Immunology 3 Flashcards
What are cytokines?
Small ___ ____ that regulate ___, ____, and ____
Produced __ ___ (when ____) in response to ___ ___.
Act over ___ distances and a ___ time span.
Bind to ___ ____ on cells of the immune system
Responses include ___ or ___ in immune cell ____ and ____ out of the ___ and into ____.
Other names for cytokines:
_____
______ (abbreviated IL-1, IL-2, etc)
_____(any cytokine that induces cell _____)
What are cytokines?
Small secreted proteins that regulate immunity, inflammation, and hematopoiesis.
Produced de novo (when needed) in response to immune stimulus.
Act over short distances and a short time span.
Bind to specific receptors on cells of the immune system
Responses include increase or decrease in immune cell proliferation and migration out of the blood and into tissues.
Other names for cytokines:
Lymphokines
Interleukins (abbreviated IL-1, IL-2, etc)
Chemokines (any cytokine that induces cell migration)
Four ways cytokines function
1) ____: ___ cytokine can have ____ different effects
2) _____: ___ cytokines can have the ___ activity
3) ___: _ cytokines working ____ having a ____ effect
4) ____: _ cytokines working___each other.
Four ways cytokines function
1) Pleiotropy: one cytokine can have multiple different effects
2) Redundancy: Multiple cytokines can have the same activity
3) Synergy: 2 cytokines working together having a beneficial effect
4) Antagonism: 2 cytokines working against each other.
Some important cytokines and what they do
- ___ and ___: ___ ___ for __ cells
- Proinflammatory cytokines (promote inflammation):
- ____
- ___
- ___ ___ ___ ___ ___
- ___ ____ ___
- Immunosuppressive cytokines (shut-down inflammation):
- ___
- ___ ___ __ ___ ___
Some important cytokines and what they do
IL-2 and IL-4: growth factors for T cells
Proinflammatory cytokines (promote inflammation):
IL-1β
IL-6
TNFα tumor necrosis factor-α
IFN-γ interferon-γ
Immunosuppressive cytokines (shut-down inflammation):
IL-10
TGFβ transforming growth factor-β
Cytokines produced by Th1 and Th2 Cells and their functions
Cytokines made by Th1: Function to Activate________ immunity
Cytokines made by Th2: Function to Activate_________ immunity
Cytokines produced by Th1 and Th2 Cells and their functions
Cytokines made by Th1: Function to Activate cell-mediated immunity
Cytokines made by Th2: Function to Activate humoral immunity
Cytokines drive B cell _____ and Ig ___ ____
Cytokines drive B cell proliferation and Ig class switching
Interferon-g (IFN-g), a proinflammatory cytokine, enhances the ___ ____activity of _____
An intracellular pathogen infects a macrophage.
Proinflammatory cytokines render the macrophage ____at eliminating the pathogen.
Culture normal or activated macrophages with bacteria in a petri dish.
Fewer bacteria grow in dish with ____ macrophages.
Interferon-g (IFN-g), a proinflammatory cytokine, enhances the anti-microbial activity of macrophages
An intracellular pathogen infects a macrophage.
Proinflammatory cytokines render the macrophage better at eliminating the pathogen.
Culture normal or activated macrophages with bacteria in a petri dish.
Fewer bacteria grow in dish with activated macrophages.
What is Complement and How does it Work?
A family of ___ ____ that work together to attack ___ ____ or destroy ___ ___ cells.
Can be activated by ____ or can act ____ of antibody.
Many components of the complement system contribute to the _____ process, thus making the immune system function more effectively.
Made in____
Present in circulation ___ the ___
What is Complement and How does it Work?
A family of serum proteins that work together to attack extracellular pathogens or destroy infected tissue cells.
Can be activated by antibody or can act independent of antibody.
Many components of the complement system contribute to the inflammatory process, thus making the immune system function more effectively.
Made in liver
Present in circulation all the time
Holes made by complement in the cell membrane allow for ___ ___ to rush ___ causing the cell to ___
Holes made by complement in the cell membrane allow for extracellular fluids to rush in causing the cell to rupture.
