Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
261 Cards in this Set
- Front
- Back
What are the two branches of immunity and how do they differ?
|
Innate and aquired immunity
Innate--born with, FAST acting, acts via barriers (skin), cells, and serum proteins Aquired or adaptive--improves with exposure and is mediated by B and T cells |
|
What is the first line of defense?
|
skin and mucous membranes
|
|
What is the second line of defense?
|
Phagocytosis by neutrophils and monocytes/macrophages
Complement activation: cell lysis, inflammation, opsonization (proteins stick to surface of microbe to tag it and signal the phagocytic cell. Inflammation calor, dolor(pain), rubor, tumor Fever Natural killer cells--lytic |
|
How is fever helpful?
|
Raises temp which may allow enzymes to work more efficiently, increases generation time therefore decreasing replication of bacteria
|
|
What type of cell is a NK cell?
|
A NONSPECIFIC lymphocyte
|
|
What is the third line of defense?
|
Activation B and T lymphocytes
|
|
What do B cells do and what do they recognize?
|
B cells recognize cell bound OR soluble antigens (Ag)[RECOGNIZE ANTIGENS ANYWHERE]produce antibodies (Abs)
|
|
What is an antigen?
|
Anything that stimulates and immunologic response--an antibody generator
anti gen |
|
What kind of immunity do B cells provide? T cells?
|
B cells--humoral mediated immunity
Ab mediated immunity T cells--cell mediated immunity |
|
What do T cells recognize and produce?
|
T cells recognize ONLY cell bound foreign molecules--antigens, they produce CYTOKINES to direct other cells
|
|
What type of cells produce cytokines?
|
Cytokines USUALLY produced by T cells, can also be produced by B cells and others.
|
|
Which type of response is specific? nonspecific?
|
specific--adaptive
non-specific--innate |
|
What type of cells is the adaptive response due to?
|
B and T cells
|
|
What are the 4 main properties of aquired immunity?
|
1 recognition of self vs. non self
2. specificity 3. heterogeneity, adaptibility, diversity 4. memory--allows for quicker response (vaccine) |
|
What happens to self reactive cells?
|
They should be destroyed early in the development of T and B cells
When they are not destroyed they undergo Ag tolerance Can result in autoimmunity |
|
Where do B cells mature? T Cells?
|
B cells in the bone marrow
T cells begin in bone marrow and then in the thymus self reactive B cells destroyed in bone marrow; T cells in thymus |
|
What is the top part of the Ab called and what is characteristic of it?
|
top is called the n terminal, it is the variable region
|
|
Is a T cell receptor membrane bound?
|
yes it is NOT secreted
|
|
Is an antibody secreted by a B cell or membrane bound?
|
Both
|
|
What type of chains make up an antibody?
|
heavy and light
heavy and light on top and heavy below |
|
What are the common types of B cell Ags?
What are the rare forms? |
protein or carbohydrates
Nucleic acid and lipid |
|
What autoimmune disease makes antibodies against DNA?
|
Lupis
|
|
What configuration do B cells recognize antigens in?
|
B cells recognize soluble Ag, often in native configuration (i.e. NOT PROCESSED)
|
|
Are B cells good at recognizing extracellular Ags?
|
yes
|
|
What configuration do T cells recognize antigens in?
|
T cells recognize processed Ag presented with the MHC--major histocompatibility complex
|
|
What is the function of a MHC?
|
A major histocompatibility complex binds to a piece of chopped up protein and sits on surface of cell for T cell receptor to recognize
Acts as a "flagpole" |
|
What are the 2 classes of MHC's?
|
Class I CD8+
Class II CD4+ |
|
What are the 3 major types of MHC class II?
|
dendritic, macrophages, B cells
|
|
What does it mean for a protein to be "processed"?
|
To be chopped up
|
|
Will all peptides associate with the MHC? What does this correspond to?
|
no.
Corresponds to the reason why some people respond well to infectious organisms and other do not. |
|
What types of cells make a bridge between innate and adaptive immunity?
What job does each fulfill? |
Antigen presenting cells (APC) present antigens to T cells. Activate T cells to produce cytokines
Professional APC's--macrophages, dendritic cells, and B cells. Present Ag in assoication with MHC class II. |
|
Is there a gene for every Ag?
|
No. That would take up 60% of the genome.
The variable region determines specificity. |
|
What is an immunoglobulin?
|
Same as an Ab
|
|
What is the V region? D? J?
|
V variable
D diversity J joining genes creative genetics |
|
Do B cells or T cells exhibit memory?
|
Both!
|
|
What kind of response do memory cells allow for?
|
memory allows for quicker and better response when next recognizing an Ag
|
|
How long does an initial response take? A memory response?
|
initial (primary immune response)2 weeks
memory (secondary immune response)a few days |
|
What happens to affinity with subsequent exposure in memory cells?
|
Increased affinity
|
|
What happens when a T or B cell recognizes an Ag?
|
It proliferates and goes to eliminate the pathogen
|
|
How do you measure a T cell primary and secondary response?
