Ch. 8: The Immune System Flashcards
what are the two divisions of the immune system?
innate
adaptive
defn + aka: innate immunity
composed of defenses that are always active against infection, but lack the ability to target specific invaders
it is the responses that cells can carry out without learning
aka: nonspecific immunity/nonspecific immune response
defn + aka: adaptive immunity
the defenses that target a specific pathogen
slower to act, but can maintain immunological memory with an infection to mount a faster attack in next infections (developed as immune cells learn to recognize and respond to particular antigens)
aka: specific immunity/specific immune response
what is a summary of the relationship between the innate and adaptive immunity parts?
the innate part acts near entry points into the body and is always at the ready
if it fails to contain a pathogen, the adaptive division kicks in, mounting a later but highly target attack against the specific invader
what produces all white blood cells (leukocytes) through what process?
the bone marrow
through hematopoiesis
immune func (3): spleen
- a location of blood (white blood cells and platelets) storage and B-cell activation, which turn into plasma cells to produce antibodies as part of adaptive immunity
- a recycling center for red blood cells
- a filter of blood and lymph for the immune system
why are B cells mature but naive when they leave the bone marrow?
they have not yet been exposed to an antigen
what is immunity involving B-cells referred to as? why?
humoral immunity
these antibodies dissolve and act in the blood, rather than within cells
where do t-cells mature?
what type of immunity do T-cells correspond to and why?
mature in the thymus
the agents of cell-mediated immunity because they coordinate the immune system and directly kill virally infected cells
defn + immune func: thymus
a small gland just in front of the pericardium, the sac that protects the heart
func: site of T-cell maturation
immune func: lymph nodes
provide a place for immune cells to communicate and mount an attack
B-cells can be activated here too
a place for antigen-presenting cells and lymphocytes to interact
what are gut-associated lymphoid tissue (GALT)? (group + 4 specific)
immune tissue found in close proximity to the digestive system (a site of potential invasion by pathogens)
- tonsils and 2. adenoids (head)
- Peyer’s patches (small intestine)
- lymphoid aggregates (appendix)
defn: lymphadenopathy
the swelling of the lymph nodes that occurs with activation of the immune system
immune func: lymph nodes
- filter lymph
- a site where immune responses can be mounted
immune func: bone marrow
the site of immune cell production
how can we divide the specific/adaptive immune system?
- humoral immunity (driven by B-cells and antibodies)
- cell-mediated immunity (driven by T-cells)
immune func (3) + aka: skin
aka: integument
func: 1. our first line of defense (think about it: a cut allows pathogens in)
2. provides a physical barrier between the outside world and our internal organs
3. prevents most bacteria, viruses, fungi, and parasites from entering the body
defn: defensins
antibacterial enzymes that can be found on the skin
immune func: respiratory system
- respiratory passes are mucous membranes lined with cilia to trap particulate matter and push it up toward the oropharynx where it can be swallowed or expelled
- mucus also helps to prevent bacteria and viruses from gaining access to lung tissue
what other body aspects have nonspecific immune defenses?
- sweat
- mucous membranes around the eye
- mucous membranes around the oral cavity
2+3 produce a nonspecific bacterial enzyme (lysozyme) secreted in tears and saliva
defn + func: complement system
defn: consists of a number of proteins in the blood that act as a nonspecific defense against bacteria (cannot be modified to target a specific organism over others)
func: the proteins punch holes in the cell walls of bacteria, making them osmotically unstable
what are the two pathways that the complement system can be activated?
- CLASSICAL PATHWAY = requires the binding of an antibody to a pathogen
- ALTERNATIVE PATHWAY = does not require antibodies
defn + produced by?: interferons
defn: proteins that prevent viral replication and dispersion
produced by: cells that have been infected with viruses
func (5): interferons
- protect against viruses
- cause nearby cells to decrease production of both viral and cellular proteins
- decrease the permeability of viral and cellular proteins, making it harder for a virus to infect them
- upregulate MHC class I and class II molecules, resulting in increase antigen presentation and better detection of the infected cells by the immune system
- responsible for many flu-like symptoms that occur during viral infection
defn: macrophages
a type of agranulocyte that reside within the tissues
where do macrophages derive from and what can they turn into?
