Lecture 15 - Adaptive Immunity Flashcards
what line of defense is adaptive immunity?
third line of defense
when does adaptive immunity develop?
adaptive immunity develops during our life as an adaptation to infection with an indaver
what does it mean when adaptive immunity is delayed?
adaptive immunity is delayed, meaning the responses follow innate immunity by several days (7-14 days)
are the responses of adaptive immunity specific or non-specific?
responses of adaptive immunity are specific to a foreign invader, so its specific to each pathogen
does adaptive immunity have memory or non-memory?
adaptive immunity makes memory to prevent reinfection by the same invader, so this response is more powerful if it happens again
what are the 5 hallmarks of adaptive immunity?
-Third line defense
-Adaptation
-Delayed
-Specific
-Memory
where are antigens (Ag) located?
they are located on invaders
what are Antigens often made out of?
Ag’s are often proteins or polysaccharides
how is the adaptive immune system specific to antigens?
the immune cells recognize the antigens on invaders using specific binding (aka they identify specific molecules on the pathogen)
antigens are located on the pathogens, and ____ defense recognizes it
3rd line defense recognizes it
what is an example of an antigen from our labs?
H-antigen in E. coli 0157 H:7
how do antigens respond when immune cells recognize them?
they respond by producing antibodies, killer cells, and activated macrophages to destroy invaders
where does the name of the antigen come from?
antibody-generators
what are the two categories of lymphoid organs?
primary and secondary
what do primary lymphoid organs consist of?
bone marrow and thymus
what generates and matures in primary lymphoid organs?
lymphocytes (B cells and T cells; b for bone marrow and t for thymus)
what do secondary lymphoid organs consist of?
lymph nodes, tonsils, spleen, SALT, and MALT
what happens in the site of secondary lymphoid organs? what is an example?
this is where antigens are brought together with lymphocytes.
example: lymph carrying excess tissue fluids brings antigens to lymph nodes that contain lymphocytes.
what are the two components of adaptive immunity?
- Humoral: antibody-mediated immunity (makes antibodies)
- Cellular: cell-mediated immunity (makes killer cells)
what does humor mean in humoral immunity?
fluids (blood, tissue fluids)
what is humoral immunity against?
it is against extracellular antigens; outside of the cell. example: circulating bacteria or toxins, foreign RBCs
what is humoral immunity mediated by?
B lymphocytes (cells)
where do B cells develop and mature in humoral immunity? what do they gain (what receptors)?
B cells develop and mature in bone marrow, where they gain specific B cell receptors (BCRs)
where do B cells travel to after they gain their receptors? what are they called here?
They travel to secondary lymphoid organs to “lie in wait” or circulate, they are called naive B cells
why are they called naive B cells?
because they are not yet activated
each B cell is specific to what?
each B cell is specific to each antigen
what is cellular immunity against?
cellular immunity is against intracellular antigens; inside the cell. (example: viral-infected cells, cancer cells, and transplanted tissue)
what is cellular immunity mediated by?
T lymphocytes (cells) and macrophages
where do T cells develop and mature? what do they gain (what receptors)?
T cells develop in bone marrow and mature in the thymus. This is where they gain specific T cell receptors (TCRs)
where do the T cells travel after gaining TCR’s in cellular immunity?
they travel to secondary lymphoid organs to “line in wait” or circulate called naive T cells
what are two T cell types?
-Cytotoxic T cell (CD8+)
-Helper T cell (CD4+)
in cytotoxic T cells, what does the TCR bind to?
TCR binds to Ag-MHC 1 complex
what doe MHC stand for?
major histocompatibility complex
what do cytotoxic T cells do?
all the cells breakdown internal antigens and display them on MHC 1
what does the helper T cell bind to?
the TCR binds to Ag-MHC 2 complex
in helper T cells, what breakdown the foreign Ags and display them on the MHC 2?
Antigen presenting cells (APCs) breakdown foreign Ags and display them on MHC 2
we develop B cells and T cells specific (via receptors) to what?
we develop B cells and T cells specific (via receptors) to an enormous diversity of possible antigens (>1 billion). example: measles virus
what do naive B cells scout for?