B cell? |
T Cell measure cytokine response.
B cell measure antibody spike |
|
Is the memory response fail proof?
|
No, remember chicken pox. Doesn't always work
|
|
What is the best type of vaccine? When can this cause problems?
|
attenuated
Ex. small pox. People w/ weakened immune response can't fight off the weakened form and die |
|
When would it be a good idea to use a heat or chemically killed microbe vaccination?
|
Use for people with weakened immune response. Will break bonds or proteins. might not work because of denaturation
|
|
What is a toxoid?
|
A type of vaccine. chemically teat a toxin so it doesn't have its function anymore. BUT retain its Antigenic determinants
|
|
What is the difference between passive and active immunity?
|
Passive is from antoher organism. Ex. mother IgA or purified gamma globulin from infected people or animals.
The BEST!! Active is from an individual's immune system and produces memeory cells. |
|
In what disease could you vaccinate after infection?
|
Rabies. Takes a long time to get symptoms
|
|
What are some pathologies related to the immune response?
|
organ transplants, allergies, autoimmune response
|
|
What is a TCR? BCR?
|
A T cell receptor.
B cell receptor |
|
What does a megakaryocyte become?
|
Breaks off to platelets
|
|
What are the 3 main blood type lineages?
|
lymphoid, myeloid, erythoid
|
|
What type of cells are natural killer cells? How do they differ from other lymphocytes?
|
NK's are NONSPECIFIC lymphocytes
|
|
What types of cells are formed from the erythroid lineage?
|
RBC's and platelets
|
|
What is a PMN? What do they usually refer to?
|
PMN = polymorphonuclear leukocytes. Usually refers to neutrophils.
|
|
What types of cells are formed from the myeloid lineage?
|
Granulocytes--PMN leukocytes
= neutrophils, eosinophils, basophils Mast cells |
|
What types of cells are formed from the lymphoid lineage?
|
lymphocytes, B and T AND NK cells
|
|
Do neutrophils activate T cells?
|
no doesn't have any CD4+ Class II
|
|
Are RBC's nucleated?
|
Not in mature RBC's
|
|
Which is better dendritic cell or macrophage?
|
dendritic cell because most effective at stimulating a T cell response
|
|
What is a plasma cell?
|
A B cell that produces antibody
|
|
If a patient has an increase in eosinophils what does that mean?
|
Either they have allergies or a parasitic worm infection
|
|
How is blood development directed?
|
By colony stimulating factors (CSF) and other cytokines
|
|
How are colony stimulating factors (CSF) and other cytokines activated? Where are they produced?
|
CSF's and other sytokines are activated by helper T (Th) cells and macrophages.
Produced by bone marrow stromal cells |
|
What is type of WBC is the largest?
|
The monocyte
|
|
Where are macrophages found? What is the difference between monocytes and macrophages?
|
Macrophages are in the tissue. The monocyte is the precursor to the macrophage
|
|
What determines committment of distinct blood cell lineages?
|
Need the growth factor (CSF)AND the CSF receptor.
|
|
What are some types of CSF?
|
1. multilineage CSF--IL3 (IL=interleukin)
2. Granulocyte-Machrophage CSF (GM-CSF) 3. M-CSF 4. G-CSF 5. Erthropoietin (EPO) |
|
Where is IL-3 produced and when does it act?
|
acts early and is produced by T cells and mast cells.
|
|
What does IL-6 do? Is it a CSF?
|
an inducer of hematopoiesis during infection. Produced in bone marrow cells, T cells, B cells, macrophages
|
|
Where does hematopoiesis occur? In adult?
|
In the yolk sac, then fetal liver, then fetal spleen. In adult in bone marrow. From about 4th month of life.
In adult in the long bones. |
|
How long do RBC's live? Neutrophils? T Cells?
|
RBC's--120 days
Neutrophils--2-3 days T cells--20-30 years |
|
Why does apoptosis occur? What happens if there's a problem with apoptosis?
|
maintain level of all cells
problem=cancer |
|
Pertaining to apoptosis, why do some leukemias and lymphoma's result?
|
**Increase CSF receptor expression
Viral infection (ex. HTLV-1 and IL-2R) causes increased cytokine receptor expression **Increased production of CSFs |
|
What are the primary lymphoid organs?
|
Primary--thymus and bone marrow
Secondary--lymph node, spleen, blood, lymph system, gut associated lymphoid tissue (GALT) |
|
What is GALT?
|
gut associated lymphoid tissue (GALT)
secondary lymphoid organ |
|
Do B cells need to be at the site of infection?
|
No, they secrete antibodies that go to teh infection. Whereas T cells actually have to be on site
|
|
Where do cytokines and CSF's have to be in order to do their jobs?
|
in the bone marrow
|
|
Where does B of B cell come from?
|
From bursa of fabricius (chickens)
We can think of it as bone marrow |
|
What is the order in which T cells are deteremined to be or not to be self reactive? What % of T cells will be destroyed?
|
First see if T cell recognizes MHC, then see if it binds to self Ag.
