BRS Immunology Flashcards
Function of immune system?
Removal of foreign material/microorganisms
Is innate immunity specific or non specific?
Nonspecific
Innate immunity is developed when?
By birth
The protective factors in innate immunity are independent of what?
Antigenic stimulus.
Is innate immunity fast or slow?
Fast
Is innate immunity first or second?
First
Is adaptive immunity specific or nonspecific?
Specific
How is adaptive immunity actively acquired? (2
Infection or vaccination
How is adaptive immunity passively acquired? 2
Placental transfer
Injection of specific antibody
4 main types of physical and chemical barriers to microbial invasion in innate immunity?
- Skin and mucus membranes block and secrete
- Defensins in phagocytic vacuoles are secreted and damage bacteria
- Cathelicidins are released in granules to cause pores to form in bacteria
- Lysozyme is released in lacrimal and saliva secretions
What cells are involved in early detection of pathogens? (3)
- Macrophages
- Neutrophils
- Dendritic cells
Macrophages, neutrophils, and dendritic cells all possess what type of special receptor?
Pattern Recognition receptors
Pattern recognition receptors recognize what?
Which are found where?
Pathogen-Associated Molecular patterns (PAMP’s)
Found on many microorganisms
One of the most important types of PRR’s is what?
Toll-like receptors
Toll like receptors recognize what?
PAMP’s on selective microorganisms
Upon binding a toll-like receptor to a PAMP, what does the cell do?
Releases Interleukin
Function of interleukin? 3
- Incite inflammation
- Incite phagocytosis
- Removal of organism
Natural killer cells detect host cells with what main feature?
Depressed levels of major histocompatability class I molecules which is caused by viruses
NK cells binding to an infected cell’s MHC class I is through what receptor?
Killer-activated receptor
How can a cell with adequate MHC class I levels prevent destruction by NK cells?
NK cells have a Killer Inhibition Receptor which determines if a cell has adequate MHC I levels
What initiates inflammation?
Microbial induced release of pro-inflammatory cytokines
Pro-inflammatory cytokines include? (2)
TNF-Alpha
IL-1
Pro-inflammatory cytokines induce what? 2
Adhesion molecules on leukocytes (Integrins)
Adhesion molecules on endothelial cells (selectins)
How do neutrophils slow their flow in order to undergo diapedesis into injury site?
By neutrophils’ integrins binding to endothelial selectins and intracellular adhesion molecules (ICAM)
Phagocytic cells are recruited by what chemokines? 3
IL-8
Macrophage inflammatory protein (MIP)
Interferon-gamma (IFN-gamma)
First cells to arrive at seen of infection?
Neutrophils
What follows neutrophils to infection site? (3)
- Macrophages
- Monocytes
- Lymphocytes
Phagocytized membrane-enclosed organisms are destroyed in phagocytic vacuoles by what? 4
- Lysosomal enzymes
- hydrogen peroxide
- Nitric oxide
- O2-anion
Repair of the damage caused by excessive inflammation is done by what two ways?
- Down-regulate cytokines
2. Produce extracellular matrix
How are cytokines down-regulated in post-infection?
IL-4, IL-10, and TGF-Beta down regulate the cyotkines
How is extracellular matrix produced in post-infection?
PDGF and TGF-Beta induce it following increased proliferation and activation of fibroblasts
Chemokines are induced to release by what event?
Injury
How do chemokines function?
Transmit signals through seven transmembrane receptors that activate and recruit leukocytes to tissue damage sites
Two categories of chemokines based on sequence pair of amino acid cysteine?
- C-X-C Chemokines (Alpha)
2. C-C Chemokines (Beta)
Alpha chemokines attract what mostly?
Neutrophils
Examples of alpha chemokines include what? 5
IL-8, platelet factor 4, IFN-gamma, inducible protein 10, macrophage activation factors
What do beta chemokines attract mainly?
