Lecture 9: The Adaptive Immune System Flashcards
The Adaptive Immune System
Acquired
Very specific
Has a memory component
Consists of two components:
- Humoral (antibody mediated) immunity
- B cells are respon. for this - Cell mediated immunity
- T cells (*specifically cytotoxic ones) are respon. for this
• Acquired (meaning)
NOT born with - instead, develops over course of your life b/c of pathogens your encountering on daily basis
- Begins as soon as a pathogen is encountered for the very first time
- Adaptive response will not occur until a pathogen is encountered
• Very specific (meaning)
• Very targeted to a specific feature of a given bacterium, virus, toxin
- going after something about E.coli, something about HIV or SARS-COV-2 (not random or non-specific)
- • Immunity to one pathogen will not confer immunity to another
- NOT cross-reactive responses
• Has a memory component (meaning)
• Produces a more effective response when a pathogen is encountered for the second time-faster and stronger
- if you’ve seen something and mounted a response against it today it, its something you will have memory and protection against net time you encounter material
- ~long-term protection b/c it remembers any adaptive interaction that took place before
- 2nd response is much quicker & will produce higher levels of immune activation, immune response & stronger response overall
Antibodies:
Something YOU make to protect you
• Proteins produced by the immune system that bind and inactivate foreign antigen
Immunogens:
Any foreign material that has the ability to active the adaptive immune system
- NOT YOU
- get the attention of adaptive immunity
• Normally protein, polysaccharide, lipid material *=ALL ORGANIC
Epitopes:
• The actual portion of the ANTIGEN that binds to the antibody
- each spike protein will be referred to as an antigen & antibodies binding to this are doing so with specific regions referred to as epitope
• A single antigen will have more than one epitope
- each antibody will have their own specific epitope that they bind to, in order to induce protection & nutrilization
• Increases the ability of an antigen to activation the immune system –> immunogenicity
- some antigens so a much better job of activating the immune system then others
– some antigens will be less immunogenic & won’t have same opp. to activate immune system & that means some antigens are better for vaccination then others b/c they’ll be stronger in terms of how they turn on the immune system
• Each epitope requires a distinct antibody
Hapten:
• LOW MOLECULAR WEIGHT compound that is too small on its own to activate adaptive immunity
- not big enough to get the attention of the immune system
• NOT IMMUNOGENIC
- Can bind to other molecules such as protein in blood and tissues
- Becomes strongly immunogenic
- An allergy forms
- Ex) penicillin
Describe penicillin
antibiotic used to treat infection
- penicillin is a HAPTEN that specifically will bind to PROTEINS that are be present in blood & tissues for ex
- & whole thing gets attention of immune system
- & is said to be STRONGLY IMMUNOGENIC (allows opp. for immune system to react against penicillin which you don’t want)
- whole point of penicillin was to help you treat an infection (not to kill off drug & remove from insides of body)
Antibodies (Ab) are…
glycosylated protein molecules
- b/c are AA sequences that have sugar groups that are added to various locations
Antibodies (Ab) are AKA
Also called IMMUNOGLOBULINS (Ig)
Describe the structure of antibodies
Consist of 4 subunits
• TWO identical HEAVY chains- have many aa’sn
• TWO identical LIGHT chains- have less aa’s
- CHAINS are assembled creating THREE distinct regions
- 2 identical variable regions (Fab regions)
- 1 constant region (Fc region)
Explain the 2 identical variable regions (Fab regions)
formed from heavy & light chain that come together
• Provide the specificity of the antibody
- allow foreign material to initiate a response
- get bound to that foreign material specifically at that site & if you want to bind a diff kind of foreign matter, you will then need a brand new antibody in order to do it
- has to be more than 1 antibody when you have foreign material that has diff components or antigens b/c each antibody is so specific
think: same way police has to interact with bad guys (Fab region)
Explain the 1 constant region (Fc region)
b/c not an infinite # of possibilities but instead are only 5
- type of Fc region will determine which of the 5 we have
• Allows for INTERACTION (talk) with immune cells
- Fc region allows antibody to be able to send messages & to be able to communicate with other elements of the immune system
• Based on differences in the Fc region there are FIVE different types of antibody
think: in Fc region, police has opp. to interact with other members of the force, to communicate diff types of info they found
Classes of Antibody
- Immunoglobulin M (IgM)
- Immunoglobulin G (IgG)
- Immunoglobulin A (IgA)
- Immunoglobulin D (IgD)
- Immunoglobulin E (IgE)
Immunoglobulin M (IgM):
Pentameric
• Five different antibody units form IgM; each antibody can bind 2 identical antigens
• Always the first antibody to be produced in
response to an antigen; 1 st antibody that reacts to an infection which later on you can switch and produce different antibodies
• Primary antibody response
- Found on the surface of B lymphocytes
- Remains in the blood; b/c so large even with increased pore size during inflammation
- Unable to enter the tissues
- Low affinity for antigen; doesn’t bind with strong affinity
- Very good at agglutination; can bind 10 identical antigens
. Immunoglobulin G (IgG):
- Monomer; only binds 2 identical antigens
- Most predominate antibody in the blood
- Also present in the tissues; foot and muscle
If you go to doctor b/c you think you contracted the HIV, they’ll ask you q’s about when you think that might’ve happen but also ask you to come back & get retested. What is the reason?
