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87 Cards in this Set

  • Front
  • Back
What does the immune system defend against?
Viruses: nonliving, not cellular, NA with ptn coat
Bacteria: non-nucleated, single cell microorganism
Parasites: multicellular worms and protozoans
What kind of system is the immune system?
Dynamic and integrated network
What 2 categories can protection by the immune system be divided into?
1) Recognition
2) Response
Describe recognition
Immune system can distinguish between self and nonself
Can recognize molecular patterns that characterize and rapidly deal with gps of pathogens
Can detect subtle chemical differences between pathogens
Describe the immune response
Immune recognition triggers an effector response that elimiates/neutralizes the invader
-> Get a variety of effector fcts suited to the disposal of the particular pathogen
How can the I.S. distinguish btw self and nonself?
The body's cells have unique markers (MHC)
MHC identifies the cell as self
What is self tolerance?
Ability of the I.S to attack abnormal or foreign cells but spare our own normal cells
What are non-self markers?
Molcules o the surface of foreign or abormal cells or particles that act as flags to the immune system as "nonself" (like for graft rejection)
What is MHC?
Set of genes that encode for Ag presenting ptns
Class I and II
They present different peptides from self/nonself Ag
Where is MHC I?
On every nucleated cell in the body (.: not on RBCs)
Which cells rec'z MHC I?
NK cells
CD8 T cells (CTL)
Which cells express MHC II?
on professional APCs
Which cells recognize MHC II?
CD4 (Th cells)
What is the role of MHC ptns?
Bind small pepties and preset them at the cell surface for the inspection of the TCR
Describe the innate immune system
First line of defense
Prevents most infections or eliminates them within a few hours
Recognition elements of this system distinguish self and pathogens
It is not specialized to distinguish small differences in foreign molecules
Nonspecific host defeces that exist before infection
What are the mechanisms of innate immunity?
1) Anatomic
2) Physiologic
3) Endocytotic}
4) Phagocytic}
5) Inflammatory
How does adaptive immunity develop?
In response to infection
Adapts to recognize, eliminate and remember foreign elements
->Adaptive immunity depends on innate immunity and begins a few days after the initial infection
What is adaptive immunity?
The comprehensive second line of defence that eliminates pathoges that evade the innate system or persist anyways
Which cells mediate the adaptive immune response?
Lymphocytes:
B and T cells
Are the innate and adaptive I.S.'s independent of each other?
No
Highly interactive and cooperative system
Produces a combined response that is much more effective than a singular response
What characterizes the adaptive immune system?
Adaptive has:
Antigenic specificity
Diversity
Memory* (unlike innate)
Self/nonself recognition
What does memory ensure?
If infected with same pathogen a second, adaptive immune response will be faster the second time (innate response will stay the same)
Compare innate and adaptive:
Response time
I: hours
A: days
Compare innate and adaptive:
Specificity
I: limited and fixed
A: highly diverse, improves during course of immune response
Compare innate and adaptive:
Response to repeat infection
I:identical to primary response
A: much more rapid that primary response
Compare innate and adaptive:
Major components
I: Barrier (skin), phagocytes, pattern recognition molecules
A: Lymphocytes, Ag-specific receptors, Ab
Compare innate and adaptive:
Diversity
I: Limited number of germline enoded receptors
A: Highly diverse, large number of receptors from genetic recombination (TCR/Ig)
Compare innate and adaptive:
Memory responses
I: None
A: Persistent memory, with faster responses on susequent infection
Compare innate and adaptive:
Self/non-self discrimination
I: Perfect, no microbe-specific patters in host
A: very good, but can have a failure of self/nonself discrimination that results in autoimmune disease
Compare innate and adaptive:
Soluble components of blood or tissue fluids
I: many microbial peptides/ptns
A: Ab
How are subsets of lymphocytes defined?
By cluster desigation (D) surface markers that the cells carry (ex: CD4, CD8)
What are the Ag receptors of adaptive immunity?
-Ab, secreted or BCR
-TCR
What is the link between innate and adaptive immunity?
professional APCs
--> Especially DCs
Describe the progression of DCs.
-Immature DCs live in the peripheral tissue
-DCs migrate to the regional lymph node via the lymphatic system
-Mature DCs activate naive T-cells in lymphoid organs such as lymph nodes
Describe lymphocyte dev'l.
Lymphocytes form in the bone marrow
Stem cells follow 2 paths to become B or T cells
B cells differentiate and mature in the BM, then the spleen, where they spend the Ag-dependent part of their dev'l
Where do the T-cells dev'p?
Thymus glad process T cells that come from the BM
Where do B and T cells circulate?
lymph nodes and spleen

-> lymphocytes are densest where they devlope: BM, thymus gland, lymph nodes and spleen
How do B cells dev'p?
Pre-B cells dev'p by the first few months of life in the BM
2nd stage takes place in the spleen: activation of naive B cell after it binds a specific Ag
How do B cells defend the body?
Produce Abs that attack the pathogen (doesn't directly attack the pathogen itself)
What happens whe a B cell sees an Ag?
Differentiates into a plasma cell
Plasma cell produces Ab molecules that can combine with a specific kind of Ag
All Ab eventually enter the blood, lymph or secretions
What are Ab?
Ptns (immunoglobulins) that are secreted by activated B cells

