Microbio Week 5 Part 1 (Exam 2) Flashcards
Receptors of adaptive immunity are ________
clonal
What do T cells express?
T cell receptors
What do T cell receptors recognize?
Peptides displayed by MHC molecules
(processed antigen is recognized)
Membrane-bound heterodimeric protein composed of an alpha chain and a beta chain. Has a variable region and a constant region
T cell receptor
MHC class I has variable domains of which chain(s) for the T cell receptor to bind to?
Alpha chains
MHC class II has variable domains of which chain(s) for the T cell receptor to bind to?
Alpha and beta chains
What part of gene segments accounts for the diversity in T cell receptors?
Somatic recombination
Describe recombination of T cell receptor gene segments and recombination of immunoglobulin genes
Both are random selection of segments
What is recombination of T cell receptor gene segments mediated by?
Lymphocyte-specific VDJ recombinase that brings 2 segments close together
What is the 1st step of recombination of T cell receptor gene segments?
Recombination of D and J segments
What is the 2nd step of recombination of T cell receptor gene segments?
Recombination of V segment w/ fused D-J element
What is the 3rd step of recombination of T cell receptor gene segments?
Recombination of C segment w/ fused V-D-J element
T/F: There is not a lot of T cell receptor diversity
FALSE; there is TREMENDOUS diversity
How do T cells mature and get selected?
+ and - selection based on functional antigen receptors
What does a double negative T cell mean?
+ selection for ability to recognize antigen
What does a double positive CD4+ CD8+ T cell mean?
negative (-) selection
What does a single positive CD4+ or CD8+ T cell mean?
+ selection based on MHC reactivity
Where are T cells produced? Where do they mature?
Produced = bone marrow
Matured= thymus
Pre-T cells express one chain of antigen receptor (TCRbeta). What is it called?
Pre-TCR
What does pre-TCR promote?
Cell survival
What do immature T cells express? (2)
- Complete TCR that promotes cell survival
- CD4 and CD8
T cells that do not express __________ __________ will die
functional receptors
What type of recognition of MHC+peptide leads to selection? What type of T cells will be selected?
Weak recognition
Selected T cells = single +
What type of recognition of MHC+peptide leads to death?
Strong recognition
No recognition
Strong recognition leads to …
negative (-) selection, death
Weak recognition leads to …
+ selection, periphery
No recognition leads to …
Neglect, death
What allows T cells to be selected and migrate to the periphery?
Appropriate amount of antigen recognition in the thymus
What leads to clonal expansion? (in other words, how are T cells activated?)
Antigen recognition
Costimulation
Where do naive T cells circulate in search of their antigens?
From lymph node to lymph node
What signals are provided by Thelper cells to help macrophages and B cells?
CD40L
IFNgamma
What is the difference between naive and effector T cells in a situation in which there is an infection?
Effector T cells contract following clearance of pathogens
What is necessary for thymocytes to survive and mature in the thymus?
Expression of preTCR and TCR
What is the function of Th17 cells in response to infection?
Recruit neutrophils to the mucosa for clearance of extracellular microbes
How do activated cytotoxic T cells (CTL) kill cells infected with an intracellular microbe? What activates them?
Activated by dendritic cells
Receive help from Thelper cells to produce perforin and granzyme which lyse infected cell
Cytokines produced by dendritic cells and other innate cells determine the fate of naive T cells and the cytokine they will produce. What cytokines accurately induce Th cell differentiation?
IFNgamma induces Th2
IL-12 induces Th17
IL-6 induces Th1
IL-5 induce Th17
IL-4 induces Th2
IL-4 induces Th2
CD28 ligand and cell
B7-APC
CD40L ligand and cell
CD40-APC
MHC-I ligand and cell
TCR-CD8
MHC-II ligand and cell
TCR-CD4
IL-2 ligand and cell
IL-2R-T cells
What happens to T cells after they migrate to antigen sites in tissues?
Reactivated
Carry their function
During costimulation of T cell activation, antigen recognition (signal 1) alone induces what?
Unresponsiveness
During costimulation of T cell activation, engagement of B7 on APC by CD28 on T cells provides signal 2 and induces what?
Proliferation
What are inhibitory receptors in T cells critical for?
Limiting/terminating immune responses
Concomitant activation of CD4 T cells provides help to CD8 T cells via …
IL-2 production
(proliferation, differentiation)
Clonal expansion means
Growth
Contraction (homeostasis) means
Death
Antigen-specific T cell clones ____________ in response to antigens. This provides a large pool of effector cells to fight the infection
expand
When there’s an infection, which cells exhibit greater clonal expansion, CD8 or CD4 T cells?