99% of T cells that go to the thymus are killed |
|
Where are T cells found?
|
In the paracortex of the lymph node (LN)
|
|
What is found in the medulla of a lymph node?
|
plasma cells, secrete antibodies into the blood!
|
|
What is found in the cortex?
|
B cells, macrophages, FOLLICULAR dendritic cells
|
|
What is special about follicular dendritic cells?
|
It does NOT have MHC Class II,ie help T cells. INSTEAD they help B cells!!
|
|
Why are secondary follicles bigger?
|
Activated B cells, plasma cells ready to secrete antibody
|
|
What usually makes a primary follicle? A seondary follicle?
|
Inactivated B cells
A secondary follicle is a primary follicle and its Ag. ACTIVATED |
|
What is inside the paracortex?
|
T cells (interact with Ag) need APC's too (dendridic cells and macrophates)
|
|
How do Ag's get into the lymph node?
|
via afferent lymph vessels AND dendritic cells bring in the Ag via afferent vessels too
|
|
How do effector cells or Abs leave the lymph node?
|
Via efferent lymph vessels OR the circulatory system
|
|
How many afferents and efferents are there?
|
Mulitple afferents, single efferent
|
|
What happens in a HEV?
|
High endothelial of post capillary venules. Bring lymphocytes to lymph node
|
|
What is a draining lymphnode?
|
lymph node closest to an area of infection
|
|
Where are B cells located in the spleen?
|
In the white pulp of the spleen
In the germinal center as mature plasma cells and in the marginal zone as immature B cells. |
|
What are the two types of pulp in the spleen?
|
Red--removes old RBCs by macrophages
White--lymphoid area, immune response to BLOOD BORNE pathogens |
|
What are PALS and where are they found?
|
PALS--peri-arteriolar lymphoid sheath. They surround splenic afteries and more importantly they are T CELL RICH!!
|
|
How do pathogens and lymphocytes enter the spleen?
|
Via the blood NOT THROUGH THE LYMPHATIC SYSTEM!!
different from lymph nodes! |
|
What are some types of specialized lymphoid tissue?
|
MALT, GALT, BALT, SALT
mucosa, gut, bronchial, skin associated lymphoid tissue areas of exposure to large #'s of microbes that have adapted and have specialized lymphoid tissue |
|
What does MALT do?
|
mucosa associated lymph tissue has B cells producing IgA and intra-epithelial lymphocytes, ie GAMMA DELTA's found in gut and skin
|
|
What are two types of MALT?
|
GALT and BALT
Galt--tonsils, adenoids, appendix, peyers patches, mesenteric LN |
|
Where are M cells found and what do tehy do?
|
found in intestines they have 2 functions. 1 grab ahold of bacteria and 2 release antibodies
|
|
Where are peyer's patches found?
|
Peyer's patches in intestine
|
|
Where will you find gamma delta lymphocytes? What are gamma delta's limited by?
What are "true" lymphcytes? |
Gamma delta lymphocytes found in gut and skin. Limited in diversity.
"true" lymphocytes are alpha beta |
|
What are dendritic cells in the skin called?
|
Langerhans cells
|
|
What types of cells are associated with specialized skin lymphoid tissue (SALT)
|
dendritic or langerhans cells. Tissue macrophages. gamma delta T cells
|
|
how can Ag-specific T and/or B cells find their Ag?
|
1. Draining LN – “meeting place” – keep Ag in area to interact with lymphocytes
Products/effector cells leave LN and go to site of Ag 2. Lymphocyte recirculation – movement from blood to lymphatics and back until contact with Ag |
|
What are lymphocyte homing receptors? Where are they found?
|
Cell SURFACE glycoproteins on lymphocytes and other leukocytes that MEDIATE ADHESION to high endothelial venules (HEV).
Several different classes of lymphocyte homing receptors have been identified, and they appear to TARGET different surface molecules (ADDRESSINS) on HEV in different tissues. The adhesion plays a crucial role in the TRAFFICKING OF LYMPHOCYTES |
|
What is expression of homing receptors based on?
|
Variable expression based on stage of lymphocyte (maturity) and activation status
|
|
What is an addressin?
|
a molecule on the SURFACE of VASCULAR endothelial cells (HEV)that MEDIATES ATTACHMENT of specific leukocytes, particularly lymphocytes, to the endothelium, BINDING WITH THEIR HOMING RECEPTORS!!
