Exam II: Lecture 6 Flashcards
What are the two major parts of adaptive immunity?
- Cellular arm: production of CTLs (cytotoxic T lymphocytes)
- Humoral arm: production of B cells
Is the adaptive immune response specific or non-specific?
Specific
Does the adaptive immune response develop an immunological memory?
Yes
What do T-cells recognize?
Recognize antigens 8-20 amino acids long
What proteins present peptide antigens for T-cells to recognize?
Major Histocompatibility Complex Locus (MHC or HLA)
What is the advantage of having a ‘variety’ of MHC/HLA molecules in a population? What is the disadvantage of having a limited variety of HLA molecules in a population?
MHC polymorphism extends the range of antigens to which the immune system can respond. The more variety the better your immune system can respond
What are the two kinds of MHC?
MHC I and MHC II
What are the components of MHC I?
- Heavy Chain - alpha 1, 2, 3
2. Light Chain - beta 2
What are the components of the MHC II?
Heterodimer with alpha and beta sides
Anchor residues
The certain residues within the peptide interact with the MHC molecule
Class I MHC molecules are found in which cells?
All cells of the body
Class II MHC molecules are found in which cells? (3)
- Dendritic cells
- Macrophages
- B cells
How do MHC relate to transplants?
In a transplant, you want similar HLA molecules
Families share many HLA
Stangers share some HLA
How do HLA types correlate with attractiveness?
The more dissimilar HLA types, the more attracted you are to another person
How do MHC I present peptides?
Proteins from an infective agent (virus) > broken down in proteosme > TAP > ER > MHC I + peptide > golgi > MHC I present to T-cells > T-cell decide whether the antigen is self or nonself
Many of the peptides bound to MHC I are self-peptides
True
How do MHC II present peptides?
Viral protein > phagocytosis > MHC made in ER > peptide + MHC II are joined in cytoplasm > present to T-cell > T-cell decides whether the antigen is self or nonself
T-cells have T-cell receptors which recognize what?
The peptide presented in the groove of the MHC molecules
Each T-cell expresses one receptor, how does the body overcome this?
There are thousands of T cell varieties are present in each person
Each individual receptor can recognize a different peptide _____
epitope
The TCR has a variable region that can produce a wide repertoire of receptors (10^8 combinations possible)
True
T-cells require both a bond between TCR and Peptide on MHC, and which additional accessory molecules?
CD4 and CD8
They increase the binding affinity of the TCR and MHC molecule
MHC I is paired CD4/CD8 and binds to CTL/Helper T cells
MHC I = CD8 + CTL
MHC II is paired CD4/CD8 and binds to CTL/Helper T cells
MHC II = CD4 + helper T cells
What do CTL do once activated by MHC+peptide?
Attack the cell
What do Helper T cells do once activated by MHC+peptide?
Detach and secrete cytokines > activate immune response = activate B cells and cytotoxic T cells
How does the body keep the T-cell from recognizing itself?
The body goes through the process of testing TCR against self-antigens, and recognizes the self-antigen it is destroyed
What would happen if the T-cell or B-cell recognized the ‘self’ as foreign?
Autoimmune disorder
CTLS induce apoptosis in the target cell by activating what 3 pathways?
- The Granzyme pathway
- The Fas pathway
- The TNFalpha death pathway
Clonal Expansion
B/T cells exist in dormant state. Infection > present antigen > activation of B/T cells > increase the signal > chemotaxis
What is the Granzyme pathway?
Effector cytotoxic T cell TCR binds to MHC + peptide > T cell releases perforin molecules + serine proteases > assemble perforin channel > serine proteases enter target cell > granzyme B turns Bid to tBid > caspase cascade > apoptosis
What is the Fas pathway?
Effector cytotoxic T cell has Fas ligand > Fas ligand binds to Fas on target cell > activate caspases > apoptosis
Also removes abnormal cells (CANCER)
What is the TNFalpha death pathway?
TNF excreted from CTL > enduces apoptosis ??
Where are B cells derived from?
Bone marrow
What do B cells secrete?
Antibodies
How are antibodies produced?
Antibodies are produced by the rearrangement of a large family of genes, known as the V, D, J, and C genes
Each antibody binds to a wide variety of antigens
False
Each antibody binds to a specific antigen
TCRs can only recognize peptides while antibodies can recognize ______
whole proteins and viruses
Antibodies are membrane bound, what happens when the B cell is activated
The antibodies are secreted
Each B cells produce highly specific or general antibodies
Highly specific
What is the structure of an antibody?