CD8 T cells
Naive T cells ____________ and ______________
proliferate; differentiate
What type of T cells can proliferate and differentiate?
Naive T cells
Most effector T cells leave the lymph node, except for which ones?
T follicular helper cells (Tfh)
What is the function of T follicular helper cells (Tfh)?
Help B cells
What is the effector function of CD4 helper T cells (what do they activate)?
Activate phagocytes
Activate B cells to produce Ig
How do CD4 helper T cells activate phagocytes?
CD40-CD40L
IFNgamma production
How do CD4 helper T cells activate B cells to produce Ig?
CD40-CD40L
Cytokine production
What allows for T cell movement/migration?
Adhesion molecules + chemokine receptor
What are the 2 types of cell-mediate immunity?
CD4 helper T cells
CD8 cytotoxic T cells
What do CD4 helper T cells produce?
Cytokines that activate & recruit other cells
What do CD8 cytotoxic T cells do?
Kill infected cells
T/F: Recognition of antigens by T cell receptors is very specific
True
T cell clones express T cell receptors that can only recognize _____ peptide/MHC complex
1
Only _____ peptide/MHC complex can fit into a T cell receptor
1
T/F: Presentation of antigen to T cells by APC is very diverse
True
Several peptides can be presented by different MHC I and MHC II molecules on the surface of the same _________ _______
dendritic cell
What do T cells patrol in search of antigens with the perfect fit?
Lymph nodes
What cytokine does Th1 make?
IFNgamma
What does Th1 target?
Macrophages
What does Th1 defend against?
Intracellular pathogens
What is the role of Th1 in disease?
Autoimmunity
Chronic inflammation
What cytokine does Th2 make?
IL-4
IL-5
IL-13
What does Th2 target?
Eosinophils
What does Th2 defend against?
Parasites (helminths)
What is the role of Th2 in disease?
Allergy
What cytokine does Th17 make?
IL-17
IL-22
What does Th17 target?
Neutrophils
What does Th17 defend against?
Extracellular pathogens
What is the role of Th17 in disease?
Autoimmunity
What are 3 CD4 helpter T cell subsets?
Th1
Th2
Th17
What are different cytokines produced by?
Dendritic cells
(or other innate cells that have recognized different types of microbes)
What do cytokines determine the fate of?
Naive T cells
Activation of macrophages by Th1 cells involves what? (2)
CD40L-CD40
IFNgamma-IFNgammaR
IL-4 induces what?
B cells to produce IgE
IL-5 induces what?
Eosinophil activation
What is classically activated macrophage (M1) responsible for?
Killing and inflammation
What is alternatively activated macrophage (M2) responsible for?
Tissue repair
Inhibit inflammation
IL-17 and IL-22 induce what?
Antimicrobial peptide production by epithelial cells
What does IL-17 mediate?
Recruitment of neutrophils
How does the recruitment of neutrophils (mediated by IL-17) occur?
Via induction of cytokine/chemokine production from other cells
What cytokine do T follicular helper cells produce?
IL-21
What does IL-21 mediate the production of?
Ig by B cells
What cells are cytotoxic T cells most similar to?
NK cells
How do cytotoxic T cells mediate their function? (2)
Recognition of antigens
Killing via perforin and granzyme
How do CD8 cytotoxic T cells kill?
Release perforin and granzyme from granules
What must Th1 cells activate to lyse intravesicular microbes?
Macrophages
________ kills infected cells with help from _______
CD8; Th1
What do B cells express?
B cell receptors
What type of receptor?
Membrane-bound antibodies in association with invariant membrane proteins Ig-alpha and Ig-beta
B cell receptor
What is the structure of immunoglobulins?
Y shape
2 heavy chains
2 light chains
How many forms of immunoglobulins are there? Name them
2 forms: membrane-bound and secreted
What region of the immunoglobulin contains the antigen-binding site?
Variable region
What region of the immunoglobulin mediates effector function?
Constant region
What does the constant region of the immunoglobulin determine?
The isotype
What does the constant region of the immunoglobulin bind to? (2)
- Complement
- Fc receptors
Which part of the immunoglobulin is this describing?
Variable domains of light and heavy chains
Binding site
Which antigen is recognized by immunoglobulins, native or processed?
Native antigen
Antigen part recognized by antibody
Epitope
What leads to production of IgM?
C gene organization
What is the first C region cluster to be produced?
Cu
What is the first antibody to be produced?
IgM
T/F: There is tremendous diversity in the generation of immunoglobulins
True
Steps in the maturation of lymphocytes
- Proliferation and receptor expression
- Immature cells that do not rearrange functional receptors die (apoptosis)
- Mature cells undergo + or - selection