Ch 13: Adaptive Immunity Flashcards
What is adaptive immunity?
specific response that is acquired after exposure to antigens
antigen receptors on lymphocytes are involved in recognition of self vs. nonself
specificity of response is stored in immunologic memory and can be used to fight subsequent infections
What is the general overview of what happens during infection and how the adaptive immune system is activated?
microbe PAMPs bind to PRRs on innate cells, which then release proinflammatory cytokines (HARMFUL!)
dendritic cells process and present nonself antigens to T lymphocytes
Helper T cells are activated and use cytokines to activate other immune cells
B cells/plasma cells produce antibodies that recognize nonself antigens
What is antigen presentation?
MHC (major histocompatibility complex) class I & class II receptors present peptide antigens to T-cell receptor
What is MHC I?
expressed by all nucleated cells
antigen presentation to CD8/cytotoxic T cells
responses vs. intracellular pathogens, such as viruses
What is MHC II?
expressed by dendritic cells, macrophages & B cells
antigen presentation to CD4/helper T cells
responses vs. extracellular pathogens, such as bacteria
What is a TCR?
TCR is comprised of two chains (α/β)
- associated with CD3 complex for intracellular signaling
What kinds of antigens do TCRs recognize?
TCR only recognizes peptide antigens presented with MHC
- needs CD4 co-receptor to recognize MHC II
- needs CD8 co-receptor to recognize MHC I
What is a BCR?
BCR is comprised of four chains (2 heavy / 2 light)
- associated with Igα and Igβ for intracellular signaling
recognizes epitope of native antigen
T cells also help activate B cells
What is clonal diversity in lymphocytes?
each mature lymphocyte possesses a single antigen receptor specificity
- 500+ gene segments that undergo “shuffling” or gene rearrangement (1013 possible combinations)
How does self-tolerance develop?
Clonal Deletion creates self-tolerance
- clones with BCR or TCR that recognize self antigens undergo apoptosis
- clones of non-self BCR or TCR created
What occurs once non-self lymphocytes develop and the host is presented with a non-self antigen?
clonal selection
- single naïve clone is stimulated by foreign antigen recognition (receptor binding)
clonal expansion
- proliferation and differentiation of activated lymphocytes
Go over the development of B and T Cells
Immature B and T Cells develop in the Bone Marrow
B Cells mature in the bone marrow
T Cells mature in the thymus
Mature Naive B and T Cells then migrate to the Lymph Nodes to wait for exposure to pathogens
Which molecule is used to present antigens by a cell infected with a virus, which is an intracellular pathogen?
PRR BCR TCR MHC I MHC II
MHC I
Which process during lymphocyte development is critical for preventing autoimmune responses?
Clonal selection
Clonal deletion
Clonal diversity
Clonal expansion
Clonal deletion
What happens during activation of naïve CD4 T lymphocyte by professional antigen presenting cell (APC)?
APC = macrophage or dendritic cell
phagocytosis of bacteria, fungi, viruses (exogenous antigens)
process and present peptides with MHC II to naïve CD4 T cell
T cell differentiates into helper T cell (TH cell)
What are the types of T Helper Cells?
TH1 activate TC and NK cells (intracellular pathogens) and macrophages, B cells (intracellular and extracellular pathogens)
TH2 activate eosinophils, B cells (eukaryotic parasites)
TH17 recruit neutrophils (bacteria and fungi)
Treg inhibit immune responses (termination)
memory CD4 T cell saved for later
What happens during activation of naïve CD8 T lymphocyte by professional antigen presenting cell (APC)?
APC = macrophage or dendritic cell
infected by virus (endogenous antigens)
process and present peptides with MHC I to naïve CD8 T cell
CD4 TH cell helps with activation
T cell differentiates into cytotoxic T cell (TC cell)
What are cytotoxic T Cells?
TCR/CD8 recognizes antigen/MHC I on virus-infected cell
- TC secretes perforins & granzymes
- triggers apoptosis of target cell
What are superantigens?
bacterial proteins that bind non-specifically to TCR
- T cell activation 100x greater than with normal antigens
- large release of cytokines → inflammation
- toxic shock syndrome toxin (TSST)
MHC II presentation of antigen to CD4 T cells directly results in a _______ response.
Natural killer cell Helper T cell Cytotoxic T cell Mast cell Red blood cell
Helper T Cell
Which chemicals are used by a cytotoxic T lymphocyte to kill virus-infected cells?
