Chapter 51 Flashcards
Historically, the response of vertebrates to microbial invasion was divided into (2)
specific and nonspecific forms of defense
Now, a vertebrate’s response to microbial invasion is composed of (2)
innate and adaptive immunity
What is the key to the function of the immune system?
ability to distinguish self from nonself cells
Adaptive immunity is characterized by
genetic rearrangements that generate a diverse set of molecules that can recognize virtually any invading pathogen
What is the largest organ of the body?
skin
What is the skin’s surface pH?
3 to 5, because of the oil and sweat glands
Why is the acidic nature of skin important?
it’s acidic enough to inhibit the growth of many pathogenic microorganisms
Sweat contains the enzyme
lysozyme, which digests bacterial cell walls
What do epithelial cells produce as a defense?
produce a variety of small anti-microbial peptides
The skin is also home to (3)
normal flora; nonpathogenic bacteria; fungi
What happens to pathogenic bacteria that attempts to colonize the skin?
they are generally unable to compete with normal flora
The epidermis of the skin is how many cells thick?
10 to 30 cells thick
In addition to the skin, what are three other potential routes of pathogen entry?
digestive tract; respiratory tract; urogenital tracts
Each tract is lined by
epithelial cells, which are continuously replaced like in skin
What covers each epithelial surface?
a layer of mucus, secreted by cells scattered in between epithelial cells
What purpose does the mucus lining epithelial surfaces serve?
traps pathogens
What kills microbes present in food? (3)
saliva (which contains lysozyme); acidic stomach; digestive enzymes
How are microorganisms in inhaled air dealt with?
trapped by mucus in smaller bronchi/bronchioles before reaching warm/moist lungs (where they would likely flourish)
What happens to pathogens trapped by mucus in the bronchi/bronchioles?
mucus is swept up to the glottis by cilia from the epithelial cells and can be swallowed
What effect does smoking have on respiratory tract defenses?
nicotine paralyzes cilia of the respiratory system which results in unclean tracts
How does urine function as a pathogenic defense?
Acidic urine continually washes out pathogens from the urinary tract
What are four additional defense mechanisms that commonly occur in people?
vomiting, diarrhea, coughing, sneezing
Innate immunity involves (2)
soluble factors AND different types of blood cells
What is the characteristic portion of gram-negative bacteria that make it recognizable as part of innate immunity?
lipopolysaccharide found in gram-negative cell walls
What is the characteristic portion of all bacteria that make it recognizable as part of innate immunity?
peptidoglycan found in all bacterial cell walls
The receptors involved in innate immunity can be found
in solution (they’re soluble proteins) OR membrane proteins on the surface of blood cells
What is the best studied innate receptor protein?
Toll receptor in fruit flies
How many TLRs are there in humans? In mice?
11 TLRs in humans; 13 TLRs in mice
The TLRs found in humans and mice bind to
a variety of specific targets important to pathogen survival, which therefore do not vary greatly
Give six examples of targets of TLRs found in humans and mice.
gram-negative LPS, bacterial lipoproteins, bacterial peptidoglycan fragments, yeast cell-wall components, unmethylated CpG motifs in bacterial DNA, and viral RNA
How do TLRs accommodate a wide variety of shapes?
TLRs contain leucine-rich regions that fold to form binding pockets
What comprises the innate response to an infection? (3)
inflammatory response; production of antimicrobial peptides; production of cytokines which attract B/T/phagocytic cells
What was the next class of receptors to be discovered after Toll/TLR proteins?
cytoplasmic receptors
How do cytoplasmic receptors work?
bind to characteristic pathogen molecules and recognize invading pathogens in the cytoplasm of cells after phagocytosis
Cytoplasmic receptors are part of the response to
viral RNA
The response to viral RNA includes which receptor?
cytoplasmic receptors
What are soluble receptors?
receptors that circulate in serum; can respond to specific pathogen molecules
Give an example of a specific pathogen molecule recognized by soluble receptors.
lectin proteins
Lectin proteins bind to
mannose
Lectin proteins are important in
activating the complement system
Give an example of an antimicrobial peptide.
defensins
How do defensins work?
cysteines on defensins interact with positively charged AAs on pathogen surface; bind to outer membrane of gram-negative bacteria; can disrupt membrane and enhance phagocytosis
In addition to working against gram-negative bacteria, defensins can work effectively against
enveloped viruses
Defensins can induce what antimicrobial enzyme?