Naive B cells scout for extracellular antigens (example: measles in blood and bodily fluids)
what do naive T cells scout for?
Native T cells scout for intracellular antigens (example: measles in cells)
how do naive B and T cells get activated?
if naive B and T cells come across the matching antigen, they get activated
what happens after naive B and T cells get activated?
they reproduce and differentiate to form:
-effector cells
-memory cells
what do effector cells do?
they destroy the invader (it takes action)
what do memory cells do?
they are saved for the next exposure to the same invader; so that they can mount a quick and intense secondary response
do we have B and T cells against our own Antigens? what happens to them?
yes we do, we destroy the B and T cells
B cells that bind to self antigens are killed where?
in the bone marrow
T cells that bind to self antigens are killed where?
in the thymus
Which of the following cells is NOT found in the adaptive
immune system?
1. Macrophages
2. T cells
3. B cells
4. NK cells
NK cells
humoral immunity:
what happens during antigen processing and presentation?
Dendritic cells within tissues engulf an Ag and break it down into peptide fragments. These are displayed on the surface as MHC II molecules. The dendritic cell moves to the secondary lymphoid organs
humoral immunity:
what happens after Ag processing and presentation?
Helper T cell activation:
-Specific CD4+ cell binds MHC II-Ag complex on APC via TCR (signal 1).
-The APC secretes cytokines (signal 2).
-Clonal expansion (division) of CD4+ cells occur.
-Differentiation of CD4+ cells into TH cells and memory TH cells.
humoral immunity:
what is signal 1 and 2 of helper T cell activation?
Signal 1: Specific helper T cell binds to the MHC II-Ag complex on the APC via TCR.
Signal 2: The APC secretes cytokines.
humoral immunity:
what happens during B cell activation?
-A specific B cell binds to the Ag via BCR (signal 1).
-The B cell engulfs the Ag and displays it on MHC II.
-A specific TH cell (from T cell activation) binds to the Ag-MHC II on the B cell and secretes cytokines (signal 2).
-Clonal expansion of B cells occur.
-Differentiation of B cells occurs into plasma (effector) cells and memory B cells.
humoral immunity:
what happens during B cell activation after clonal expansion and differentiation?
-Plasma cells make antibodies (Ab)
humoral immunity:
what is the outcome of B cell activation?
Antibodies destroy the extracellular pathogens
what gives “specificity” to adaptive immune cells?
1. PRRs on sentinel cells
2. PAMPs on pathogens
3. BCRs and TCRs on lymphocytes
4. TLRs on phagosomes
5. MHC molecules on APCs
- BCRs and TCRs on lymphocytes
In humoral immunity (and cellular), what are the activated effector and memory cells from helper T cell activation?
Effector cells: effector TH cells
Memory cells: memory TH cells
In humoral immunity, what are the activated effector and memory cells from B cell activation?
Effector cells: plasma cells
Memory cells: memory B cells
In cellular immunity, what are the activated effector and memory cells after cytotoxic T cell activation?
Effector cells: Killer T cells (TC cells)
Memory cells: Memory TC cells
In cellular immunity, what is the activated effector cell from macrophage activation?
Effector cells: activated macrophages
what are the two regions and Ag-binding sites on antibodies?
Constant region (Fc)
Variable region (Fab): the top part with two arms.
Ag-binding sites on the two tips of the Y
what are the functions of antibodies? (aka the 6 ways antibodies help to get rid of a pathogen?)
- Neutralization: The antibodies bind to the toxin.
- Opsonization: Antibodies coat the pathogen and tag it for destruction. It is destroyed by phagocytes. (The Fc region of the antibodies binds to the phagocytes).
- Complement System Activation: The inactive complement proteins bind to the Fc region of the antibodies, which activates the proteins. Then they
a) lyse the cells, b) inflammation, c) opsonization. - Immobilization and Prevention of Adherence: The antibodies bind to the flagella of the bacterium, preventing its motility.
- Agglutination/Cross-Linking: When one antibody can bind to 2 bacteria, cross-linking them.