They ATTRACT effectors (neutrophils etc) to the Lymph node |
|
How do homing receptors and addressins work together?
|
Homing receptors are attracted to addressins. When they link they hold the cell stationary, so it damage can be repaired
|
|
How do effector cells, Abs, memory cells leave the lymph node?
|
Lymphatics → thoracic duct → blood → site of infection = fight infection
|
|
Where do memory cells in the skin go?
|
Some leave via lymphatic system and some stick around for future rxns
|
|
How often does the epidermis renew itself? Why is this helpful?
|
epidermis, primary nonspecific innate defense. Renewed 15-30 days. Microbes must attach to infect, this prevents attachment
|
|
What is secreted by the epidermis when damaged? What do these do?
|
IL-8 and TNF stimulate inflammation
|
|
What does the dermis have that inhibits bacterial growth?
|
sweat and sebaceous glands.
vascularized w/ hair follicles |
|
What do langerhans cells do?
|
dendritic cells recognize Ag and recruit
|
|
What do normal folra do to inhibit microbes?
|
secrete restriction enzymes--chop up DNA and bacteriocins--inhibit other bacteria
|
|
What is an example of a bacteriocin?
|
colicin--inhibit other E coli's in the colon
|
|
Where are mucous membranes found?
|
Respiratory, Digestive, Genitourinary Tracts
|
|
What do mucous membranes secrete?
|
secrete
1. sIgA (secretory immunoglobulin) adaptive 2. Mucin 3. lysozyme |
|
What does mucin do?
|
mucin--traps microbes. use mucocillary escalator to Kick out of respiratory tract by cough and sneezing. Smokers and cyctic fibrosis patients are impaired in this function
|
|
What does lysozyme do?
|
cleavage of bacterial cell wall (b1,4 linkage of peptidoglycan
|
|
Where is surfactant found? What does it do? What do pathogen binding proteins do?
|
Surfactant in respiratory tract. Doesn't allow pathogens to bind!!
pathogen binding protein is a type that connects the microbe to a macrophage. |
|
What is an example of pathogen binding proteins? What do complement proteins do?
|
Ex. mannan binding protein. It can activate complement proteins, which lyse, stimulate inflammation, and opsonize in addition to pathogen binding protein properties!
|
|
What family do pathogen binding proteins belong to?
|
Collectin
|
|
Name 4 Chemical mediators of innate defenses.
|
1. Stomach acid / digestive enzymes
2. Lysozyme – destruction of microbes 3. Interferon - antiviral 4. Complement cascade – antimicrobial Cell lysis, opsonization, inflammation |
|
Lowered stomach acid production can result in what type of infection?
|
Salmonella
|
|
What bacteria cause ulcers? How?
|
Heliobacter pylori--increases pH of a microenvironment so it can grow
|
|
What does interferon do?
|
makes cells resistant to viral infection by changing surface receptors. Inhibits viral replication and can even stimulate apoptosis b/c w/o a host the virus would die.
|
|
What are the more potent antiviral interferons? Why?
|
a and b IFN. produced in response to ds RNA (not found in mammals)
Increase TAP--Class 1 (CD8+) |
|
What does gamma IFN do?
|
activates the immune system--produced by Th cells
|
|
What is CTL?
|
cytotoxic T lymphocyte, Tc, CD8+ = MHC I
|
|
What are the three things interferons can do?
|
1. induce resistance to viral replication
2 increase MHC Class 1 expression and Ag presentation in all cells 3. Activate NK cells to kill virus infected cells |
|
What is phagocytosis activated by? What recognizes these?
|
Activated by:
molecules on microbes binding to toll-like receptors (TLRs) Antibodies (Abs) coating microbe Recognized by monocyte/macrophages and neutrophils |
|
Describe following differences between Neutrophils and macrophages. Increase during inflammation? Found in what tissue? Forms pus? Forms granuloma? Lifespan?
|
neutrophils # increase in inflammation, found only in INFLAMMED tissue, forms pus rapidly, short lived--kamakazi!
Macrophages increase only slightly in inflammation b/c they're resident for most part, found in HEALTHY tissue too, forms granuloma, long lived b/c can survive phagocytosis. |
|
How can microbes be recognized?
|
extravation of neutrophils, opsonization of microbe, CR4 and CD14 receptors bound to LPS, TLRs
|
|
What does CD14 bind to? CD3?
|
CD14 to LPS
CD3 a complement Both bind to RECEPTOR on microbe |
|
What does toll mean? How are thise used?
|
weird.
those used in innate defenses for recognition of microbes --Have sequence similarity to toll a/k/a Pattern recognition receptors (PRRs) |
|
What is TLR4?
|
Toll like receptor Important in binding LPS in humans
|
|
What kind of protein is a toll like receptor?
|
transmembrane signaling protein results in a cascade effect, brings in phagocytic cells
|
|
What do TLR's bind to?
|
esp ds RNA on microbes. Also, proteins, LPS, sugars, rna.
