 1/2 of the developing B-cells die via apoptosis during the pro-B cells stage. This massive loss of pro-B cells is due to which of the following? A. Insertion of too many nucleotides into the leader region of the V segments by TdT B. The failure of half of the pro-B cells to upregulate RAG1 and RAG2 and commit to the B-cell lineage C. The inability of the pro-B cells to rearrange V and J segments in the immunoglobulin light chain genes D. The failure of the pro-B cell to make a complete immunoglobulin heavy chain protein
D.
Complement activation can lead to the activation of various effector mechanisms to eliminate the targeted pathogen. Which of the following does NOT describe one of the effector mechanisms of complement activation? A. Pathogen membrane perforation B. Opsonization of the pathogen C. Recruitment of immune cells D. Construction of blood vessels leading to the infection site
D.
Current hypothesis regarding the evolution of T-cells indicates that innate response and antibodies together are not sufficient to detect and clear intracellular pathogens. This is due to the ability of T-cells to detect intracellular microbes based on their ability to: A. Activate macrophages to induce inflammation B. Express PRRs in the cytoplasm that can detect intracellular infections C. Secrete cytokines that can enter into the infected tissue D. Recognize pathogen-derived peptides on host MHC molecules
D.
During pregnancy some of the antibodies can be transferred from the mother to the fetus. Which one of the following is correct about this process? A. IgG antibodies transferred to the fetus via mammary glands B. IgA antibodies are secreted from the mammary glands into the blood stream and transferred via high endothelial venules C. Before birth, the fetus is directly connected to the mother's vascular system and has direct access to all of the antibodies in the mother's blood stream D. IgG antibodies are transferred from across the placenta to the fetus
D.
Our immune system contains 3 different types of antigen presenting cells including B-cells, dendritic cells, and macrophages. These cells present peptides to CD4 T-cells via MHC class 2 molecules. Which one of the following enzyme and enzymatic pathways is most likely to be utilized by the APCs to degrade the proteins and generate MHC class II peptides: A. Ubiquitin ligases that tag proteins for degradation by the proteosome B. The lysosome-associated membrane trafficking protein, LAMP-2 C. ATP transporter proteins that deliver endocytic proteins into the cytosol for degradation D. Cysteine proteases like cathepsins that function at acidic pH
D.
Primary lymphoid organs are defined as locations in the body where lymphocytes _______, while secondary lymphoid organs are sites where lymphocytes _______. A. are stimulated; develop and mature B. undergo clonal selection; differentiate from hematopoietic stem cells C. die, are phagocytosed after death D. develop and mature; become stimulated
D.
Which of the following is true about the complement system: A. Both C5a and C3a are anaphylatoxins that help recruit immune cells B. Phagocytosis is facilitated by the binding of complement receptors to C3b C. The MAC will cause the formation of pores on the bacterial membrane D. All of the above
D.
Which of the following statements best describes the functional purpose of somatic hypermutation in B-cells: A. Increasing junctional diversity in heavy and light chain variable regions B. Irreversibly changing the immunoglobulin isotype C. Promoting alternative splicing of a B-cell receptor heavy chain transcript to produce different isotypes on the B-cell surface D. Increasing the affinity of immunoglobulins for their antigen
D.
Which one of the following T helper cell responses would be best when dealing with a helminth (extracellular parasite infection) A. Th1 cells will release cytokines that will help by increasing inflammatory mediators in the gut B. Th1 cells will release cytokines that will help by decreasing cell turnover so the helminths will be stuck to host cells C. Th2 cells will release cytokines that help to expel the worm by decreasing smooth muscle contraction D. Th2 cells will release cytokines that will help to expel the worms by increasing mucus production
D.
Which one of the following domains are commonly found in both TLRs and NLRs and used in PRR recognition: A. Variable extracellular domain B. Caspase-recruitment domains (CARD) C. C-type lectin domain (CTLD) D. Leucine-rich repeat regions (LRRs)
D.