lysozyme
Gram-bacteria/enveloped viruses are targeted by
membrane attack complexes (MAC)
MACs come from
the complement cascade
Bacteria/fungi/enveloped viruses are targeted by
antimicrobial peptides
Antimicrobial peptides come from (2)
circulating phagocytes OR directly from epithelial cells
Bacteria/fungi are targeted by
circulating phagocytes
Circulating phagocytes come from (3)
cytokines; chemokines, complement cascade
Virus-infected cells are targeted by
natural killer (NK) cells
Natural killer cells come from
directly from virus-infected cells
What are the two types of interferons?
interferon type I and interferon type II
Type I interferons are synthesized when
a virus infects a cell
How do type I interferons act when a virus infects a cell?
act as messengers to protect normal, uninfected cells in the vicinity; induce degradation of RNA and block protein production in these cells; leads to cell death but stops spread of virus
Type II interferons are synthesized by (2)
T lymphocytes; natural killer cells
What is the name for type II interferons in humans?
IFN-gamma
IFN-gamma is secreted as part of
the immunological defense against infection and cancer
Cytokines are produced in response to signaling from
TLR receptors; internal receptors
Cytokines attract and cause (3)
attract nonspecific phagocytic cells; cause inflammation; signal to the adaptive immune system
What are the three basic defending leukocytes?
macrophages; neutrophils; natural killer cells
Phagocytic cells are associated with what type of immunity?
innate immunity
What are macrophages and what do they do?
large, irregularly-shaped cells that kill microorganisms by ingesting them through phagocytosis
Once a microorganism is inside the macrophage, what happens?
membrane-bound phagosome fuses with lysosome and lysozomal enzmes kill and digest the microoroganism
What other unusual molecule can be found within phagosomes?
oxygen-containing free radicals, which are reactive and degrade the pathogen
Oxygen-containing free radicals are found in what structure?
phagosomes in macrophages; neutrophils
(T/F) Macrophages exclusively digest bacteria.
False, they can digest viruses/debris/dust
Where are macrophages found in the body?
extracellular fluid that bathes tissues
What are monocytes?
undifferentiated macrophages found in the blood
In response to an infection, what do monocytes do? (2)
squeeze through endothelial cells and go to site of infection; there, they mature into active phagocytic macrophages
What is the most abundant circulating leukocyte?
neutrophils, which account for 50-70% of peripheral blood leukocytes
What is the first type of cell to appear at a site of damage/infection?
neutrophils
How do neutrophils digest pathogens?
also by phagocytosis similar to that of macrophages except that they produce even more oxygen radicals
In addition to oxygen radicals, what else do neutrophils produce as a defense?
defensin peptides
(T/F) Natural killer cells attack invading microbes.
False, they kill cells of the body that have been infected by a virus.
How do natural killer cells work?
kill cells of the body via apoptosis
On a molecular level, how do natural killer cells work? (3)
NK cells release perforins, which insert into the membrane and create pores; NK-produced granzymes enter pores and activate proteins that induce apoptosis; macrophages digest remaining cellular debris
NK cells attack tumor cells, often before
the tumor has a had a chance to divide sufficiently to be recognized as a tumor - this makes NK cells a very important defense against cancer
NK cells are said to play a role in
immune surveillance
(T/F) Inflammatory response involves only the immune system.
False, it involves several systems of the body.
The inflammatory response can be either ____ or ____
localized or systemic
What is an acute inflammatory response?
a response that starts rapidly but lasts for a short amount of time
What are some chemical alarm signals released by infected/injured cells? (3)
histamine; prostaglandins; bradykinin
Chemical alarm signals like histamine cause
vasodilation of local blood vessels, which increases flow of blood to site and causes the area to become red and warm; increase permeability of capillaries in area which causes edema; swelling puts pressure on nerves which causes pain
What is edema?
tissue swelling
The increased capillary permeability as part of the inflammatory response does what? (2)
initially promotes migration of phagocytic neutrophils from blood to extracellular fluid; neutrophils can digest pathogens
The pus associated with infections is a mixture of (3)
dead/dying pathogens; tissue cells; neutrophils
Neutrophils that are sent to an injury site as part of an inflammatory response do what? (2)
digest pathogens; signal other monocytes to enter and become macrophages to help digest
What is one manifestation of the acute inflammatory response?
fever
On a molecular level, what causes fever?
when a macrophage with a TLR on surface binds to pathogen, interleukin-1 is released and carried to brain, where it causes neurons in hypothalamus to raise body temp above 37 C
Why is an increased body temperature as a result of fever necessary?
promotes activity of phagocytic cells and impedes growth of microorganisms
Which cytokine is associated with fever?
interleukin-1
In addition to stimulating phagocytosis, how else does fever contribute to the body’s defense? (2)
causes spleen and liver to store iron; this reduces blood levels of Fe which bacteria need to grow
Why is a very high fever dangerous?
can denature critical enzymes
What is considered the max temperature limit?