TLR bind to these items on a microbe. |
|
Where are TLRs found?
|
ON cell membrane OR on cytoplasmic membranes (bind to DNA, RNA etc)
|
|
What happens when TLRs get stimulated?
|
inlfammatory response
|
|
What is a chemokine?
|
small cytokine causes inflammation
|
|
What does diapedesis mean?
|
movement thru a vessel wall
|
|
How do neutrophils get to the site of infection?
|
roll around in blood stream, lightly adhered to endothelial cells, bind tight when a flag is up, via diapedesis get thru vessel wall, into cell via migration
|
|
What are CRs? FcR?
|
complement receptors
FcR= binds to Fc region of Ab |
|
How does complement induce phagocytosis?
|
complement binds to bacterium, then sends another complement out to bind to a receptor on a phagocyte, covalently bonds bacteria to phagocyte.
|
|
What do IL8 do? What do IL-1 and IL -12 do? IL6? IL-1, 6, TNF a? IL-12? TNF a?
|
IL8--chemokine cytokine (inflammatory)chemotactic for WBCs neutrophils esp.
IL-1, IL-12 – important in Th cell activation Th1 (IL-12) versus Th2 activation IL-6 – hematopoietic and B cell maturation IL-1, IL-6, and TNFa – acute phase response IL-12 – activate NK cells TNFa – stimulates clotting (prevent movement of microbes into blood) and increases movement into lymph |
|
Is it possible to have a cytokine that has an opposing function to another cytokine? What produces cytokine?
|
Yes.
produced by lymphcytes and macrophages |
|
Which cytokines are involved in acute phase response?
From where and what proteins are produced? What is their function? Why won't they bind to human cells? |
IL-6, TNF-a, and IL-1
From the liver C-reactive protein and MBL (mannan-binding lectin) are produced. Bind to structural features on sugars of microbe – allow for: Opsonization Alternative pathway of complement activation Won't bind to human cells b/c structural features of microbe specific. NOTE: CRP linked to cardiovascular risk |
|
What causes septic shock?
|
Recognition of microbe by TLRs and other receptors
Overproduction of inflammatory cytokines (ex. TNF-a) Systemic inflammatory reaction--can be fatal |
|
What are the 4 major symptoms of inflammation?
|
rubor, palor, dolor, calor
|
|
When will you see a granuloma?
|
in chronic inflammation. TB and SCHISTOSOMA eggs
|
|
Which cytokines stimulate fever? How does it work?
|
IL-1, IL-6 and TNF-a
Interacts w/ hypothalamus--messes w/ thermostat, mm and fat cells. Increase temperature by mobilztion |
|
What is the effect of increase in temperature?
|
Increases chemical reactions
Slows down microbe growth |
|
What kind of cells do NK cells kill?
|
kill virally infected cells and tumor cells (altered self cells)
|
|
What is the function of NK cells?
|
To control the situation unitl the T cells can come in and kill.
|
|
What is the difference between an autoantigen, alloantigen, xenoantigen?
|
Autoantigen - a self Ag (autologous)
Alloantigen – an antigenic difference within a speices (allogeneic) Xenoantigen – an antigenic difference between species (xenogeneic) |
|
What are haptens?
|
Haptens – small molecules that are antigenic but NOT immunogenic
often need to be attached to a carrier to become immunogenic |
|
What make for the most potent immunogens? Will carbohydrates stimulate a T cell? B cell?
|
Proteins followed by carbohydrates.
Carb will stimulate B cell--no T cell. Protein will stimulate both. |
|
How is a "Good" Ag made? Must be presented otherwise no-go!
|
foreign, large size 100,000 daltons, aromatic AA (tyr, phe), D AA can't be processed.
|
|
What is the difference between TH1 and TH2?
|
TH1--T helpers activated
TH2--B cells activated |
|
What acounts for differences in immune response among individuals?
|
BCR and TCR genetics, might lack one of them, etc.
|
|
In the example of leprocy an intracellular disease which response TH1 or TH2 is better?
|
TH1--activates T helper cells kill infections b/c intracellular response. If TH2 cells then activate B cells and response isn't effective.