The Classical and Alternative Complement Pathways
Three ways the complement system can be activated
___ Pathway
____ Pathway (also an alternative pathway)
____ Pathway
The Classical and Alternative Complement Pathways
Three ways the complement system can be activated
Classical Pathway
Lectin Pathway (also an alternative pathway)
Alternative Pathway
Classical Pathway
When we have a couple of ____ attaching to ____ on the ___ of a ___, the complement cascade will ___ (once it starts it will continue all the way through)
3 molecules called C1q, r and s are activated by ___ and ___
Those 3 molecules become an ___ ___…they have enzymatic activity
Whenever one of these becomes an activated enzyme it will have a line on top of it
Complex is locked in bw antibodies
Enzymes always have a substrate…something that they act on
Substrate is C4 and C2
Part of C4 is chopped off
Part of C2 is chopped off
And we get c4b2a
Pieces left over C2b and C4a
Now we have another enzyme
Next take another component C3
That gets added into the process
3b gets chopped in half by 4b2a
Along comes another complement molecule C5
C5 is chopped. C5a is released and C5b is put into the membrane
All of this is happening on the surface of the cell
Once C5b is there, a couple of molecules just start to fit together.
We get C6 and C7. They get put together with 5b.
C8 (complement 8) gets pulled over with the complex
End up with 5b678
Whole molecule of 5b678 gets surrounded by last complement molecule (C9)
That forms the ___ ___ ____.
Classical Pathway
When we have a couple of antibodies attaching to antigen on the surface of cell, the complement cascade will start (once it starts it will continue all the way through)
3 molecules called C1q, r and s are activated by antigen and antibody.
Those 3 molecules become an active enzyme…they have enzymatic activity
Whenever one of these becomes an activated enzyme it will have a line on top of it
Complex is locked in bw antibodies
Enzymes always have a substrate…something that they act on
Substrate is C4 and C2
Part of C4 is chopped off
Part of C2 is chopped off
And we get c4b2a
Pieces left over C2b and C4a
Now we have another enzyme
Next take another component C3
That gets added into the process
3b gets chopped in half by 4b2a
Along comes another complement molecule C5
C5 is chopped. C5a is released and C5b is put into the membrane
All of this is happening on the surface of the cell
Once C5b is there, a couple of molecules just start to fit together.
We get C6 and C7. They get put together with 5b.
C8 (complement 8) gets pulled over with the complex
End up with 5b678
Whole molecule of 5b678 gets surrounded by last complement molecule (C9)
That forms the Membrane Attack Complex (MAC)
The Alternative Complement Pathway
May be the ___ ____ method for eliminating infectious material because it does not require ____
It can respond ____
The Alternative Complement Pathways Feed into the Complement Cascade at Different Points
Lectin Pathway
- ___ __ ___
- (___ and___)
Alternative Pathway
- ___ ____
- (___)
The Alternative Complement Pathway
May be the most effective method for eliminating infectious material because it does not require antibody.
It can respond immediately.
The Alternative Complement Pathways Feed into the Complement Cascade at Different Points
Lectin Pathway
Microbial Cell Wall
(Glycoproteins and glycolipids)
Alternative Pathway
Microbial Surfaces
(LPS)
Initiators of the Alternative Pathway of Complement Activation
Initiators of the Alternative Pathway of Complement Activation
Gram-positive and gram-negative bacteria
LPS from gram-negative bacteria
Teichoic acid (gram-positive bacteria)
Fungal and yeast cell walls (zymosan)
Some viruses
Some tumor cells
Parasites (trypanosomes)
Biological Effects Mediated by Complement Products of the Complement Cascade
Contribution to the _____ response
- ___ ___ ___ ___
_____of particulate ____, increasing their _____
- ___ ___
Biological Effects Mediated by Complement Products of the Complement Cascade
Contribution to the inflammatory response
C3a, C4a, C5a, C3c
Opsinization of particulate antigens, increasing their phagocytosis
C3b, C4b
Clinical Correlation: Four ways complement contributes to the immune response
- ____: the complement pathway itself
- _____: enhancement of phagocytosis
- ___ of the ___ ___:
- Extravasation: the process of leukocyte ____ out of the ___ into ___ spaces.
