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49 Cards in this Set
- Front
- Back
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1˚ effector molecules of the humoral immune response?
Goal of Adaptive immune system? |
Antibodies.
To MAKE antibodies. |
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Key players in the Adaptive Immune System? 3
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-B cells
-T cells -APCs |
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What do B cells differentiate into? Which one makes antibodies?
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-Plasma cells --> Antibodies
-memory cells |
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T lymphocytes differentiate into?
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CD4s
CD8s |
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CD4s differentiate into what? What types of immunity are those cells involved in?
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Th1 (CMI)
Th2 (Humoral; better at activating B cells) Th17 |
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Describe the Proliferative Cycle of B cells:
6 steps |
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How do antigen-“naïve” B cells get activated, proliferate, and differentiate into effector plasma cells (or memory B cells)?
How do antibodies do their job? *3 big picture stages |
1. Hematopoiesis
2. Induction (Activation and Differentiation) 3. Antigen Elimination |
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Describe the MATURATION AND SELECTION OF B LYMPHOCYTES:
4 Big picture steps What occurs at each step? |
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T/F. The process of B cell Maturation and Selection is antigen-dependent.
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FALSE. You're thinking of T cells, homey.
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What signal causes a proB cell to become a preB cell?
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IL-7
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What's receptor editing?
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-Some immature B cells that were recognizing self-antigen are given a "second chance" to rearrange their light chains into a configuration that will make them into functional immature B cells.
"Immature B cells with high affinity receptors of self antigens are subject to negative selection. "Those that recognize self antigens can be induced to undergo “receptor editing” – where additional L chain V-J recombination can occur. "IgM and IgD are co-expressed." |
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First antibody that's made in a maturing B cell? Second one?
What does it do once it has these two? |
-IgM, then IgD. It MUST co-express these two.
-Once it has these two, it's ready to be released to the periphery to go look for its cognate antigen. |
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What are the peripheral lymphoid tissues?
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-Lymph nodes
-Spleen -Mucosal-Associated Lymphoid Tissues *MALT – mucosa-associated lymphoid tissues *BALT – bronchus-associated lymphoid tissues *GALT – gut-associated lymphoid tissues |
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What do the 2˚ lymphoid tissues all have in common?
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All have a lymphoid follicle. Rich in follicular dendritic cells and B cells.
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-B cells are effective against _____ invaders.
-What are the two ways B cells respond to antigens? |
-Extracellular
-T cell independent activation -T cell dependent activation |
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ACTIVATION OF B CELLS VIA THE T-CELL INDEPENDENT PATHWAY --what do B cells recognize independently? 3
Why do these molecules activate B cells? |
-Polysaccharides
-Lipids -Small chemicals -Because they have Multiple identical “repeats” or epitopes leads to CROSS-LINKING of BCRs, which intensifies the activation signal sent to the B cell nucleus. |
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What are the invariant molecules associated with the BCR complex?
What do they do that's important? |
-Igα and Igβ.
-They send a signal (SIGNAL 1) to the B cell nucleus that leads to activation of transcription factors important for B cell proliferation & differentiation. |
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What's SIGNAL 2 in B cell activation in the T-independent pathway?
(there are two kinds) |
1) Microbes activate the complement system C3 -> C3b
(C3d fragment) C3d + CR2 receptor = second signal = B cell activation 2) LPS + Toll-Like Receptor = second signal = B cell activation |
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What's the ONLY thing B cell activation in the T-independent pathway eventually leads to the production of?
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Plasma cell secreting IgM!
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3 subsets of B cells?
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-Follicular B cells
-Marginal Zone B cells -B-1 B cells |
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What's unique about Follicular B cells?