40.6 C, anything above this can be fatal
During an acute inflammatory response, how does the liver aid in phagocytosis? (2)
liver releases acute-phase proteins at levels 1000x above serum concentration; these proteins bind to pathogens and promote their phagocytic ingestion
What are the two phagocytic cells associated with the inflammatory response?
neutrophils and macrophages
What is the complement system?
the chemical defense of a vertebrate body that consists of a battery of proteins that become activated by the walls of bacteria/fungi
Approximately how many different proteins are associated with the complement system, and where are they found?
30 different proteins that circulate freely blood plasma
How are complement proteins activated?
mannose-binding lectin protein OR reactions involving charged species on surface of pathogens
When the complement system is activated, what happens? (3)
complement proteins aggregate to form membrane attack complex (MAC) that inserts itself into the pathogen plasma membrane; MAC channels extracellular fluid into pathogen; pathogen swells and bursts
What is C3b?
a complement protein that coats the surface of invading pathogens
What does C3b do?
helps direct neutrophils and macrophages to the pathogen for digestion; useful for pathogens that don’t have a lipid membrane that MACs can attach to
Mast cells and basophils
release histamine and other mediators in response to stimulation by complement cells
An effective chicken pox vaccine was developed in
1991
Which virus causes chicken pox?
varicella zoster
The scientific study of immunity began with
Edward Jenner in 1796
Smallpox is caused by what virus?
variola virus
What is vaccination?
injecting a harmless agent to confer resistance to a dangerous one
Modern resistance to malaria/herpes involve delivering antigens associated with what virus?
vaccinia virus, which is related to the cowpox virus
What is an antigen?
molecule that provokes a specific immune response
Generally speaking, what are the most effective antigens?
large, complex proteins
What is the relationship between foreign-ness and immune response?
the more foreign an antigen is, the greater the immune response will be
What is another name for epitopes?
antigenic determinants
All cells in blood ultimately derive from
the division/differentiation of hematopoietic stem cells
What is hematopoiesis?
division/differentiation of hematopoietic stem cells to produce cells in blood
Where are hematopoietic stem cells originally found, and where do they migrate afterwards?
originally found in yolk sac; migrate to fetal liver/spleen and then to bone marrow
Hematopoietic stem cells give rise to what two types of cells?
lymphoid progenitors; myeloid progenitors
Lymphoid progenitors give rise to (3)
B lymphocytes; T lymphocytes; natural killer cells
B lymphocytes come from
lymphoid progenitors
T lymphocytes come from
lymphoid progenitors
Natural killer cells come from
lymphoid progenitors
Myeloid progenitors give rise to
erythrocytes; platelets; all other cells of the immune system
Which general blood cell is responsible for adaptive immunity?
lymphocytes
Monocytes give rise to
macrophages
Eosinophils are important in
the elimination of helminths (flatworms)
How do eosinophils eliminate helminths? (2)
secretion of digestive enzymes through perforin pores inserted into helminth plasma membrane; phagocytosis
In addition to the elimination of helminths, what else do eosinophils do?
play a role in exacerbating chronic inflammatory diseases like asthma or inflammatory bowel disease
(T/F) Basophils are phagocytic.
False, they are not phagocytic.
(T/F) Mast cells are not phagocytic.
True, they are not phagocytic.
Which cell is particularly important in the allergenic response?
mast cells
Dendritic cells are important in
the activation of T cells
Which cells form a link between innate and adaptive immunity?
dendritic cells
What is the function of helper T cells? (2)
recognizes foreign peptides on antigen-presenting cells; induces release of cytokines that activate B cells or macrophages
What is the function of cytotoxic T cells?
recognizes and kills “altered-self” cells like virally infected or tumor cells
What is the function of B cells? (3)
binds specific, soluble antigens with membrane-bound antibody; serves as antigen-presenting cell to helper T cells; when activated, it differentiates into plasma cells and memory B cells
What is the function of plasma cells? (2)
derived from activated B cells; is a biochemical factory devoted to secretion of antibodies against antigens
What is the function of natural killer cells?
rapidly recognizes, kills virally infected cells
What is the function of monocytes? (2)
precursor of macrophages; located in blood
What is the function of macrophages? (2)
phagocytic tissue cell that is a component of the body’s first cellular line of defense; serves as antigen-presenting cell to helper T cells
What is the function of neutrophils? (2)
phagocytic tissue cell that is a component of the body’s first cellular line of defense; found in blood in large numbers until attracted to sites of inflammation
Which cells serve as antigen-presenting cells to helper T cells? (3)
B cells; macrophages; dendritic cells
What is the function of eosinophils?