Due to genetics |
|
What can high or low doses of response do?
|
High--tolerance
Low--not worth energy Neither work well |
|
Which is more immunogenic: aggregated or nonaggregated?
|
aggregated--get better response
|
|
Which is more effective: IV, SC, IM?
|
IM b/c will stay in system longer
In blood will be removed quickly |
|
What type of protein will make the best antigenic?
|
more complex and multideterminant (multiple sites to be recognized)
|
|
What is a B and T epitope?
|
site of recognition on outside of Ag. B cells bind to B epitopes etc.
|
|
Which is more internal B or T epitope?
|
T more internal (tight)
B more external. Makes sense because T cells recognize pathogens intracellularlly. |
|
Are B cell epitopes sequential? T cells?
How large are the aa? In order for a T cell to respond what must the Ag interact with? |
B cells--can be sequential or not. 8-22aa
T cells are sequential CD8+ 8-10aa CD4+ 13-18aa Ag must fit into TCR and MHC |
|
What makes a polysaccharide more immunogenic?
|
bound to proteins or lipids.
more complex allows for(ABO blood groups) |
|
Do lipids and nucleic acids make good immunogens?
|
No. Lipids act as haptens when attached to proteins. Glycolipids can serve as immunogens.
Nucleic acids--if conjugated w/ protein then can be immunogenic. Anti-DNA Ab's aren't a good thing= lupis |
|
What is an immunodominant epitope?
|
Immunodominant epitopes are capable of inducing a more pronounced immune response
|
|
What kind of responses do immunodominant epitopes create?
|
stimulate early (and often the best) responses
|
|
What happens if an immunodominant epitope is mutated? What disease is this associated with?
|
can weaken effect of immune response.
HIV/AIDS |
|
What do mitogens do? Are they Ag specific?
|
Activate t and B cells
Ex. LPS is a B cell mitogen Concanavalin A (ConA) – T cell mitogen NOT Ag specific |
|
What type of response is generated from a T independent Ag?
|
B cells response--no memory cells
|
|
What type of response does a T dependent (TD) Ag require?
|
T cell help, i.e. cytokines. Generates immunological memory
|
|
Can TI 1 or 2 be Ag specific?
|
TI 2 can be Ag specific
|
|
What is required for a hapten to exhibit immunogenic response?
|
T cell help. Need a carrier bound by conjugate
|
|
Will differences like o,p,m spots on a ring be important to immune response?
|
Yes
|
|
How do cross reaction occur?
|
Non-related molecules can share epitopes and an immune response against one can “cross-react” with the other
|
|
How do hypersensitivities and autoimmunity occur?
|
If a “self-protein” becomes modified, one could react to the self-protein
Some microbe proteins may have same epitope as self proteins |
|
How does a hapten-carrier produce Ag recognition?
|
Recognized by APC, engulfed, carrier peptides presented to Th cells.
When recognized, Th secretes cytokines to activate B cells (T cell help) B cell recognizes hapten and secretes Abs |
|
What are adjuvants? What does it do? What is this used for?
|
Adjuvants are compounds that when mixed with immunogens, makes them more immunogenic
creates a stronger immune response. used in vaccines and expt studies |
|
How do adjuvants work?
|
increase half-life of immunogens
increase production of inflammatory cytokines improved presentation and costimulation of APCs to T cells |
|
What is an example of an adjuvant?
|
an Ag in oil makes the Ag stay around longer= better immune rxn
Aluminum hydroxide or alumninum phosphate. (alum) CFA (freunds complete adjuvant oil in water w/ killed mycobacteria) experimenal uses only oil in water (Freunds incomplete adjuvant) DC's Angitgen--Ag pulsed APC |
|
Whta is Ag specificity of a b cell due to?
|
membrane bound Ig (part of the BCR complex)
|
|
How are B cells expanded?
|
clonal selection and proliferation allows for the expansion of B cells specific for one antigen
|
|
What is an activated B cell?
|
plasma cells that secretes soluble Abs
given B cell produces Ab with 1 Ag specificty |
|
What are some functions of Ig?
|
pathogen neutralization, completment fixation, Ab dependent cellular cytotoxicity (ADCC), Opsonization, Inflammation
|
|
What is the difference between plasma and serum?
|
Plasma – fluid fraction Serum – clotted plasma
|
|
What can be used to determine multiple myelomas?
|
Electrophoresis
cancer of B cell producing monoclonal Ig--increase IgG |
|
What are Rence Jones proteins?
|
Bence-Jones protein – produced in urine of patients with overproduction of light chains
|
|
What are 3 methods of enzymatic clevage of Ig?
|
Porter
Nisonoff Edelman |
|
How does Porter cleavage work?
|
use papain--yield FAB and Fc region
Nisonoff used pepsin--yild two F(ab)2 and Fc Edelmann uses mercaptoethanol yields 2L and 2H chains |
|
What links H chains together?
