Practice Immune Response Flashcards
1
Q
Immune Response - Phase 1 with 7 steps
A
- 1st few days afte rinfection, mostly non-specific response involving negative test
- Interferon release (alpha and beta) as warning to cells to reduce transcription and 1/2 life of RNA and also interferon which…
- stimulates NK cells to start killing cells - nonspecific response
- neutrophils attack esp if there’s a break in skin
- mobilization of immune cells - diapedesis = immune cells moving from circulation to site of invaders
- toll-like receptors bind to infected cells
- macrophages ingest virus and sound the alarm by displaying peptides from invader
- secreting tumor necrosis factor which stimulates NK cells
- secrete gamma interferons which stimulate monocytes to make more macrophages
- secrete other signals that turn on Interleukin-1 (pyrogen which may stimulate T cells to proliferate)
- may stimulate inducer T cells
- secretion of other types of cytokines named after cell that secretes them
- present the antigen (macrophages do this)
- antigen-presenting cells = APC
- making MHC-2 surface marker
- bring in virus to cell, fuse w/lysosome
- fuse pieces of virus to MHC-2 surface marker
- release MHC-2/chunk of virus particles out of cell and display on surface
- to show - this is what the invader looks like to the immune system
2
Q
Presenting the antigen continued
A
- present the antigen (macrophages do this)
- antigen-presenting cells = APC
- bring in virus to cell, fuse w/lysosome
- fuse pieces of virus to MHC-2 surface marker
- virus comes in and broken into peptides and then fuses w/rough ER for making MHC2 molecule
- release MHC-2/chunk of virus particles out of cell and display on surface so seen to other immune cells
- to show - this is what the invader looks like to the immune system
- when helper T-cells “sees” antigen in context of MAC-2
- helper T cells are MHC-II restricted and do not recognize virus w/out MHC-II
- have lots of TH w/lots of diversity
- make immune synapse –> T helper cells and macrophage
- w/MHC-2 “loaded on surface” w/externally derived stuff!
- MHC-2 w/virus chunk is “T CELL RECEPTOR” w/CD4 co-receptor
- only forms w/chunk in teh MHC-2
3
Q
Phagocyte Mobilization
A
- measles gets in - nearby are small blood vessels
- site of inflammation where cytokines are released
- neutrophils in capillary come out via diapedesis (extravasation) and start eating up viruses and damaged cells
- also macrophages in tissues or some monocyte in capillary which recognize call and squeeze their way out and convert into macrophages in tisue and eat up invader
- signal moelcule tracking cells to move toward it - chemotaxis agents diffuse away from inflamed site which attracks immune cells to go thru wall of capillary (extravasation) to get to place in tissue
- when cell eats something it fuses w/lysosome to make 2ndary lysosome and lower pH and activate enzymes to eat it all up
- after digest invader they put small peptide fragments into groove of MHCII (antigen presentation) - wave signal to show others what they look like and be on alert
4
Q
Immune Synapse
A
- when immune synapse formed - cells talk to one another
- macrophage - interleukin1 tells T cell to proliferate
- Helper T cell - signals to macrophage
- MIF (macrophage inhibition factor) turns down macrophage roaming, so they hang around area and start replicating - stimulate replication of bound T cells
- interleukin-2 (T cell growth factor): increase T cell proliferation/don’t affect macrophage - inducer T cells signal more T cells
- only infection-specific T cells go into rapid proliferation - “clonal selection” (only cells bound by MHCII and Tcell receptor are turned on by signals)
5
Q
Immune synapse for early antigen presentation
Macrophage - Makes MHCII
A
- immune synapse is where CD4 receptors (co-receptor) and T cell receptor and MHCII receptor
- Tcell receptor only recognizes the antigen in context of MHCII groove that’s in it; not antigen alone
- T cell receptor is MHCII restricted
- Tcell’s CD4 marker is on surface and so start secreting substances due to recogn btwn Tcell receptor and antigen in MHCII receptor
6
Q
Overview of Immune Response
A
- Early response with Phase I and mostly non-specific immunity
- then either goes to:
- cell-mediated immunity or
- humoral (antibody) immunity
7
Q
Cell-Mediated Immunity
A
- involves Helper T-cells Type I - activated from early response
- macrophage has ate thing and displayed MHCII from external antigen
- but helper T cells that linked w/MHCII stimulated cytotoxic T cells via IL2 to get strong response
- TH1 releases Interleukin-2 which stimulates release of CD8 (cytotoxic) T cells - which recognize infected body cells which have changed surface markers taht T cells recognize
- Cytotoxic T cells have T-cell receptor that are restricted TO MHC 1
- are on all nucleated cells - normal body cells
- virus-infected cells, making virus, put chunk of that virus on its MHC-1 (internally synthesized antigens), so body knows that cell is infected
- usually CD8 is MHC1 restricted; CD4 is MHC2 restricted
- also clonal selection for these cytotoxic T cells
