Microbio Week 5 Part 2 (Exam 2) Flashcards
Selection of immature B cells occurs where?
Bone marrow
The selection of immature B cells in the bone marrow occurs in an _________________ manner
antigen-independent
What are the 2 checkpoints in the maturation of B cells?
- preBCR
- IgM
(both promote survival)
How is the BCR diversity generated in order to reach 1011?
Random recombination of gene segments and removal/addition of nucleotides.
What are the 2 critical steps involved in the maturation of pre-B and immature B cells in the bone marrow?
pre-BCR and IgM
Isotype switching is associated with…
Cytokines
Affinity maturation is associated with…
Point mutations
Hypervariable regions are associated with…
Antigen-binding site
Plasma cells are associated with…
Antibody secretion
Which of the following would likely lead to a decrease in CD4 cells only?
Defect in CD40 expression
Defect in IFNγ production
Defect in MHC Class I expression
Defect in RAG expression
Defect in MHC Class II expression
Defect in MHC Class II expression
Which of the following will lead to a decrease in B cells?
Defect in RAG expression
Defect in MHC Class II expression
Defect in IFNγ production
Defect in B7 expression
Defect in IL21 production
Defect in RAG expression
What does the expression of pre-BCR and signal from IgM in B cells promote?
Survival
T/F: Receptor editing only occurs for T cells
FALSE; it only occurs for B cells
Light chain recombination that results in change of Ig specificity
Receptor editing
Eliminate immature B cells that can bind with high affinity ubiquitous self antigens
Negative selection
What distinguished B cells from T cells?
A. BCR diversity is not achieved by random rearrangement
B. Selection of B cells depends on antigen recognition
C. Expression of pre-BCR in contrast to pre-TCR induces cell survival
D. Receptor editing only occurs for B cells
E. T cells recognize native proteins
D. Receptor editing only occurs for B cells
B cells vs T cells:
Types of antigens recognized
B cells = protein, lipid, polysaccharide, nucleic acid
T cells = protein
B cells vs T cells:
Antigen form
B cells = UNprocessed
T cells = processed
B cells vs T cells:
Positive selection
B cells = antigen INdependent
T cells = antigen dependent
B cells vs T cells:
Negative selection
Both are antigen dependent
B cells vs T cells:
Receptor editing
B cells = yes
T cells = no
B cells are activated by antigen recognition, which results in ________ ___________ and ___________
clonal expansion; differentiation
Where do plasma cells that produce high affinity Ig migrate to?
BM or mucosal tissues
How long do plasma cells that produce high affinity Ig survive for?
Years
T/F: Memory B cells secrete Ig
FALSE
How long do memory B cells survive for?
A liftetime
Where do memory B cells survive for a lifetime?
Mucosal tissues and blood
Describe the secondary antibody response in comparison to the primary antibody response
Quicker
Larger
IgG more abundant
High affinity
What allows for signal 2 and enhances B cell activation?
Engagement of CR2 or TLR
What are the 2 types of antibody responses?
T dependent
T independent
Which antibody response?
-Response to nonprotein antigen
-IgM
-Low affinity Ig
T independent
Which antibody response?
-Response to protein antigen
-Isotype switching
-High affinity Ig
T dependent
Small molecules that cannot elicit immune response by themselves, but do so after binding to larger proteins/cells
Haptens
Name common haptens
Penicillin, nickel, poison ivy
What do B cells process?
Antigens
B cells and T cells recognize different ___________ of the same protein
epitopes
What epitopes do B cells recognize?
Native conformational epitopes
What epitopes do T cells recognize?
Peptide fragments
What does the recognition of peptide presented by B cells induce? (2)
CD40L upregulation in T cells
Production of cytokines
Engagement of CD40 and cytokine receptor on B cells leads to their proliferation and differentiation in _______ cells
plasma
What 3 things happen in the germinal center?
- Isotype switching
- Affinity maturation
- Selection of high-affinity B cells
4 steps of germinal center reaction
- Activation of B cells + migration into germinal center
- B cell proliferation
- Somatic hypermutation + affinity maturation; isotype switching
- Exit of high affinity AB secreting cells + memory B cells
What is immunoglobulin isotype switching?