|
disulfide bonds at hinge region
|
|
What links L chains to H chains?
|
disulfide bonds @ CL region.
|
|
What are the 5 classes of heavy chains? What are the types of light chains?
|
5 classes of heavy chains (isotypes: IgG, IgM, IgA, IgE, and IgD…a/k/a g, m, a, e, and d)
2 types of light chains (k or l) |
|
Where does an Ab bind?
|
N-terminal end where the VL and VH are joined
|
|
What binds to Ag?
|
F(ab)
|
|
What does Fc do?
|
biologic activity Complement and ADCC.
|
|
Is there inter or intra chain bonding? What type?
|
Yes, there's both. All by disulfide bonds
|
|
How many AA in an Ig domain?
|
100-110 aa long. has an intra-chain disulfide bond
|
|
Molecules with this fold are members of the what family?
|
Ig gene superfamily
|
|
Where is variability concentrated?
Which one makes the most contact with Ag? |
Called Complementarity determining regions
a/k/a Hypervariable regions (CDR): CDR1, CDR2, and CDR3 CDR3 makes most of the contact with Ag |
|
What are framework regions?
|
less variable regions
|
|
What are subclasses of H chain isotypes due to?
|
differences in C region
|
|
What % of human Ig have kappa? lambda?
|
kappa--60%
lambda--40% |
|
Which Igs have an extra domain? How do isotypes differ?
|
Ig m and E
Isotypes differ in glycosylation |
|
Which forms of Ig are monomers? dimers? Trimers? tetramers? Pentamers?
|
G, D, E are monomers
A can be dimer, tri, tetramer M is pentamer |
|
Which Igs are high in plasma? tissue fluids? In secretions? In fetal passive immunity? on mast cells? In brain?
|
IgG and M are high in plasma
IgG high in tissue fluids IgA high in secretions (dimers) IgG fetus immunity IgE on mast cells None in brain unles damage to BBB |
|
How many binding sites on IgM?
|
10 Ag binding sites
|
|
Does IgM ever exist as a monomer? When does IgM first appear? What is IgM good at? Why?
|
Only on surface of mature B cell
Appears first during a primary immune response. best at C’ activation best agglutinating Ab because has so many binding sites! |
|
When is IgG a dimer? How many binding sites does IgG have? How many subclasses?
|
NEVER--always a monomer.
2 Ag binding sites 4 subclasses |
|
Where does IgG predominate? How long does IgG live?
|
blood and lymph
Longest half life of isotypes (23 days vs. 2-5 days) |
|
When is IgG present?
|
appears in late primary and early secondary immune response
|
|
What does IgG do?
|
can activate C’
some subclasses cross the placenta opsonin and mediates ADCC |
|
What are Ig monomers good for?
|
flags
|
|
What is IgA's function? When is it a monomer? dimer? tetramer?
|
Secretory Ig
monomer on surface of B cell dimer (can be tetramer) when in secretions |
|
What holds Igs together?
|
J chain
|
|
What component is present? What does it do?
|
Secretory component (SC) present
protective protein--protects against drying and enzymes SC ~70,000 mw MUCOPHILIC – attaches to epithelial and traps Ags in mucous where lysozyme can help degrade |
|
What is the MAJOR Ig in the BODY?
|
IgA
|
|
Is IgD a monomer? What is it's function?
|
Yes monomer only. Unknown function--second receptor on B cell (after M cell). Coexpressed on surface of B cell. Maybe cooperates in initial B cell activation.
|
|
What is reagin? Where is it found?
|
reagin – binds to basophils and mast cells
Found in IgE. |
|
What happens when IgE binds Ag? What does IgE protect against?
|
causes degranulation of mast cell = allergic reaction
a/k/a Type I hypersensitivity (Immediate type hypersensitivity) protection against parasitic worms – causes acute inflammatory reaction |
|
Why is IgE lowest in serum?
|
cleared from serum when binding to mast cells
short half-life in blood but long on surface of mast cell |
|
What must occur for IgE to work?
|
Must bind allergin in between two IgEs
|
|
what is the difference between an isotype, allotype, and idiotype Ig?
|
Isotypes – SELF 5 major classes in humans (A-E)
determined by C-regions of the H-chain some describe light chain isotypes as well (k and l) Allotypes – allelic forms of the same protein that can vary within a SPECIES usually 1-2 a.a. changes (ex. same Ab, different AA sequences) Idiotypes – due to the variable region of the Ig (differences in a.a. sequences due to variable binding to Ags) essentially a clonal marker for a given B cell. CDRs |
|
How can we produce millions of different Abs with limited genes?
|
Ig gene rearrangement
|
|
How was Ab gene arrangement discovered?
|
myeloma cancerous B cells producing too much Ab--IgG. Howed segments differed in size from germline and mature cells
|
|
What are the gene segments of a Heavy Chain? Light chain?
|
Heavy Chain:
V, D, J and C region genes Light Chain V, J, and C region genes |
|
How is selection of genes performed? When does it occur?
|
selection is random and occurs BEFORE Ag stimulation
|
|
What can happen AFTER Ag stimulation?
|
Class switching. Can change isotype--ex. IgA to IgG etc
|
|
How many alleles can be expressed at once?
|
One at a time. Have 2
|
|
During the process of Ig gene rearrangement, if the first allele is successful, what happens?
