16 Immunology II (Acquired Immunity) Flashcards
3 lines of defense against pathogens?
- Surface entry barriers (1st line)
- Internal chemical and cellular barriers (2nd line)
- Acquired (aka specific, adaptive) immunity (3rd line)
Acquired immune sys is characterized by discrimination. What does this mean?
- It’s able to distinguish foreign from “self” molecules
2. can differentiate b/w two similar foreign molecules
Acquired immune sys is characterized by diversity. What does this mean?
It can recognize ALL possible foreign molecules
Acquired immune sys is characterized by memory. What does this mean?
It can REMEMBER a foreign molecule if it was previously encountered
Two components of acquired immunity?
- Humoral immunity
2. Cell-mediated immunity
What’s humoral immunity?
Production of antibodies by B-cells in response to antigens
What’s cell-mediated immunity?
Activation of T-cells for the ctrl of “intracellular” microbes
In humoral immunity, what is an antigen?
Any substance that stimulates the B-cells to make ANTIBODIES
In humoral immunity, what is an antibody?
Proteins made by B-cells which’re able to specifically recognize and bind to only that antigen
What occurs if an antigen is too large?
Only a small portion of the antigen (“epitope”) is able to stimulate antibody production
T or F: A single bacterial cell will contain only ONE epitope.
F
A single bacterial cell will contain many different epitopes
Structure of antibody?
- Four polypeptide chains
2. Two “ends”
What’re the two ends of an antibody?
- One end = constant end > same structure in all immunoglobulin molecules
- other end = variable > differs in structure b/w immunoglobulin molecules
What end specifically recognizes and binds a unique antigen?
The VARIABLE end
T or F: One antibody can bind two different types of antigens.
F
Both antigens must be the SAME
What is antibody specificity?
Ea. antibody specifically recognizes its own complementary antigen and shouldn’t “cross-react” w/ a diff antigen
What is antibody diversity?
A specific antibody can be made for EVERY diff antigen
What cell produces antibodies?
B-cells
How does the body make so many diff antibodies?
Humans carry a complete collection of MANY diff B-cells, ea. of which is able to recognize only one specific antigen
Outline the steps of B-cell differentiation when it encounters an antigen?
- Antigen is recognized by, and binds to, its specific B-cell
- Binding of antigen triggers the B-cell to divide and differentiate into MEMORY cells and PLASMA cells
- Plasma cells make antibodies
- Memory cells circulate in the blood and rapidly respond to the same antigen should it enter the body again
What theory describes why we don’t have B-cells that make antibodies against OUR OWN antigens?
The Clonal Deletion Theory (“Self-tolerance”)
Describe the Clonal Deletion Theory.
- During embryonic development, B-cells against our own antigens are produced
- When a developing B-cell binds to self-antigen, it gets destroyed
- Only B-cells carrying receptors for non-self antigens are RELEASED from the bone marrow and enter the blood
List the 5 types of antibodies:
- IgG
- IgA
- IgM
- IgE
- IgD
This antibody is found in secretions (breast milk, mucus, saliva, etc.)
IgA
This antibody forms large complexes with antigen which are easily cleared
IgM
This antibody is the main antibody found in circulation (80% of total antibody)
IgG
This antibody is involved in development of allergies
IgE
The fn of this antibody is unclear (may help regulate the immune sys)
IgD
This antibody blocks attachment of microbes to mucosal tissue surfaces
IgA
This antibody is able to cross the placenta and therefore protect the fetus)
IgG
Which antibodies are produced during a first-time exposure? How long does it take for them to first appear?
IgM first, the IgG.
It takes 3-6 days for igM to first appear
What happens when the antigen is no longer present?
Antibody levels decline
What happens during the second exposure to the same antigen? Why?
A faster and stronger igG response occurs due to the presence of pre-existing memory cells that can detect that antigen, which then change into new plasma cells and start to produce more immunoglobulins
What four things does binding of antibody to antigen accomplish?
- Interacts w/ parts of the innate immune sys (triggers complement production, helps inflammatory response, etc.)
- Opsonization (coating of bacteria > better phagocytosis)
- Neutralization (blocks attachment of pathogen to host cell surface)
- Agglutination (“clumping” of antigen+antibody > facilitates better phagocytosis and/or filtering out of circulation)
Type A ppl have antibodies against…
type B blood
Type B ppl have antibodies against…
type A blood
Type AB ppl have antibodies against…
no blood type
Type O ppl have antibodies against…
both type A and type B blood
If given the wrong blood, what kind of reaction occurs?
Agglutination (a clumping rxn)
What kind of antibodies can be made in the lab?
- Polyclonal antibodies
2. Monoclonal antibodies
How would polyclonal antibodies be made?
- Purify antigen for which you want antibodies
- Inject into animal which will see it as foreign
- Inject a second “booster” dose of antigen
- Draw plasma from animal > should contain immunoglobulins against the diff. epitopes of the microbe’s antigens (bacteria)
How would monoclonal antibodies be made?