4 |
-Only ones that participate in T-dependent activation (they live close to the T cells)
-They create germinal centers -They can isotype switch to other forms of Ab. -They recognize PRO antigens. |
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Characteristics of antigens involved in the T-dependent pathway: 4
What are the implications of this? |
-Soluble protein antigens:
*Tend not to have multiple epitope repeats *Are not able to cross-link BCRs *Are only capable of stimulating weak immune responses on their own. -B cell activation by protein antigens requires T cell help. |
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-Describe all the action that's going on in the parafollicular region during the T-dependent activation of a B cell.
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-APC presents antigen to naive T cell
-T cell proliferates/differentiaties/migrates -B cell migrates/presents antigen to effector CD4 cell |
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What steps occur to get B cells in the lymphoid follicle ready to interact with Th cells? 4
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-Increased expression of B7 co-receptor
-+ expression of cytokine receptors -Decreased receptors for follicle chemokines; allows B cells to leave the follicle. -Migration to T cell area |
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What are the 3 SIGNALS in activation of B cells?
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1) Antigen BCR engagement.
2) Co-stimulation; CD40L and CD40 3) Secretion of cytokines (like IL-2, 4, 5) from Th cells activates the B cell. |
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So what comes first? T cell activation or B cell?
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-T cell first
-Followed by the B cell |
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After B cell activation, what happens in the germinal centers?
What 3 key things to Th signals stimulate? |
-Activated B cells undergo rapid proliferation and clonal expansion in GERMINAL CENTERS.
-Helper T cells signals stimulate: *Heavy chain class switching *Somatic hypermutation *Affinity maturation |
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On the Antibody, where does class switching occur?
What effects does class switching have on the antigen binding sites? |
C region of the heavy chain.
No effect. |
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Describe class switching.
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-The process by which a B lymphocyte changes the isotype of the antibodies it produces
-IgM -> IgG, IgE, or IgA -without changing the specificity of the antibody. -When a mature B cell switches antibody class, all that changes is the constant region of the heavy chain. |
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What kind of signals are at play in determining the outcome of class switching?
What mediates these signals? |
Heavy chain class switching is initiated by CD40L-mediated signals.
IFN-g= IgM->IgG IL-4= IgM->IgE TGF-ß= IgM->IgA |
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Describe X-linked hyper-IgM syndrome:
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-caused by mutations in CD40L.
-can't perform class switching; IgM is the sole antibody. |
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Describe Somatic Hypermutation in B cells:
What about Affinity Maturation? |
-In the germinal center, the goal is to make better antibodies.
-They proliferate at a high rate there; point mutations are made in the V region of the B cells. -This CHANGES the antigen-binding site of the BCR. -The best B cells are now selected from the pool of B cells in the GC. This is called Affinity Maturation. -Follicular dendritic cells also play a role by presenting antigen to the B cells in the GC. |
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Why is the process of Affinity Maturation important?
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-Well, obviously it selects for more effective B cells.
-It's important that the B cells continually get better at binding a specific antigen, because as the body fights off an infection, there's continually less and less antigen around. So the B cells must bet better at binding it. |
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What happens to the B cells once they are selected and passed through the GC?
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1. Differentiate into Ab-secreting PLASMA cells that migrate to the medulla and either live there or migrate to the BM where they can live and continue to produce antibody for years.
2. Differentiate into memory cells. Memory cells do not secrete antibodies, but rather circulate in the blood and survive for months or years in the absence of additional antigenic exposure, “lying in wait”. |
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1˚ vs. 2˚ antibody responses:
-lag time -size of peak response -predominant Ab -Ab affinity |
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Describe the process of antibody feedback.
-3 step process |
-Turns off antibody production when enough has been made.
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What are the different effector functions of antibodies?
6 |
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Which Ab is best at activating complement?
Which Ab is best at opsonizing Ab? Which Ab is best at mucosal immunity? |
IgM
IgM IgA |
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Describe the function of Neutralization of invaders by antibodies: 3
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Describe the function of Opsonization and Phagocytosis of invaders by antibodies: 3
-best against what type of invader? -what type of patient is vulnerable to this kind of pathogen? |
-The major mechanism of defense against encapsulated bacteria, such as pneumococcus, and the spleen is an important site of phagocytic clearance.
