Lecture 9: Last for Unit 3 before exam
WHICH part of the immune response is most useful against intracellular pathogen?
CMI
terms for antibody understanding
Fc: amino acid is less variable, more conserved. Fab: antigen binding ends, each on the Y tips. 2 copies of the light chain: small 2 copies of the heavy chain: larger
when we get a vaccine, we are more likely to develop a (secondary or primary response) to a pathogen when we encounter it?
secondary, therefore we are more likely to live
antibody
secreted proteins that bind to antigens with high affinity
APC present antigen on
MHCII receptors
antibodies also go through
somatic recombination
complement
substance in the blood that complements antibodies
antigen on MHCII is recognized by what receptor on Th cells? what recognizes the MHCII itself?
T cell receptors; the CD4 protein
when B cells present antigen, what do helper T cells do?
the T helper cell recognizes it in the same way that it recognized the antigen on the APC cell. the helper T cell then releases cytokines
when the activated helper T cell secretes cytokines, what happens?
the b cell becomes activated. they will form plasma cells, which are the antibody factories and act immediately. Memory B cells don't immediately act, but circulate in the body in case you are exposed to the same pathogen again
what does the cytotoxic T cell think when it sees an antigen on an MHCI cell?
the cell presenting the antigen is infected and needs to be destroyed. the cytotoxic T cells release perforins which make holes in the infected cell. they also release granzymes which prevent the pathogens inside from growing more
the variable regions vs conserved regions.
the light chain: where somatic recombination is happening. the heavy chain also has some recombination zones. this has the effect that the place that binds the antigen is variable whereas the part that binds the cell receptor is more conserved
cytotoxic T cells are important because
they can directly kill infected human cells. many viruses, protists, and fungal infections occur inside cells, so cytotoxic T cells are necessary
if we can recognize many antigens, how does our immune system recognize so many antigens?
adaptive immune system recognizes billions of antigens. this occurs because lymphocytes each recognize a DIFFERENT antigen via the BCR or TCR
if the human genome is only so large, how do we have such specificity in our immune system? we don't have room to encode a gene for each antigen?
through somatic recombination
main output of AMI response
antibodies
agglutination
antibodies clump together in a big mass. two tips of the antibody crosslink cells together. pathogens are held together by antibody glue so they can't reach other tissues in the body
CD8 Cells get their info from an ______ _____ ____ using an _____ molecule
antigen presenting cell. MHCI molecule.
what is an antigen
anything that elicits an immune response
how do we produce tolerance in T and B cells
as they mature, any cell that can't distinguish between self and non-self are destroyed
antibodies action in complement activation
complement protein has Fc receptors. helps complement protein find pathogen. create the MAC complex which leads to the death of the pathogen.
what causes the B cells to be activated?
cytokine release from helper T cells
what most directly activates the B cell
cytokines released by the activated helper T cell
CD8 T cells are those that will develop into ______ __ ______
cytotoxic T cells
key to vaccines
deliver antigen without pathogen
cell mediated immunity
does not act with antibodies but acts with cells; alert and activate immune cells so that they can carry out their function ie: cytotoxic T cells
why do we have conserved and variable regions in antibodies
due to somatic recombination
each antibody is sensitive to ONE ______
epitope
each protein is made up of many ______
epitopes that are each recognized by a single antibody
activation of CD8 (cytotoxic) T cells
future cytotoxic T cells get their information from APC but the antigen presenting cells in this scenario utilize the MHCI receptors to present antigen. The CD8 recognizes the MHCI receptor. dendritic cell presents antigen. the CD8 T cell is activated and proliferates, become cytotoxic T cell or killer T cell.
antibodies generally act (inside or outside) human cells; therefore?
generally act inside human cells. so would not interfere with virus replication
activated helper T cell
has the ability to activate B cells and produce cytokines
CD4
helper T cell.
CD4 protein is found on
helper T cells
to ensure that we want to kill a particular antigen, we must receive the signals from?
helper T cells and B cells. this occurs through recognition of the antigen by the TCR and recognition of the MHCII through CD4 to ensure that the process is really desirable.
T cells and B cells are initially generated through _______ in the ____ ______; after they are produced, they go through additional developmental states, one of these developmental states is _____ _____
hematopoiesis, bone marrow. somatic recombination
what leads to immune cells
if we don't eliminate T and B cells that recognize our bodies own antigens as pathogens when T and B cells are developing.
there are several types of antibodies:
igA, IgM
memory leads to _____
immunity
when T cells and B cells are first produced, how does their genetic capacity compare to the other somatic cells in the body?
initially, have the same genetic capacity as other cells in the body. all have the same genes
antibody mediated immunity
involves antigen presentation through MHCII how the body produces immunity
why don't we want all of the antigens to react to one pathogen?