derive from: blood-born monocytes
can become: a resident population within a tissue (becoming a permanent, rather than transient, cell group in the tissue)
what happens to macrophages when a bacterial invader enters a tissue? (5)
the macrophages become activated and do 3 things
- it phagocytizes the invader through endocytosis
- it digests the invader using enzymes
- it presents little pieces of the invader (mostly peptides) to other cells using a protein called major histocompatability complex (MHC)
also 4. release cytokines
func: MHC
binds to a pathogenic peptide (antigen) and carries it to the cell surface, so it can be recognized by adaptive immune cells
defn: cytokines
chemical substances that stimulate inflammation and recruit additional immune cells to the area
what type of cells display MHC class 1 molecules?
all nucleated cells in the body
any protein produced within a cell can be loaded onto MHC-I and presented on the surface of the cell
impact: any protein produced within a cell can be loaded onto MHC-I and presented on the surface of the cell
allows the immune system to monitor the health of these cells and to detect if they’ve been infected with a virus or another intracellular pathogen
only the cells that are infected would present with an unfamiliar (nonself) protein on their surfaces
then cells that have been invaded by intracellular pathogens can be killed by a certain group of T-cells (cytotoxic T-lymphocytes) to prevent infection of other cells
why is the MHC-1 pathway called the endogenous pathway?
it binds antigens that come from inside the cell
summary (5): how MHC molecules work
- MHC molecules are joined with antigens
- the MHC-antigen complex then goes to the cell surface to display the antigen
- this allows the immune system to monitor the health of cells
- MHC-I is in all nucleated cells and presents endogenous antigens
- MHC-II is in antigen-presenting cells and presents exogenous antigens
what type of cells present MHC class II molecules?
professional antigen-presenting cells like macrophages, which pick up pathogens from the environment, process them, and then present them on MHC-II
defn: antigen
a substance (usually a pathogenic protein) that can be targeted by an antibody
why is the MHC-II pathway called the exogenous pathway?
these antigens originated outside the cell
what 4 types of cells are professional antigen-presenting cells?
- macrophages
- dendritic cells in the skin
- some B-cells
- certain activated epithelial cells
what are the 5 innate immune cells and what is their role as a group?
nonspecific and form the first line of defense against pathogens
- macrophage
- mast cell
- granulocytes
- dendritic cell
- natural killer cell
func: macrophage
an immune defender that engulfs and consumes pathogens
func: mast cell
releases histamine and other inflammation-promoting chemicals
func: dendritic cell
presents antigens to adaptive immune cells, inducing them to attack bearers of the displayed antigens
location + func + most well-describe version: pattern recognition receptors (PRR)
location: macrophages and dendritic cells
best-described: toll-like receptors (TLR)
func: able to recognize the category of the invader (bacterium, virus, fungus, parasite)
– this allows for the production of appropriate cytokines to recruit the right type of immune cells
defn + func: natural killer (NK) cells
a type of nonspecific lymphocyte
able to detect the downregulation of MHC and induce apoptosis in these virally infected cells (the body’s own cells that are infected); also goes after cancer cells
what 3 types of cells are included in granulocytes?
- neutrophils
- eosinophils
- basophils
char (3): neutrophils
- the most populous leukocyte in blood
- very short lived
- phagocytic (target bacteria)
how do neutrophils follow bacteria? (2)
- using chemotaxis (the movement of an organism according to chemical stimuli)
- the neutrophil senses products given off by bacteria, moving up the concentration gradient to the source - can detect bacteria once they have been opsonized
defn: opsonized
marked with an antibody from a B-cell
what other 4 types of cells can attack opsonized bacteria?
- natural killer cells
- macrophages
- monocytes
- eosinophils
what is responsible for the formation of pus during infection?
dead neutrophil collections
char + func: eosinophils
char: contain bright red-orange granules
func: primarily involved in allergic reactions and invasive parasitic infections
how do eosinophils work? (2)
- upon activation, they release large amounts of histamine, an inflammatory mediator
- this results in vasodilation and increased leakiness of the blood vessels, which allows extra immune cells to move out of the bloodstream into tissue
what type of pathogens is inflammation particularly useful against?
extracellular pathogens (i.e. bacteria, fungi, and parasites)
char (2) + func: basophils
char: 1. contain large purple granules
2. the least populous leukocyte in the bloodstream under normal conditions
func: involved in allergic responses
char (3) + func: mast cells
- closely related to basophils
- have smaller granules
- exist in tissues, mucosa, and epithelium
func: releases large amounts of histamine in response to allergens, leading to inflammatory responses
why might it take a few days for physical symptoms of the adaptive immune system to subside after exposure to a pathogen?