- Antibody-Dependent Cellular Cytotoxicity (ADCC): Antibodies stick to the virus-infected cell, and they coat the cell. The antibodies call WBCs to help kill this abnormal virus-infected cell.
what are the 4 types/classes of antibodies or immunoglobulins?
IgM
IgG
IgA
IgE
what is similar between all the types of antibodies?
they all have the same constant region
What are the qualities of IgM antibodies?
-It is a pentamer: meaning it has 5 antibodies that stick together, so 5 antibodies can bind to 10 antigens. It is potent and has 10 Ag-binding sites.
-It is the first class of antibodies to be produced during infections. ALWAYS first!
-Short-lived
-It is too big to get in the tissues, so it just circulates in the blood (and tries to find pathogens and kills them).
What are the qualities of IgG antibodies?
-It is the most abundant antibody in tissue fluids.
-It is made 2nd during infections.
-Long-lived
-It can enter the tissues; it crosses the placenta and provides protection for the fetus.
-It is just a monomer; a single unit.
why should a mother be vaccinated when pregnant?
Because when she’s vaccinated she provides protection to the fetus. This is why the IgG antibody is important because it provides protection for the fetus.
What are the qualities of IgA antibodies?
-It is a dimer; 2 antibodies bind together and can bind to 4 pathogens (4 Ag binding sites).
-It is common at mucous membranes and in secretions: mucus, tears, saliva, and breastmilk
What are the qualities of IgE antibodies?
-It is produced during parasitic infections and allergies
what is primary vs secondary responses within antibodies?
Primary: it is the first time exposed to a pathogen.
Secondary: Exposed to the same pathogen again.
During primary response, why is there a lag before antibodies start to appear?
Because steps 1-3 of B cell activation (Antigen processing & presentation, Helper T cell activation, and B cell activation) are occurring and take 7-14 days to complete.
which antibody is made first in primary response? Is it short or long-lived?
IgM, it is short-lived. It is slow and low.
which antibody is made next in primary response? Is it short or long-lived?
IgG, it is long-lived.
during secondary response, how do the two antibodies differ from primary response?
-The IgM response is the same as the primary response; slow and low.
-The IgG response is quicker and higher than the primary response due to memory cells.
During the primary and secondary responses, how does IgM differ?
Primary: IgM is lagged, slow, and low.
Secondary: IgM is lagged, slow, and low.
They are both the same.
During the primary and secondary responses, how does IgG differ?
Primary: IgG is smaller but still higher than IgM. There is a lag in the beginning. It is long-lived.
Secondary: IgG is much much bigger and more powerful because of the memory cells from the 1st exposure. The IgG levels don’t completely go away after the primary response, since it is long-lived. There is a smaller lag before the secondary response of IgG.
why are memory cells so effective in IgG during the secondary response?
- They are high in number.
- It is learned from the 1st exposure, so they have a high affinity to the antigen.
In the first exposure, naive cells are there until activation. So during the secondary response, there are memory cells.
how do memory cells exist in vaccines?
Vaccines mimic the primary response without actually being exposed, so if you get exposed, you have these memory cells.
define the term seronegative
when you have no exposure to pathogen, so no specific Ab is present
define the term seropositive
when you are exposed to pathogen, so there is a specific Ab production within 7-10 days.
what two ways can you seropositive by?
you can be seropositive due to exposure to the pathogen or a vaccine
define titer
the amount of specific Ab’s present
if the titer is rising, what does it mean?
that means you have an active infection, and you’re actively fighting it off
if the titer is small but steady, what does that mean?
it is due to past exposure, so the IgG is working
what is cellular immunity mediated by?
cell-mediated immunity: T cell
what are the 3 steps of cytotoxic T cell activation?
- Antigen processing and presentation
- Cytotoxic T cell activation
- Macrophage activation
in cellular immunity, what happens during antigen processing and presentation?