-Patients who have undergone splenectomy are highly susceptible to disseminated infections by encapsulated bacteria. |
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Describe the function of Abs in ADCC:
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-AB-dependent Cellular Cytotoxicity
1) Killing by NK cells--IgG coats the cell 2) Killing by Eosinophils--IgE coate the parasite. |
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Describe the function of Abs in activation of the Complement System:
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-They activate the Classical Pathway of the complement system--> Opsonization, MAC, inflammation
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Functions of Abs in mucosal tissues:
How does the Ab get into the gut? Which Ab is involved? |
-poly Ig receptor binds IgA; gets endocytosed and transported into gut lumen to promote mucosal immunity.
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Describe the process of Neonatal Immunity:
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Maternal antibodies are actively transported across the placenta to the fetus and across the gut epithelium of neonates.
Results in protection of the newborn from infections via “passive immunity”. After birth, neonates ingest maternal antibodies in milk and bind these antibodies via FcRn receptors in intestinal epithelial cells. Newborns essentially acquire the IgG antibody profiles of their mothers and are protected from infectious microbes to which the mothers were exposed or vaccinated. *Effector function is determined by the Fc region?? |
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Describe Conjugate Vaccines:
What's an example? |
-Some microbial polysaccharide antigens (which cannot stimulate T cell help) are chemically coupled to PROTEINS, so that helper T cells are activated and high-affinity antibodies are produced against the polysaccharides.
-The Hib (haemophilus influenzae type B) vaccine is an example. |
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3 WAYS microbes can evade humoral immunity:
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A mouse strain is developed in which the μ constant domain exons are deleted from the antibody heavy chain gene. An adult mouse of this strain is sacrificed, and its blood and spleen are examined. Which of the following best describes the condition of this mouse?
A. B-cell levels in blood and spleen are normal, but serum contains no antibody. B. B-cell levels in blood and spleen are normal, and serum contains IgG and IgE. C. B-cell levels in blood and serum contain IgG and IgE, but spleen tissue lacks B cells. D. B-cell levels in blood are normal, but spleen tissue lacks B cells, and serum lacks antibody. E. B cells are lacking from blood and spleen, and serum lacks antibody. |
E. B cells are lacking from blood and spleen, and serum lacks antibody.
*There's no IgM, so you can't proceed to make a mature B cell at all. |
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Patients with deficiencies in antibody production can often present with the same types of infections as are seen in patients with phagocytic cell deficiencies. Which of the following statements best explains this observation?
A. Plasma cells are the direct progenitors of certain phagocytic cells. B. Antibodies are important opsonins that promote microbe recognition by phagocytes. C. Macrophages can differentiate into antibody-producing plasma cells. D. Macrophages are essential for the presentation of antigen to antibody-producing B cells. |
B. Antibodies are important opsonins that promote microbe recognition by phagocytes.
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Mary is a 3-year-old patient who presents with a fever, labored breathing, and shortness of breath. Her history includes recurrent bacterial infections (sinusitis and otitis media) since 1 year of age. She has been prescribed oral antibiotics as often as six times per year. After each course of treatment, the infections subside, but a recurrence of symptoms often follows within several weeks. Laboratory tests indicate mild neutropenia, but no other hematological abnormalities. Her serum IgG and IgA levels are far below those of age-matched controls, whereas her serum IgM levels are significantly elevated. When immunized with tetanus toxoid, a vaccine she has received before, she makes no detectable IgG antibody response. Which of the following is the most likely cellular or molecular defect in this patient?
A. Failure of her B cells to undergo Ig class switching. B. A block in all B cell differentiation C. Rag-1 deficiency D. Toll-like receptor deficiency E. DiGeorge syndrome |
A. Failure of her B cells to undergo Ig class switching.
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