- ___ of ___ ____
Clinical Correlation: Four ways complement contributes to the immune response
Lysis is the complement pathway itself
Opsonization: enhancement of phagocytosis
Activation of inflammatory response:
Extravasation: the process of leukocyte migration out of the blood into tissue spaces.
Clearance of immune complexes
Clinical Correlation: The C3b fragment is particularly important for _____ of infectious material.
C3b (and Ab) attach to ____
C3b attaches to ____ on ____
Bacteria are rapidly ___
Clinical Correlation: The C3b fragment is particularly important for opsonization of infectious material.
C3b (and Ab) attach to bacteria.
C3b attaches to receptors on phagocytes.
Bacteria are rapidly engulfed.
Clinical Correlation: Removal of immune-complexes from the blood is extremely important.
____ binds to an ____ in the circulation.
This can __ __ ___ in ___
The C3b fragment binds to the ___ portion of the ____
Complement receptors on ____ bind to ___
Immune complexes are transferred to ___ ___ and removed from the ___.
In __ and ___
Clinical Correlation: Removal of immune-complexes from the blood is extremely important.
Antibody binds to an antigen in the circulation.
This can clog blood vessels in kidney.
The C3b fragment binds to the Fc portion of the antibody.
Complement receptors on erythrocytes bind to C3b.
Immune complexes are transferred to phagocytic cells and removed from the circulation.
In liver and spleen
Why is Complement Important at Oral Surfaces?
Destroys ___ ___ ____, and other organisms upon ___ using ____ pathway.
Contributes to the destruction of ___ ___ ____ cells through the ___ pathway. ___ is very good at this.
Removal of pathogens and foreign antigens through _____
Promotes local _____ response. Can be either ___ or____
Chronic inflammation can result in excessive ___ ___
Why is Complement Important at Oral Surfaces?
Destroys bacterial, fungal, yeast, and other organisms upon contact using alternative pathway.
Contributes to the destruction of virus-infected tissue cells through the classical pathway. IgA is very good at this.
Removal of pathogens and foreign antigens through opsonization.
Promotes local inflammatory response. Can be either good or bad
Chronic inflammation can result in excessive tissue damage.
Generation of the immune response
The immune response is generated in the ____ lymph nodes, after antigen has been brought there by an ___
Antigen-specific_ cells and _ cells are ____ and sent out to the site of ____
Cartoon
Foreign Ag, e.g., bacteria or virus infects mucosal tissue
____ cells and ______ cells (i.e., ___s) transport___ to ___ __ ___ via blood or lymphatics
T cells and B Cells Circulate to Lymph Nodes via ___ and____
___ ____ of lymphocytes passing thru the lymph node
Activation of __ ____ T cells and B cells by ___ and____
The ones specific for that Ag will get activated
Return of activated T cells and B cells to ___ ___ via ___
Generation of the immune response
The immune response is generated in the draining lymph nodes, after antigen has been brought there by an APC.
Antigen-specific T cells and B cells are activated and sent out to the site of infection.