it can lead to cytokine store so systemic inflammatory responses
what is the effect of an antigen having to be doubly recognized in order to activate a helper T cell
two-protein-protein interaction 1. T cell receptor on the helper T cell recognizes and binds a particular antigen in the MHCII complex 2. the CD4 protein on the helper T cell recognizes the MHCII protein on the antigen presenting cell. This double recognition activates the helper T cell. this is a check
somatic recombination
undergo unique DNA recombination process that gives each T cell and B cell a UNIQUE T cell receptor and B cell receptor.
what do uninfected human cells do? what do pathogen antigens do>
uninfected cells present cellular peptides. these are parts of itself that are not recognized by the immune system. present pathogen antigens on MHCI antigen. alert cytotoxic T cells to the presence of something inside of them`
neutralization can apply to
viruses or toxins
how does somatic recombination work?
we have 4 parts of a gene for a T cell receptor present in all of our cells. in somatic recombination, we take this gene and cut the DNA and discard the rest of it. by having a few segments of each gene, body T cells have different receptors --> we don't have to have millions of different genes
why does the antigen presentation have a lot of checks and balances
we want to make sure that this is the correct path. over-stimulation can be damaging
CMI response uses a more universal system of antigen presentation?
yes, MHCI is produced by all body cells
MHCII cells are limited to _____ ______ and _____
macrophages, neutrophils, and dendritic cells
what are the steps that have to occur for a B cell to be turned into a plasma cell?
1. Antigen presentation by an APC to a TH cell and activation of that TH cell 2. Interaction with and processing of the antigen by the B cell itself 3. Interaction of the activated THcell with the B cell
in order for the helper T cells to produce antibody mediated immunity, it has to receive the same signal from what two cells?
1. Antigen presenting cells 2. B cells * both of these are recognized by both the CD4 protein and the TCR protein
perforins
make holes in the infected cell
opsonization
making phagocytosis better (phagocytic cells have Fc receptors. Fc can bind to receptors on antigen presenting cells.) if the Fab end binds to an antigen, it pulls the antigen closer for the process of phagocytosis
antibody mediated immunity involves what cells?
1. antigen presenting cells 2. helper T cells 3. B cells
how does the adaptive immune system activate helper T cells with the end goal of producing antibodies?
1. antigen presenting cells take up microbial antigens and migrate to a local lymph node. 2. They process and present the antigen on their OWN cell surface using the MHCII system 3. The MHC molecule forms a bond with TH cells that have T cell receptors that recognize and bind to that particular antigen 4. the TCR recognizes the antigen in the MHCII while the CD4 protein on the T cell recognizes MHCII proteins (double recognition)
the general process of antigen presentation in dendritic to T cells
1. dendritic cells: main antigen presenting. shows T cells what antigen it needs to be responsive to. 2. chops up antigen into epitopes 3. presents antigen on MHCI or MHCII 4. T cells, which have a specific receptor for MHC, recognize antigen as it is displayed. this event activates the T cells for all future effects of that cell
types of vax
1. live attenuated virus: live pathogen that has been through many life cycles so it loses pathogenic properties. 2. inactivated or killed vaccine: dead virus particles that have been killed by chemicals. retain antigens that can be used by the immune system 3. subunit -- individual antigen: present individual antigens that are the MOST POTENT 4. toxoid: inactivated toxin (active poisonous component) grow up the bacteria, inactivate the toxin, the inactivated toxin no longer has poisonous activity, but does retain some antigen properties.
functions of antibodies
1. neutralization 2. opsonization 3. complement activation 4. agglutination
what are the major hallmarks of the immune system
1. specificity 2. memory: immune system can kick in quicker due to memory T and B cells 3. tolerance: world is full of antigens, body might respond to all of these, but we need to eliminate the response to self.
antibody mediated immunity occurs in response to what?
microbial antigens
neutralization
multiple antibodies are bound to the surface of a virus or a toxin. the antibodies block the ability of the virus or toxin to attach to host cell receptors. this is bad for the virus because a critical step in virus replication is attachment of the virus to its host
AMI and CMI collectively have the effect of doing what?
AMI patrols: interstitial spaces, blood, lymph, and epithelial surfaces CMI patrols: cytoplasmic and vesicular *system that surveys the entire body because of the MHCI and MHCII systems
do antibodies have one job?
no, they have multiple activities
do vax contain live pathogens?
no, we deliver antigens to create the primary immune response. do not recreate the illness.
what T cells and B cells respond to a given pathogen?
only the T cells and B cells that recognize that antigen are activated and are supposed to respond
immunoglobulins
other name for antibodies
innate immune response
phagocytic cells trap and destroy. presenting antigen to T cells in local lymph nodes and other lymphatic tissues
B cells have the ability to
present antigen on MHCII receptors on its own
granzymes
prevent the pathogens inside from growing more
remember the primary immune response vs the secondary immune response
primary: slower secondary: stronger and faster response due to the memory cells
AMI activation output
production of memory cells and the production of antibodies by plasma cells
antigens tend to be_____
proteins (could also be lipids or polysaccarides)