Monocytes and T lymphocytes
Examples of beta chemokines include what?
MCP’s
MIP
RANTES
What are cyotkines?
Intracellular signaling proteins acting locally by binding to high affinity receptors
Two main characteristics of chemokines as a whole?
- Redundant: Many cytokines induce same response
2. Pleiotrophic: A single cytokine can induce many different responses
Steps of Neutrophils undergoing diapedesis? 6
- Injury occurs and induces release of IL-1 and TNF-alpha
- IL-1 and TNF-alpha cause selectins to be expressed
- Endothelial selectins bind to PMN’s selectin receptor to cause “rolling”
- IL-8, MIP, and MCP release cause activation of PMN’s integrins
- Integrins bind to endothelial ICAM’s
- Diapedesis occurs and is facilitated by PECAM-1
What are lymphokines?
Cytokines made by lymphocytes
What are examples of endogenous pyrogens? (3)
IL-1
IL-6
TNF-alpha
What induces MCP, IL-8, and the acute phase resposne?
Endogenous pyrogens (IL-1, IL-6, TNF-alpha)
Functions of TGF-Beta 5
- Wound healing
- Immunosupressive
- Inhibits IL-2
- Inhibits proliferation of many cells
- promotes switching of B cell synthesis to IgA
Humoral immunity is mediated by what?
Antibodies
Humoral immunity is responsible for what?
Neutralizing microorganisms and toxins and removes antigens in the body fluids by amplifying phagocytosis or lysis by complement
Cell-mediated immunity is mediated by what types of cells? (3)
Cytotoxic T
NK Cells
Activated macrophages
Cell-mediated immunity is responsible for what?
Eradicating microorganisms inside body cells
Two central lymphoid organs?
Bone marrow
Thymus
What happens at the central lymphoid organs?
Immunocompetent cells are developed
Peripheral lymphoid organs include what? (4)
- spleen
- lymph nodes
- Tonsils
- peyer’s patches
What happens at peripheral lymphoid organs?
Immunocompetency is expressed
Multipotential stem cells oiginate where? (2)
- fetal liver
2. bone marrow
When stem cells migrate to fetal thymus, they acquire what?
Phenotypic characteristics of T cells
T cells are characterized by what special protein markers?
Clusters of Differentiation (CD)
What are the major CD’s on all peripheral T cells?
CD2 and CD3
CD4 defines what subset of T Cells?
Helper T cells
Helper T cells do what?
Aid responsiveness of B cells and other immunocompetent cells
Helper T cells differentiate into what 3 types?
Based on what?
Th0, Th1, Th2
Cytokines expressed
CD8 defines what subset of T cells?
Cytotoxic T cells
Regulatory T cells (Tregs) are composed of what two types?
- Naturally occurring with (CD4, CD25, and FoxP3 markers)
2. Adapative
Naturally occurring Tregs can do what?
Supress other T cells
Adaptive Tregs are functional when?
End of immune response
Antigenic receptors are specific for what?
Each antigen epitope
What are the two types of antigenic receptors on T cell membranes?
Alpha:Beta TcR
Gamma:Delta TcR
The homing area exists where?
Periarteriolarly in spleen
Paracortical and deep cortical regions in lymph
GI
Bronchus
What percentage of T cells leave thymus?
What happens to rest?