the immune response takes time to form specific defenses against the pathogen
char: humoral immunity
- governed by B-cells (produces the antibodies)
- involves the production of antibodies that are specific to the antigen of the invading microbe
- may take up to a week to become fully effective
defn: B-cells
lymphocytes that originate and mature in the bone marrow and are activated in the spleen and lymph nodes
summary: B-cells vs. T-cells
B-CELLS: antigens stimulate this cell to divide and produce antibodies that neutralize invaders or tag them for killing
T-CELLS:
killer: destroys an infected cell in which it detects the presence of antigens
other (helper, regulatory): coordinate the immune response
aka + location: antibodies
aka: immunoglobulins (Ig)
char: 1. can be displayed on the cell surface or be secreted in body fluids
2. when bound to an antigen, response depends on the location
what are the 3 main possibilities for the response that antibodies may undergo for those that are secreted into body fluids?
- OPSONIZATION: once bound to a specific antigen, antibodies may attract other leukocytes to phagocytize those antigens immediately
- AGGLUTINATION: antibodies may cause pathogens to clump together (agglutinate), forming large insoluble complexes that can be phagocytized
- antibodies can block the ability of a pathogen to invade tissues, essentially neutralizing it
how do cell-surface antibodies work?
the binding of antigen to a B-cell causes activation of that cell, resulting in its proliferation and formation of plasma and memory cells
what happens when antigen binds to antibodies on the surface of a mast cell?
degranulation (exocytosis of granule contents), releasing histamine and causing an inflammatory allergic reaction
structure (4) + diagram: antibodies
- Y-shaped molecules
- made up of 2 identical heavy chains and 2 identical light chains
- the light and heavy chains are held together by disulfide linkages and noncovalent interactions
- each has an antigen-binding region at the end of which is called the variable region (domain) at the tips of the Y
func: variable region (domain) of the antibody
there are specific polypeptide sequences in this domain which will bind only one specific antigenic sequence
what is part of why it takes so long to initiate the antibody response?
each B-cell undergoes hypermutation of its antigen-binding region, trying to find the best match for the antigen
defn: clonal selection
only those B-cells that can bind the antigen with high affinity survive
defn + char: constant region (domain)
the remaining part of the antibody
char: the region that cells such as NK cells, macrophages, monocytes, and eosinophils have receptors for, and that can initiate the complement cascade
how many types of antibodies does each B-cell make?
only one
what are the 5 antibody isotypes?
IgM
IgD
IgG
IgE
IgA
can be used at different times during the immune response, for different types of pathogens, or in different body locations
defn: isotype switching
cells can change which antibody isotype they produce when stimulated by specific cytokines
why don’t all B-cells actively or constantly produce antibodies?
antibody production is energetically expensive
defn + func: naive B-cells
defn: B-cells that have not yet been exposed to an antigen
func: wait in the lymph nodes for their particular antigen to come along
what happens to a B-cell upon exposure to the correct antigen? (2)
- primary response (takes 7-10 days): it will proliferate and produce 2 types of daughter cells (plasma cells and memory B-cells)
- the plasma cells eventually die, but the memory cells may last the organisms’ lifetime
defn + char: secondary response
if the same microbe is encountered again, the memory cells rapidly proliferate and differentiate into plasma cells to produce antibodies specific to that pathogen
rapid, robust
what is the basis of the efficacy of vaccination?
the development of lasting memory cells
func: plasma cells vs. memory B-cells
plasma cells: produce large amounts of antibodies
memory B-cells: stay in the lymph node, awaiting reexposure to the same antigen
defn: positive selection (T-cells)
allowing only the maturation of cells that can respond to the presentation of antigen on MHC (others undergo apoptosis)
defn: negative selection (T-cells)
causing apoptosis in cells that are self-reactive (activated by proteins produced by the organism itself)
defn + func: thymosin
defn: a peptide hormone secreted by thymic cells
func: facilitates the maturation of t-cells
what is true of the T-cell once it has left the thymus?
what happens to the T-cell upon exposure to antigen?
left the thymus: mature but naive
exposure to antigen: they will undergo clonal selection so that only those with the highest affinity for a given antigen proliferate
what are the 3 major types of T-cells?
