Feb. 24th (Exam 2) Flashcards
What are the two goals of the primary immune response?
What do these goals entail?
- Stop the infection ASAP
- aka develop the effector cells and molecules
- Prevent reinfection by the same pathogen
- temporarily strengthen defenses to prevent reinfection aka Protective Immunity
- develop an immunological memory - Memory Cells
Where does protective immunity come from?
Antibodies made by effector B cells during a primary infection are made and sustained for several months after infection has been cleared; these antibodies are the source of the protective immunity, ensuring that another infection by the same pathogen in that time won’t cause disease.
What are memory cells?
They are a reserve of long-lived B and T cells
Review question:
What are the three ways that antibodies clear pathogens?
- Neutralization
- Opsonization
- Activation of Complement system
Check for Understanding Question
After the primary infection, what is present?
Where are they present?
Where do they originate?
What do we call this?
There should be high affinity, pathogen-specific antibodies.
They float around in the blood, lymph, tissues, and mucosal surfaces.
They come from plasma cells that are either in the bone marrow or in the tissue below mucosal surfaces.
This is called Protective Immunity and it is present for months after an infection is cleared.
What is the fate of most plasma cells?
They will die.
How do plasma cells die?
- Complexes of the antibody (they secrete) and the antigen bind to a receptor called Fc(gamma)RIIB1, and this leads to apoptosis (kinase pathway)
- They lose contact with the stromal cells - adhesion molecules that provide survival signals
- They lose survival signals from stromal cells (IL-6)
What are long-lived plasma cells?
What do they do?
How do they stay alive?
They are a small population of plasma cells that reside in the bone marrow.
They sustain a low, steady-state of circulating, antigen-specific abs
They survive via interactions with the stromal cells that they adhere to and that secrete IL-6.
What happens when there is a subsequent infection because we have long-lived plasma cells?
The pathogen is immediately met with the high affinity abs.
Abs then can participate in the innate response, binding to pathogen and delivering it to effector cells of innate immunity.
What happens if this innate immune response is insufficient?
We will see that the ab speeds up the delivery of the pathogen to Antigen Presenting Cells, initiating the secondary immune response.
When are memory B cells made?
Re-explain the idea of this.
They are made during the primary response to a pathogen - it gets activated by the pathogen in the secondary lymphoid tissue and a Follicular Helper T cell activating it.
This creates a clone of pathogen specific B cells (most of them are effector cells) a few are memory cells.
When does the secondary immune response occur?
When a second infection happens AND is not successfully cleared by the combination of the innate immunity and the steady-state level of pathogen specific antibodies.
Why is the secondary immune response better AND faster?
- The pathogen specific memory cells far outnumber the naive lymphocytes that are present when a first infection happens.
- The memory cells, similar to effector cells, are more readily activated than the naive cells
- Memory B cells have undergone have undergone isotype switching, somatic hypermutation, and affinity maturation
What does affinity maturation in the secondary immune response result in?
A second generation of memory B cells that are better suited than the memory cells that were produced in the primary response.
What is another word for the secondary immune response or any of the subsequent responses after?
anamnestic response
meaning…
without loss of memory
What is the Vaccinia vaccination?
What does it induce?
This is a live virus vaccine that comes from a virus that is a close relative to the small pox virus.
It induces the persistence of virus-specific abs (from memory B cells) and virus specific T cells for life.
What are naive (specifically) lymphocytes dependent upon for their survival?
What happens if they don’t get them?
They need to receive survival signals through their antigen receptors.
They will die via apoptosis in due time if they don’t get the survival signals?
What makes memory lymphocytes different in this regard?
What state are most memory cells in?
What about the rest of them?
They don’t require survival signals through their antigen receptors - their stimulation is antigen-independent.
Most of the memory cells are in a quiescent state.
The rest (a very small fraction) are dividing and replenishing to replace the cells that have died.
What drives the antigen-independent activation and proliferation of memory cells?