Cartoon
Foreign Ag, e.g., bacteria or virus infects mucosal tissue
Dendritic cells (DCs) and Langerhans cells (LCs) (i.e., APCs) transport Ag to regional lymph nodes via blood or lymphatics
T cells and B Cells Circulate to Lymph Nodes via Blood and lymphatics
Constant process of lymphocytes passing thru the lymph node
Activation of Ag-Specific T cells and B cells by DCs and LCs
The ones specific for that Ag will get activated
Return of activated T cells and B cells to infected tissue via blood
Stages in the inflammatory response
1.____
Loads of mediators of ___ ___ are released and they change the permeability of the cell wall of the ___ and ___
So they get dilated
2.___ __
___ ___ ___ thru the wall
Some of these would be B and T cells that were activated in the lymph node
They get signal to enter circulation here
3.____ of ___ ___
Stages in the inflammatory response
1.Vasodilation
Loads of mediators of vascular permeability are released and they change the permeability of the cell wall of the venules and capillaries
So they get dilated
2.Vascular permeability
Cells come in thru the wall
Some of these would be B and T cells that were activated in the lymph node
They get signal to enter circulation here
3.Accumulation of immune cells
The Cytokine/Chemokine ‘Big Picture’ is Enormously Detailed and Complex
This makes you wonder how something like inflammation can work_____without just coming apart
The Cytokine/Chemokine ‘Big Picture’ is Enormously Detailed and Complex
This makes you wonder how something like inflammation can work homeostatically without just coming apart
Cellular cooperation in the immune response
Cytotoxic T cells, Helper T Cells, B cells
Cytotoxic T cell
- ____ ____infected cells,____ infected cells and _____cells
Helper T Cell:
- Helps Killer T by Production of ____ and ____ used by the immune system
- Helps B cell by releasing ___ ___ for B cell to differentiate into plasma cell
B cell:
- Releases ___ molecules
Cellular cooperation in the immune response
Cytotoxic T cells, Helper T Cells, B cells
Cytotoxic T cell
Terminates virus infected cells, bacterium infected cells and cancer cells
Helper T Cell:
Helps Killer T by Production of cytokines and chemokines used by the immune system
Helps B cell by releasing Differentiation factors for B cell to differentiate into plasma cell
B cell:
Releases Ab molecules
Immunological memory and its role in immunity
- For the adaptive immune system to function efficiently, it must respond ____ to an antigen when it is encountered a ___ time.
- This is immunological memory.
- It is used to generate a ‘_____’ ___ _____
*
Immunological memory and its role in immunity
For the adaptive immune system to function efficiently, it must respond rapidly to an antigen when it is encountered a second time.
This is immunological memory.
It is used to generate a ‘secondary’ immune response.
Antigenic stimulation leads to ____ of __ and __ cells, referred to as ‘___ ____’, and to the generation of ‘____’ cells
Start with stem cell in ___ ____
From the stem cell we Make 4 different antibody producing cells
Each one of those has its own antigen specificity
Along comes Antigen for number2
That will cause __ ___ __ to divide and make a lot of 2 B cells
There is not expansion of 1, 3, and 4
A lot of those B cells will make____ cells. A few of them will make a _____cell.
These are the cells that are responsible for the ____ response later on
This whole thing is the ____ for T cell
The only difference is that they are not making ____
Antigenic stimulation leads to proliferation of B and T cells, referred to as ‘clonal selection’, and to the generation of ‘memory’ cells
Start with stem cell in bone marrow.
From the stem cell we Make 4 different antibody producing cells
Each one of those has its own antigen specificity
Along comes Antigen for number2
That will cause that b cell to divide and make a lot of 2 B cells
There is not expansion of 1, 3, and 4
A lot of those B cells will make plasma cells. A few of them will make a memory cell.
These are the cells that are responsible for the secondary response later on
This whole thing is the same for T cell
The only difference is that they are not making antigens
Immunoglobulin Production During a Primary and Secondary Immune Response
You have primary exposure to antigens
After some period,you will have an ____ response
This will be ____ the first time around
Then the IgM will switch over to make ___
Then hopefully got rid of antigen.
Indiv has recovered from infection
Sometime later
The secondary antigen (__ ___ a ____ time)
Two differences bw graph on right and left
1) A lot ___ ____ made second time around
2) Slope of second yellow curve is much steeper. This means that the secondary response happens more_____. This is because you have memory cells
3) Second time around, not much ___made bc most memory cells are not ___. The majority are ___. You primarily get ___ response second time around
Immunoglobulin Production During a Primary and Secondary Immune Response
You have primary exposure to antigens
After some period,you will have an antibody response
This will be IgM the first time around
Then the IgM will switch over to make IgG
Then hopefully got rid of antigen.
Indiv has recovered from infection
Sometime later
The secondary antigen (same antigen a second time)
Two differences bw graph on right and left
1) A lot more antibody made second time around
2) Slope of second yellow curve is much steeper. This means that the secondary response happens more quickly. This is because you have memory cells
3) Second time around, not much IgM made bc most memory cells are not IgM. The majority are IgG. You primarily get IgG response second time around