1-2%
Apoptosis
What are the stages of development of Th1 cell? 8
- CD34 Stem cell is the start
- After getting thymic hormones, becomes cortical thymocyte
- Acquire CD2, CD25, CD44
- Acquire CD1, CD2, CD4, CD8 and lose CD44 and CD25
- Acquire TCR-CD3 complex and lose CD1 in medulla
- Leave thymus and 90% obtain alpha:Beta TCR
- 70% become ThO with CD4+ and CD8-
- Become Th1 and secrete IL-2, IFN-gamma, and TNF-alpha
What are the stages of development of Th2 cell? 8
- CD34 Stem cell is the start
- After getting thymic hormones, becomes cortical thymocyte
- Acquire CD2, CD25, CD44
- Acquire CD1, CD2, CD4, CD8 and lose CD44 and CD25
- Acquire TCR-CD3 complex and lose CD1 in medulla
- Leave thymus and 90% obtain alpha:Beta TCR
- 70% become ThO with CD4+ and CD8-
- Become Th2 and secrete IL-4, IL-5, IL-6, IL-10, IL-13
What are the stages of development of cytotoxic and supressor T cells? 8
- CD34 Stem cell is the start
- After getting thymic hormones, becomes cortical thymocyte
- Acquire CD2, CD25, CD44
- Acquire CD1, CD2, CD4, CD8 and lose CD44 and CD25
- Acquire TCR-CD3 complex and lose CD1 in medulla
- Leave thymus and 90% obtain alpha:Beta TCR
- 25% become CD8+ and CD4-
- Differentiate into either cytotoxic or suppressor T cell
What are stages of development of gamma:delta TCR T cells?
- CD34 Stem cell is the start
- After getting thymic hormones, becomes cortical thymocyte
- Acquire CD2, CD25, CD44
- Acquire CD1, CD2, CD4, CD8 and lose CD44 and CD25
- Acquire TCR-CD3 complex and lose CD1 in medulla
- Leave thymus and 4% obtain gamma:delta TCR with CD3+, CD8-, and CD4-
What do T cells with alpha:beta TcR’s respond to?
Peptide antigens bound to MHC
What do T cells with gamma:delta TcR’s respond to?
Nonpeptide antigens but lack MHC restrictions
Function of T cells with gamma-delta receptors? 2
- antibacterial
2. Increased Cell mediated immunity against viruses
Th1 cells are involved in what? 3
- Activation of B cells, Tc cells, Th cells, and APC’s
- Downregulation of Th2 cell functions
- Increased CMI
Th2 cells are involved in what? (5)
- B cell differentiation
- Activation of eosinophils
- Downregulation of Th1 cell functions
- Class switching
- increased antibody
If stem cells remain in bone marrow, they acquire what?
Phenotypic CD markers of B cells
What distinguishes the B-cell antigenic receptor from the T cell?
Membrane bound, epitope-specific, monomeric IgM antibody
Upon antigenic and cytokine stimulus, what will B cells do?
Synthesize and secrete its antibody
B cell homing areas exist primarily where? (4)
Splenic follicles
Red pulp
Lymph nodes
MALT
T and B cells gain immunocompetency when?
Antigenic stimulus
What is the clonal selection theory
The total population of T and B cells is made up of millions of individual clones of cells, each dfined by specific receptor for a particular antigen epitope.
Antigen is modified by by what?
APC’s
Antigen selects what cells upon presentation?
Those T or B cells with membrane-bound receptor specific for its epitope
What are the stages of B cell development?
- Stem cells
- Gains CD19, CD22, and mu chain D-J gene arrangements to become pro-B Cell
- Addition of CD9, CD10, and V-DJ-C gene arrangements with mu chains appearing to become Pre-B cell
- Add CD20, CD21, CD37 and lose CD9 and CD10 while IgM and IgD receptors appear to become immature B cell
- Become mature B cell
- Activation by antigen and T cell cytokines IL-2, IL-4, IL-5, and IL-6 cause B cell to activate
- Activated B cell becomes either plasma cells or memory cells
Plasma cells secrete what antibody?
IgM
Plasma cells have an Ig switch to what?
IgG, IgA, IgE
What is an epitope?
Short sequence of amino acids or sugars in an antigen molecule that binds to the hypervariable region on an antibody
What is the number of repeats of an epitope called?
Valence
Does a microorganism have more than one epitope?
yes
What is a hapten?
Portion of antigen molecule that contains epitope
A superantigen can do what?
