Immunology - Part I Flashcards
1
Q
How does the immune system defend itself against invading agents?
A
lots to do with cell recognition
parts & players
immune response
innate immune system first and then specific immune system
2
Q
2 major kinds of immune defenses
A
- innate immunity: non-specific event (doesn’t matter type of invader - always present and on); defensive mechanisms always there and always on
- adaptive/specific immunity: specific to invader; adapts to particular invader coming in, very specific; part of response is to recognize measles virus and remember you had measles before
need both to work well
immune system tells us how cells recognize each other and that enables us to tell tissues that don’t belong - “self vs. non-self”
3
Q
Innate Immunity
A
- “first line” of defense includes: surface barrier and all openings in body protected
- protect outer barrier and then protection of outer openings - first line of defense and all innate
- Skin - unbroken skin is an excellent barrier - like armor but flexible; 15% of body wt (largest organ in body), subacris glands - produce oils and sweat glands also secrete which together are low pH so have some immune cells and lysozyme in them, includes snot, sweat, tears
- antibodies in bodily secretions that bind invader on skin
- barrier and guarding entrances
- physical and chemical protections/defenses
- temp regulation
- all openings in skin protected by some immune function:
- respiratory system have roaming macrophages and trap organisms in mucus via cilia
- urogenital tract w/decreased pH to prevent growth of microorganisms
- digestive tract has lymphoid nodules called “peyers patches” w/immune cells in area that are involved in immune response and balance btwn GI tract and immune system
- tonsils - lymphoid nodules that surround opening to digestive tract (we have 3 sets of 2) to protect against invaders
- adenoids which are pharyngeal tonsil and loaded w/immune cells
4
Q
Innate Immunity: Cellular, protein, and other mechanisms - 2nd line of defense (assume they got inside)
Lymphatic System
A
2nd line of defense:
- lymphatic system:
- thymus - big in young organisms, get smaller w/age
- spleen - stores excess blood and lymph cells
- appendix - may be important in youth
- Peyer’s patches in digestive tract
- lots of lymphatic ducts draining thru lymph nodes and vessels (drain excess tissue fluids)
- act as immune check points - can attack w/immune cells before blood is infected
- lymph system also absorbs fat from gut
- immune surveillance - help prevent cancers and other infections
5
Q
Lymphatic System as innate immunity continued
A
- lymph ducts bring in fluids from the tissues
- net pressure in capillaries is more so leak into tissues
- so lymph removes excess fluid from tissues and draining it away into lymph nodes where make sure become go back in; lymph nodes are check points
- check points catch early cancers - most people get little cancers and immune system recognizes them and knocks them out
- immunocompromised person sees more cancer than expected
- spleen stores extra wbc and rbc
- lymphatic cetner is where stuff gets screened by wbc; spleen is bag w/cells so if bag gets ripped it doesn’t heal
- capillary bed where fluid leaks from tissues and this fluid is picked up by lymphatic vessels but fluid does not leak back into tissues
- one way flow away from tissues
- in gut there are villi/lymphatic vessels that absorb fat called lacteal
- everywhere there’s capillaries there’s also lymphatic capillaries
- outer layer of skin has no blood circulation; ex. cornea and lens of eye don’t have blood circulation
- all lymph nodes put fluid in thoracic duct and dumps into left subclavian vein
- all fluid that has been looked thru the checkpoints (lymph nodes) get returned to blood
- lymphatic system drains all system of body - look at downstream lymph nodes after cancer
6
Q
Innate Immunity: Cellular, protein, and other mechanisms - 2nd line of defense
New blood and Immune cells from bone marrow
A
- have multipotential hematopoetic stem cell that can differentiate to make either red or white cells and platelets
- all bone marrow structures from same progenitor cell and all stimulated by erythropoeitin hormone from kidney
- give drug to cancer patient to increase bone marrow function - related to EPO
- new blood and immune cells from bone marrow; blood stem cells make all immune cells includes:
- rbcs, neutrophils, monocytes
- red and white blood cells from glomera
- blood cells all originate from bone marrow
- can actually increase production (erythropoitin) hormone from kidney stimulates RBC production
- basophils and eosinophils are related to allergies and parasitic infections - referred to as granulocytes, have histamine
- neutrophil - lasts 8 hrs, always making new cells
- adults have 10-12 diff wbc’s @given time (1% total blood cells)
- average person makes 10 billion cells/hr
- aplastic anemia - when you stop making blood cells (sometimes resolves, somtimes need bone marrow trnasplant)
- mylodysplastic syndrome - stop making platelets, neutrophils and rbc’s
- rbcs, neutrophils, monocytes
7
Q
if bleeding…
A
- make 3-10 billion blood cells/hr and if bleeding, make up to 10x that to make up for loss
- rbc last 120 days; neutrophils last 8 hrs
- aplastic anemia: bone marrow stops and get transfusions and sometimes it starts again and somtimes it doesn’t
- caused by various sources of infections/chemicals
- can save w/bone marrow transplant
- erythrocytes are rbc
- leukocytes are wbc, includes lymphocytes
- megakaryocytes stay in bone marrow so don’t circulate
8
Q
Innate Immunity: Cellular, protein, and other mechanisms - 2nd line of defense
Non-specific Immune Cells
A
Nonspecific immune cells - innate immunity
- phagocytic cells:
- neutrophils “polymorphoneutrophils” - most abundant wbc, tend to increase during infection
- tend to be 1st cells on scene of infection or inflammation
- release toxic substances when they take in invader
- pus = bodies of dead neutrophils
- destroy themselves when they attack; can release fibrous traps
- release O2 radicals, digestive enzymes keep pagaged up and “nets” (neutrophil extracellular traps - strands of DNA to trap invader) when they attack;
- as they die they release DNA strands and controlled cell death - apoptosis
- release cytokines are cellular signaling molecule to notifying immune system what is going on
- monocytes: horseshoe-shaped nucleus
- precursor of macrophages
- once it leaves blood it becomes macrophage when in tissues
- macrophages: eat everything that is not “self”
- “dendritic cells in skin”
- “langrhans” in other tissues, etc., historical naming system based on histology
- b/c of these “dendritic” processes off the cell body
- in liver called kupffer cells; in lung called dust cells or in brain called microglia
- neutrophils “polymorphoneutrophils” - most abundant wbc, tend to increase during infection
9
Q
Innate Immunity: Cellular, protein, and other mechanisms - 2nd line of defense
Non-specific Immune Cells
A
nonspecific immune cells includes: phagocytic cells and natural killer cells
- NK cells
- punch holes in cells that are non-self
- protein is “perforin”, released from vesicles and will assemble in membrane of target cell
- perforin self-assembles in the membrane of non-self cell, making a hole and causing lysis
- NK releases enzyme called granzyme which reprograms DNA in targe cell to go into apoptosis and die
- thought to be important in surveillance
- also important in immune surveillance for cancer defense
10
Q
Innate Immunity: Cellular, protein, and other mechanisms - 2nd line of defense
Other Non-specific Mechanisms: interferons
A
- Interferons - antiviral proteins secreted by virally infected cells when first discovered; part of nonspecific mechanisms
- alpha and beta in all cells
- alpha and beta released AFTER viral infection
- ‘warning’ signal to other cells so once you’re infected w/virus you release interferon which tells surrounding cells to save themselves and alter metabolism to harder to get infected by virus
- for local cells turns down transcription and shortens RNA 1/2 life
- release of these cause nearby cells to alter metabolism so virus replication is interferred with
- other - signal for more T cells
11
Q
Innate Immunity: Cellular, protein, and other mechanisms - 2nd line of defense
Other Non-specific: Temperature Response
A
- temperature response
- hypothalamus ‘sets’ the normal temp - 37 degrees
- various signal molecules (pyrogens) can reset normal temp to make it higher via fever-inducing signal
- endogenous pyrogens: come from organism itself; signal made by organism not invader
- exogenous pyrogens - stuff like bits of bacterial cell wall that indicate invasion is happening
- body actually works to maintain higher temp after its been reset
- why increase in temp?