- cytotoxic T cell is killer cell - targets the virus-infected cells w/their MHC1 marked and kills them
- kills cell via perforin (punches holes) and granzyme which signals the target cell to enter apoptosis (programmed cell death) - orderly esp compared to necrosis (cause surrounding tissue damage - cell death by injury)
- cleaner wya to remove affected cells
- cell-mediated immunity takes a while to start - 1 week
- after build up immune system it comes down after suppressor T cells turn down response so immune response doesn’t go on for weeks and damage own body
- important in transplant rejection - cyclosporin turns down cell-mediated immunity
8
Q
Memory Cells
A
- regulatory T cells have some role in this
- memory cells hang around for years - why/how your immune system is primed for things like measles
- you have cytotoxic T cells and helper T cells that become memory cells ; activated cytotoxic T cells held in reserve and if not used they become memory cells - to help w/immunity for that specific virus so kill of more rapidly next time
9
Q
Humoral/antibody-mediated immunity Immunity
A
- B cells w/B-cell receptors circulating - membrane-bound antibody has hydrophobic end that allows it to stick in membrane and bind antigen
- antibody on surface binds directly to antigen and signals phagocytosis of entire complex
- brings it in, chops it up and sticks it on MHC-2 on surface
- TH2 recognizes it and forms immune synapse w/Bcell
- interleukin-4 is released (or IL2)
- B-cell stimulating factor stimulates B cells to become anti-body producing factory = plasma cells
- B cells bound to TH cells and receiving stimulating factor turn into plasma cells
- some B cells will become memory cells too
- B antibodies w/out hydrophobic end get produced and are released and go out and target antigens - they stick to them and mark them for destruction
- no high gear antibody production until T cells activate this!
10
Q
Antibody-mediated immunity
A
- Th cell sees MHCII and releases signals and then B cells found thing and displaying and they are releasing IL2 and IL4
- Plasma cells create ER and make tons of antibodies which circulate in body and lymph and stick on surface of invaders and these antibody molecules themselves don’t do the killing but mark them for destruction
- Antibodies “mark for destruction” by increasing the rate of phagocytosis; by increasing attack by the complement system; by increasing attack by natural killer cells
- In this pic could say that Thelpersub 2 for anti-body mediated immunity
11
Q
How do antibodies work?
A
- occupy all sites on antigen - phagocytosis
- clump stuff up to stick together or precipitate so more like for - phagocytosis
- activate other mechanisms - complement rxn increase if antibodies are on there
- antibody on antigen could neutralize by not letting them stick to what normally would
- antibodies change as process continues; diff classes can enhance diff mechanisms to remove antigen
- production of antibodies also has random change component so slightly diff ones can be made
- effector for cell mediated immunity is antibody which marks for destruction
- process of enhancing phagocytosis by marking w/antibody = opsonization
12
Q
Cell-mediated vs. Humoral Immunity
A
- 2 arms of immune response
- cell-mediated - ‘internal’ antigen; TH1 mediated; cytotoxic T-cell=killer/effector
- humoral (in the fluid): all types of antigen; TH2 mediated; antibody = effector that marks antigen for destruction
13
Q
Activation of lymphocytes eg T cell
A
- T-cell activated when receptor binds to target antigen and then it changes form and produces more cytoplasm to get ready to fight infection
- packaging granules w/killing substances in them
14
Q
Resting B cell and activated B cell
A
- starting lymphocyte and then activated to see active B cell - with lots of rought ER and lots of proteins for export which are antibodies
- antibody factory
- immune receptor is present on all types of cells and will recognize very specific invading organism
15
Q
Class I vs Class II MHC
A
16
Q
Immune synapse for cell-mediated immunity
A
- infected body cell w/internally synthesized antigens
- immune synapse II where infected body cell is making MHCI and puts antigen into its groove at surface and cytotoxic cell has MCH1 restriction
- so releases substance to destroy infected cell
- all internally synthsized peptides here
17
Q
Clonal Selection in B cells
A
- Only B cells bound to something are stimulated to become plasma cells and stimulated to become antibody producing factories
- So have clonal selection going on here
- Immunity mechanism – plasma cells are produced and some are memory cells which are there for response years later, so won’t get mumps again 25 years later due to memory cells
- Process of enhancing phagocytosis by marking with antibody=opsonization
18
Q
3 types of immune synapes
A
- Cytotoxic T cells recognizing the infected body cells thru display of MHCI; these antigens here are produced from w/in the cell
- Helper T cells which recognize antigen in context of MHCII on macrophage; antigens are displayed after having been eaten by macrophage
- Helper T cells see antigen on MHCII from a B cell; antigen after having been recognized by B cell as antigen was floating free or as part of complex