important in the elimination of parasites; involved in chronic inflammatory diseases
What is the function of basophils?
circulating cell that releases mediators like histamine, prostaglandins for inflammation
Where are mast cells located?
under mucosal surfaces
What is the function of mast cells? (2)
releases mediators like histamine, prostaglandins; triggered by inflammatory and allergenic responses
What is the function of dendritic cells?
antigen-presenting cells to naive helper T cells; helps activate naive cytotoxic T cells
The adaptive immune system is characterized by what four traits?
specificity of antigen recognition; wide diversity of antigens that can be recognized; memory, where the immune system responds faster to an antigen the second time; ability to distinguish self-antigens from nonself
What are lymphocytes?
type of white blood cell involved in immune response
What are the two principal classes of lymphocytes?
B cells and T cells
What kinds of proteins do lymphocytes have on their surfaces?
have receptor proteins on the surfaces that recognize epitopes
Which system dominates in the early part of pathogen response, and which system dominates later?
innate system dominates first, and then adaptive system dominates
Which cells bind antigens/have the receptors necessary to bind antigens?
B cells and T cells
Describe B cell receptors. (2)
immunoglobulin (Ig) molecules with a Y-shaped structure; each B cell has a single Ig that binds to a single antigenic determinant
Describe T cell receptors. (2)
simpler than Ig molecules; can only bind to antigens bound to another cell
(T/F) Lymphocytes tend to have similar specificities.
False, they tend to be unique.
What is a naive lymphocyte?
lymphocyte that hasn’t encountered an antigen before
What is clonal selection?
amplification of a clone of an immune cell stimulated by antigen recognition
What happens to the cells produced by clonal selection?
some respond to the antigen, others become memory cells
What is humoral immunity?
part of adaptive immune system involving B cells that produce soluble antibodies specific for foreign antigens
(T/F) T cells secrete antibodies.
False, T cells do NOT secrete antibodies
What is cell-mediated immunity?
part of adaptive immune system mediated by T cells
What are the two types of T cells?
cytotoxic T cells; helper T cells
What are the two ways someone can acquire immunity?
infection/immunization; getting antibodies from another human (like a mother)
What is active immunity?
activation of specific lymphocytes and generation of memory cells
What is passive immunity?
obtainment of antibodies from another human (like your mother), without generating memory cells
(T/F) Antibodies are immortal.
False, they degrade with time.
T cells are produced in
the thymus
What are the two sets of organs in the immune system?
primary lymphoid organs; secondary lymphoid organs
What organs are part of the primary lymphoid organs? (2)
bone marrow; thymus
What organs are party of the secondary lymphoid organs? (3)
lymph nodes; spleen; mucosa-associated lymphoid tissue (MALT)
Where do B cells mature?
bone marrow
What is the name for immature B cells?
progenitor B cells
Which process gives rise to B cells?
hematopoiesis
Where does DNA rearrangement of immunoglobulin genes occur?
in the bone marrow when B cells are maturing
How many Ig molecules does a B cell contain on its surface?
10^5
What happens to lymphocytes that bind to self-antigens?
are killed via apoptosis
Where is MALT located?
small intestine
Where do progenitor T cells get produced?
bone marrow
Where do progenitor T cells go from the bone marrow?
thymus
What receptor is located on T cells?
T-cell receptor (TCR)
TCR is produced by
gene rearrangements as T cells mature in thymus
How many TCRs can be found on one T cell?
10^5
B cells recognize what kinds of epitopes?
epitope of an intact antigen that may or may not be a protein
T cells recognize what kinds of epitopes?
only recognize the peptide fragment of a protein antigen, and peptide fragment must be bound to series of self-proteins
What is the major histocompatability complex? (2)
set of protein cell-surface markers anchored in plasma membrane which helps immune system identify “self”; all cells of a given individual have the MHC protein
What percent of B cells are ultimately released from the bone marrow?
10%
What percent of T cells pass the two-step screening?
5%
Under what conditions are T cells eliminated in the thymus during the selection process?
if the T cells’ TCRs bind to strongly or don’t bind at all to MHC proteins
What explains swollen glands during an infection?
lymphocytes responding to antigens pass out of capillaries and back into lymph nodes
The immune response to neisseria meningitidis occurs in
the spleen
Which blood vessel carries blood to the spleen?
splenic artery
What is the white pulp?
regions of the spleen immediately surrounding arterioles
Where are antigens released in the spleen?
ground tissue
How do antibodies and active lymphocytes exit the spleen?
splenic vein
The mucosa-associated lymphoid tissue (MALT) includes (3)
tonsils; appendix; follicles located under mucosal surfaces
The MALT follicles are composed of (2)
lymphocytes (mostly B cells but some T cells); macrophages
How does the MALT tissue serve as a line of defense?
any antigens that pass through mucosa are stopped by lymphocytes in the follicles
Adaptive immunity first arose in
cartilaginous fish
Which immune organs do sharks and rays have? (3)
thymus; spleen; MALT
Bone marrow with hematopoiesis first originated in
amphibians
Lymph nodes first appeared in
birds
Describe the second form of adaptive immunity found in jawless fish. (3)
don’t have B/T cells, but instead lymphocytes have receptor proteins with repeats of leucine; similar diversity; different structure
Cytotoxic T cells have what protein on their surface?