Dendritic cells within tissues engulf an antigen, break it down into peptide fragments, and display them on their surface in MHC I molecules. They then migrate to secondary lymphoid organs.
explain the picture of cytotoxic t cell activation in cellular immunity
-There is a dendritic cell with an MHC 1 receptor
-A naive CD8+ Cytotoxic cell with an antigen and TCR binds to the MHC 1. This is signal 1.
-This causes the dendritic cell to release cytokines into the cytotoxic cell. This is signal 2.
-This causes clonal expansion and differentiation.
-We now get 3 Tc killer cells - effector cells, and 1 memory cell that is saved for later.
what happens during step 2 of cellular immunity: cytotoxic T-cell activation?
-A specific cytotoxic T cell binds to the MHC 1-Ag complex on the APC via TCR (signal 1).
-The APC secretes cytokines (signal 2).
-Clonal expansion and differentiation of cytotoxic T cells into killer T cells and memory TC cells.
what do normal and abnormal cells display after cytotoxic t cell activation?
normal cells display “self” peptides on MHC 1 molecules, whereas abnormal cells display “foreign” peptides on MHC 1 molecules
what are the killer t cell mechanisms?
-The infected/tumor cells present Ag in MHC I molecules
-The killer T cells recognize the MHC 1-Ag complex via TCR
-The killer T cells kill abnormal cells using perforins, proteases, and induced apoptosis
what is apoptosis?
programed cell death by killer T cells to infected/tumor cells
what is macrophage activation in cellular immunity?
The TH cells active macrophages during humoral immunity:
-The outcome is improved phagocytosis
-There is no clonal expansion and differentiation, so no memory
which of the following is part of the humoral responses?
1. Killer T cells
2. Plasma cells
3. Activated macrophages
4. Eosinophils
- Plasma cells
Explanation:
1. Killer T cells: cellular immunity response
3. Activated macrophages: cellular immunity response
4. Eosinoships: innate immunity
Which of the following places these events in the correct order?
- APC presents Ag in MHC molecule
- Ag is processed by APC
- B cell is activated
- Helper T cell recognizes Ag-MHC complex
- TH produces cytokines
2, 1, 4, 5, 3
Which of the following antibodies are found in secretions at mucous membranes, including mucus, saliva, and tears?
IgA
IgM
IgG
IgD
IgE
IgA
Which type of specific immune cell destroys virus-infected cells?
Killer T cell
A doctor takes a blood sample from an arthritic patient to check for antibodies to Lyme disease. The patient has no specific antibodies to the Lyme disease bacterium; therefore, the patient is _______________ for the disease.
Seronegative
study the graph on the practice questions
The HIV virus specifically attacks helper T cells in the body. Explain why this has such widespread effects for the immune system.
When helper T cells decrease in number, you will have fewer TH cells created to activate other immune cells when antigens are present. As a result, the following cell activations and outcomes would not occur:
B cells differentiating into plasma cells which attack specific extracellular antigens in blood and bodily fluids with antibodies (humoral immunity)
Cytotoxic T cells differentiating into killer T cells which attack specific intracellular antigens in abnormal cells with perforins, proteases and induced apoptosis (cellular immunity)
Macrophages differentiating into activated macrophages which attack abnormal cells with improved phagocytosis (another form of cellular immunity)
There is even evidence that Helper T cells are involved in innate immunity
This widespread immune suppression leaves your body vulnerable to infections and cancer. Patients with HIV usually die from one of these secondary complications.
CHALLENGE QUESTION. Using your knowledge of both the innate and adaptive immune systems, explain the body’s responses to an invading virus.
In the innate immune system, the virus first has to breach the first line defenses of the skin and mucous membranes. Then, the second line defenses are alerted due to phagocyte recognition of pathogen-associated molecular patterns (PAMPs). Lymphocytes, known as natural killer (NK) cells, destroy virus-infected cells. Protein substances, including antimicrobial peptides and complement, aid in virus destruction. Interferon, a protein substance, specifically prevents the spread of a virus because it alerts neighboring cells of a viral infection. The processes of inflammation, fever and RNA interference (siRNAs were discussed in the DNA lecture) also help to slow the spread of disease. Even with all of these defenses, the virus is not completely cleared from the body. So, after several days, the adaptive immune system is activated due to recognition of specific antigens (Ag) on the virus. The humoral arm of the system produces antibodies (Ab) that attack the specific virus when extracellular. The cellular arm of the system produces killer T cells that destroy specific virus-infected cells with perforins, proteases and induced apoptosis. The adaptive immune system can destroy all viruses (in most cases), and it results in long-lasting immunity due to production of memory cells.