Which one of the following is TRUE about the Pre-B cell Receptor: A. It is composed of fully rearranged immunoglobulin heavy chains and the VJ region of a rearranged light chain B. It does not require signaling via Ig-alpha and Ig-Beta C. It is expressed at very high levels on the surface of the pro-B cells D. It signals w/o binding a foreign antigen
D.
Which one of the following statements about T cell priming and activation is NOT correct? A. T cell activation happens in many locations including, but not limited to the lymph nodes, Peyer's patches, and the tonsils B. T cell activation transforms naïve T cells into differentiated effector T-cells C. T cell activation requires interaction between naïve T-cells and antigen presenting cells (APCs) D. T cell activation primarily occurs in primary lymphoid organs
D.
You are performing an experiment using naïve B cells from a patient to induce a switch from the production of IgM antibodies to IgE antibodies. You stimulated these cells with an antibody against CD40 and the cytokine IL-4. In the lymph node of an individual undergoing an immune response, these signals would normally be provided by which of the following? A. Germinal center stromal cells B. Follicular dendritic cells C. Other B cells in the germinal center D. Tfh cells in the germinal center
D.
You decided to generate a knockout mouse line that has the receptor CXCR5 deleted only in the T cells. The ligand for this receptor is CXCL13 which is secreted by the follicular dendritic cells that reside in the B cell zone of the lymph nodes. Which one of the following would you expect to see in this mouse? A. No defects in any type of antibody response B. A lack of discrete B and T cell zones in the lymphoid organ C. An increased number and size of germinal centers D. A defect in T-cell dependent antibody responses
D.
Which of the following steps is NOT involved with cytotoxic T-cell activation and function? A. Perforin and granzymes are released triggering apoptosis of infected cell B. Fas-FasL signaling pathway is activated triggering apoptosis C. Antigen presented with MHC class 1 is recognized by the T-cell D. Histamine is released from cytoplasmic granules recruiting macrophages to the site of infection
D. B/c apoptosis does not trigger inflammation (macrophage recruitment)
Some self-reactive B-cells can escape selection in bone marrow but are eliminated or inactivated after they leave the bone marrow. Which of the following best explains the reason behind this mechanism? A. Immature circulating B-cells are more sensitive to antigen stimulation than the developing B cells in the bone marrow B. Circulating immature B cells do not encounter tissue-specific antigens in peripheral organs and tissues C. Immature B cells are trapped in the bone marrow by strong B-cell receptor crosslinking D. Not all self-antigens are expressed or present in the bone marrow during B cell development
D. (I think) could be A?
At what stage does V to J and V to DJ recombination occur in T-cells?
DN2 Pro-T cells Allows for pre-TCR to form RAG1/2 activated at the end of DN2
Survival signaling in Pre-B cells via IL-7 leads to
Decreased RAG1/2 activity Decreased VDJ recombination - Allelic exclusion Decreased Pre-BCR and IL-7 signaling Decreased proliferation Eventually RAG1/2 are turned on so light chain VJ gene rearrangement occurs
What cells link adaptive and innate immunity?
Dendritic cells
What cells are the main APCs for T-cells vs. B-cells?
Dendritic cells for T-cells Follicular Dendritic cells for B-cells (not actually dendritic cells) These cells cause B and T cells to migrate to their respective areas in the lymph
Inflammatory cytokines released from macrophages do what?
Dilate small local blood vessels (allows for more cells to enter) Cause fever (systematic)
What do TLRs do to function?
Dimerize - this allows for inflammatory and interferon genes to be expressed TLR signaling activates interferon regulatory factors
APECED
Disorder that causes a bunch of bad things like dry skin, organ problems, diabetes, lots of autoimmune stuff -Absence of AIRE
Delta: gamma T-cells
Either the beta chain or delta and gamma chain will rearrange Delta-gamma T-cells will form a DG TCR and commit to this lineage (still DN) - NOT pre-TCR in this case There are 2 chances to commit to this lineage, once before the beta chain rearranges and once after beta chain during alpha, gamma, and delta rearrangement Alpha chain rearrangement always eliminates delta locus
How to defensins work
Electrostatic attraction allows them to enter the transmembrane space and form a pore to lyse the bacterial cell Defensins have high affinity for bacteria compared to our cells
Where do MHC class 2 peptides get their peptide fragments?