CD8 protein (CD8+ cells)
Helper T cells have what protein on their surface?
CD4 protein (CD4+ cells)
CD8 proteins are found on
cytotoxic T cells
CD4 proteins are found on
helper T cells
How are CD4/CD8 cells activated?
these cells must recognize peptide fragments bound to MHC proteins
How are CD4/CD8 cells distinguished? (2)
they recognize different classes of MHC proteins; they differ in roles after being activated
What is the name for proteins encoded by the MHC complex in humans?
human leukocyte antigens (HLAs)
The genes encoding MHC proteins are
highly polymorphic (in some cases, over 500 alleles), so HLAs are different for each individual, like a fingerprint
What are the two classes of MHC proteins?
MHC class I proteins; MHC class II proteins
Where are MHC class I proteins found?
present on every nucleated cell of the body
Where are MHC class II proteins found?
found only on antigen-presenting cells (macrophages, B cells, dendritic cells)
Cytotoxic T cells respond to which class of MHC proteins?
cytotoxic T cells respond to peptides bound to MHC class I proteins
Helper T cells respond to which class of MHC proteins?
Helper T cells respond to peptides bound to MHC class II proteins
(T/F) B cells recognize MHC proteins.
False, they don’t recognize MHC proteins - only Tc and Th cells do.
Where are T cells normally activated, and why?
normally activated outside of primary lymphoid organs (in secondary lymphoid organs) so that they don’t target self cells, and instead target foreign antigens
The TCRs of Tc cells recognize
peptides of endogenous antigens bound to MHC class I proteins
What are endogenous antigens?
self-protein or viral protein produced by an infected cell – produced by self cells
Which cell in particular presents antigens that activate Tc cells?
dendritic cells
What is cross-presentation?
process in dendritic cells in which virus/tumor cells are ingested and then viral/tumor peptides are placed on MHC Class I proteins
What happens when a Tc cell binds to a dendritic cell undergoing cross-presentation? (4)
binding to dendritic cells occurs at CD8 site; activated Tc cells are generated; memory Tc cells are generated; activated Tc cells circulate through body to bind to similar dendritic cells with the same foreign peptide
How do Tc cells induce apoptosis? (3)
Tc cell secretes perforin monomers to create pores in target membrane; granzymes enter and activate caspases; caspases cause apoptosis
What do Th cells secrete?
low-MW proteins called cytokines
What is the purpose of cytokines in the context of Th cells?
they initiate signaling cascades in immune system cells that promote activation or differentiation
(T/F) Cytokines promote activation/differentiation of immune system cells only.
False, they can initiate cascades in other cells, too.
Cytokines are secreted at what concentration?
cytokines are secreted at low concentrations because they are very potent and so that they only bind to nearby cells
What is an exception to the norm that cytokines only bind to nearby cells?
IL-1, which travels to the hypothalamus to induce fever
What is another name for humoral immunity?
antibody-mediated immunity
What are the two types of immune responses?
humoral or cell-mediated
How do B cells acquire foreign antigens?
receptor-mediated endocytosis
How are foreign antigens made presentable to Th cells? (4)
once inside macrophages/dendritic cells/B cells, they are degraded in acidic endosomes or lysozymes; bind to MHC class II peptides and are displayed on surface; Th cells recognize and bind to this complex
The CD4 protein of Th cells bind to what part of MHC class II proteins?
CD4 protein binds to conserved regions of MHC class II protein
Naive Th cells express
a protein called CD28
What must CD28 do?
must bind to protein B7 if the T cell is to be activated
Where is B7 found? (2)
only on antigen-presenting cells; highest levels on dendritic cells
Why is B7 important?
form of regulation necessary due to the potency of cytokines
Activated Th cells give rise to
both effector Th and memory Th cells, just like Tc cells
Which cells mediate transplant rejection?
T cells
What happens when T cells encounter non-self MHC-peptide complexes on transplanted tissues?
