Adaptive Immunity Flashcards
1
Q
Why do we need both innate and adaptive immunity?
A
- without innate immunity, lose control of infection and die very quickly
- without adaptive immunity, can control infection for a bit but eventually lose control
2
Q
Describe immunological memory
A
- antibodies are made by B cells which bind to viruses, bacteria, pathogens, etc. and are basis of vaccination
- the more antibody you have against something, the more protected you are
- give someone vaccine A for influenza, there is a period of time where you can’t detect any antibodies in their blood against influenza; lag phase
- lag phase is the time required for dendritic cell to pick up influenza and go to lymph node to turn on T and B cells; this time you are dependent on innate immune system
- after a few days, you will start to develop antibodies against influenza called primary immune response; antibodies increase, plateau, then once influenza is cleared antibody levels decrease
- for the rest of the person’s life, they will have a low level of antibodies against the influenza virus (never goes back down to baseline)
- if they see this influenza again from vaccine A, there is no lag phase and they immediately have a large and robust response against influenze and they clear it very quickly; secondary immune response
- secondary immune response does not require dendritic cell to pick up influenza and bring to lymph node; this response involves you turning on B cells that are already waiting to respond to influenza
- at the vaccine A and B point, the person got exposed to influenza A and another unrelated influenza which person has not seen before- influenza B
- immune system mounts response to influenza A but can’t do this with influenza B because it has never seen it before; immune system will mount a secondary response to influenza A and concurrently mount a primary response to influenza B and clear the influenza but it will take a bit longer
- this graph explains why you do not need to worry about how many vaccines kids get; immune system can multi-task exposure to several antigens and generate multiple primary responses and concurrently generate secondary responses
3
Q
What are antigen-presenting cells?
A
- dendritic cells, macrophages, and to a lesser extent B cells
- these cells pick up an antigen and present it to a T cell or B cell that is specific for that antigen
- transition between innate and adaptive immune response
4
Q
What is an antigen?
A
- anything that the adaptive immune system will respond to
- something that can generate an antibody response (molecule to which antibody can specifically bind)
- proteins, carbohydrates, nucleic acids
5
Q
Describe structure of antibody
A
- has two arms
- constant domain; allows protein to talk with immune system and doesn’t change
- another arm does the work (like the beater in a mixer)
- many antigen-binding domains in variable region that changes a lot
- when antibody binds to its antigen, it tags the pathogen for destruction by phagocytes like macrophages and neutrophils
6
Q
How do antigen presenting cells execute the presenting of the antigen to the T cells?
A
- B cells bind to native antigen; B cell can bind to influenze virus, doesn’t require processing, antibody binds to influenza virus and starts to kill it
- B cells make the antibodies
- T cells can’t recognize native antigen- only processed fragments of antigen; the crucial job of the antigen presenting cell is to pick up antigen, grind it and process into specific way to display to T cell so T cell can recognize it
- T cell then orchestrates the immune response
- antigen presenting cells present antigen on Major Histocompatibility Complex (MHC) proteins
- MHC is the mouse molecule that we have best studied, human equivalent is human leukocyte antigen (HLA)
- in order to do transplants, HLA has to match
- MHC is widely expressed in body and there are two types; MHC1 is expressed on almost all nucleated cells, MHC2 is only expressed on professional APCs
7
Q
How does MHC work with intracellular pathogen?
A
- APC directly infected by intracellular pathogen; pathogen injects its nuclear material into the cell and the cell starts making the proteins, all nucleated cells have MHC which picks up random samples of proteins that cell is making and goes to surface of cell- now any passing cell can look at the surface of that cell and see a sample of what is going on inside of the cell
- ex: T cell comes across a skin cell with lots of influenza virus so it knows that is a cell it should attack
- also works for tumour cells
-CD8 T cells recognize MHC1
8
Q
How does MHC work with extracellular pathogen?