What happens if the first allele is non-productive? |
then the process stops
if the first allele is non-productive, then the other allele will be re-arranged |
|
Is gene rearrangement controlled or uncontrolled?
|
controlled. occurs in specific order
|
|
What order do genes rearrange in?
|
H chain first, then kappa light, then lambda light chains
|
|
What is the progression of a B cell?
|
hemopoietic stem cell to lymphoid cell to proB cell (heavy completed) to preB (kappa light complete) to immature B cell (lambda complete) to Mature B cell (changes in RNA processing)
|
|
From a mature B cell how does development progress?
|
mature to memory cell OR activated by Ag, then differentiates to plasma cell then can switch isotypes or classes.
|
|
What does the J gene join?
|
join variable region with constant region
|
|
How to select ONE V region and not two or more?
|
flanking the V region DNA are recombination signal sequences (RSS)
hepatmer, 12 or 23 bp intervening sequence, then an AT-rich nonamer sequence 12/23 bp rule – a 12 bp sequence can join with a 23 bp sequence |
|
How are the genes bound?
|
D and J join first, then V joins D
|
|
What is a RAG?
|
recombination activating genes
|
|
What do RAGs do?
|
RAG enzymes bring together
the 12/23 sequences. |
|
How are functional and non-functional DNA sequences made? Note: non-functional is circular
|
V(D)J recombinase – the complex of enzymes important in recognizing and excising the intervening sequences (looping out)
|
|
What are types of recombinases that are expressed only in B and T cells? What do they do?
|
RAG1 and RAG2 – recombinase activating genes
expressed only in B and T cells “recognize” and bring together the RSS other components of VDJ recombinase are expressed in other cells (helpful in DNA repair) DNA ligase, DNA-dependent protein kinase, etc. |
|
What does Tdt do?
|
Terminal deoxynucleotidyl transferase (Tdt)
adds back nucleotides in the “joining” region Non-germline bases (= N nucleotides) |
|
Why are IgM and IgD expressed first?
|
they are the constant region sequences closest to the VDJ sequences.
|
|
Do light chains have D regions?
|
no
|
|
How many heavy and light chains will a B cell express?
How many alleles do humans have for IgH? IgL? |
One of each.
four for IgL and 2 for IgH 2 for kappa and 2 for lambda Can express maternal/maternal; maternal/paternal; or paternal/paternal combinations. |
|
How many heavy chain options are there for V, D, andJ?
|
65 VH, 27 DH, 6 JH
|
|
What happened in the following ex: VH32 with DH15 with JH2 OR VH32 with DH8 with JH2 ?
|
Combinatorial V-(D)-J joining--Generation of Diversity - Ig
|
|
Does the Ag bind to the heavy chain or light chain?
|
BOTH--
either one or combination of the two binds to variable region of both. |
|
Are the VDJ or VJ regions bound in a precise way? What does this lead to? (2 things)
|
Junctional flexibilty. Not precise. Increases diversity. Can also produce non-productive rearrangements.
|
|
What happens in P region nucleotide addition (P addition)?
|
addition or deletion of bases by the repair enzymes
happens in the joining together of the two cut sequences essentially simultaneous with junctional flexibility |
|
What happens in N-region nucleotide addition (N-addition)
|
addition of bases by Tdt (only in H chain)
can add up to 15 bases completely random bases are added (not coded for) |
|
What happens in somatic hypermutation?
|
mutation that occurs in a mature B cell (after Ig gene rearrangement)
mutation rate = ~10-3/bp/generation (hypermutation) “normal” mutation rate = ~10-8/bp/generation |
|
What estimate has been given for # of possible Abs when junctional flexibility, P-addition, N-addition, and
somatic hypermutation are added to genetic variation? |
10 to the 16th Ab
|
|
Where is there a higher area of mutation?
|
In VDJ region
|
|
Where are mutations in heavy chains? light chains? Why?
|
Mutation in CDR3—hypervariable region. In heavy chain
Light chain in CDR1 Have most of interaction with the Ag—Variable region |
|
What is affinity maturation?
|
Ag specific B cells will then mutate and potentially generate higher and higher affinities
|