TCRs on these T cells bind weakly to the MHC complex because the structure of the non-self MHC-peptide complex resembles the structure of a self MHC-foreign peptide complex
What is cyclosporin?
drug that blocks activation of lymphocytes to suppress immune system rejection of a transplant
(T/F) Cytokines are released exclusively by Th cells.
False, many other cells do, as well.
What is IL-12? (2)
a cytokine released when PAMP molecules bind to TLRs; IL-12 binds to Th cells to increase their level of activation
What does tumor necrosis factor-alpha do?
bind to blood vessels to induce local/systemic increase in vascular permeability
Plasma B cells produce
soluble antibodies of the same specificity as the same antibodies produced by the parent B cell
Draw the structure of an immunoglobulin molecule.
pg. 1070
What region of the immunoglobulin is responsible for its specificity?
the specificity resides in the amino-terminal half of each Fab region
What is the variable region of the immunoglobulin?
the amino-terminal half of the Fab region
Which chains of the immunoglobulin have variable regions?
both the light chain and heavy chain have a variable region
Which chains of the immunoglobulin have constant regions?
both the light chain and heavy chain have a constant region
In mammals, the light-chain constant regions consist of (2)
a kappa sequence and a lambda sequence, which have equivalent functions
In mammals, the heavy-chain constant regions consist of (5)
gamma, alpha, mu, epsilon, delta sequences (basis for IgG, IgA, IgM, IgE, IgD)
Which characteristics of the immunoglobulin determine the specificity for antigen epitopes? (3)
size, shape, and AA sequence in the antigen-binding site
How many epitopes can bind to an immunoglobulin?
2 epitopes
The function of immunoglobulins depends on
its class
The class of immunoglobulins depends on
the Fc portion of the heavy-chain constant region
How does the Fc region help in the elimination of antigens? (2)
Most cells have Fc receptors, so when an antigen binds to an antibody, a phagocyte can bind to the Fc region and make it easier to eliminate the antigen; specific immunoglobulins can interactions between non-specific cells and antigens
(T/F) Antibodies kill pathogens directly.
False, they target pathogens and let phagocytes destroy them.
Describe the function of IgG. (3)
major antibody secreted during secondary response; neutralizes antigens by promoting phagocytosis; activates complement
Describe the function of IgA. (2)
most abundant form of antibody in body secretions; high density of IgA-secreting cells in MALT
Describe the function of IgM. (3)
first antibody to be secreted during primary immune response; promotes clumping and precipitation; activates complement
Describe the function of IgE. (2)
Fc binds to mast cells + basophils; allergen binding to V regions promotes release of mediators which triggers allergic reaction
Describe the function of IgD. (2)
present only on surfaces of B cells; serves as antigen receptor
What is the shape of IgM? (2)
monomeric in the membrane of a B cell; secreted as a pentamer
What is the shape of IgD?
monomer
What is the shape of IgG?
monomer
What is the shape of IgA?
dimer
What is the shape of IgE?
monomer
Which immunoglobulins are monomers? (3)
IgG, IgE, IgD
Which immunoglobulins are found on mature, naive B cells?
IgM, IgD
How are B cells activated by IgD?
B cells can be activated by the cross-linking of two IgD molecules
Once a B cell is activated, what happens to IgD?
IgD is no longer displayed on the cell surface?
Which immunoglobulin(s) are normally not secreted by B cells?
IgD
Which immunoglobulin is the major antibody in blood plasma/tissues?
IgG - makes up 75% of plasma antibodies
Which antibodies involved in providing passive immunity to a fetus?
IgG (through placenta), IgA (through breastmilk)
Which immunoglobulin is the major antibody in external secretions?
IgA
Which antibody has a low concentration in plasma?
IgE
On secretion, most IgE becomes
bound to mast cells and basophils that recognize the Fc portion of IgE
Which antibody provides a defense against helminth worms, and how?
IgE, through perforin pores
How many different antigen binding sites can a human B cell generate?
10^10
How is the variable region assembled, and why is this important?
assembled by joining 2-3 DNA segments together; provides genetic diversity needed to recognize many epitopes
What is the name for the process that generates variable regions?
DNA rearrangement
How is DNA rearrangement different from crossing over in meoisis? (2)
DNA rearrangement occurs between loci on the same chromosome; DNA rearrangement is site-specific
When does DNA rearrangement occur?
as a progenitor B cell matures in the bone marrow
What happens after DNA rearrangement occurs in the bone marrow?
mRNA is produced that can be translated as either a heavy or light chain
What is allelic exclusion?
DNA rearrangement occurs for the heavy chain and light chain loci on only one homologue, which makes the B cells of only one specificity
What are V/D/J segments?
50 V segments, 30 D segments, 6 J segments - clusters of DNA sequences found in human immunoglobulin heavy-chain gene loci
(T/F) V segments are similar in size to each other.