Change in constant region of heavy chain
What signal does isotype switching require?
CD40L signal from Tfh cells
What is the type of heavy chain isotype determined by?
Cytokines produced by Tfh cells (IgG or IgE) or tissues (IgA)
What does switch recombination bring VDJ exon next to?
A different C gene
In switch recombination, does specificity of the Ig change?
NO, it has the same V region
In switch recombination, does the C region change?
YES, it reflects the function of the Ig
Selection of B cells with high affinity antigen receptors
Affinity maturation
High affinity B cells interact with follicular dendritic cells that display what 2 things?
What do these 2 things help do?
Antigen
Tfh
Promote survival via CD40-CD40L
What Ig is produced in salivary glands?
IgA
Name the effector functions of antibodies/immunoglobulins (7)
ON EXAM
- Neutralization of microbes and toxins
- Opsonization and phagocytosis of microbes
- AB dependent cellular cytotoxicity
- Lysis of microbes
- Phagocytosis of microbes opsonized w/ complement fragments
- Inflammation
- Complement activation
What is the role of the variable region of an AB?
Neutralization
What is the role of the constant region of an AB?
Elimination
How does neutralization of microbes occur?
Binding molecules on microbes required for infecting cells that blocks colonization
Which antibodies are the most effective at neutralizing microbes?
ABs w/ high affinity for antigens
What does clustering of FcR require?
Recognition of multivalent antigen by Ig
What FcR promotes phagocytosis of Ig-coated microbes by phagocytes?
FcgammaRI/IIA
What FcR induces killing of Ig-coated infected cells by NK cells (ADCC)?
Fcgamma/RIIIA (CD16)
What FcR induces degranulation of mast cells and basophils/eosinophils?
FcERI
(E = epsilon)
What is required for antibody-mediated opsonization and phagocytosis? (2)
- Multivalent AB coated microbe
- FcR clustering
What cells bind to IgG-coated cells via FcgammaRIII (CD16)?
NK cells
What kind of killing is FcERI involved in?
IgE- and eosinophil-mediated killing of helminths
When killing helminths, FcERI binds to _____ portion of the IgE-coated ____________
Fc; helminth
What does FcERI binding to the Fc portion of the IgE-coated helminth trigger?
Degranulation of toxic mediators that kill helminth
What does IgE- and eosinophil-mediated killing of helminths NOT target?
Infected cells
What other process is FcERI involved in?
FcE-mediated allergic disease
What does this describe?
Mast cells/basophils are coated with IgE specific for allergens via their FcERI
FcE-mediated allergic disease
Clustering of FcERI bound to IgE by multivalent allergen in FcE-mediated allergic disease triggers what to occur?
Degranulation
When discovering the complement system, Jules Bordet demonstrated the presence of a _______ _____________ component in antiserum (alexin) that mediate bacteriolysis
heat sensitive
“Activation of complement involves the ____________ ____________ of those proteins to generate __________ (Zymogens) with proteolytic activity
sequential proteolysis; enzymes
What are plasma proteins activated by?
Microbes
What does complement activation result in?
Phagocytosis, inflammation, and destruction of microbes
What is the most important step of early complement activation?
Cleavage of C3 by C3 convertase
What is the net result of the cleavage of C3 by C3 convertase?
Coating of microbes with C3b
What does the late step of complement activation result in?
Membrane attack complex (MAC)
What does the membrane attack complex (MAC) consist of?
C5b
C6
C7
C8
Multiple C9s that form a pore
Most microbes have evolved to be resistant to MAC-mediated lysis. Which microbe is susceptible due to its thin cell wall?
Neisseria
What prevents complement fixation at the surface of mammalian cells?
Plasma + membrane proteins
When regulating complement activation, what inhibits proteolytic activity of C1r and C1s by dissociating them from C1q?
C1 INH
When regulating complement activation, what do CR1, DAF, Factor H, and MCP bind to?
C3
When regulating complement activation, what do CR1, DAF, and C4BP bind to?
C4b
When regulating complement activation, what inactivates C3b/C4b attached to cell surface?
