lec 15- the immune response part 2 Flashcards
what do antibodies do?
- bind to and neutralize a bacterial toxin
- coat the pathogen which promotes phagocytosis
- activate complement
overall: target pathogens and eliminate them via phagocytosis
what is the secreted form of B-cell receptors?
antibodies
what is the structure of an antibody?
-2 identical light chains
-2 identical heavy chains
-each light chain is joined to a heavy chain by a disulfide bond
- both light and heavy chains consist of one variable and one constant region (light have one domain, heavy has 3 or 4)
what is the Fab fragment?
-fragment antigen binding
-composed of the light chain and part of the heavy chain
what is the Fc fragment?
-fragment crystalizable
-a portion of the constant region of the heavy chain
what do the Fab and Fc fragments bind to?
Fab binds to the antigen and Fc binds to Fc receptors on cells
what is an epitope?
the portion of an antigenic molecule that is bound by an antibody
can an antigen have multiple epitopes?
yes,
what does a B-cell do when it recognizes its antigen?
it will multiply and produce clones of itself, all of which will secrete antibodies
do B-cells tend to recognize inner epitopes?
no, they recognize external epitopes
what are the hypervariable regions of an antibody also known as?
complementary-determining regions (CDRs)
what do the 6 hypervariable regions of heavy and light chains form?
antigen binding sites
what are the three steps of the generation of B cell antigen recognition diversity?
- somatic recombination
- junctional diversity
- combinatorial diversity
what is somatic recombination?
-to generate variable region of light chains, V and J segments are joined
-to generate variable region of heavy chains, one V, D, and J segments are joined
- V, D, and J segments are randomly chosen from many
what is junctional diversity?
addition of new and random nucleotides at the V and J segments of light chain and D and J segments of heavy chain
what do the randomly chosen V gene segments code?
they code CDR1 and CDR2
what does junctional diversity code?
CDR3
what is combinatorial diversity?
-B cells with intact heavy chains undergo clonal expansion, light chain generation then takes place (same heavy chains but light chains can be different)
-different light chains combine the already generated heavy chains
-before B cells leave bone marrow, they undergo a selection so they dont recognize themselves
-three steps that lead to the creation of circulating B cells with unique specificity
A clone of mature B cells released from bone marrow have:
one antigen specificity and express lgM receptors, meaning first class of antibodies are lgM class antibodies
what happens when B cells leave the bone marrow?
-they circulate between blood and lymph, need antigen to be activated
-need help of T cells to secrete antibodies
-takes place in lymph node
-B cells will phagocytose the antigen and preset pieces of it to helper T cells
what are class I MHC molecules?
molecules that are expressed on all nucleated cells, generally present viruses to cytotoxic T cells (CD8) which kills infected cell
what are class II MHC molecules?
molecules that are expressed on professional antigen presenting cells, present extracellular pathogens that must be phagocytosed before presentation
what is the structural difference between class I and II MHC molecules?
class I: one transmembrane alpha chain of three domains that are non-covalently complexed to B2 microglobulin
class II: two transmembrane chains- alpha and beta
what ends up in the binding sites of class I and class II MHC molecules?
pieces of antigens
when does the T cell receptor recognize antigens?
when they are being presented by an MHC molecule that the T cell also recognizes
what T cells recognize class I MHC and class II MHC?
class I: CD8 cytotoxic T cells receptors
class II: CD4 helper T cells receptors
what are the three types of T cells and what do they do?
cytotoxic T cells (CD8)- kill infected cells
helper T cells (CD4)- regulate other white blood cell activites and activates macrophages
regulatory T cells- supress activity of other lymphocytes, and help control immune responses
what does MHC stand for?
major histocompatibility complex
what encodes MHC proteins?
-stable germline genes from 3 families that encode:
class I heavy chain isotypes
class II alpha chains isotypes
class II beta chains isotypes
what is the most polymorphic gene system in the body?
MHC
how many allotypes of MHC class I do humans have?
12, 6 from mom and 6 from dad
does each MHC molecule display a range of peptides?
yes multiple peptides can fit in the binding sites
how do T cells function?
T cells function by making contact with other cells, the T cell receptor recognizes antigen attached to MHCs and induce changes in the cell
do T cell precursors from the bone marrow express CD8 and CD4?
no, they only express it once in the thymus
what happens to T cells in lymph nodes?
T cells are always activated in a lymph node by dendritic cells first and then go on to perform their effector functions
what happens to T cells after activation by dendritic cells?
helper T cells stay in lymph node and help cells make antibodies, cytotoxic T cells leave lymph node and kill infected cells
what happens to a T cell if they do not encounter an antigen on a dendritic cell to scan?
they continue to circulate between blood and lymph, then they die/apoptosis occurs if they never find an antigen
what does ITAMS stand for?
immunoreceptor tyrosine based activation motifs
what are the 3 signal transduction pathway steps for T cells?
- T cell ITAMS are not phosphorylated
- binding of MHC to T cell receptor leads to ITAMS phosphorylation by Lck
- ZAP-70 binds phosphorylated chain ITAMS and is phosphorylated by Lck
what is Lck?
-Lck (lymphocyte specific protein kinase) a tyrosine kinase
where are B cells?
circulating between blood and lymph, and encounter antigen in lymph node
what is linked recognition?
B cells and T cells recognize the same antigen but different epitopes
what causes a cognate pair?
linked recognition
what do B cells in cognate pairs sometimes turn into?
lgM secreting plasmoblasts
what is a plasmoblast?
immature blood cells that secrete antibodies while still dividing
why do B cells secrete lgM and where do they exit?
to generate antibodies, usually low affinity so they exit blood stream through lymphs and form a germinal center
where does somatic hypermutation occur?
at the germinal center
what is somatic hypermutation?
the process a B cell undergoes when it enters the germinal center
what does somatic hypermutation do?
generates antibodies of higher affinity for the antigen
what is affinity maturation?
the process B cells undergo if they display a higher affinity
what does affinity maturation do?
makes a B cell with high affinity undergo class/isotype switching again with the aid of a helper T cell
what do B cells become after affinity maturation?
either plasma cells or memory cells
what drives the single nucleotide substitutions in centroblasts (activated B cells)?
activation-induced cytidine deaminase (AID), made by B cells
what determines if B cell becomes plama cell or memory cell?
-helper T cells (specifically Tfh cells)
-need for antibodies makes plasma cells
-when an infection subsides, the same cytokines direct formation of memory cells
where are long lived and short lived plasma cells?
long lived = bone marrow
short lived = lymph node
what are long lived antibodies that are in bone marrow and ready to circulate and act called?
serological memory
what activates long lived memory B and T cells?
if the pathogen establishes re-infection
how does CD8 T cells kill infected cells?
-only one infected: recognize the infected cell then programs it to die, while neighbouring cells are fine
-multiple infected cells: recognized infected cell then programs it to die, then goes to second then third. First is dead, second is dying, third is being attacked
