Immune System, Lecture 3

Question 1

Lymphocyte Receptors - T cell Receptpr

Answer 1

• antigen must be combined with major histocompatibility (MHC) protein and presented
• presented antigen able to recognize T cell receptor as part of activation stage
• only identical twins have same MHC proteins
• otherwise, no two individuals have same MHC proteins on cell membranes (“identity tags” — genetic markers of self)

Question 2

MHC class I and MHC class II

Answer 2

MHC class I – on most cells (erythrocytes do not have)
- cytotoxic T cells require antigen to be presented with this class

MHC class II – mainly on macrophages, B cells
- helper T cells require antigen to be presented with this class
- most regulatory T cells involve antigen presented with class II, small number with class I (never quite known with the regulatory ones but more likely to be presented with class II)
- MHC proteins not required for NK cells – more non-specific binding like innate (bind more with general binding, do not need this specific presentation)

Question 3

Antigen Presentation - exogenous antigen

Answer 3

• exogenous - antigen outside immune cell enters by phagocytosis
  steps
• phagocyte recognizes and ingests antigen by phagocytosis
• antigen broken down (antigen fragment) and a piece combined with MHC class II
• vesicle moves resulting complex to surface
• exocytosis and insertion (antigen presentation) on cell membrane surface
• helper T cell with correct T cell receptor can bind antigen presentation (clonal selection)
• macrophages and B cells key ones with MHC class II for exogenous antigen presentation to helper T cells

Question 4

Antigen Presentation - endogenous antigen

Answer 4

• endogenous - antigen already inside body cell
  steps
• intracellular viral protein acts as antigen
• viral protein broken down and a piece combined with MHC class I
• vesicle moves resulting complex to surface
• exocytosis and insertion (antigen presentation) on cell membrane surface
• cytotoxic T cell with correct T cell receptor can bind antigen presentation (clonal selection)
• most body cells (except red blood cells) have MHC class I for endogenous antigen presentation to cytotoxic T cells

Question 5

Adaptive Immune Response

Answer 5

activation stage
- after recognition gives us clonal selection; activation gives multiple rounds of clonal expansion (proliferation - increasing clonal numbers / differentiation - increase clonal specialization)
- all clones formed (whether proliferated or differentiated) able to recognize specific antigen from initial clonal selection
- ultimately form:
◦ effector cells - carry out immune attack
◦ memory cells - not active in attack; stored for future encounters with same specific antigen
attack stage - forms
- cell-mediated: no antibodies involved
◦ especially - intracellular pathogens, cancer cells
- antibody-mediated: formed antibodies involved
◦ especially - extracellular pathogens (outside cell)

Question 6

Helper T cell - activation

Answer 6

helper T cell activation with binding antigen presentation (clonal selection) starts clonal expansion, but not enough for full activation:
- antigen presentation - binding (clonal selection)
- costimulus - nonantigen binding (costimulus is a second binding without the antigen)
- secretion of cytokines (like interleukin 1 (IL-1) / tumor necrosis factor alpha (TNF - α)) → cytokines are going to help stimulate the helper T cells (full activation along with two bindings)

all 3 steps and now fully activated helper T cell secreting interleukin 2 (IL-2):
- stimulates full helper T cell clonal expansion; some effector and some memory cells
- effector cells releasing even more IL-2 and other cytokines
→ “antigen presenting cell”: generic name; cell doing antigen presentation

Question 7

Activated Macrophage and Natural Killer - attack

Answer 7

• activated helper T cell releases IL-2 and interferon type II (interferon gamma)
• trigger macrophages and NK cells to proliferate and become “activated” versions
• activated versions can secrete cytotoxic chemicals that destroy target cells
• these “activated” macrophages and NK cells are non-specific (innate) binding, but reliance on activated helper T cells make them part of adaptive immune response

my notes:
- under release of chemicals from helper T cell a macrophage will become an activated macrophage/natural killer cells
- these are cell-mediated attacks because they are releasing chemicals
- macrophages are one of the biggest defenses because they can do a number of things

Question 8

Cytotoxic T cell - activation

Answer 8

• cytotoxic T cell activation with binding antigen presentation (clonal selection)
• while not shown activation often also involves costimulus and secretion of cytokines
• maximal activation requires the helper T cells contributions (IL-2 and other cytokines) to stimulate full cytotoxic T cell clonal expansion; some effector and some memory cells

Question 9

Cytotoxic T cell - attack

Answer 9

• activated effector cytotoxic T cells circulate and will recognize virus infected cells
  with recognition effector cells:
• release perforin
  ◦ similar to MAC; creates a channel for intracellular
  entry
• release granzymes
  ◦ digestive enzymes enter via performin - created
  channel
  result:
• virus infected cells self destruct (can lose a lot of cells depending on how many are infected)
• virus released into extracellular where other defenses can more easily attack

my notes:
- perforin will punch a hole in membrane of cell that will allow things to get in (granzymes from cytotoxic T cells)
- cells gets killed and once virus is exposed it can be be killed easily as well by antibodies
- if this virus has affected a lot of cells this process can be problematic to survival because the killing of too many cells is not safe (have to have other defenses)

Question 10

Regulatory T cell - role

Answer 10

• used to be called suppressor T cells
• suppress immune responses to keep from over-reacting (provides some balance)
  ◦ if immune system reacts excessively could cause
  attack on own cells and lead to autoimmune
  disease
  ◦ helps provide self-tolerance
  ◦ exact mechanism - ? - inhibit T cell proliferation
  and some cytokine production produce inhibitory
  cytokines; react to IL-2 in a negative; prevent
  some costimulation
  also:
• help control inflammation (one of the innate processes) by acting as negative regulators → such that it does not spread to far to normal tissue from scar tissue
• help with accepting organ transplantation -> to prevent organ rejection as there will not be as much immune response recognizing it is not foreign matter (regulatory T cells help accept the transplant)