- helper
- suppressor
- killer (cytotoxic)
func (2) + aka: helper T-cells
aka: CD4+ T-cells
func: 1. coordinate the immune response by secreting chemicals (lymphokines) which are capable of recruiting other immune cells (ie plasma cells, cytotoxic T-cells, macrophages) and increasing their activity
2. respond to antigens present on MHC-II molecules
what happens with the LOSS of helper T-cells? + example
prevents the immune system from mounting an adequate response to infection
this happens with HIV
what happens with an advanced HIV infection + aka?
weak pathogens can cause devastating consequences as opportunistic infections
aka: acquired immunodeficiency syndrome (AIDS)
why are helper T-cells most effective against bacterial, fungal, and parasitic infections?
because they respond to antigens on MHC-II molecules and MHC-II presents exogenous antigens
func diff: CD4+ vs. CD8+ T-cells
CD4+: better at fighting extracellular infections
CD8+: better at targeting intracellular infections
aka (3) + func (2): cytotoxic T-cells
aka: Tc, CTL (cytotoxic T-lymphocytes), CD8+ T-cells
- capable of directly killing virally infected cells by injecting toxic chemicals that promote apoptosis
- respond to antigens presented on MHC-I molecules
why are cytotoxic T-cells most effective against viral (and intracellular bacterial or fungal) infections?
because they respond to MHC-I and MHC-I presents endogenous antigens
mnemonic for what T-cells correspond to what MHC class?
CD X MHC = 8
CD4+ cells respond to MHC-II (4x2 = 8)
CD8+ cells respond to MHC-I (8x1 = 8)
func (3) + aka: regulatory T-cells
aka: suppressor T-cells
- express CD4, but can be differentiated from helper T-cells because they also express Foxp3 protein
- help to tone down the immune response once infection is contained enough
- turn off self-reactive lymphocytes to prevent autoimmune disease (self-tolerance)
func: memory T-cells
similar to memory B-cells
lie in wait until the next exposure to the same antigen
when activated, they carry out a more robust and rapid response
diagram: lymphocytes of specific immunity
what are the 5 types of infectious pathogens?
- bacteria
- viruses
- fungi
- parasites (including protozoa, worms, and insects)
- prions
walk through an example of how the adaptive immune system responds to bacterial (extracellular pathogen) infections –> a person suffers a cut and bacteria are introduced into the body (8 steps)
- MACROPHAGES are always on the lookout for potential invaders, they engulf the bacteria and release inflammatory mediators. They also digest the bacteria and present antigens from their pathogen on their surfaces along with MHC-II
- CYTOKINES attract inflammatory cells, including neutrophils and more macrophages
- MAST CELLS are activated by the inflammation and degranulate, leading to histamine release and increase capillary leakiness, augmenting the ability of the immune cells to leave the bloodstream to travel to the affected tissue
- the DENDRITIC CELL leaves the affected tissue and travels to the nearest lymph node, where it presents the antigen to b-cells
- B-CELLS that produce the correct antibody proliferate through clonal selection to create plasma cells and memory cells
- ANTIBODIES then travel through the bloodstream to the affected tissue, where they tag bacteria for destruction
- at the same time, DENDRITIC CELLS also present the antigen to T-cells, activating CD4+ T-cells (which come in 2 types: Th1 and Th2). The Th1 release interferon gamma (IFN-gamma) which activates macrophages and increases their ability to kill bacteria. Th2 cells help activate B-cells and are more common in parasitic infections
- after the pathogen is gone, PLASMA CELLS die, but memory B AND T CELLS stay and allow for a faster response upon secondary exposure to the pathogen
walk through an example of how the adaptive immune system responds to viral (intracellular pathogen) infections
- the virally infected cell begins to produce INTERFERONS, which reduce the permeability of nearby cells so that the virus is less likely to infect those cells, REDUCE THE RATE OF TRANSCRIPTION and TRANSLATION in these cells, so that the virus cannot multiply, and cause SYSTEMIC SYMPTOMS (malaise, muscle aches, fever, etc.)