reason; you always start by producing IgM against foreign material once its produced you switch to diff type of antibody after initial infection
for HIV you begin by Igm then switch to IgG test used looks for IgG, if you have just been infected you are not producing antibody or IgM
IgG is produced after infection has taken place so ppl get tested 3 and 6 months after bc you will be producing IgG
Immunoglobulin A (IgA):
Dimeric; bind 4 antigens • Secreted at mucosal sites • Saliva, tears, mucous • Important defense against respiratory, reproductive, digestive tract infections
Immunoglobulin D (IgD):
Monomer
• Located on the surface of B cells
• Important in activation of B cells to begin
producing antibody against a specific antigen
Immunoglobulin E (IgE):
Immunoglobulin E (IgE):
• Monomer
• Binds to receptors located on the surface of
mast cells and basophils
• Binding of IgE-antigen complex triggers
degranulation and histamine release
• Allergy
Describe how Ige causes release of histamine
Antibody attaches with the FCIge receptor on the basophils and mast cells
allergen in bound to the fab region of antibody
outcome- degranulate in response to allergen bound to Ige bound to FC Ige receptor and histamine gets released causing allergic symptoms
List then 5 major antibody functions
- Neutralization:
- Opsonization:
- Agglutination:
- Antibody mediated cytotoxicity:
- Complement activation
. Neutralization:
Antibodies bind to antigen blocking attachment
sites
• Prevents bacteria, virus and toxin entry into
tissues and host cells
Opsonization
Antibodies coat the surface of the bacterial
cell
• Attracts phagocytes
• Greatly enhances the rate of phagocytosis
• Phagocyte has the ability to interact with
the Fc region of the antibody
- Agglutination:
• Each class of antibody can bind to a minimum of 2
identical antigen units; igM; 10 IgA; 4
• Clumps together many antigens
• Allows phagocytosis to occur more efficiently
Antibody mediated cytotoxicity:
Attachment of antibody to parasites recruits
eosinophils; eukaryotic pathogen coated with Ige
• Eosinophils attach to the Fc component of
antibodies
• Activated eosinophil releases reactive oxygen
species and hydrolytic enzymes
• Parasite is destroyed
- Complement activation:
• Complement is a system consisting of a series of
proteins found in the blood; inactiave proteins in off position inside of the blood
• Can be activated by antibody that is bound to
a bacterial cell
• Classical pathway of complement
activation
• Create a number of different immune responses
when activated
MAC attack complex forms • Inserts into the membrane of bacterial cell forming a pore • Contents of the cell leak and the bacterium dies
What do all nucleated cells have?
ALL nucleated cells have MHC1 in PM (ALL EXCEPT RB AT MATURITY)
MHC1
found in PM of all nucleated cells
identifies a self cell
what do antigen presenting cells have?
MHC1 and MHC2
exogenous antigen
foreign material located outside of the cell in ECF
presented with MHC2- activates antibody immunity
endogenous antigen
foreign material located inside of the cell
- presented with MHC1- actiavtes cell mediated immunity
B cells
are antigen presenting cells and produce antigen
Macrophages and dendritic cells also perform antigen presentation
• All antigen presenting cells can insert MHC II into the plasma membrane
When are antibodies produced?
are produced against exogenous antigen
• Antigen that exists outside of the cell in the surrounding extra-cellular fluid
• Can be bacteria, virus, parasite, toxin, etc.
• Once antibodies are secreted from B cells they can bind to and neutralize/opsonize
these exogenous antigens
Describe the steps of Antibody Mediated Immunity
- B cell phagocytoses exogenous antigen
• Digested content in the phagolysosome will not be exocytosed to the extracellular fluid
• Instead it will be complexed together with MHC II and inserted into the plasma membrane - T helper cells bind to MHC II-Antigen complex resulting in T helper cell activation
• The activated T helper cell releases cytokines that bind to receptors on the B cell resulting in B cell proliferation;
Cytokines are released from T helper cell in response to TCR contact with MHC II-Antigen
complex Cytokine binds to cytokine receptor in B
cell plasma membrane triggering the proliferation of the B cell
Result: A clonal
population of
the B cell; WILL ALL PRODUCE THE SAME ANTIBODIES AGAINST EXOGENOUS ANTIGENS
- Some of these newly produced B cells will become plasma cells
• Actively transcribe, translate and secrete an identical antibody protein to the extracellular fluid
• These antibodies are specific to the original exogenous antigen
A smaller fraction of newly produced B cells will become memory cells
• These will be used in subsequent encounters with the same antigen
• They will not produce antibodies during the current response
Primary antibody response:
Occurs the very first time a specific antigen is encountered
• Can be a natural encounter or an artificial encounter (ex:
vaccination)
• Produces a weak antibody mediated response
• Slow production of low levels of antibody
• Results in the production of memory B cells: major goal
• Secondary antibody response:
Occurs every additional time
(after the primary response) a specific antigen is
encountered
• Produces a strong antibody mediated response
• Rapid production of high levels of antibody
• So rapid that the pathogen will not be able to
establish infection
• No disease occurs
Tolerance
Tolerance prevents immune responses against self-antigens
• Any immune cells that are found to recognize self-antigens are
destroyed early on in development
• Helps to prevents auto-immune disease
Cell Mediated Immunity
• Recognizes and destroys abnormal cells present in the body
• Cells infected with virus or obligate intracellular bacteria
• These are endogenous antigen because they are present inside of the host cell
• Involves cytotoxic T cells
• Diseased host cell will display endogenous antigen in the plasma
membrane complexed together with MHC I
• Cytotoxic T cells will bind to MHC I-Antigen complex using their T cell receptor
(TCR)
• This results in activation of the cytotoxic T cell
triggering it to release perforins and granzymes
that cause death of the infected host cell
In order to clear a viral infection
both antibody
mediated immunity and cell mediated immunity
are required
