Immunology 3

Question 1

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 _____)

Answer 1

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)

Question 2

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.

Answer 2

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.

Question 3

Some important cytokines and what they do

• ___ and ___: ___ ___ for __ cells
• Proinflammatory cytokines (promote inflammation):
  
  • ____
  • ___
  • ___ ___ ___ ___ ___
  • ___ ____ ___
• Immunosuppressive cytokines (shut-down inflammation):
  
  • ___
  • ___ ___ __ ___ ___

Answer 3

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

Question 4

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

Answer 4

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

Question 5

Cytokines drive B cell _____ and Ig ___ ____

Answer 5

Cytokines drive B cell proliferation and Ig class switching

Question 6

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.

Answer 6

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.

Question 7

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 ___

Answer 7

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

Question 8

Holes made by complement in the cell membrane allow for ___ ___ to rush ___ causing the cell to ___

Answer 8

Holes made by complement in the cell membrane allow for extracellular fluids to rush in causing the cell to rupture.

Question 9

The Classical and Alternative Complement Pathways

Three ways the complement system can be activated

___ Pathway

____ Pathway (also an alternative pathway)

____ Pathway

Answer 9

The Classical and Alternative Complement Pathways

Three ways the complement system can be activated

Classical Pathway

Lectin Pathway (also an alternative pathway)

Alternative Pathway

Question 10

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 ___ ___ ____.

Answer 10

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)

Question 11

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

• ___ ____
• (___)

Answer 11

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)

Question 12

Initiators of the Alternative Pathway of Complement Activation

Answer 12

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)

Question 13

Biological Effects Mediated by Complement Products of the Complement Cascade

Contribution to the _____ response

• ___ ___ ___ ___

_____of particulate ____, increasing their _____

• ___ ___

Answer 13

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

Question 14

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 ___ ____

Answer 14

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

Question 15

Clinical Correlation: The C3b fragment is particularly important for _____ of infectious material.

C3b (and Ab) attach to ____

C3b attaches to ____ on ____

Bacteria are rapidly ___

Answer 15

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.

Question 16

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 ___

Answer 16

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

Question 17

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 ___ ___

Answer 17

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.

Question 18

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 ___

Answer 18

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

Question 19

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 ___ ___

Answer 19

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

Question 20

The Cytokine/Chemokine ‘Big Picture’ is Enormously Detailed and Complex

This makes you wonder how something like inflammation can work_____without just coming apart

Answer 20

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

Question 21

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

Answer 21

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

Question 22

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 ‘_____’ ___ _____
  *

Answer 22

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.

Question 23

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 ____

Answer 23

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

Question 24

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

Answer 24

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

Question 25

History of Smallpox Vaccination and Global Eradication

1796: The first smallpox vaccine was developed by ___ ___.

Edward Jenner (1749 – 1823)

Noted that____ did not get smallpox.

Theorized that they were protected because of something in the ____ on the ____

Much later it was determined to be ___ ___, a relative of the smallpox that is ___virulent for___. (Naturally Vaccinated)

1958: The first proposal for ___ ___ was made to the ___ ___ ___by the ____.
1966: The World Health Assembly intensified the eradication program, increased the ____ by $2.4 million per year specifically for this effort.
1967: ___ million smallpox cases in___countries with more than _ billion people in those areas.

Major reservoir was ___, particularly __ ____ countries.

Second reservoir was in ___(Bangladesh, India, Nepal, Pakistan, and Afghanistan).

Third reservoir was the____ archipelago,

Fourth reservoir was ___

Strategy for erradiation:

Identify __ ___ of smallpox. ____ household members and close contacts to break the chain of ___.

Answer 25

History of Smallpox Vaccination and Global Eradication

1796: The first smallpox vaccine was developed by Edward Jenner.

Edward Jenner (1749 – 1823)

Noted that milkmaids did not get smallpox.

Theorized that they were protected because of something in the blisters on the cows.

Much later it was determined to be cowpox virus, a relative of the smallpox that is less virulent for humans. (Naturally Vaccinated)

1958: The first proposal for global eradication was made to the World Health Assembly by the USSR.
1966: The World Health Assembly intensified the eradication program, increased the budget by $2.4 million per year specifically for this effort.
1967: 10-15 million smallpox cases in 31 countries with more than 1 billion people in those areas.

Major reservoir was Africa, particularly sub-Saharan countries.

Second reservoir was in Asia (Bangladesh, India, Nepal, Pakistan, and Afghanistan).

Third reservoir was the Indonesian archipelago,

Fourth reservoir was Brazil.

Strategy for erradiation:

Identify every case of smallpox. Vaccinate household members and close contacts to break the chain of transmission.

Question 26

1975: Smallpox persisted in the ___ of ___. Resources were poured in, including staff and transport.
1977: The world’s___ indigenous smallpox patient was identified in Merka, ___, on October 26, 1977.

Searches for ____ cases continued for 2 years, during which time thousands of rash illnesses were investigated. None proved to be smallpox.

Two cases of smallpox occurred in ____ in 1978 as a result of a___ ___. Smallpox was gone as a naturally transmitted disease.

December 9, 1979: Two years after the last case in Somalia, the World Health Organization officially certified that smallpox had been ___ ____

1980: The World Health Assembly recommended that all countries ___ routine vaccination.

Stocks of virus were given to 5 countries to prevent its use as a bioweapon

Answer 26

1975: Smallpox persisted in the Horn of Africa. Resources were poured in, including staff and transport.
1977: The world’s last indigenous smallpox patient was identified in Merka, Somalia, on October 26, 1977.

Searches for additional cases continued for 2 years, during which time thousands of rash illnesses were investigated. None proved to be smallpox.

Two cases of smallpox occurred in England in 1978 as a result of a laboratory accident. Smallpox was gone as a naturally transmitted disease.

December 9, 1979: Two years after the last case in Somalia, the World Health Organization officially certified that smallpox had been globally eradicated.

1980: The World Health Assembly recommended that all countries cease routine vaccination.

Stocks of virus were given to 5 countries to prevent its use as a bioweapon

Question 27

Successful Vaccination Campaigns

Diptheria

Polio

Inactivated killed vaccine

Oral Vaccine (live)

Answer 27

Successful Vaccination Campaigns

Diptheria

Polio

Inactivated killed vaccine

Oral Vaccine (live)

Question 28

Successful Vaccination Campaigns

Note the drop in SSPE (subacute sclerosing panencephalitis).

SSPE is a rare progressive ______ deterioration of unknown origin.

Suspected to be a late sequela of ___ ____ virus (but not rubella virus - German measles), occurring ____ years after infection.

The rubeola vaccination program began in 1963. The number of SSPE cases spontaneously ____ about 12-15 years later – suggests that SSPE may be related to ____ infection.

Believed, though not proven, that SSPE is a rare situation in which the immune system is generating an ____ reaction to the latent ____ virus infection in the ___.

Answer 28

Successful Vaccination Campaigns

Note the drop in SSPE (subacute sclerosing panencephalitis).

SSPE is a rare progressive psychoneurological deterioration of unknown origin.

Suspected to be a late sequela of rubeola measles virus (but not rubella virus - German measles), occurring 10-20 years after infection.

The rubeola vaccination program began in 1963. The number of SSPE cases spontaneously dropped about 12-15 years later – suggests that SSPE may be related to rubeola infection.

Believed, though not proven, that SSPE is a rare situation in which the immune system is generating an adverse reaction to the latent measles virus infection in the brain.