Link multiple T cells to MHC of APC via T-cell regions independent of their specific peptide binding sites resulting in activation of many nonspecific T cells and APC, causing secretion of extraordinary amounts of cytokines
What can thymus independent antigens do?
Activate B cells polyclonally without regard to B-cell specificity and without Th cell involvement
Thymus independent antigens are found where?
LPS on Gram negative bacteria
What is an antibody?
Mucoproteins found in gamma-globulin fraction of serum on electrophoresis
General structure of antibodies?
Four chain protein with two heavy and two light chain polypeptides linked by disulphide bonds
What determines which of the five classes an antibody is?
Amino acid sequence on H chain
H and L chains are each divided into what regions?
- constant region
2. variable region
The amino acid sequence of variable regions on heavy and light chains varies with what?
The epitope toward which the particular antibody is directed.
What area of the variable region is extremely specific for each H and L chain?
Hypervariable region
The hypervariable region of each H and L chain associate to form what?
Two epitope binding regions known as the antibody idiotype
What is a monoclonal antibody?
Antibody of a single specificity
How do you make a monoclonal antibody?
Fuse splenic B cells from immunized animal with malignant plasma cells to form hybridoma that secretes the desired antibody
IgG is composed of what chains?
Two L and Two H chains
Four subclasses of IgG?
Lambda 1, lambda 2, lambda 3, lambda 4
What does papain cleave igG into?
- Two Fab fragments
2. One Fc fragment
What can Fab do?
Contains one reactive site so can bind antigen but cannot agglutinate antigen
What can Fc do? (4)
- Activate complement
- Control catabolism of IgG
- Fix IgG to tissues or cells via Fc receptor
- mediates placental transfer of antibody
What can pepsin do to IgG?
Splits IgG behind the disulfide bond leaving the two Fab’s together to form F(ab’)2 and Fc
What can F(ab’)2 do?
Is bivalent so can bind antigen and form lattice to remove antigens
What happens to Fc after pepsin action?
Degraded
Which is removed faster from circulation, F(ab’)2 or intact IgG?
F(ab’)2
How common is IgG of all antibodies?
Most common
What does IgG look for when binding to a cell?
Cell that possesses a receptor for the Fc fragment from IgG
What are the two structural forms of IgM?
Monomer
Pentamer
IgM monomer is made by what cells?
B cells
IgM is kept where?
And has what function?
B cell membrane
Serves as B-cell receptor specific for a single antigenic epitope
How does the hypervariable region of IgM monomer differ between cells?
It differs for each B-cell clone
Secreted igM exists as what?
Pentamer form
What is structure of IgM pentamer?
Five monomeric IgM molecules joined together by J chain
What causes IgM pentamer to be secreted?
Antigen and cytokine activation of B cells
How similar are IgM pentamer and IgM monomer hypervariable regions of the same cell?
The same
Of the 10 binding sites on IgM pentamer, how may are high affinity?
5
When is IgM release in relation to other immunoglobulins?
First
What does IgM do?
Fixes complement
What are three forms of IgA?
- Monomer
- Dimer
- Dimer plus secretory piece
IgA dimer is transported across what barriers?
Via what?
Which is a receptor for what?
Respiratory and intestinal mucosal barriers
Secretory piece
IgA Fc region on the mucosal epithelium
The secretory piece also has what function besides transport of IgA dimer?
Protect IgA from ptoeolysis
Two subclasses of IgA?
Alpha1 and alpha2
IgA is found in high concentrations in what?
Secretions
IgA is found in what locations or secretions? (4)
Mucosal tissues
Saliva
Tears
Colostrum
What does IgA do?
Blocks bacteria, viruses, and toxins from binding to host cells
IgE has how many constant domains?
4
What mediates the B-cell switch to igE production?
IL-4
Why are IgE levels so low?
Its Fc region binds avidly to mast cells and basophils
How does IgE bind to mast cells and basophils?
