Exam 1 -- Ch. 3 (B-cells and Antibodies--adaptive system) Flashcards
What is the component of the Ag (antigen) that the Ab (antibody) interacts with? What part of the Ab is there?
epitope, which is the antigenic determinant
variable region of Ab binds to epitope
What are molecules too small to cause an immune response, but combined with a carrier molecule a response is generated?
Haptens
What is an example of a hapten?
penicillin
What can anitbodies also be called?
immunoglobulins
What are proteins that are produced in response to an Ag?
antibodies, which are highly specific
What is the part of the anitbody called in a serum fraction?
gamma globulin
What is the structure of an antibody?
Four polypeptides
- two heavy chains (identical)
- two light chains (identical)
Constant Region
Variable Region
What joins the chains of the anitbody?
disulfide bridges
What is the antigen binding portion of the antibody called?
Fab
Antigen Binding portion
What is the stem part of the antibody called?
Fc region
Describe the constant region and the variable region of the antibody.
Constant regions– stay the same (stem)
Variable regions– changes (antigen-binding portion; “Fab”)
What are the five classes/isotypes of immunoglobulins? What are they based on?
Based on constant region–heavy chain of Ab; and they play diff roles.
“GAMED”
IgG, IgA, IgM, IgE, IgD
What are the four subclasses of IgG?
IgG1, IgG2, IgG3, IgG4
What is the most dominant Ab’s in serum (blood)?
IgG
What Ab can cross blood vessels?
IgG
What Ab can cross the placenta?
IgG
What Ab activates the complement system? Specifically which one?
IgG, and IgM
the Classical pathway
What does IgG enhance? What does it help eliminate?
enhances phagocytosis
helps eliminate bacteria, viruses, and bacterial toxins
What is the most abundant Ab in the body?
IgA
Where do we find IgA?
- ass. with mucous membranes
- found in mucus, tears, saliva, as “secretory IgA”
What Ab is associated with mucous membranes?
IgA
We know IgA is found in mucous membranes, but how is it protective there?
prevent viral and bacterial attachment to mucosal lining = neutralization
What kind of structure is IgA and how is that beneficial?
dimer
- allows transport into GI tract
What Ab can cluster pathogens together? And what is that called?
IgA and IgM; agglutination
What Ab is found in breast milk?
IgA; and can coat baby’s GI tract
What structure is IgM?
pentamer (5)
Which Ab is the predominant Ab against RBC antigens?
IgM
Which is the first type of Ab to appear in response to “new” antigen?
IgM; is an excellent activator of compliment system
T/F. IgM can cross vessels easily.
False– IgM cannot cross vessels easily, like the placenta
Which Ab is associated with allergies?
IgE
What does the IgE antibody do?
- bind to mast cells and basophils
- release histamine
- attracts phagocytes
- effective against parasitic worms
Which Ab is effective against parasitic worms?
IgE
What part of the Ab of IgE do mast cells bind?
Fc (stem)
Upon first exposure to antigen some make IgE, but what happens on the second exposure?
Ag binds IgE, which is on Mast cells, and causes degranulation
What are two possible results when the IgE Ab is involved in a response?
- Small local impact
2. Large systemic impact
What does a small local impact entail from involvement of IgE?
- increase capillary permeability
- usually a local effect (runny nose)
What does a Large systemic impact involve for an IgE response?
- massive degranulation throughout body–> can decrease blood volume drastically to point of a heart attack
- contraction of smooth muscle of respiratory tract (difficult breathing –> suffocation)
Which Ab can cross placenta, an OK complement fixer, good opsonizer, and helps NK cell kill?
IgG
Which Ab if first Ab made, a great compliment fixer, and a good opsonizer?
IgM
Which Ab causes allergies, defends against parasites, and causes anaphylactic shock?
IgE
Which Ab is in mucosal secretions, is resistant to stomach acid, protects mucosal surfaces, and is secreted in milk?
IgA
Where do B cells come from?
Hematopoietic stem cells
What are B cells?
WBCs (from bone marrow) that make antibodies
How many different kinds of B cells are there? How many are made a day? How many are in the blood?
100 million kinds of B cells
1 billion new ones produced a day
3 billion in blood
Do B-cells have specific or general Ag receptors for one Ag?
specific
What are the receptors that are on B cells?
Ab’s, specifically IgM or IgD
How is a B cell activated?
Ag binds to Ab on the B-cell and activates it
The Ag will select what B-cells proliferates, what is that called?
Clonal selection (2 fates)
What are the two fates of B-cell once it is activated?
- plasma cells produce Ab 2000/sec
2. Memory cells last for decades
Once the Ag/Ab complex is formed what occurs?
tags foreign cells/molecules for destruction
What are the 5 protective mechanisms of binding antibodies to antigens?
- agglutination
- opsonization
- neutralization
- antibody dependent cell mediated cytotoxicity
- complement activation
What do theses 5 protective mechanisms consists of?
- agglutination
- opsonization
- neutralization
- antibody dependent cell mediated cytotoxicity
- complement activation
- clumping Ag
- enhances phagocytosis
- block viruses and toxins
- tag worm with Ab
- lysis and inflammation
What is the antibody titer?
measures the level of Ab in blood, telling us the intensity of response
When it comes to Ab memory, what Ab is most involved in the primary response? What about the secondary response?
Primary response = IgM
Secondary response = IgG
What is the secondary Ab response important for? Which Ab is involved?