True, they are equal in size, but have different nucleotide sequences - same goes for D/J segments
What is the first DNA rearrangement in maturing B-cells? (2)
site-specific recombination event joining one of the D segments onto one of the J segments; intervening DNA is deleted/degraded
V segments stand for
variable segments
D segments stand for
diversity segments
J segments stand for
joining segments
An immunoglobulin (Ig) protein is encoded by
V/D/J segments + constant region
What is the second DNA rearrangement in maturing B-cells?
combined DJ joins to V segment
Light chains are encoded by
V/J segments + constant region
What are the two types of constant regions in DNA rearrangement, and which region do they bind to?
a mu or sigma constant region, which binds to the variable region
IgM has what kind of constant region?
mu constant region
IgD has what kind of constant region?
sigma constant region
How many different V/D/J combinations can be formed?
~9000
What additional mechanisms allow for further DNA rearrangement beyond V/D/J segments?
nucleotides are added/deleted from each segment to shift reading frame; genes show elevated mutation rate
What is somatic hyper-mutation?
genes that code for Ig proteins show elevated mutation rates to allow for more diversity (up to 10^10 possible variable regions)
Draw the structure of a TCR.
draw pg. 1074
How many chains does TCR have?
2
Which region of TCR binds to an MHC-peptide complex?
amino-terminal domian – the variable region, distal to the membrane
Which region of TCR is constant?
membrane-proximal domain – constant region
(T/F) TCRs are secreted.
FALSE, TCRs are NOT secreted.
Which is more effective, the primary response or secondary response to an antigen?
the secondary response is more effective
Which is more rapidly activated, memory cells or naive lymphocytes?
memory cells
The class of immunoglobulin produced is dictated by
the identity of the cytokines derived from activated Th memory cells that bind to the B cells in the 2ndary response
What is immunological tolerance?
process where immune system learns to not react to self-antigens
When does the process of immunological tolerance begin in humans?
fetal stage
The failure of immunological tolerance leads to
autoimmune diseases
Autoimmune diseases, generally, are caused by
the failure of immunological tolerance
What happens when autoimmune diseases are produced? (3)
autoreactive T cells become activated; autoreactive B cells produce autoantibodies; extensive organ damage occurs
How many known autoimmune diseases are there?
more than 40
What percentage of the population is affected by autoimmune diseases?
5 to 7%; 2/3 of this are women
What drugs are administered to suppress the immune system? (2)
corticosteriods; nonsteroidal anti-inflammatory drugs (such as aspirin)
What is the most common form of allergy?
immediate hypersensitivity
Immediate hypersensitivity is the result of
overproduction of IgE in response to allergens
What is the most common allergy and where does it come from?
seasonal hay fever, provoked by pollen from ragweed
What happens the first time someone encounters an allergen?
allergen binds to/activates B cells; activated Th cells releases IL-4 cytokine; IL-4 dictates production of IgE from B cell; IgE rapidly binds to mast cells/basophils; IgE secretes histamine/prostaglandins which produces symptoms of allergy
What happens the second time someone encounters an allergen?
allergen binds to IgE which rapidly binds to mast cells/basophils; IgE secretes histamine/prostaglandins which produces symptoms of allergy
What is systemic anaphylaxis? (3)
life-threatening because BP drops; epiglottis swells to block trachea; bronchial constriction prevents exit of air from lungs
What is anaphylactic shock?
combination of blocked trachea; air blocked from leaving lungs; drop in BP
What is local anaphylaxis? (3)
itchy welts/hives; mild asthma; diarrhea (mild reaction)
What are some allergy treatments?
antihistamines; drugs that block activation of mast cells/basophils; hyposensitization
Delayed type hypersensitivity is mediated by
Th cells and macrophages
Delayed-type hypersensitivity symptoms occur
about 48 hours after a second exposure to the antigen
Give an example of delayed-type hypersensitivity.
contact dermatitis
A delayed-type hypersensitivity response requires
the antigen entering the body to travel to a secondary lymphoid organ (i.e. lymph nodes), where they activate Th cells; Th cells then travel around the body and release cytokines to activate macrophages
What acts as the antigen on blood cell surfaces?
protein-sugar complex
How do the antigens on blood cell surfaces differ?
differ with regard to the sugar present (or absent, in the case of O)
Which class of antibodies recognize the monosaccharide differences in our red blood cells?
IgM antibodies produced in response to carbohydrates on bacteria living inside of us
IgM, in the context of blood groups, can
recognize the monosaccharide differences in our red blood cells (only the IgM produced in response to bacterial carbohydrates)
What is another important blood-borne antigen?
