BLD 434 Final Flashcards
What is the general mechanism of somatic recombination
An enzymatic process that generates diversity of B and T cell receptors by RAG-1 & RAG-2 cutting gene segments and splicing them back together
What cells are involved in somatic recombination
B and T cells
What is the general mechanism of somatic hypermutation
Increased point mutations initiated by AID enzyme throughout the heavy and light chain V regions (not C regions)
What is accomplished in somatic recombination
isotype switching that changes antibody function
What cells are involved in somatic hypermutation
B cells
What is accomplished in somatic hypermutation
generates antibody diversity
What is the general mechanism of isotype switching
When activated B cells encounter specific signaling molecules via their CD40 receptors they undergo antibody class switching, the constant region of the heavy chain is changed, variable region stays the same
What is accomplished with isotype switching
changing a B cell’s production of antibody from one class to another
What cells are involved in isotype switching
Naive B cells
What is the goal of positive selection
Ensures only useful T cells that are able to bind MHC are released to the periphery
Where does positive selection occur
Inner cortex in the thymus
How does positive selection occur
selects for developing T cells with receptors that recognize peptide antigens presented by self MHC (Double positive thymocytes undergo + selection)
What cells are involved in positive selection
alpha-beta T cells
What is the goal of negative selection
Weeds out cells that are reactive/bind too tightly to self antigens because they can harm our body
What cells are involved in negative selection
B and T lymphocytes
Where does negative selection occur
Medulla
How does negative selection occur
T cells that bind too avidly to self antigen presented by DC or macrophages are deleted by apoptosis
What is the “two signal hypothesis”
A T cell must receive a minimum of two signals to respond to an antigen
What cells, receptors/ligands are involved in the two signal hypothesis
- primary signal through TCR binding cognate peptide/ MHC I or II
- A co-stimulatory signal through co-stimulator molecules on APC
List the surface proteins of naive T cell and APC
on surface of naive T cell: CD28 & TCR
on surface of APC: MHC II & B7
What would happen if the two signal hypothesis was not satisfied
It will prevent new naive T cells from joining the fight because they cannot receive their second signal
What is linked recognition
when an antigen is processed and presented by the B cell to the Tfh cell, in order for B cell to become activated
What are the cells, receptors/ligands involved in linked recognition
CD40 and CD40L
What is the outcome of linked recognition
T cell help for B lymphocytes to activate isotype switching and somatic hypermutation
(T dependent Ab responses)
What two cytokines induce differentiation of Th1?
IL-12 and IFN-gamma
What are the characteristic cytokine(s) of Th1?
IL-2 and IFN-gamma
- function is to activate macrophages
What cytokine induces of Th2?
IL-4
What is the defining TF for Th2
GATA-3
what is the defining TF for Th1
T-bet
What are the characteristic cytokine(s) of Th2?
IL-4 and IL-5
activate cellular and antibody response to parasites
What cytokine(s) induce differentiation of Th17?
IL-6 and IL-21
what is the defining TF for Th17
ROR gamma T
What are the characteristic cytokine(s) of Th17?
IL-17 and IL-6
Enhance neutrophil response to extracellular bacteria
What cytokine(s) induce differentiation of Tfh?
IL-16, TGF-beta, and IL-23
what is the defining TF for Tfh
BcI6
What are the characteristic cytokine(s) of Tfh?
IL-21
Active B cell maturation of antibody response
What cytokine(s) induce differentiation of Treg?
TGF-beta
what is the defining TF for Treg
FOXP3
What are the characteristic cytokine(s) of Treg?
TGF-beta and IL-10
Suppress other effector T cells, limits inflammation
Identify the signature cytokines produced/secreted by Tc
Cytotoxins: perforin, Granzymes, Granulysin, Serglycin
Cytokines: ING-gamma, LT, IL-2
Kill virus infected cells
Identify the signature cytokines (5) produced/secreted by Th1
- IFN-gamma
- GM-CSF
- TNF-alpha
- LT
- IL-2
Helps macrophages to suppress intracellular infections
Identify the signature cytokines (5) produced/secreted by Th2
- IL-4
- IL-5
- IL-10
- IL-13
- TGF-beta
help basophils, mast cells, eosinophils and B cells respond to parasite infections
Identify the signature cytokines produced/secreted by Th17
- IL-17
- IL-21
- IL-22
- IL-26
Enhance neutrophil response to fungal and extracellular bacterial infections
Identify the signature cytokines produced/secreted by Tfh
- IL-21
- IL-4
- IFN-gamma
Help B cells become activated, isotype switching and increase antibody affinity
Identify the signature cytokines produced/secreted by Treg
- TGF-beta
- IL-10
- IL-35
Suppress activities of other effector T cell populations
What cells function as professional antigen presenting cells?
Dendritic cells, B lymphocytes and Macrophages
Identify the common CD markers used to identify human B cells
CD19 and CD20
What cell markers are used to identify all T cells, cytotoxic T cells and helper T cells
All: CD3+
Cytotoxic: CD4+ & CD8+
Helper: CD3+ & CD4+
What are NK cell markers
CD56 and/or CD16
Innate immunity
the immunity that you are born with, fast, yet fixed response, limited specificity
Adaptive immunity
genes are arranged during development, slow response at first, variable, high specificity
Active immunity
the immunity that results from the production of antibodies by the immune system in response to the presence of an antigen
Passive immunity
the short-term immunity that results from the introduction of antibodies from another person or animal, ex: mother to baby
Primary immunity
first response to the antigen; fast in innate and slow in adaptive
Secondary immunity
the second response to the antigen, fast, adaptive immunity has memory for this antigen
Cell mediated immunity
the immune response that involves the activation of phagocytes, antigen-specific cytotoxic T-lymphocytes, and the release of various cytokines in response to an antigen
Humoral immunity
the immunity by molecules found in extracellular fluids such as secreted antibodies, complement proteins, and certain peptides
When are B-1 cells first produced
fetus
When are B-2 cells first produced
after birth
Are B-1 cells self renewing
Yes
Are B-2 cells self renewing
No, they are replaced in the bone marrow
Do B-1 cells have high or low spontaneous Ig production
High
Do B-2 cells have high or low spontaneous Ig production
Low
What is the major isotype secreted by B-1
IgM»IgG
What is the major isotype secreted by B-2
IgG>IgM
What is the level of somatic hypermutation of B-1 cells
little to none
What is the level of somatic hypermutation of B-2 cells
High
N-regions in VDJ functions in B-1 cells?