IgG, important for a faster response
Describe the Modular Design of the Heavy chain part of the Ab.
there are multiple copies of four gene segments that code the antibody’s heavy chains
(V, D, J, C)
What do the V, D, J, and C stand for on the heavy chains?
variable
diversity
junctional
constant
The Fc region is a string of gene segments where are……?
(Fc is constant part of heavy chains)
Cm, Cd, Dg, Ce, Ca
Describe the Modular Design of the light chain part of the Ab.
there are multiple copies of 3 gene segments that code that antibody’s light chain (V, J, C)
(NO D region!!)
What are the light chains availability for its constant region?
L or K
What is junctional diversity?
how we “glue” the various gene segments together; an imperfect process that includes deletion and addition of nucleotides(DNA bases) b/w the gene segments
What is the Combinatorial Process?
combination of heavy and light chains (the two Variable segments light up and give MORE specifity)
Overall, what are the three things that give Antibody Diversity?
- Modular Design
- Junctional Diversity
- Combinatorial Process
On a given B cell are all the BCR’s the same?
YESSSSSS
- recall IgM and IgD serve as the BCR’s
What are B cells called that have never encountered their cognate antigen?
“naive” or “virgin” B cells
What are B cells called that have been activated?
“experienced” B cells
Describe the pathway of the B-cell signaling its nucleus. (~ 4 steps)
- B cell encounters its “cognate antigen”
- BCR binds the epitope
- Mult. Ag or sights on Ag bind to BCRs
- BCRs cluster or “crosslink”
When the BCRs cluster or “crosslink” what occurs?
the Ig-alpha and Ig-beta interact with enzymes inside the cell ——> when clustered together the signal may be strong enough to activate the nucleus
What are the Ig-alpha and Ig-beta portions of the BCRs?
They are NOT part of the Ab, but are ass. with the BCRs and are the integral membrane proteins
How many signals do B-cells need to be “activated”?
Two!
- B cell receptors binding Ag and then cluster
- Co-stimulatory signal enhances signaling
What are the two sources of B-cell Co-Stimulation?
- T-cell dependent co-stimulation (BETTER)
2. T-cell independent co-stimulation
Which Co-stimulation of the B-cell is it when some antigens have repeating patterns and will heavily cluster the BCRs and additional receptors bind the antigen or complement, all independent of Tcells?
T-cel independent co-stimulation
How does the T-cell Dependent Co-stimulation work? (~5 steps)
- B- cell encounters its cognate antigen
- B-cell endocytosis its cognate antigen
- B-cell presents peptide fragments on MHC II on its surface
- T cell meets its cognate antigen (MHC II peptide on B-cell)
- T cell’s CD40 binds the B-cell’s CD40L
***DUAL CONFIRMATION
How does the T-cell Independent Co-stimulation work?
- B-cell encounter its cognate antigen that has repeating sequence/pattern
- BCRs cluster (1st signal)
- Co-stimulatory receptor (TLR or complement receptor = type of PRP, a bacterial component)
- no T-cell needed to stimulate response
What is the Un-natural B-cell co-stimulation involve?
- Anitgen (mitogen) binds to B cell molecules that are not BCRs
- the non BCR molecules cluster
- BCRs cluster with non BCR molecules
- signal NOT dependent on cognate antigen for a given B cell
Why do some pathogens use the un-natural B-cell co-stimulation way? What does it result in?
rely on this to confuse the immune system and skip the specificity
results in polyclonal activation of B cells
After activation and proliferation, what do B cells go through next?
maturation process
What are the the three processes for the B-cell maturation process?
- Somatic Hypermutation
- Career Decision
- Class Switching
What does the Somatic Hypermutation part of B-cell mutation involve?
- BCR genes undergo mutation and selection
- creating a greater affinity of the BCR for its cognate antigen
Ont he B cell chromosomes (regions containing V, D, and J gene segments) undergo one mutated base pair per __________ per DNA replication cycle.
1000 bases per DNA replication cycle
- very restricted to these chromosomes and these regions
- fine tunes antigen specificity of BCR and antibodies
What is changed during the Somatic Hypermutation part of B-cell maturation process?
changes the antigen binding region of the antibody —> therefore may INCREASE or DECREASE affinity of Ab for its cognate antigen, or affinity remains unchanged
What are the three possibilities during Somatic Hypermutation of the B-cell when the antigen bonding region of the Ab is changed?
- Increase affinity of Ab for Ag
- Decreases the affinity of the Ab for its Ag
- affinity of Ab for Ag is unchanged
In order for B-cells to continue proliferating they need ongoing signal, how does this affect them?
- B-cells mutating toward higher affinity BCRs are STIMULATED more easily
- B-cells mutating toward lesser affinity BCRs are NOT stimulated and cease to multiply
What are the Two Career Choices that B-cells have during the maturation process?
- Plasma Cell
2. Memory cell
What do Plasma cells do? Where to they usually go? How long do they live?
- create Ab’s, up to 2000 per second
- back to spleen or bone marrow
- few days
What do Memory cells do?
- wait for next time
- provide faster secondary response
How do we make different classes of antibodies? How do we class switch them?
- Make classes: “GAMED”
- determined by Fc (constant) region of heavy chains
- B-cells cut and paste diff constant regions
What class of the constant region of an Ab is most common?
IgM, b/c that is first in line on the constant region
What are the overall goals of B-cells and Ab?
- create diversity in Ab structure
- rapid response to make fore B-cells to combat specific Ag
- rapid ability to create Ab’s specific to Ag
- fine tune Abs
- create long-lasting memory of Ag’s