Antibodies Interferons Complement proteins Perforin and granzymes Defensin and MACs
Perforin and Granzymes
What are T-dependent antigens?
proteins bind to BCR and are processed by B cell and presented with MHC II to TCR of helper T cell
- bacterial surface proteins or adhesins
- viral capsid or envelope proteins
- exotoxins
What are T-independent antigens?
polysaccharides can only bind to BCR in native form (not presented with MHC)
- bacterial capsules
Walk through T-dependent B Cell Activation.
native antigen binds to B-cell receptor on naïve B cell
- endocytosis of antigen and processing
B cell presents antigen to activated TH cell
- MHC II/antigen is recognized by TCR/CD4
- chemical mediators from TH (e.g. IL-2)
B cell activation
- clonal expansion and differentiation
What is clonal differentiation?
plasma cells → antibodies
regulatory B cells
What happens to B Cells after the pathogen has been cleared?
termination of immune response
- apoptosis of plasma cells
memory B cells
- anamnestic response
What are antibodies? What are the parts of the antibody?
immunoglobulin (Ig) proteins that are secreted by plasma cells
Fab
- fragment of antigen binding
Fc
- binds to C1q and initiates complement pathway
- binds to Fc receptors on phagocytes
What are the functions of antibodies?
do not actively kill microbes
they bind to antigens and tag microbes for elimination
inflammation
phagocytes
complement
mechanical barriers
What is agglutination?
antibodies cross-link cells or particles
renders microbes immobile
enhances phagocytosis
What is opsonization?
coating microbes with antibodies
enhances phagocytosis through binding of Fc receptor on phagocytes
What is neutralization?
antibody binds to…
bacterial adhesins
viral spikes
exotoxins
…and then the microbe or toxin cannot interact with host cells/tissues
What is complement activation?
B Cell activate the complement cascade
antibodies interact with C1q
classical pathway → MACs
What are IgM?
monomer is used as an antigen receptor on B cells (BCR)
pentamer is an antibody used for complement initiation
first Ig produced during primary immune response to antigen
also produced in response to T-independent antigens
What are capsular polysaccharides?
T-independent antigens that stimulate production of IgM (but not IgG)
What are IgG?
monomer is an antibody produced during primary response (follows IgM)
main antibody produced during memory response
becomes most prevalent in blood
maternal IgG can cross placenta
neutralization, opsonization, complement fixation
What are IgA?
monomer is an antibody in the blood
dimer is secreted on mucosal surfaces (IgA enhances mechanical barriers such as mucus)
mucosal immunity
neutralization
What are IgD?
monomer is used as an antigen receptor on B cells (BCR)
small amounts in the serum (unknown role)
What are IgE?
Fc of monomer binds to antibody receptor on eosinophils, mast cells & basophils
when antigen binds IgE, it stimulates the anti-parasite response
(release of chemical mediators → inflammation)
also important to allergy response
What are the phases of the immune resposne?
primary response
- first exposure to antigen
latent period
- lack of antibodies synthesis
synthesis of antibodies
- level of synthesis (titer)
- IgM first followed by IgG
secondary response
- re-exposure to the same antigen
- anamnestic (memory) response
- rapid and amplified
Which immunoglobulin isotype becomes the most abundant in blood during the anamnestic response?
IgA IgD IgE IgG IgM
IgG
BCR and TCR have all the following in common EXCEPT:
Antigen-binding site is comprised of two different polypeptide chains
Receptor has two antigen-binding sites
Transmembrane domain anchors receptor to the cell surface
Receptor associated with other proteins for intracellular signaling
Polypeptide chains have constant and variable regions
Receptor has two antigen-binding sites
What are the types of acquired immunities?
ACTIVE exposure to antigen latent period antibody response & memory cells long-term protection
PASSIVE
transfer of immunity (antibodies)
immediate protection but short-lived
no memory
What is natural active immunity?
infection
- exposure via portals of entry
- recovery leads to extended immunity
- e.g. catch chickenpox at school
What is natural passive immunity?
mother-child
- placenta (IgG)
- breast milk/colostrum (IgA)
- protect infant until it develops active immunity
What is artificial passive immunity?
immunotherapy (passive immunization)
- non-immune person receives antibodies from immune person or animal
- protect until microbe/toxin is cleared or active immunity is stimulated
- tetanus, rabies, hepatitis A
What is artificial active immunity?
vaccination (active immunization)
- exposure to antigens via i.m. injection
- no disease or mild symptoms
- polio, measles, influenza
- boosters may be necessary
What are the origins of vaccines?
Smallpox
variolation
variola = smallpox
IF you recover, you do not get infected again
Edward Jenner 1798
milkmaids did not contract smallpox
gave a boy cowpox and then smallpox → the boy survived!
vaccinia = cowpox (harmless) protected against smallpox (deadly)
What are the types of vaccines?
whole/cellular
- live/attenuated (Sabin polio)
- killed/inactivated (Salk polio)
individual antigens
- surface proteins (viral spike vs. hepatitis B)
- surface polysaccharide (capsule vs. pneumonia)
- exotoxins (toxoid vs. tetanus)
What is the wakefield study?
suggested (without evidence) a link between MMR vaccine & autism
some argued that thimerosal (vaccine preservative with Hg) caused autism
article was later declared a fraud and retracted but vaccine fears continue
What observation gave Edward Jenner the idea for the first vaccine?
Cows with cowpox never got chickenpox
Milkmaids with cowpox never got smallpox
A boy who had chickenpox did not get smallpox
A boy who had smallpox did not get chickenpox
Milkmaids with cowpox never got smallpox
What type of immunity is acquired by an infant that is breastfeeding?
Artificial active
Artificial passive
Natural active
Natural passive
Natural Passive