Endocytic vesicles Take up antigen using receptor mediated endocytosis These receptors are recycled
What cells express L-selectin and what does it interact with?
Endothelial cells or APCs, it interacts with ICAM-1
TH17 cells do what?
Enhance neutrophil response For extracellular bacteria, fungi
What are specific sections of the antigen in which antibodies bind to known as?
Epitope
Neutrophil Extracellular Traps (NETs)
Extracellular fibrillar networks produced by neutrophils in response to infectious agents - Contain a *framework of nuclear chromatin* with *embedded granule proteins. * - Prevent the spread of microbes by *trapping* them in the fibrils. - Loss of neutrophilic nuclei ---> death of neutrophil (suicide)
T/F: Allelic exclsuion only happens in the heavy chain of B-cells
False
T/F: Developing B-cells turn on RAG1 and RAG2 expression in the pro-B cell stage and continuously express these proteins until the B-cell maturation is complete in the bone marrow.
False
T/F: During T-cell development large numbers of cell die via apoptosis in the thymus. These apoptotic cells are ingested by the medullary epithelial cells.
False
T/F: T-cells originate from a precursor in the thymus that migrates to the bone marrow.
False
T/F: VDJ recombination happens only in the presence of an antigen.
False
T/F: complement activation can be amplified by the action of C3 convertase that directly cleaves large numbers of C5 molecules
False
True or false: VDJ recombination requires the presence of foreign antigen to occur
False
T/F: the alpha chain of the TCR undergoes allelic exclusion.
False This allows for T-cells to express either dual or single receptors
T/F: Expression of MHC class 1 antigen presentation on the cell membrane is dependent on the cell having a large number of pathogen-derived peptides. Therefore, in cells that are not infected by a pathogen, almost all of the MHC class 1 proteins are degraded and none of them reach the cell surface.
False (I think)
Germinal centers what are they
Foreign antigen activated B-cells go here, they form a germinal center around the FDCs SHM and CSR occur at germinal centers
How to mature B and T-cells enter the lymph nodes?
High endothelial venules (HEV)
What is the T-cell growth factor/enhancer?
IL-2
The naive B-cell expresses what immunoglobulin?
IgM
Heaviest antibody isotype? Most common?
IgM (largest b/c pentamer)- has no SHM so it makes a lot of binding regions IgG b/c they are good at all antibody functions
Define Central Tolerance
Immature self-reactive T or B cell clones that recognize self-Ag are eliminated during development. - Negative selection in thymus - Receptor editing in bone marrow or clonal deletion However. some self-reactive cells escape these processes
Where does negative selection of self reactive B-cells occur?
In the bone marrow (the B-cells that bind to cell surface antigen)
NOD-Like Receptors (NLRs)
In the cytoplasm and activate when bacterial ligands bind to them NLRs activate NFkB
What do hyper variable regions (CDRs) in the heavy & light chains of BCR variable regions do?
Increase specificity and determine the binding specificity of antibodies
What branch of the immune system are dendritic cells?
Innate
Compare and contrast innate vs. adaptive immunity recognition mechanisms
Innate is rapid (in hours), fixed, and limited specificity, constant magnitude during response Adaptive- slow (days to weeks), variable, numerous highly selective specificities improve during response
MHC 1 is for _______ antigens while MHC 2 is for _______ antigens.
Intracellular (endogenous), extracellular (exogenous)
What is allelic exclusion's job?
It allows homogenous B-cell receptors to have high affinity binding because only 1 type of immunoglobulin will be expressed
What does the TAP protein do?