Via Fc epsilon receptors on these cells
Binding of antigen to cells with IgE triggers release of what?
Vasoactive amines such as histamine that cause atopic disease such as hives and anaphylaxis
Does IgE cross placenta?
No
Does IgE fix complement conventionally?
No
Binding of IgE to IL5 activated eosinophils results in what?
Elimination of parasitic Helminths
IgD is found where?
B-cell membranes of 15% of ewborns and on adult blood lymphocytes in conjunction with IgM
IgD acts as what on B cells?
Receptor for antigen
3 main reasons for diversity of antibodies in humans?
- Genetic diversity
- Random Selection
- Allelic exclusion
Do the same genes or different genes code for the variable and constant regions of H and L chains?
Different
Explain the rearrangement of genes in antibody synthesis?
The variable region and constant region genes are rearranged during differentiation such that any one of the different variable region genes can be linked to a single constant region gene.
For formation of the L chain, what additional gene sequence is needed?
What does it link?
Joining segment
Links VL gene to the CL region gene
For formation of the H chain, how are all the genes linked?
A diversity segment links the VH gene to the J gene. These genes are then fused with the CH gene
What determines H chain class switching?
Rearrangement of class genes in the CH region determines the switch from mu and delta to gamma3, gamma1, alpha1, gamma2, gamma4, epsilon, and alpha2.
What mediates H chain class switching?
T-cell cytokines (IL-4, IL-13, IFN-gamma, TGF-Beta
Explain the steps of Kappa light chain synthesis?
- Germ line DNA has one V region joined to a J region resulting in B-cell DNA (Rearrangement)
- B-cell DNA is transcribed into primary RNA.
- Splicing forms a mature mRNA
- Translated into Kappa L-chain polypeptide
How does Lambda light chain synthesis differ from kappa?
Instead of just one constant gene for Kappa, there are six possible constant exons that can be used.
Random selection by each B cell from the variety of V, D, and J germ line genes results in what?
A huge variety of possible structures for VL and VH epitope binding regions.
Why does allelic exclusion occur in antibody synthesis?
Only one of the two parental alleles is expressed by a single B cell
What do HLA’s control?
- Discrimination between self and nonself
2. Antigen presentation to T cells
One restriction on HLA’s control?
Only can control discrimination and presentation to the same HLA type since self-MHC restriction occurs
HLA’s determine what?
Individual’s susceptibility to immunologic disorders and infections agents.
HLA’s are organized into what three classes of MHC?
MHC-I
MHC-II
MHC-III
Class I HLA/MHC are what type of molecule?
Found where?
Glycoproteins
Membranes of most nucleated cells
Class I HLA’s are linked to what cell?
Through what molecules? (2)
Cytotoxic T Cell
- CD8
- Present epitopes to specific Tc receptors
What is structure of Class I MHC?
Alpha chain with 3 domains
Beta-2 microglobulin (invariant protein)
The peptide binding site is where on class I MHC’s?
Between domains alpha1 and alph2
MHC I’s bind peptides of what length?
8 to 10 AA’s
Class II HLA’s are what type of mlecules?
Found where?
Glycoproteins
Membranes of dendritic cells, macrophages, activated T cells, and B cells
What are the three regions that encode Class II HLA’s?
DP, DQ, and DR
Class II HLA’s are linked to what type of cell?
Through what molecules? (2)
Helper T cells
- CD4
- Present epitopes to specific Helper T cell receptors
What is the structure of Th cell?
Two chains alpha and beta with two domains each
The peptide binding site of MHC II’s is formed by what?
Juxtaposition of alpha1 and beta1 domains
What size of peptide do MHC II’s bind?
13-18 AA’s
Class III HLA’s control what?
Certain cerum proteins
Describe the polymorphism of HLA’s
Many alleles of class I and II are present at each locus on chromosome 6 allowing haplotypes from both parents to be inherited and expressed codominantly.
