Lecture 1: Intro to the immune system Flashcards
What do B cells (B lymphocytes (white blood cells)) produce?
Antibodies
Where do B cells mature?
In the bone marrow
What part of the immune response do B cells belong to?
The adaptive/acquired and humoral (fluids/lymph/blood) immune response
What is a vaccination?
Introduction of a dead or weakened antigen (bacteria/virus/toxin) to the immune system so that the adaptive immune system can “meet” the antigen and produce antibodies against it so that if you run into that antigen/infection again your body already knows how to mount a response against it (so if you get sick you won’t get nearly as sick)
What is the primary difference between the innate and adaptive immune responses?
The adaptive immune response has the ability to “remember” specific pathogens
The adaptive response is also systemic rather than restricted to a specific mucous membrane, such as the sinus cavity
What are the three main characteristics of the adaptive immune response?
- It is specific (through antibodies)
- It is systemic (via the blood and lymph)
- It has a memory
What are the two components of the adaptive immune response?
- Humoral immunity (blood and lymph systems)
2. Cellular defenses
What are antigens?
An external “invader” or foreign object: essentially “non-self” material
Bacteria, viruses, fungus, toxins, pollen, and even cancerous cells
What is immunocompetence?
The ability of a B cell to recognize “friend or foe,” this ability is developed while maturing in the bone marrow.
Also how to recognize and bind a particular antigen
While also developing “self-tolerance” so the immune system doesn’t attack the healthy cells of the body it belongs to
Membrane bound antibodies
Expressed on the surface of B cells
Each B cell expresses one unique type of membrane bound antibody so that your adaptive immune system is highly diversified and prepared for attack
What happens when a mature but inactive B cell meets its “perfect match” antigen?
The B cell becomes activated and goes into “berserker mode,” dividing and producing two specific B cell sub-types
What two types of cells do B cells produce once activated by their antigen?
Effector cells: active fighters which can produce free floating versions of their membrane bound antibodies that can target the specific antigen
Memory cells: long lived “mages” that preserve the genetic code for the successful antibody that originally matched the invading antigen
Memory B cells
Hang around and are able to mount a faster attack when the body is re-exposed to a previously experienced pathogen.
This is why vaccines against diseases like measles, mumps, rubella, and chickenpox are so effective. The memory B cells make our immune systems more effective so we don’t become reinfected even when re-exposed to these antigens.
The secondary immune response is both stronger and faster than the initial immune response when the B cell needed to “meet” its “perfect match” antigen for the first time
Another name for effector B cells
Plasma cells
What organelle do plasma cells have an abundance of?
Rough endoplasmic reticulum
This is to pump out tons of free floating antibodies
What do free floating antibodies do?
They travel through the blood and lymph, binding to their antigen match, thus marking those antigens for death/phagocytosis
They can also block the binding sites on viral and bacterial toxins to prevent them from binding to your tissues
What is agglutination?
When free floating antibodies (which have multiple binding sites) bind to multiple antigens forming clumps so they have a harder time getting around and are easier for macrophages to consume and digest
Why aren’t babies immunized right after birth?
Because in the first few months their immune systems are passively acquired through the placenta and breast milk and their B cells can’t create memories from those acquired free floating antibodies
History of cowpox and small pox
Sticking scabs from infected people into other people to confer some degree of immunity
Milkmaids (who were exposed to cowpox) wouldn’t develop small pox because the two diseases are similar enough to act like a rudimentary vaccination
So Jenner inoculated a boy with cowpox and then exposed him to smallpox but the boy didn’t get sick
Pasteur repeated this with more scientific rigor in chickens using old and weakened bacterial cultures as the initial inoculation
Vaccination comes from vacca for cow
What is an antibody
a Y shaped host protein (immunoglobulin Ig_) produced in response to antigens
Structure of an antibody
Y shaped
2 identical heavy chains(determine class G, A, E, D, M) IgG is most common
2 light chains (kappa or lambda)
The heavy and light chains are linked by disulfide bonds
Variable ends for binding and specificity
Base of the Y is the constant region
Antigen binding sites
Antigens can bind antibodies using their membrane, cytoplasm, nucleus, organelles, or a combination of sites.