Which of the following does NOT form a memory population after activation and differentiation?
1. Macrophages.
2. Cytotoxic T cells
3. Helper T cells
4. B cells
- Macrophages
The stimulation of B cells to divide and mature is provided by:
1. Plasma cells
2. Cytotoxic T cells
3. Macrophages
4. Erythrocytes
5. Helper T cells
- Helper T cells
Macrophages and dendritic cells are
1. antibody producing cells
2. T cells
3. lymphocytes
4. antigen presenting cells
5. B cells
- antigen presenting cells
Which is the first antibody class made during the primary response to an antigen?
IgM
Ag-Ab binding may result in all of the following EXCEPT:
agglutination
opsonization
fever
neutralization
immobilization
fever
explain the 3 steps of humoral immunity AKA B cell activation
- Antigen processing and presentation
a. Within tissues, dendritic cells (APCs) engulf an antigen and break it down into peptide fragments of their surface as MHC II molecules.
b. This dendritic cell then migrates to the secondary lymphoid organs. - Helper T cell activation:
a. Witin the secondary lymphoid organs, helper T cells or CD4+ cells get activated by two signals:
1- Helper T cells (CD4+) specific to the antigen bind to the MHC II-Ag complex on dendritic cells via their TCR.
2- Dendritic cells secrete cytokines.
b. Helper T cells undergo clonal expansion and differentiation into effector (TH) cells and memory TH cells. - B cell activation (final step):
a. Within the secondary lymphoid organs, B cells get activated with two signals:
1- B cells specific to the Ag bind to the Ag via BCR.
2- B cells, also APCs, engulf the Ag, break it into peptide fragments, and display it on their surface as MHC II molecules. Effector TH cells specific to the Ag bind to the MHC II-Ag complex on the B cell via BCR and secretes cytokines.
b. B cells undergo clonal expansion and differentiation into effector (plasma) cells and memory B cells.
c. Plasma cells make antibodies that destroy the extracellular Ag.
explain the 3 steps of cellular immunity AKA T cell activation
- Ag processing and presentation:
a. Within tissues, dendritic cells engulf an Ag, break it down into peptide fragments, and display it on their surface as MHC I molecules. They then migrate to secondary lymphoid organs. - T cell activation:
a. Within secondary lymphoid organs, cytotoxic T cells get activated by 2 signals:
1- Cytotoxic T cells (CD8+) specific to the Ag, bind to the MHC I-Ag complex on dendritic cells via TCR.
2- Dendritic cells secrete cytokines.
b. Cytotoxic T cells undergo clonal expansion and differentiation into effector T cells (killer Tc cells) and memory Tc cells.
c. Killer Tc cells bind to the MHC I-Ag complex on infected/tumor cells via TCR and destroy them using perforins and protease. - Macrophage activation:
a. WIthin secondary lymphoid organs, macrophages get activated by 2 signals:
1- Effector TH cells (from humoral immunity) bind to the MHC II-Ag complex on macrophages. (Macrophages are also APCs).
2- TH cells secrete cytokines.
b. Macrophages become activated, meaning they’re highly efficient in phagocytosis.
For cytotoxic T cells, name the marker on its surface, what the TCR binds to, and what it is displayed on.
Cytotoxic T cell:
- CD8+
- The TCR binds to MHC I-Ag
-All of our nucleated cells display internal or ENDOGENOUS Ag on MHC I.
For helper T cells, name the marker on its surface, what the TCR binds to, and what it is displayed on.
Helper T cell:
- CD4+
-The TCR binds to MHC II-Ag
- APCs (dendritic cells, B cells, and macrophages) display EXOGENOUS Ag on MHC II