- Inject antigen into mouse to make immunoglobulin-producing plasma cells
- Remove the plasma cells and fuse w/ long-living tumor cells (“Hybridoma”)
- A hybridoma makes a single specific type of immunoglobulin that will only recognize a SINGLE SPECIFIC epitope
Diff applications of monoclonal antibodies?
- diagnostic tests
2. therapeutics (block action of cellular proteins or other molecules by BINDING to them)
Pharmaceutics that end with the suffix “-mab” represent what?
Monoclonal antibodies
Two components of acquired (specific) immunity?
- Humoral
2. Cell-mediated
Ultimate purpose of antibodies?
To get rid of antigens which may be part of a microbe that could harm you
3 purpose of cell-mediated immunity?
- eliminate human cells infected w/ a microbe (esp. viruses
- Eliminate “self” cells which become a threat to host (e.g. cancer), OR foreign cells introduced from another human (transplant)
- To regulate fn of cells involved in innate immunity (macrophages) and humoral immunity (B-cells)
Why is humoral immunity (the other arm of acquired immunity) not able to kill viruses inside cells?
Antibodies can’t enter cells
Cell-mediated immunity is mediated by which cells?
T-cells (T-lymphocytes)
Two types of T-cells? Where are they made?
- Helper T cells (Th)
- Cytotoxic T-cells (Tc)
Both are made in the thymus
How’re T-cells activated?
They must make contact w/ a specific antigen via their receptors (T-cell receptors)
What occurs if Th or Tc cells contact their antigen?
They divide into functional and memory Th/Tc cells
An activated helper T-cell does what?
Secrete chemical signals (“cytokines”) that “help” other immune sys cells work better:
- Increase phagocytic activity of macrophages
- Stimulate B-cell development
A memory helper T-cell does what?
Persists, and allows for faster response if the same “activating” antigen is encountered again
What do Cytotoxic T-cells do?
Search for other cells carrying the SAME antigen which originally activated it (e.g. virus-infected cells, cancerous cells, etc.)
What occurs when a Tc attaches on to target cells?
They release toxin-containing granules, which form pores in membrane of targeted cell and kill it
Main diff b/w Tc cells and Th cells?
Tc cells kill other cells, Th cells don’t directly kill cells
Overall, what does humoral immunity do?
Produce antigen-specific antibodies via B-cells
Overall, what does cell-mediated immunity do?
Kill “foreign” cells by T-cells
Four characteristics of the acquired immune sys:
- Inducing (acts only when needed)
- Discriminates (self vs. non-self)
- Remembers (better response after 2nd exposure)
- Adaptive (deals w/ diversity of microbes)
What kinds of molecules allow for the communication b/w the diff parts of the immune sys?
Cytokines
What’re cytokines?
a set of >100 diff molecules that act as chemical messegers b/w immune sys cells
Cytokines are produced by…
the immune sys cells
Effects of cytokines?
2
- Regulating intensity and duration of immune response
2. Regulating proper immune sys development
4 types of cytokines?
- Chemokines
- Hematopoietins
- Interleukins (IL-1 to IL-25)
- Tumor Necrosis Factors (TNF)
What do chemokines do?
- Attract phagocytes to where they are needed
- Regulate the inflammatory response
What do hematopoietins do?
Stimulate and regulate blood cell formation
What do interleukins do?
- Regulate growth & differentiation of lymphocytes
- Numerous other biological effect (inc’l endogenous pyrogen)
What do tumor necrosis factors do?
- Promote inflammation & fever; stimulates immune system
- Help regulate production of other cytokines & growth factors
What’re two factors about cytokines that make them significant?
- Cytokines have disease potential if their balance is upset
- Cytokines have a therapeutic potential
How’re cytokines affected by some cancers, such as lymphoid tumors?
They cause the over-production of cytokines due to overproduction of lymphocytes
How do long-term bacterial infections affect cytokine production?
They simulate prolonged, low-level production of cytokines > long-term physiological effects
What term is used to describe some bacterial toxins and viral infections that trigger a sudden, massive over-production of cytokines
“Cytokine Storm”
What’re two negative outcomes of cytokine storms?
- Fever, shock, widespread blood clotting
2. Potential for tissue & organ damage (& may be lethal)
2 ways cytokines can be used for therapies.
- Cytokines can be used as drugs
2. Drugs can be used to block cytokines
Name a cytokine that can be used as a drug. What does it do?
Interleukin-2 (Proleukin)
It..
- stimulates T-cell production
- is used to treat renal cancers, melanoma
Name a drug that blocks cytokine activity. How does it work?
Humira (adalimumab)
This monoclonal antibody blocks the action of TNF > reduces inflammation caused by some “autoimmune” diseases
Why is Humira associated w/ an increased susceptibility to infections?
HUMIRA is a TNF blocker medicine that can lower the ability of your immune system to fight infections
