Immune System, Lecture 1 Flashcards
Immune System Overview
- immune system - collective of things that provide immunity
- immunity: ability to resist or eliminate
- susceptibility: lack of resistance (opposite of immunity)
- constantly coming in contact with potentially harmful substances:
◦ pathogens: viruses and microbes (bacteria, fungi,
parasites) -> come from the outside into the body
◦ abnormal cells originating in body (inside the
body)
◦ external and internal (innate/adaptive) defenses
all working together
What are some Immune Functions?
- defending against invading pathogens
- removing worn out cells damaged by time, trauma or disease (ex. red blood cells last 120 days, after that immune system deals with the damaged ones)
- facilitating wound healing and tissue repair (particularly innate system)
- identifying and destroying abnormal cells originating in body (immune surveillance)
- also undesired immune response (allergies, autoimmune disease (body attacking normal body tissue), transplanted organs and tissue graft rejections)
External Defenses
- barriers; not immune responses (just trying to prevent things from getting past them)
- 1st line of defense
- immediate
- there are both physical and chemical external defenses
External Defenses - physical examples
physical
→ skin - when intact - prevent crossing (usually will not get past skin)
→ hairs - nasal cavity - filter
→ mucus - upper respiratory and GI tracts - sticky and bind (a lot of pathogens get trapped in mucus)
→ reflexes - coughing/sneezing - expelling (breathing something in, and trigger coughing or sneezing to bring it back out)
External Defenses - chemical examples
chemical
→ sebum - oil in skin surface / slight acidic, poor environment for pathogen growth (can get trapped in oils, so you do not get bacterial growth)
→ lysozyme - in tears, perspiration (sweat), saliva, nasal secretions, tissue fluids - antimicrobial properties can break some pathogen cell membranes (cannot stay intact after coming in contact with lysozyme)
→ stomach acid - highly acidic, can kill some pathogens (with stuff staying in stomach for a while, it allows to eliminate and/or kill pathogens)
Internal Defenses - immune responses
immune responses - 2 types (something comes in contact with pathogen, and something occurs in response)
- innate
- adaptive
encounter stage - pathogen and immune cell meet in body
- locations for encounter
◦ resident immune cell populations - especially in
lymph nodes, spleen, lymphatic tissues
◦ circulation - blood and lymphatic
→ if we did not have encounter, we would not get internal response (need to be in some proximity to each other)
Leukocytes (white blood cells)
- formed in red bone marrow by leukopoiesis
- pluripotent stem cell - myeloid and lymphoid stem cells - progenitor cells - precursor cells (blast cells)
specific focus in this course:
myeloid cells - neutrophils (they are important, because they are some of the first to arrive)
◦ neutrophils will arrive to sites where a quick
immune response is required (not just a barrier
anymore) - monocytes - form macrophages (mature into macrophages) - usually monocytes are circulating and when we need them they form into macrophages
◦ slower to get there, but they give some of the
largest response on the innate side
lymphoid cells (more for adaptive system) - B lymphocytes - form plasma cells (plasma cells can then develop into antibodies - key adaptive responses)
- T lymphocytes - can break into many things
- Natural Killer (NK) cells
Innate Immune Responses
- non-specific / general
- 2nd line of defense
- rapid response, but limited
recognition stage - pathogen and immune cell binding (become bound together in some way, physically) - general or non-specific recognition
- toll receptors or toll proteins on pathogen surface act as pattern-recognition receptors (if it encounters pathogen (pattern on surface of pathogen), it can recognize pattern) -> does not recognize specifics, more so general patterns
- bind large numbers of pathogen-associated molecular patterns and trigger innate immune responses
- “recognition” often carbohydrates or lipids on pathogen surface
- often innate responses are to contain and limit spread while adaptive mounts a more specific response
Innate - Interferon
- cells infected with viruses produce proteins (interferons) to “interfere” with viral replication
type I interferon:
- virus infected cells release into extracellular fluid to bind non-infected cells
- binding triggers non-infected cells to start antiviral proteins
- antiviral proteins can prevent viral replication if cell becomes infected
- can work in most cells as long as have type I interferon receptor
type II interferon or interferon-gamma:
- potentiates (increases effectiveness) type I
- releases cytokines (small proteins that act in cell signalling/communication) triggering proliferation (increasing numbers) of immune cells, secretion cytotoxic chemicals
- involved in “activated” versions of macrophages and NK cells (has some extra functions in response to response to type II interferon)
Innate - phagocytosis (critical one)
- pathogens engulfed and destroyed (taken into cell)
- phagocyte - any cell that can do phagocytosis
◦ neutrophils - quick response
◦ macrophages - largest capacity
4 phases: - recognition: binding pathogen on cell membrane of phagocyte (found on surface of whatever pathogen it is)
- ingestion: phagocytosis or endocytosis to bring into phagocyte forming phagosome (pathogen inside vesicle)
- digestion - lysosome (a bunch of digestive enzymes) binding to phagosome forming phagolysosome (contents of lysosome now in contact with pathogen for breakdown) -> those two things migrate together and get phagolysosome
◦ the digestive enzymes from lysosome can go to
phagosome and break it down - kill: pathogen no longer functional with release of end products internally inside phagocyte or exocytosis to release externally outside phagocyte (pathogen is not longer a functional one) -> killing does not necessarily mean destroying
Innate - alternative complement pathway
- complement proteins - plasma proteins from liver continually circulating inactive in blood
- inactive C3 binds pathogen; activates and triggers cascade of activation starting from C3
activated proteins “complement” or enhance immune reactions:
- opsonization by attachment of portion of C3 (C3b) to pathogen:
◦ enhances phagocytosis
◦ opsonin (marker) - makes easier to recognize (put
it on bacteria, marks it for phagocyte to
recognize)
- development of membrane attack complex (MAC) by activating C5-C9:
◦ insertion in pathogen cell membrane to form
“pores”
◦ allow inflow of fluid and material into pathogen
intracellular environment - kills
my notes:
- opsonization means when you get binding, C3 becomes active and inserts a little piece of itself on pathogen and the piece that inserts is called C3b
- this is helpful because most phagocytes have a receptor for C3b on them (makes the binding between the pathogen and phagocyte a whole lot easier)
- once we get C3 we get a cascade of activation (C5-C9 - can insert into cell wall of pathogen)
- pore creates a passageway to allow debris and fluid to rush into pathogen that can possibly kill the pathogen