It allows peptide fragments to enter the ER from the cytosol for MHC 1 presentation
As the number of T-cells decreases what happens to the TCR's affinity for self-MHC antigens?
It increases
Rearrangement of Light chain genes starts at ____ and moves to _____ if no viable receptor is made. If no successful receptor is made overall then what happens?
Kappa --> Lamba Apoptosis
B-cell receptor loci: Name light chain segments Name heavy chain segment
LC: VJ HC: VDJ Both have C
What integrin/Adhesion molecule initiates contact between T-cell and APC?
LFA-1 on the T-cell ICAM on the dendritic cell Causes conformational change for tighter binding and signal cascade of kinases
DiGeorge Syndrome
Lack a thymus
Which T-cells recognize which MHCs
MHC 1 --> CD8+ (Cytotoxic) MHC 2 --> CD4+ (T-helper)
Comment on differences between MHC 1 and 2 expression
MHC 1 expression is ubiquitous MHC 2 is selectively expressed on antigen presenting cells (APCs) such as dendritic cells, macrophages, and B-cells
If you eliminate MHC 1 what happens to the population of T-cells? What happens w/ MHC 2 elimination?
MHC-1 removal causes only CD4 T-cells to be develop MHC-2 removal causes only CD8 T-cells to develop
Who are the 2 first responder cells to infection?
Macrophages (tissue resident) Neutrophils (circulate in the blood)
Important IgG functions
Neutralization, Complement activation, opsonization Crosses the placenta at high concentration before birth and decreases after birth until the infant starts making its own
Name the types of phagocytic cells
Neutrophils Macrophages Dendritic cells
What does IgD do?
No known function- they think it activates B-cells Used as cell marker
Non-productive rearrangement at the light chain can be rescued using
Other copies of V or J genes
CD4+ T-helper cell differentiation
PAMPs from pathogens recognized by PRRs on APCs cause the release of polarizing cytokines to bind to STATs and differentiate T-cells
Pattern Recognition Receptors (PRRs) self vs. non-self
PRRs are on the surface of macrophages & neutrophils and they will bind to microbes + their components (not our cells) These get internalized and broken down in the phagolysosome (acid, toxic oxygen products, toxic nitrogen oxides)
TLRs are a type of what and what differentiates them?
Pattern Recognition Receptors They are on the plasma membrane and the endosome They bind to different things like RNA - making the endosome useful for viral detection
Activation Induced Cytidine Deaminase (AID) does what?
Performs SHM and CSR Attacks single stranded DNA and makes quadraplex to guide AID to transcribed switch region to initiate cytidine deamination Converts C to U in mutations
What does the surrogate light chain allow for?
Pre-BCRs to signal, cluster, and proliferate Signaling thus leads to survival
What do T-cell receptors need to activate?
Presentation of antigen by the MHC
Primary vs. Secondary Lymphoid organs
Primary = bone marrow and thymus Secondary = GALT, lymph nodes, spleen Primary is where development begins and secondary is where they mature.
List the T-cell development phases and the status of the TCR receptor as well as CD proteins.
Pro-T-cell: DN(2-) Pre-T-cell: DN(2-) - Pre-TCR forms Immature T-cell: DP(2+) - Both CD4 and CD8 present - Eventually functional TCR forms Mature T-cells: SP(1+) Have TCR and either CD8 or CD4
IgA functions
Protects against mucosal pathogens in the gut lumen (Dimeric) Can be transferred by the mother to child through breast milk (mammary glands)
4 main enzymes involved in VDJ recombination. Briefly explain their roles
RAG 1 and 2, Artemis, TdT RAG1/2 cleaves the RSS, eventually they form a hairpin Artemis opens the hairpin forming Palindromic (P) nucleotides. Tdt adds random N nucleotides to cause imprecise joining P -- N -- P The addition of random nucleotides at each VDJ joint causes non-germline amino acids to be coded for in TCR chains
Somatic Hypermutation (SHM) vs. Class switch recombination CSR
SHM- targets rearranged gene segments encoding the Ig variable regions to produce high affinity antibodies CSR- changes in splicing allow for antibody isotype swapping? --> for DS breaks
Where are B-cells activated?