2 heavy and 2 light chains
Each molec has 2 Ag binding sites and one complement or FcR binding site
What are the AB subclasses?
IgM
IgG
IgE
IgA
IgD
What does IgM do?
Ab that naive B cells synthesize and insert into their own plasma mb
Predominant class produced after initial contact with an antigen
What is IgG?
most abundant Ab
produced in large amts
What is IgE?
Protects vs parasitic worms with Th2
Ab mediator for common allergic responses
What is IgA?
Found in secretions of digestive, respiratory and genitourinary systems
What is IgD?
On the surface of many B cells
fct: involved in antimicrobial mechanism with basophils
What are the 3 ways in which Ab can participate in host defense?
1) Neutralization
2) Opsonization
3) Complement activation
What is neutralization?
Bacterial toxins are neutralized by Abs so that they can't attach to anything and are then ingested by macrophages
What is opsonization?
The bacterial toxin is completely covered with Ab and is then ingested by macrophages
What is complement activation?
Bacteria in plasma are surrouded by Ab which activate complement which causes lysis ad ingestion of the bacteria
What is the B cell primary response?
Initial encouter with a specific Ag and release of specific Ab that reaches its peak in a few days
Formation of B memory cells
What is the B cell secondary response?
Later encouter with the same Ag triggeres a much quicker response
B memory cells rapidly divide, making more plasma cells ad Abs
Why are the vaccines generated based o B cells and not T cells?
We don't have required control of intracellular region
Hard to generate intracellular vaccines because we don't know what's going on
Describe immunization.
Active immunity can be established by vaccination
Inject patient with attenuated/dead form of the pathogen adjuvant
What is the point of immunization?
Triggers formation of Ab ad memory B cells
Why are booster shots required?
To keep the Ab titer high/inc titerss
After secondary vaccine, have much higher titer of Ab compared to after the initial vaccination
What are the 2 main populations of T cells?
CD4+
CD8+
What happens to developing T cells in the thymus?
get both CD4+ and CD8+
-> double positive cells
->eventually lose one of these to just be just CD4+ or CD8+
What are CD4+ cells?
CD8+?
CD4+: Th-cells
CD8+: Cyt T-cells
What do T cells do?
directly attack a pathogen
-> Cell mediated immunity
What are the effector molec of CD8+ cells?
Perforin
Grazyme
Granulysin
Fas ligands
(also: IFN-y, LT-a, TNF-a)
What do Th1 cells activate?
With what molec?
Macrophages
IFN-y
GM-CSF
TNF-a
CD40L
Fas ligad
(also: IL3,LT-a, CXCL2)
Important inflammatory response
CD40 regularly produces cytokines
What do Th2 cells activate? Effectors?
B-cells
IL-4/5/13
CD ligand
(also: IL-2/10. G-CSF, TGF-CCL11, CCL17/TARC)
What is Th17 for?
inflammatory reponse
What does Th17 do?
neutrophil recruitment
IL-17a/R-17f
IL-6
(also: TNFa, CXL1, GROa)
What do Treg cells do?
expresss anti-inflam cytokines
IL-10
TGF-b
(Also:GM-SF)
Describe T cell activation
naive T cell activated when an APC binds to its receptor:TCR
->this causes it to rapidly divide into clones of the same T cells
-the cells of these clones differentiate into effector ad memory cells
What are the 2 signals required for T cell activation?
signal 1: Interaction btw TCR amd MHC
signal 2: costimulatory signal btw CD28 (on T cell) and B7 (on APC)
How are CD4+ cells activated? (Th cells)
Cell activation initiate by interaction of TCR-CD3 with Ag-MHC II on the surface of APC
This starts a cascade of events in the T cell that results in the growth and prolif of the T cell
This is due to inc of IL-2 secretion by the T-cells ad inc of IL-2 receptors on the T cell surface
What is IL-2?
Potent T cell growth cytokine
Works in an autocrine manner to promote growth, prolif and diff of the T ell
What happens if there is no Ag & .: no Ag-MHC II interaction with the TCR?
If only co-stimulatory signal, there is no response
What happens if there is no costimulation? (only Ag-MHC II interaction with TCR)
No activation
T cell becomes unresponsive (anergic)
What happens if there is Ag-MHC II interaction with the TCR and a costimulatory signal?
Get T ell activation
What is the main role of CD8+ T cells (CTLs)?
Kill cells
What is required on cells so that they aren't killed by CTLs?
MHC I
->Tc cel rec'z and destroys self cells that have been altered or infected
How is Tc cell activated?
1) TCR on CD8+ has to interact with an antigen-MHC I on the surface of a target cell
2) CD8+ T cell must be stimulated by cytokines (especially IL-2)
What suppliesTc cells with IL2?
Activated Th cells
Describe cell death by CD8+ T cells?
CTL rec'z ad binds virus infected cells
CTL programs target for death, induing DNA fragmentation
CTL migrates to new target
Target cell dies by apoptosis
How does a Tc cell kill a tumour cell?
1) Adheres to the cell
2)releases perforin, which forms ringlike holes in the tumour cell's mb and granzymes pass through these rings to trigger apoptosis
What do Tc cells release? Why?
Lymphotoxins perforin and granzyme to kill cells
What do Th cells do?
Regulate the fct of B cells, T cells, phagocytes and other leukocytes
What do suppresor T cells do?
They are regulatory T cells that suppress lymphocyte fct, .: regulating immunity and promoting self tolerance
What kind of immuity do T cells help produce?
Cell mediated immunity
(and adaptive immunity in general)
What kind of immunity are B cells involved in?
Ab-mediated (humoral) immunity
What are the stages of adaptive immunity?
-Recognition of Ag
-Activation of lymphocytes
-Effector phase (immune attack)
-Decline of Ag causes lymphocyte death (homeostatic balance)
-Memory cells remain for later response if needed
Why is homeostatic balance required?
If not controlled, you could die of an inflamatory response rather than an infection
Need to be able to turn off the system as well