Memory B cells - interactions with stromal cells of the bone marrow and the cytokines they produce
Memory T cells - IL-7 and IL-15 cytokines
How can we distinguish naive B cells, Plasma cells and Memory B cells?
Distinguish them based on the criteria.
- Undergoes somatic hypermutation
- Undergoes isotype switching
- Secretes abs
- Has surface immunoglobulin
Naive - no somatic hypermutation, no isotype switching, no abs secreted
Plasma - no surface immunoglobulin, underwent isotype switching and somatic hypermutation during B cell activation in the germinal center
Memory - have surface immunoglobulin, underwent isotype switching, somatic hypermutation and does NOT secrete antibodies.
What is the unique cell surface marker that is only expressed in memory cells but not naive or plasma cells?
CD27
- What type of abs are secreted at the beginning of the primary response?
- What will give rise to the more specific, high affinity abs IgG IgA IgE?
- Where do the memory B cells come from?
- Low affinity IgM abs
- a. somatic hypermutation
b. affinity maturation
c. isotype switching - The memory B cells come from clones of the B cells that were making abs that have the highest affinity for antigen.
Relatively, only referring to the specific type of memory cells, when are they at their highest level?
Usually two months after the initial infection - those cells are sustained for life.
How can we be sure that low-affinity antibodies and IgM are not made in the secondary response?
How does this happen?
The activation of naive pathogen specific B cells is suppressed -
How?
immune complexes made of the pathogen (or antigens) are bound to antibodies that were made by the B cell in the primary response (ones that have high affinity).
These complexes bind to the B cell receptor of the pathogen specific B cell (IgM) and to an inhibitory Fc receptor called Fc(gamma)RIIB1
This cross-links the B cell receptor and the Fc receptor and delivers a negative signal for inhibition of the activation and subsequent apoptosis.
Review question:
When does the secondary response happen?
Happens when the reinfecting pathogen overcomes the combined defenses of innate immunity and the steady-state level of pathogen-specific antibody.
What makes memory B cells better than naive B cells in regard to how they recognize antigen (binding), internalization (receptor mediated endocytosis) and their interactions with follicular helper T cells?
What are the effects of these differences on the secondary response when another infection happens?
- They are better at binding (higher affinity) - due to the affinity maturation and somatic hypermutation that has occured
- The high affinity of their antigen receptors makes them better at internalizing antigen
- They have more MHCII and other costimulatory molecules on their surface that make the interactions with FH T cells more efficient.
Effect 1 - a smaller population of pathogen is needed to initiate a B cell response
Effect 2 - once the memory B cells are activated, it doesn’t take them as long to differentiate into plasma cells
*we see that abs is detectable only 4 days into the infection rather than 8 days.
How does Hemolytic disease of the newborn happen?
This disease can happen when a father who is RhD+ (polymorphic erythrocyte antigen) meaning he has that antigen on the surface of his RBCs, has a child with a mother who is RhD-.
This only occurs after subsequent pregnancies with an infant who took on the RhD+ phenotype, however. The first birth, when the fetal blood is exposed to the mothers causes the mother to produce antibodies against it which are mainly lots of IgM and small amounts of IgG - not very many of the fetal red blood cells are killed.
However, the mother will develop an immunological memory to this and memory B cells that produce IgG that have much higher affinity will be made and can kill off tons of the RBCs of the fetus when they inevitably cross the placental membrane.
RhOGAM is given to the mother to mask the antigen if it is exposed to the mother’s immune system so this memory cannot be formed.
Why is the suppression of the naive B cells during the secondary immune response good/bad for certain viruses?
- Measles/Small pox
- Flu
- For these diseases, which don’t change their antigens very much, this is great because we can have the full attention of the memory B cells that are just more specific in making antibodies etc. etc.
- After you make memory B cells for specific epitopes of the original virus that you were infected with, only those cells are allowed to function and we can’t get a novel response.