Secondary lymphoid tissue by foreign antigen Give rise to plasma cells and memory cells
What is the most common primary immunodefieiency?
Selective IgA deficiency
What does S1PR1 do?
Signals mature T-cells to leave the thymus and travel to secondary/peripheral lymphoid organs through the bloodstream
B-cell anergy
Some B-cells will bind to soluble self-molecules in the periphery These cells turn themselves off, they remain in the system to bind to PAMPs in the future (hypothesis)
Why are antibodies and innate immunity not sufficient responses for immunity?
Some cells are infected by intracellular pathogens that can escape these extracellular mechanisms
BCR is generated in the bone marrow. This requires VDJ recombination of its immunoglobulin genes. What must happen for this rearrangement to occur?
Stimulation by bone marrow stromal cell
TREG cells do what?
Suppress other effector T-cells - like inflammatory responses Must react w/ same APC as the T-cell that they are inhibiting
B-cells can be T-cell-dependent or independent what are some differences?
T-dependent is strictly antigens/proteins while T-independent can be other components (LPS)
What is the difference between the structure of the TCR vs. the BCR
TCR has alpha and beta chains, BCR has heavy and light chains
What determines the isotype of the antibody
The heavy chain
Proteolysis for MHC class 1 peptides is performed by?
The immunoproteosome that breaks down ubiquitinated antigen into peptide fragments
In what medium do dendritic cells migrate/travel?
The lymph (not blood)
Where do Naive T-cells encounter foreign antigen?
The lymph nodes (presented by APCs) --> secondary lymphoid organs
What is thymic involution?
The thymus making T-cells decreases with age
Recombination Signal Sequence (RSS) 12-23 rule:
There will be 23 pair spacer between heptamer and nonamer There will be a 12 pair spacer between a nonamer and a heptamer Always 12 and 23 next to each other, cannot be 12 and 12 or 23 and 23
What is special about thymus epithelial cells in relation to MHC
They express both MHC 1 and 2 (more of class 2 though)
Where do mature T-cells go?
They leave the thymus and travel to secondary lymphoid tissues
Why do we turn off RAG1/2 in the heavy chain?
To prevent DNA damage during cell division and to prevent the generation of other heavy chain variants --> Allelic exclusion
T/F: B cells develop from hematopoietic stem cells in the bone marrow through a process that includes the loss of potency of cells in successive steps, eventually becoming committed to a single lineage.
True
T/F: Unlike B cell immunoglobulin light chain rearrangement during the development, T cells alpha chain rearrangement does not have strict allelic exclusion leading to the production of T-cells that express more than 1 type of alpha chain of the T cell receptor
True
T/F: While the innate immune response starts at the site of infection, the adaptive immune response is initiated in a secondary lymphoid organ. Despite these differences in location, components of the innate immunity has a vital function in the induction of T-cell responses in the nearest lymph node by activating tissue dendritic cells and inducing their migration to the lymph node.
True
True or false: a single progenitor cell gives rise to a large number of lymphocytes each with a different specificity
True SPECIFIC BEFORE FOREIGN ANTIGEN contact in circulation
True or False: immature B-cells have both their light chain and heavy chains rearranged
True- express IgM
Comment on the Pre-B cell's heavy and light chain genes? Is there surface Ig expressed?
VDJ has completed rearrangement in heavy chain, light still not rearranged Pre-BCR expressed with the heavy chain and the surrogate light chain - not technically IgG
Comment on the Pro-B cell's heavy and light chain genes? Is there surface Ig expressed?
VDJ is occuring in the heavy chain genes, not light No
Naive B-cells and T-cells enter the lymph nodes the same process which is ?
rolling, activation, adhesion, and diapedesis
What induces class switching of antibodies?
various cytokines some inhibit some induce