- sequester iron in liver (stimulates iron binding protei) - so not available to microorganisms - iron is limiting factor for microorganism growth
- microorganisms can’t grow as quickly at increased temp
- increased temp increases activity and number of phagocytic cells
- @ moderate increase in temp is useful like 102 because it inhibits growth of microorganisms
- increase temp –> increase WBC and phagocytic activity
12
Q
Innate Immunity: Cellular, protein, and other mechanisms - 2nd line of defense
Other Non-specific Mechanisms:Complement system
A
- complement system - series of more than 20 proteins in blood that attack “nonself”/invader cells by punching holes in them via assembling selves similar to porforin
- assembles a membrane attack complex, fast rxn
- C3 protein is at center of rxn; critical center component, assemble into core and go into cells
- not porforin
- enhanced by antibodies and other factors
13
Q
Innate/non-specific Immunity: cellular, protein and other mechanisms -
Inflammation
A
- beginning of response, release histamine, cytokines(communication proteins that are released by immune system)
- redness (erythema), swelling (edema), attraction for immune cells
- neutrophils are first on scene and start eating up invaders; bacteria w/splinter so neutrophils jump out of blood stream and attack bacteria
- mast cells (associated w/tissues, in granula wbc family)
- release histamines - cause swelling and “leakiness” of blood vessels
- blood cells can get to injury site - esp neutrophils, monocytes - attack invaders, platelets (clotting process)
- inflammation is a cry for help
- diapedesis - cells leaving circulation to enter tissue spaces due to signal from cytokines
- splinter to fester, surrounding cells begin to die and dead neutrophils so spliter gets looser
14
Q
Innate/non-specific Immunity: cellular, protein and other mechanisms -
Toll-like receptors/Pattern recognition receptors
A
- toll-like receptors - recognize general invaders (like bacteria and viruses) but don’t care about identity of said invader
- not much known - might be ‘warning’ immune system of potential threat
- found originally in drosophila, general pattern recognition receptors so can recognize and alert immune system of bacteria
- tell immune system via cytokines - can distinguish virus, bacteria, fungi a bit apart
15
Q
Innate/non-specific Immunity: cellular, protein and other mechanisms -
Non-specific ID card model
A
- as long as what is in the body is ID’d as “self” then none of the non-specific immune responses happen
- know who and what to attack; all cells in body have surface markers on them that identify them as belonging to your body; helps know who and what to attack
- a ‘negative test’ - they don’t attack unless you don’t have proper ID marker
- thought to be important for surveillance
- sometimes cancer with cancerous phenotypes will alter surface ID card identifiers and get attacked this way
- cancer that changes the ‘self’ marker can get attacked
- not all cancers are this way so immune system can miss them
16
Q
Adaptive/Specific Immunity Terms:
antibody vs. antigen vs. epitopes vs. CD markers
A
- antibodies - Y-shaped proteins in blood and lymph that have SPECIFIC binding sites for targets (antigens); have 2 antigen combining sites for certain shape/charge
- w/2 binding sites they can hold things together for agglutination to make complex which easier to be eaten by phagocytic cells
- antigens - any kind of shape/molecule that can be bound by immune receptor (like antibodies)
- bacterium may have dozens of antigens that antibodies could recognize
- can have >1 epitope
- epitopes - antigenic determinant; protein structure on an antigen that can be recognized by an antibody; they can have varied effects on killing the antigen
- CD “clusters of differentiation” markers - surface molecules that can be identified by binding certain antibodies
- helpful in identifying subpopulations of cells
- CD4 and CD8 are important
- lymphoma w/CD20 marker - antibody specific CD20 can help kill lymphoma
20
Q
Specific Immunity - Cell surface ID markers
A
- genes on chromosome 6 - 3 types/classes that code for cell markers
- major histocompatility complex (MHC) aka transplantation antigens aka HLA = human leukocyte antigens
- class III: genes for complement proteins (not really coding for surface markers)
- class II MHC: glycoproteins on surface of immune cells, macrophages, beta-cells and just a few T cells
- alpha and beta subunits create a groove on surface to bind a peptide
- used to “present antigen” these cells are called APC antigen presenting cells
- class I (MHC/HLA): glycoproteins on all nucleated cells, every cell including immune cells, except for trophoblast cells, and rbc
- 2 chains but one is heavy chain and other is beta-2macroglobulin
- hugely polymorphic - 170 variations of heavy chain
- diff people’s HLA markers are diff so hard to find perfect tissue match for transplantation
- so mom’s immune system won’t reject developing embryo
- also creates a groove that a peptide fits into
- both alpha and beta are highly polymorphic so hard to find a match for bone marrow transplants
- help prevent mimic viruses from wiping out a whole population
- 2 chains but one is heavy chain and other is beta-2macroglobulin