The TCR is a dimer of what? 2
Either alpha and beta chains (95%)
Or gamma and delta chains (5%)
What do TCR’s recognize
Antigenic epitopes as peptidic fragments bound to either class I or clas II HLA molecules on an APC
What determines whether humoral or cell-mediated immunity will occur?
The coreceptors on the T Cell (CD4 or CD8)
What two things must bind together for humoral immunity?
CD4 to Class II
What two things must bind together for cell mediated immunity?
CD8 to Class I
Union of specific TCR and coreceptor with the peptide HLA membrane complex is associated with what?
Signal transduction of CD3 complex into cytoplasm
Genetic diversity in TCR’s are accomplished through what?
TCR’s
How are TCR’s synthesized? 3
- Germ line DNA undergoes rearrangement by recombinase enzymes RAG-1 and RAG-2
- Randomly selected V gene is joined to a J gene and is transcribed
- Transcript combined with Constant region gene and translated
What controls the genetic expression of TCR’s?
Allelic exclusion
What is affinity the measure of?
Binding energy between an antibody and univalent epitope
What is avidity?
Total binding energy between an antibody and a multivalent antigen
What is the complement complex a part of?
Both innate and adaptive immunity
The complement complex is comprised of what?
Nine major factors (C1 to C9) most of which are pro-enzymes present at constant levels in serum.
What does the classical complement pathway result in?
Lysis of microbial or mammalian cells to which IgM or a doublet of IgG1, IgG2, or IgG3 antibody has been bound to the membrane followed by sequential fixation of C to the antigen-antibody complex.
What are the steps of the classical complement pathway? 8
- C1qrs is bound initially via C1q
- Cleavage of C4 and C2
- C4b and C2a bind to the cell surface as C4b2a
- C4b2a act as C3 convertase that cleaves C3 into C3a and C3b
- C3b complexes with C4b2a to become a C5 convertase that cleaves C5 into C5a and C5b
- C5b combines with C6 and C7 and insert into cell membrane
- C8 and C9 combine with C5b,6,7 complex to form the membrane attack complex ( MAC)
- The MAC causes increased permeability leading to cell lysis
The alternate pathway is activated by what? 4
- Cell walls of certain Gram-negative and Gram-positive bacteria
- Viruses
- Yeasts
- Aggregated IgA
The alternate pathway acts independent of what? (4)
- Antibody
- C1
- C2
- C4
Steps of alternate pathway of complement? 5
- Initiation by cell wall absorption of small amounts of C3b in normal serum
- Binding of Factor B to C3b
- Factor D catalyzes Factor B into Ba and Bb
- The resulting complex C3bBb has C3 convertase activity to generate additional C3b
- C3bBbC3b forms and acts as C5 convertase leading to further reactions resulting in MAC.
The mannose-binding lectin pathway follows what?
Binding of an acute phase protein, MBL, onto mannose residues on cell walls of certain bacteria, fungi and viruses
The MBL complex acts similar to what?
C1 and so follows classical pathway forming C3 and C5 convertases that result in cell lysis via MAC.
C3a and C5a also have what functions?
- Vasodilators
2. Chemotaxis allowing cells and cytokines to join response
Binding of fragment C3b to microorganisms promotes what?
Opsonization through C3b receptor on phagocytic cells
If antigen entry is intravenous, where is it taken up?
Spleen
If antigen entry is non-intravenous what happens
Antigen is trafficked to the lymph node draining the site of entry and then processed by APC’s
What are the steps of exogenous protein antigen processing?
- Pinocytosis from extracellular environment
- Processed in acidic endosomal vesicles
- Vesicles then bind to the cleft in MHC class II molecules
- Molecules are transported to cell membrane where they can be presented to CD4 T Cells
- CD4 T cells activate B cells for antibody synthesis
Viruses and intracellular parasitic antigens are processed in what steps? 4
- Synthesized endogenously within APC cytoplasm and ER
- Processed to peptides by proteasomes
- Peptides bind to the cleft in MHC class I molecules
- MHC’s migrate to the APC membrane where they are presented to CD8 T cells to initiate CMI
CMI is directed against who?