Proteins are ideal, but polysaccharides, nucleic acids, and other polymers can also be antigenic
Pasteur “pasteurization”
Heat inactivation of bacteria
Worked on chicken cholera and anthrax
Also developed a rabies vaccine
Hypo-immune diseases
Weakened immune response HIV/AIDS
Hyper-immune response
Autoimmune, like leukemia where the body attacks itself “over reaction”
Innate immunity
The immunity you have because you are you (genetics) Some people have better “natural” immunity against certain antigens than others
Adaptive immunity
The immunity you develop through living
What are the three types of lymphocytes (White blood cells)?
Natural Killer NK T cells (mature in the thymus) B cells (mature in the bone marrow)
T cells (destroy)
Destroy infected cells (some bacteria, all viruses)
B cells (destroy)
Secrete antibodies to attack extracellular pathogens (most bacteria)
Where lymphocytes produce an immune response
Malt, Balt, Galt
lymph nodes spleen tonsils appendix peyers patches in the intestines other mucosal associated lymphoid tissue (MALT)
Other antigens
non-self human tissue (like transplants)
pollen
protozoa
you own tissue from a different part of your body (ex: arm skin grafted onto the leg)
What are epitopes?
Antigen binding sites
This is a specific region on an antigen (the foreign object) that is recognized by T cells or B cells
The spot on an antigen that binds to the unique portion of the short Y arms of the antibody
Antibodies can attach to multiple antigens (because they have two N-terminal specific end sites) but that bond only occurs between the n-terminus and one specific/unique epitope
Antigen binding sites (fab)
The N terminus that determines specificity of the antibody
The variable regions at the short end of the heavy and light chains combine to form this region
Biological activity site (fc)
Constant region (long base of the Y) on the heavy chains
Determines the immunological fate of an antigenic microbe
Can activate the serum proteins in the immune response
Specificity vs sensitivity
Specificity is the selectivity of binding a particular epitope
Sensitivity is the amount of antigen a technique can detect
Cross reactivity
the ability of some antibodies to bind to epitopes that are similar to their perfect match (ex cow pox vs small pox)
Different clones of plasma cells will make antibodies to the same antigen, but some may be a more perfect fit than others
Avidity
strength of the overall fit between n-terminal antigen binding sites and all of the epitopes on an antigen
Affinity
the association constant between antibody and an antigen (how close/tight the fit is)
Polyclonal antisera
IgM antibody isolated from human blood
Injected into rabbit, acts as an antigen
Rabbit makes anti human IgM antibodies
Multiple B cell lines against the antigen develop
These multiple lines of antibodies are isolated as a heterogeneous mixture known as polyclonal antiserum
Generally less specific, more variable, esp if one or several of the rabbits die
Polyclonal characteristics
highly sensitive (because multiple epitopes are targeted by the mixture)
Not as selective, due to multiple epitope targeting that can result in background staining since some different molecules may have shared epitopes
Difficult to standardize since there can be batch to batch and lot to lot variation
Monoclonal antibodies
Inject mouse with antigen
B lymphocyte cell selected based on desired epitope specificity
Fused with highly proliferative cancer cell line (myeloma) to form hybridomas (produces antibodies like B cells and retains immortality of cancer)
Hybridomas divide rabidly producing a single “cloned” cell line, producing identical antibodies
Allows unlimited production via cell culture or implantation in mouse peritoneal cavity
Monoclonal advantages
Homogeneity
Absence of non-specific antibodies
No batch to batch or lot to lot variability
Paratope
The (specific) region on an antibody arm that binds to the epitope region of an antigen
Short arms can be?
kappa or lambda