Rh factor
The Rh protein is either
present (Rh positive) or absent (Rh negative)
What happens if an Rh negative person receives a transfusion of Rh positive blood?
Rh negative person will produce antibodies to foreign Rh protein on transfused cells
(T/F) Mother and fetus can have different Rh statuses.
True
Mother (Rh negative) and fetus (Rh positive) having different Rh statuses results in
hemolytic disease of newborns (HDN)
What are the consequences of HDN?
First child is usually not harmed, but during first birth mother can be exposed to child’s blood so she produces anti-Rh antibodies; if she exposed to the second child’s blood, IgG antibodies can destroy fetal blood cells
Blood typing is done by
taking advantage of circulating IgM antibodies which are produced against foreign antigens but not against self
How many blood groups have been identified?
over 20
What is autologous blood donation?
when people stockpile their own blood before elective surgery bc they’re likely to mismatch
What happens in a transfusion reaction? (3)
intravascular hemolysis of transfused RBCs is detected; results from IgM binding to foreign antigens and activating complement system; RBCs are destroyed via osmotic lysis
What molecule is released during a transfusion reaction?
hemoglobin released from RBC is converted to bilirubin
Describe bilirubin.
toxic and causes severe organ damage, especially to kidneys
What is the major treatment to a transfusion reaction?
stop transfusion and administer large amounts of intravenous fluids to wash bilirubin out of body
What are polyclonal antibodies?
Antibodies secreted by B-cells with many different specificities
What are monoclonal antibodies?
antibodies that exhibit specificity for one epitope only
How are polyclonal antibodies isolated in labs? (2)
Inject antigen into vertebrate; periodic bleeding of animal allows isolation of serum antibodies
How are monoclonal antibodies isolated in labs?
mouse is immunized several times with antigen and killed; B lymphocytes which are now specific for antigen are harvested from mouse spleen; B cells fused with cancerous myeloma cells for immortality
What is a hybridoma?
outcome of B-cell/myeloma cell fusion
What does AIDS stand for?
acquired immunodeficiency syndrome
AIDS is characterized in part by
destruction of Th cells
How can AIDS be monitored?
by examining reactivity of patient’s leukocytes with a monoclonal antibody against CD4 (Th cell marker)
For a pathogen to establish itself in a host, what must happen?
must evade both nonspecific and specific immune systems
Influenza is known because
it alters its surface antigens and avoids immune system recognition
What are the viral proteins expressed by the influenza virus? (2)
hemagglutinin (HA) and neuraminidase (NA)
What is antigen drift?
Influenza virus has an RNA genome that is replicated by a viral RNA polymerase that lacks proofreading ability, which means mutations are likely to accumulate over time
What is antigen shift?
sudden appearance of a new subtype of influenza in which HA and NA proteins are completely different
Malaria is caused by what organism?
protozoan parasite Plasmodium that is transmitted when humans are bitten by Anopheles mosquito
How does salmonella typhimurium commonly cause food poisoning?
can alternate between expression of two flagellar proteins so that antibodies for one protein can’t recognize the other
How does mycobacterium tuberculosis cause illness?
once it is phagocytosed into macrophages, they inhibit the phagosome from fusing with lysozomes and successfully multiply within the macrophages
Give two examples of bacteria that invade mucosal surfaces.
Neisseria meningitidis; Neisseria gonorrhoeae
How do bacteria invade mucosal surfaces?
secrete proteins that degrade the IgA antibodies that protect the mucosal surface
Particularly pathogenic strains of bacteria work by
blocking the binding of phagocytosis-induced complement protein Cb3, which slows the phagocytic response
How does HIV work?
human immunodeficiency virus binds to CD4 proteins on Th cells and utilizes these proteins to get inside the Th cells
(T/F) HIV only infects Th cells.
False, HIV can infect monocytes too since monocytes also express CD4.
Once HIV enters and infects the Th cell, what happens?
releases replicated viruses to other Th cells such that they all become infected and die
When is an individual considered to have AIDS?
when the Th cell levels drop dramatically
How does the immune system initially respond to HIV infection?
produces anti-HIV antibodies and eliminates infected cells using Tc cells
How does the HIV infection progress? (2)
eventually HIV kills Th cells more rapidly than can Th cells proliferate for memory purposes; HIV causes decrease in MHC class I expression on infected cells which makes them less likely to be earmarked for destruction
What are the implications of HIV being a retrovirus?
HIV can integrate itself into a genome and hide in a latent form
AIDS was first discovered when young men died of
pneumonia or Kaposi’s sarcoma
Pneumonia generally affects
those who are immunosuppressed
In 2010, how many people lived with HIV?
34 million