20
Q
cowpox vs. small pox exposure
A
- When exposed to smallpox cause more rapid and larger and stronger response and then when fight off the cowpox completely
- Population of memory cells already there with right receptors so when that repeat pathogen arrives then they accept it
- there was immunity to smallpox since inoculation w/cowpox stimulated dev of lymphocyte clones w/receptors taht bind to smallpox antigens too
- 2ndary exposure to cowpox rather then smallpox would have produced a strong if not stronger antibody response
21
Q
Helper T cell central to full immune response
A
- Helper T cells are central to immune process
- HIV targets CD4 helper T cells which knocks helper T cells out and destroys effectiveness of both arms of the immune system; so people infected tend to die of other things because knocks immune system all around
- Pneumonia – most people don’t get pneumonia from this protozoan but people with HIV may because compromised immune system
22
Q
Life Cycle of HIV
A
- CD4 on helper T cells matches with and has to bind w/CCR5 to fuse ferroins with member of T cell, so need both receptors for cell to get affected;
- if have mutation in CCR5 co-receptor then immune from HIV – try to develop vaccines that block CCR5 so co-immunity
23
Q
Antibody Structure - 2 binding sites and 4 polypeptide chains
A
- Antibody molecules are proteins w/2 binding sites – one on left and one on right, Fa and Fb; made of 2 light chains and 2 heavy chains
- Tail that sticks out and is called the Fc portion = constant fraction; recognized by mast cells; phagocytes and complement
- Portions close to center of antibody are very similar
- In antibody binding regions – the sequence is quite variable so the light chain has a constant and a variable region and heavy chain has a longer constant region and a variable region
- Within variable regions there are some areas that are hypervariable and we think that those regions are most important for the specificity of the particular binding of that antibody
- opsonization = coat antigen w/antibody
24
Q
5 classes of antibodies - immunoglobulins Ig
A
- Based on sequence of constant region there are 5 classes of antibodies – IG is short for immunoglobulin:
- If sequenced all IgG constant parts – all would be identical and are similar but diff from IgE type
- Lots of variability in antigen binding parts
- IgM is usually found in a pentamer to help agglutinate things its binding to which helps with more phagocytosis since stuck together in globs
- Usually in typical immune response the IgM antibodies are the first type of antibodies produced – IgM for virus first and
- then IgG next and most abundant type of antibody in the blood; during 2ndary response
- for humoral response; good for complement action too and phagocytosis promotion
- IgD are presence on surface of B cells serving as receptors
- IgA usually as dimer and secreted in bodily secretions – breast milk, tears, sweat, part of protection upon surface of skin
- IgE usually involved in release of histamine – allergy reactions; originally to attack parasites
25
Q
Timing of antibodies during 1 immune response
A
- Beginning of response and have IgM which fades out when IgG picks up and becomes dominate type for good long time until it fades
- IgM agglutinates the invader more regularly then the IgG
- 1.5-2 weeks you feel better but infection still there but no longer infectious
26
Q
Allergy -
A
- Antigen called allergen gets recognized by B cell receptors which bind and becomes converted to plasma cell and antibody producing factory
- Starts making IgE antibodies instead of IgM which are specific to the allergen and as circulate the blood they find mast cells which are from stem cells of bone marrow and have in granular cells histamine
- so pick up IgE antibodies and bind from Fc ends and then they sit around until you are re-exposed AGAINT to that allergen
- and so when bind to antibodies bounded to Mast cells release their histamine and other chemicals that causes all the allergy symptoms
- Allergy shots – small amount of allergen so under threshold of violent rxn
27
Q
A
- Strong rapid response – acute allergic rxn to an antigen to which body has become hypersensitive (violent release from lots of mast cells b/c there’s lots of IgE attached to mast cells) called anaphylaxis (guarding against)
- more than jsut histamine could be released ex prostaglandins
- Example of all possible symptoms – swelling of lips and eyes and hives
- epipen - epinephrine helps b/c constricts blood vessels and helps w/swelling and increase bp and increase HR and FOC and relaxes airways
- type 1 hypersensitivity is immediate
- type 4 hypersensitivity is delayed type ex. poison ivy - hours or days after exposure due to urushiol = oil from poison ivy, local inflammation can cause local tissue damage
- delayed hypersensitivity; cell-mediated, not antibody
- ex. TB test -small amount of TB peptide under your skin to see if developed a hardened swelling then positive for skin test so have been exposed to tuberculosis but doesn’t mean you have active TB – need more tests to follow