A
- only professional APCs have MHC2
- extracellular pathogens go into MHC2; in order to do that you have to pinocytose or phagocytose something from the outside and bring it in, use proteazes inside of phagosome to degrade it, and load this up into MHC2 and put MHC2 on surface
- only phagocytes (professional APCs) have MHC2 because MHC2 isn’t helpful unless you can phagocytose
- MHC2 presents to CD4 T cell
9
Q
Where does APC processing occur?
A
- APCs process antigen right after they engulf pathogen
- they then travel through lymphatics to a lymph node (or through blood to spleen) where they will present the antigens to naïve T cells
- this provides activation signal to T cell
- dendritic cell also provides costimulation (other growth factors) to turn on T cell in lymph node
10
Q
What makes T cells very specific?
A
- each T cell has only one specificty of T cell receptor (TCR)
- a TCR will only react to one antigen (eg. a T cell that recognizes influenza won’t recognize HIV)
11
Q
How can we explain that we have enough TCRs for every antigen but there are approx 10^12 different antigens and we only have about 28000 genes in our entire genome?
A
- Germline theory: 1 gene for every receptor; this was proven wrong with the human genome project
- Somatic Diversification Theory: recombination of a limited number of gene sequences leading to a large number of distinct receptors
- little gene segments that immune system mixes and matches to form large diversity of receptors
12
Q
What are postulates of the clonal selection theory?
A
- each lymphocyte bears a single type of receptor with a unique specificity; each B cell will only have one type of receptor on the surface
- interaction between a foreign molecule and a lymphocyte receptor capable of binding that molecule with high affinity leads to lymphocyte activation
- differentiated effector cells derived from an activated lymphocyte will bear receptors of identical specificity to those of the parental cell from which that lymphocyte was derived
- lymphocytes bearing receptors specific for ubiquitous self molecules are deleted at an early stage in lymphoid cell development and are therefore absent from the repertoire of mature lymphocytes
13
Q
What is negative selection?
A
- process undergone by B and T cells to eliminate autoreactive molecules that target “self”
- 10^18 possible receptors with all of the diversity
- goal is to reduce the chance of autoimmunity
- also called central tolerance
- in bone marrow or thymus, cells are screened against a panel of our own antigens; transcription factors show the diversity of proteins to the B cells and T cells filtering through
- if a T cell or B cell recognizes one of our own antigens it is marked for death immediately because that is a potential dangerous B or T cell; these will undergo apoptosis
14
Q
What is positive selection?
A
- T cells also undergo positive selection
- B cells recognize native antigen so as long as they don’t try to attack us, they are probably going to be useful
- T cells on the other hand recognize processed antigen; even if it is not binding our own protein, it still might not be useful to us
- possibility that the T cell isn’t recognizing anything
- T cells are screened against a panel of our own antigens in MHC; if they don’t recongize anything in there they are useless because they won’t be able to recognize a foreign protein in MHC
- these are wasteful and we don’t have space for them so we get rid of them
- in MHC restriction you show an irrelevant antigen in MHC and it needs to be able to bind at least a little bit to that
15
Q
Where does t cell development occur?
A
- thymus
- t cell precursors travel from the bone marrow to develop in the thymus
- mature t cells leave the thymus and travel to secondary lymphoid tissue
- undergo negative and positive selection in the thymus
(B cells go through everything- growth, negative selection- all in the bone marrow)
16
Q
Describe the geography of an adaptive immune response
A
- antigen uptake by APCs in tissue; dendritic cells or other ACPs move it to the secondary lymphoid tissue
- in secondary lymphoid tissue, APCs show it to T cells which turns the T cells on
- T cells go on to help the B cells
- when activated, B cells turn into either memory cells or plasma cells
- plasma cells produce antibodies (lack most other parts of cell except ER, nucleus, and protein)
19
Q
What occurs during activation of B cells?
A
- antigen recognition induces expression of effector molecules by the T cell which activates the B cell
- B cells proliferate
- differentiation to resting memory cells and antibody-secreting plasma cells
- memory cells can last as long as the host survives
20
Q
How can B cells be activated without T cells?
A
-doesn’t work very well; need a lot of B cell receptors on the surface by cross linking them with antigen that has a lot of repetitive things in it