Factor I
When regulating complement activation, what inhibits MAC formation?
S protein
CD59
Name the plasma proteins that prevent complement fixation at the surface of mammalian cells (5)
C1 INH
C4BP
Factor H
Factor I
S protein
Name the membrane proteins that prevent complement fixation at the surface of mammalian cells (4)
CR1
DAF
MCP
CD59
What is important for Neisseria infection?
MAC
Name some functions of the complement system (4)
- Opsonization of microbes to induce phagocytosis
- Increase vascular permeability
- Increase extravasation of plasma proteins and monocyte/neutrophils
- Increase microbicidal
activities
(2-4 are done by anaphylatoxins)
Where can these forms of protective immunity be found extracellularly?
Antibodies
Complement
Phagocytosis
Neutralization
Interstitial spaces, blood, lymph
Where can these forms of protective immunity be found extracellularly?
Antibodies (especially IgA)
Antimicrobial peptides
Epithelial surfaces
Where can these forms of protective immunity be found intracellularly?
Cytotoxic T cells
NK cells
Cytoplasm
Where can these forms of protective immunity be found intracellularly?
T cell and NK cell dependent macrophage activation
Vesicles
What are the 3 mechanisms of innate immunity to extracellular bacteria?
- Complement activation
- Opsonization and phagocytosis
- Stimulation of inflammatory reactions via anaphylatoxin
Humoral immunity eliminate microbes and neutralize their toxins via antibodies that recognize …? (2)
- Cell wall antigens
- Secreted and cell-associated toxins
Igs induce __________ and _________ of microbes and complement activation
opsonization; phagocytosis
Bacterial protein antigens processed by DC activate CD4 helper T cells for what 3 things?
- Production of IL-17 and neutrophil recruitment
- Production of IFNg and activation of macrophages
- B cell help
Innate immunity involves what 2 particular cells?
Phagocytes
NK cells
What is cell-mediated immunity crucial for?
Adaptive immunity to intracellular bacteria
In adaptive immunity to intracellular bacteria, what do CD4 T cells differentiate into?
Th1 effectors via IL-12
In adaptive immunity to intracellular bacteria, how are macrophages activated?
T cell signals (IFNgamma)
Name an example of adaptive immunity to intracellular bacteria
Antibodies against TB
Lysis of infected cells is done by…?
Cytotoxic CD8 cells
What 2 cells phagocytose fungi for intracellular killing?
Neutrophils
Macrophages
Which responses are protective during innate immunity to fungi?
Th1
Th17
What can cause an increased risk for oral candidiasis or thrush?
Upper dentures
Dry mouth
What do innate and adaptive immune responses block? What does this lead to?
Block infection
Leads to elimination of infected cells
What 2 things does innate immunity have to respond to viruses?
IFNalpha
NK cell killing
__________ neutralize viruses, activate complement, and lead to ______________ of viral particles
Antibodies; opsonization
What cells kill viro-infected cells?
CD8 T cells
What is the limitation for parasites/protozoa?
Weak innate immunity
What 2 things are involved in adaptive immunity to protoza?
- Macrophage activation
- Cytotoxic T lymphocytes
For adaptive immunity to protozoa, how do macrophages become activated?
By Th1 cell-derived cytokines
For adaptive immunity to protozoa, what do cytotoxic T lymphocytes respond against?
Lytic protozoa (malaria)
For adaptive immunity to helminths, what does the activation of Th2 cells result in?
Killing of the helminth
(NOT infected cells!)
Describe the process of adaptive immunity to helminths, which results in killing of the helminth. (4)
- Production of IL-4 -> induces IgE
- Production of IL-5 -> stimulates eosinophils
- Release of major cationic protein + major basic protein
- Degranulation of eosinophils + killing of helminth
What is a common evasion mechanism for bacteria, viruses, and parasites?
Antigenic variation
What is responsible for influenza pandemics?
Reassortment of virus RNA genomes (antigenic shift)
What does the most effective vaccine lead to?
Production of high-affinity neutralizing antibodies + memory cells
(lifelong immunity)
What does the caries vaccine lead to enhanced levels of?
Antigen-specific secretory IgA