Intracellular-dwelling microorganisms and aberrant, endogenous cells such as cancer cells
What is antibody-dependent cellular cytotoxic reaction?
Feector cell is linked to the target cell by an antibody bridge with the Fab portion binding to the specific membrane antigen on the target cell and the Fc portion binding to the Fc receptor on an activated effector cell
Activation of T cells is initiated when?
Specific CD4 or CD8 T cell receptor binds to the appropriate APC peptide-HLA complex
What molecules strenghten the binding of TcR to APC:HLA complex? 3
- CD28
- CD2
- LFA-1
What is function of CD28?
Binds to B7.1 on APC and increases IL-2 synthesis
What is function of CD2?
Binds to leukocyte functional antigen (LFA-3)
What is function of CTLA4?
Binds to B7.2 which down regulates IL-2 synthesis following activation
An activation signal to the T cell is transduced through what?
CD3 complex of 3 polypeptides: gamma, delta, epsilon, and two zeta
Th1 cell induces what?
Following what?
CMI
Binding of Th1 to the peptide-class I MHC
What do Th1 cells secrete? 5
- IL-2
- IFN-gamma
- TNF-alpha
- IL-12
- IL-18
Function of IL-2
Necessary for T and B cell transformation
Function of IGN-gamma?
- Enhances CMI by activating macrophages and NK cells
- Triggers HLA antigen presentation by endothelial cells
- Suppress antibody formation by down-regulating IL-4 synthesis
Function of TNF-alpha
Activates macrophages, and syergizes with IL-1 in inducing and stimulating the acute phase response
IL-12 and IL-18 function?
Aid the transition of macrophages, Tc cells, and NK cells to CMI
The Th2 cell induces what?
Following what? (2)
Activation of B Cells and humoral immunity
- Binding to peptide-class II MHC
- Stimulation by IL-2
Th2 secretes what upon activation?
- IL-4
- IL-5
- IL-10
- IL-13
IL-4 does what? 4
- Develops antibody synthesis by stimulating B-cell differentiation
- Helps in IgE production
- Down regulates IFN-gamma by Th1
- Suppress CMI
IL-5 does what? 3
- Works with IL-4 and IL-2 to aid B-cell differentiation
- Stimulates growth of eosinophils
- Facilitates IgA synthesis
IL-10 does what?
Inhibits Th-1 release of IFN gamma and IL-2 thus reducing activation by IFN-gamma
IL-13 does what?
Mimics IL-4 actions, inhibiting Th1 cytokine release
B-cell response is initiated by what?
Antigen selecting the clone of B cells with the membrane-bound IgM antigen receptor that is specific for the antigen epitope
What triggers differentiation of B-cell clone into a large blast cell? 2
- Binding of antigen
2. Stimuli from IL-2 and IL-4 from T cells
What stimulates continuation of B cell differentiation?
IL-5
H and L chains of B cell antibodies are synthesized under stimulation of what?
IL-5
What causes the B cell to differentiate into a plasma cell and secrete IgM?
IL-6
Gene arrangements on B cells result in what?
Switch to IgG, IgA, and IgE synthesis
What stimulates a plasma cell’s switch to IgG production? (2)
IL-4 and IFN-gamma
What influences the plasma cell’s switch to IgA production?
TGF-Beta
What stimulates a plasma cell’s switch to IgE?
IL-4
What binding is required for a B cell to switch its antibody production?
CD40 on B cell to ligand on Th cell
A secondary response to the same antigen can result in what? 4
- Shorter induction period to antibody synthesis
- More class switching from IgM to IgG
- Increased IgG with antibodies of higher affinity
- Predominant IgA synthesis in mucosal tissues