Few
N-regions in VDJ functions in B-2 cells?
Extensive
V-region in B-1 cells?
Restricted
V-region in B-2 cells?
Diverse
Primary location of B-1 cells?
Peritoneal and pleural cavities
Primary location of B-2 cells?
Secondary lymphoid organs
Requirement for T-cell help in B-1 cells?
No
Requirement for T-cell help in B-2 cells?
Yes
Memory development with B-1 cells?
Little to none
Memory development with B-2 cells?
Yes
Describe/define a T dependent B cell response
Require T cell help for proper response
Describe/define a T independent B cell response
Antigens cause B cells responses in the absence of T cell help
Is a memory response produced form T-dependent or T-independent B cell response?
T-dependant
What is the site of development for alpha-beta T cells?
Thymus
What is the site of development of gamma-delta T cells?
Thymus
Describe the T-cell receptor diversity of alpha-beta T cells
Large (90%)
Describe the T-cell receptor diversity of gamma-delta T cells
Small to medium (10%)
Does positive or negative selection occur in alpha-beta T cells?
both
Does positive or negative selection occur in gamma-delta T cells?
neither
What are the target antigens of alpha-beta T cells?
Peptides presented by MHC class I or class II molecules
What are the target antigens of gamma-delta T cells?
Self proteins resembling MHC class I molecules
Which are more abundant in blood, alpha-beta or gamma-delta T cells?
Alpha-beta
Which are more abundant in tissue, alpha-beta or gamma-delta T cells?
alpha beta
Describe the activation of alpha-beta T cells
Circulate in inactive form that requires several days of activation
Describe the activation of gamma-delta T cells
Present in tissues in a form that is quick to response to infection and other forms of stress
What is the overall function of alpha-beta T cells?
Adaptive immunity
What is the overall function of gamma-delta T cells?
Tissue homeostasis; surveillance, protection and repair
Describe the B cell receptor in regards to…
- Chains
- What it binds
- What its associated with
- Where rearrangement occurs
- Two heavy chains and two light chains
- Binds intact proteins, glycoproteins or lipoprotein
- Associated with IgAlpha and IgBeta signaling molecules
- Rearranged in bone marrow
Describe the T cell receptor in regards to…
- Chains
- What it binds
- What its associated with
- Where rearrangement occurs
- Single TCRalpha and TCRbeta chains
- Binds processed proteins as peptide fragments in MHC
- Associated with CD3 signaling complex
-CD4 and CD8 co-receptors - Rearranged in thymus
List the characteristic of IgG
- Transported across the placenta and can diffuse into extravascular sights
- Circulates in blood
What is the FcR of IgG?
- FcRN
- FcgammaRI
- FcgammaRII
- FcgammaRIII
What is the ultimate function of IgG?
- Neutralization
- Osponization
-sensitize for NK killing - Activation of complement
- ADCC (antibody dependent cellular toxicity)
List the characteristics of IgM
- First antibody isotype made in a primary immune response
- Pentamer (BIG)
- Circulates in blood
What is the FcR of IgM?
FcuR (FcmuR)
What is the ultimate function of IgM?
Activation of complement
List the characteristics of IgD
Associated with allergic reactions
What is the FcR of IgD?
Fc dependent
What is the ultimate function of IgD?
Sensitization of basophils
List the characteristics of IgE
Functions primarily in anti-parasitic immunity
What is the FcR of IgE?
FceRI
What is the ultimate function of IgE?
Sensitization of mast cells
List the characteristics of IgA
Transported across the mucosal epithelium, dimer
Diffused into extravascular sites like blood, monomer
What is the FcR of IgA?
FcalphaRI
What is the ultimate function of IgA?
Neutralization
Identify the initiation of activation of the alternative pathway
Activated by spontaneous hydrolysis of C3
Identify the initiation of activation of the classical pathway
Activated by C-reactive protein
Identify the initiation of the lectin pathway
Activated by mannose binding lectin (MBL)
What are the C3 convertase of the alternative pathway?
iC3Bb and C3bBb
What are the C3 convertase of the classical and lectin pathways?
C4b2a
What are the C5 convertase of the alternative pathway?
C3bBb3b
What are the C5 convertase of the classical and lectin pathways?
C4b2a3b
What the is MAC of the 3 pathways of complement?
C5-C9
List primary immune tissues for B and T cells
Bone marrow (b cells) and thymus (T cells)
List secondary immune tissues
Spleen, adenoid and tonsils
Describe the general characteristics of secondary lymphoid tissue
The maintain mature naive lymphocytes and initiate adaptive immune response, naive T cells interact with APC in secondary lymphoid tissue and induce T cell activate
GALT, BALT & MALT
serology testing
study of non cellular components of blood (serum) ie soluble proteins
What does a positive IgM test indicate
current or recent infection by itself
What does a positive IgG test indicate
indicates past infection or immunity
What does a positive IgG & IgM test indicate
chronic infection
What does a positive IgE test indicate
allergic reponse