Heavy chain = constant region
Light chain= variable region - has antigen-binding site
Each B cell produces a different antibody. There are ___ different B-cells producing antibodies that recognize different antigens.
10^6
How do we generate such diversity in B cells?
Gene rearrangement
There is recombination of VJ regions by deletion of VJ regions and then translation of the premanetnly rearranged, functional genes
What are the 5 different classes of antibodies B-cells secrete?
- IgM
- IgG
- IgA
- IgE
- IgD
What is the primary function of IgM?
Neaturalization and agglutination First class of antibodies produces
What is the primary function of IgG?
Most abundant
Neutralization and agglutination
Can cross the placenta
What is the primary function of IgA?
Present in mucus, saliva, breast milk
Localized defense of mucuc membranes
What is the primary function of IgE?
Triggers histamine release from mast cells - allergic reaction
What is the primary function of IgD?
Present on unactivated B-cells
Involved in clonal selection
What are the 3 ways B cells bring about cell death?
- Aggregation
- Complement-mediated lysis
- Cell-mediated lysis
What is agglutination?
Antibodies have 2 binding sites and a B-cell has multiple membrane bound antibodies so the B cell can bind to many target cells at once, trapping the virus inside all the target cells
What is neutralization?
When an antibody binds specifically to the glycoprotien that does not allow the virus to bind to its receptor which neutralizes the target cell
An antibody could bind to the capsid protein on the virus and then it would not be neutralizing
What is the advantage of having memory B and T cells? (3)
- They are primed to react quickly upon renewed stimulation by their antigens
- The secondary response produces high affinity antibodies in larger quantities
- A single infection can make a person immune to the same infection for life
Both memory B and T cellc can remain in the body for long periods of time
True
What is clonal selection of B cells?
Once B-cells are activated they either become antigen-secreting plasma cells or long-lived memory cells
The process of creating more memory cells is clonal selection
Who was Edward Jenner?
Edward Jenner inoculated a young boy with the pus from a Cowpox sore - creating one of the first WT virus vaccines
Who was Lady Mary Wortley?
Was visiting the turks and noticed them putting puss under a cut of a healthy individual and it made the person immune to small pox
Variolation
Stick puss under skin
Innoculation
Infect with microbiological agent
Gradually vaccines became popular, HPV rates drop ___% in decades since CDC recommended vaccination in 2006
64%
Attenuated Strains
Weaker form
Pass the virus in cultured cells or in an animal that is not a natural host, the virus adapts to the new host and becomes weaker
Attenuated strains remain similar enough to the original virulent for the body to generate an immune response
True
What did Pasteur do?
Injected a child with rabbit rabies virus (attenuated rabbies virus) so the child wouldn’t get sick with rabies
Inactivated Virus
Treat virus with a chemical > virus still has glycoprotins but is incapable of replication
Adjuvant
An irratant included in vaccines that encourages the immune system to come to the sight
What does CAVA stand for?
Cold Adapted Virus Attnuation
What is CAVA?
You passage the cells are low temperatures (23-30C) which generates an attenuated virus strand which can not replicate as quickly even when back in standard conditions
Live virus vaccines can cause disease if _________ is not sufficient
Attenuation
Virulent
Even more hostile
Occasionally attenuated viruses can become virulent by a process of ______
reversion
Subunit Vaccines
Take a small peice of the virus and use it for vaccination
Does not have many of the problems live/attenuated virus vaccines have
Recombinant viruses
AKA pseudotyping
Get dual immunity of the actual virus and the easier going virus
DNA/RNA vaccines are being tested for future use
True
What is Herd Immunity?
If the majority of the population is mostly protected from a disease the chance of a major epidemic is unlikely
What are the two ways Herd Immunity if achieved?
Majority gets sick
Majority gets vaccinated
The percentage of immune people for herd immunity changes virus to virus
True
Why are zoonotic virus impossible to irradicate?
They go and hide in animal species and mutate
Vaccines artifically induce a T-cell and B-cell response
True
How do you test vaccine efficacy?
Cellular Studies
- Give a person the vaccine
- Take a blood sample and isolate the antibody serum
- Treat cells with antibodies and then with the virus
- Compare cell death in culture treated with antibodies vs control