- the virally infected cell will also present intracellular proteins on their surface along with MHC-I
- CD8+ T-cells recognize the MHC-I antigen complex as foreign and inject TOXINS into the cell for APOPTOSIS so that the infection can be shut down before it spreads
- once the pathogen is gone, MEMORY T-CELLS are made that allow for a faster response in the future
what happens if the virus downregulates the production and presentation of MHC-I molecules?
natural killer cells will recognize the absence of MHC-I and will cause apoptosis of these cells
defn: self-antigens
the proteins and carbohydrates present on the surface of every cell of the body
func: self-antigens (under normal circumstances)
signal to immune cells that the cell is NOT foreign and should not be attacked
defn: autoimmunity
when the immune system fails to make the distinction between self and foreign, it may attack cells expressing self-antigens
defn: an allergic reaction
the immune system misidentifies a foreign antigen as dangerous when, in fact, it is not
defn: hypersensitivity reactions
a family of immune reactions that include allergies and autoimmunity
what are 8 examples of autoimmune diseases?
- type I diabetes
- multiple sclerosis
- myasthenia gravis
- psoriasis
- lupus
- rheumatoid arthritis
- Graves’ disease
- Guillain-Barre syndrome
how does the body strive to prevent autoimmune reactions early in T-cell and B-cell maturation?
T-CELLS are educated in the thymus, part of which involves elimination of T-cells that respond to self-antigens (negative selection)
immature B-cells that respond to self-antigens are eliminated before they leave the bone marrow
what is one common example of autoimmune disease treatment? + why
glucocorticoids (modified cortisol), which have potent immunosuppressive qualities
defn: active immunity
the immune system is stimulated to produce antibodies against a specific pathogen, exposure to this pathogen may be natural or artificial
what happens in nature exposure to pathogens in active immunity?
antibodies are generated by B-cells once an individual becomes infected
what happens in artificial exposure to pathogens in active immunity?
this occurs through vaccines and results in the production of antibodies, however the individual never experiences the true infection
they just receive the antigen that will activate B-cells to produce antibodies to fight the specific infection
what form of antigen to people receive in vaccines/nasal sprays? (2)
- a weakened or killed form of the microbe
- a part of the microbe’s protein structure
defn: passive immunity
results from the transfer of antibodies to an individual
why is passive immunity transient?
only the antibodies, not the plasma cells that produce them, are given to the individual
what are 2 natural examples of passive immunity?
- the transfer of antibodies across the placenta during pregnancy to protect the fetus
- the transfer of antibodies from a mother to her nursing infant through breast milk
how are the immune system and lymphatic system intimately related overall?
B-cells proliferate and develop within the lymphatic system, especially the lymph nodes
structure: lymphatic system
- circulatory
- made up of one-way vessels that become larger as they move toward the body’s center
- these vessels carry lymphatic fluid (lymph)
- and most join to form a large thoracic duct in the posterior chest, which then delivers the fluid into the left subclavian vein near the heart
why are local lymph nodes often removed at the same time as say, mastectomy?
certain cancers, especially breast cancer, are prone to spread via lymphatic channels
defn + char: lymph nodes
defn: small, bean-shaped structures along the lymphatic vessels
char: 1. contain a lymphatic channel, 2. artery, 3. and vein
func: provide a space for the cells of the immune system to be exposed to possible pathogens
how do lymphatic vessels play a role in equalization of fluid distribution?
- at the capillaries, fluid leaves the bloodstream and goes into the tissues
- the quantity of fluid that leaves the tissues at the arterial end of the capillary bed depends on hydrostatic and oncotic pressures (Starling forces)
- the oncotic pressure of the blood draws water back into the vessel at the venule end once hydrostatic pressure has decreased
- because the net pressure drawing fluid in at the venule end is slightly less than the net pressure pushing fluid out at the arterial end, a small amount of fluid remains in the tissues
- lymphatic vessels drain these tissues and subsequently return the fluid to the bloodstream
how can lymphatics offer some protection against pathology?
example: if the blood has a low albumin concentration, the oncotic blood pressure is decreased and less water is driven back into the bloodstream at the venule end
this fluid will collect in the tissues
provided that the lymphatic channels are not blocked, much of this fluid may eventually return to the bloodstream via the lymphatics
defn + when does it occur: edema
defn: swelling due to fluid collecting in tissue
occurs only when the lymphatics are overwhelmed
defn + location + func: lacteals
defn: small lymphatic vessels
located at the center of each villus in the small intestine
func: fats, packaged into chylomicrons, enter the lacteal for transport
defn: chyle
lymphatic fluid carrying many chylomicrons that takes on a milky white appearance
defn: germinal centers
collections in the lymph nodes where B-cells proliferate and mature
