Adaptive immunity

Question 1

What are the 2 types of T cells?

Answer 1

Cytoxic T cells
- Recognise and kill virus-infected and damaged cells
- Ability to identify cells that are behaving strangely, potential cancer cells

T helper cells
- Essential to activate B cells
- Help cytoxic T cells and B cells in their immune functions
- Antigen presenting cells, present the antigen to the T helper cell and then presents the antigen to the B cell to activate it so it starts to produce antibodies
- At least 4 different sub types

Both cells in the adaptive response –> take longer to become active than innate cells. May take a few hours or days to become fully active. Innate cells become active very quickly

Question 2

What is the role of B cells?

Answer 2

Produce antibodies
Can also produce plasma cells - B cells which have ability to produce antibodies

Question 3

What are the subtypes of T helper cells?

Answer 3

Th1 –> Help with cytotoxic T cells, B cells and macrophage activation
Th2 –> Help with B cells and alternative macrophage activation
Th17 –> Help with acute inflammation (recruitment of neutrophils)
T- regulatory cells –> suppression of ongoing responses, down-regulates innate cells e.g macrophages and neutrophils. Help to modulate the inflammatory response to prevent further damage.

Question 4

What is CD4?

Answer 4

T helper cells

Question 5

What is CD8?

Answer 5

Cytotoxic T cell
- Antigen-independent development

Becomes CTL in antigen-dependent responses
- Cellular cytotoxicity
- Cytokine secretion

Question 6

What are memory cells?

Answer 6

B cells that have membrane bound proteins that are similar to antibodies.
The presenting cell proteins depend on the pathogen it is in contact with

Question 7

What is the main structure of an antibody?

Answer 7

2 heavy chains
2 light chains
Have a constant region –> a part of the antibody that doesn’t differ between antibodies
Variable region –> modifiable structure area, depending on type of amino acids used to form the protein. Depends on the pathogen it is in contact with. Specific antibodies for specific pathogens.
Recombination

Question 8

How do T helper cells help with antibody production

Answer 8

Antigen presenting cells (innate cells) passes the antigen to the T helper cell who then passes it to the B cell to activate it.
Activation of the B cells causes an up-regulations of intercellular proteins in the B cell which up-regulate different genes that code for different regions (V, J and C) to build up variable region of the antibody.

Question 9

How are antibodies produced?

Answer 9

Once B cells are activated, intracellular proteins are up-regulated which can the up-regulate different genes that code for part of the DNA that has V, J and C regions (variable regions).

Via a process known as recombination, they have the ability to combine different V, J and C regions. Antigen can have some proteins which the B cells recognise and to combine the DNA regions.
Introns are then removed in the pre-mRNA molecule to produce mRNA. That will then be released into the cytoplasm of the B cell and protein with the variable region will be made.

Question 10

What are the stages of antibody production?

Answer 10

1. Recombination
   - Deleting DNA between randomly selected V segment and J segment. To create a variable region with specific coding proteins
2. Transcription
   - Functional gene is created–> pre-mRNA molecule created
   - DNA of differentiated B cell
3. RNA processing
   - Introns removed in pre-mRNA molecule
4. Translation
   - RNA molecule created and released into the cytoplasm where is will be translated into a protein/ antibody with the specific variable region specific to the antigen that was/is present.

Question 11

What are the different types of antibodies?

Answer 11

IgG
- Account for 80% of all antibodies
- Responsible for resistance against viruses, bacteria and bacterial toxins

IgE
- Attaches as an individual molecule to the exposed surfaces of basophils and mast cells

IgD
- An individual molecule on the surfaces of B cells where it can bind antigens in the extracellular fluid. This binding can play a role in the sensitisation of B cell involved

IgM
- First class of antibody secreted after an antigen is encountered. Concentration of it declines as IgG production accelerates. The anti-A and anti-B antibodies responsible for the agglutination of incompatible blood types are IgM antibodies

IgA
- Primarily found in glandular secretions such as tears, mucus, saliva and semen.
- Theses antibodies attack pathogens before they gain access to internal tissues

Question 12

What is IgG?

Answer 12

IgG
- Account for 80% of all antibodies
- Responsible for resistance against viruses, bacteria and bacterial toxins

Question 13

What is IgM?

Answer 13

• First class of antibody secreted after an antigen is encountered. Concentration of it declines as IgG production accelerates. The anti-A and anti-B antibodies responsible for the agglutination of incompatible blood types are IgM antibodies.

Has a very different structure to other antibodies, is able to concentrate the pathogens, which facilitates the functions of other immune cells eg. t-killer cells and macrophages.

Question 14

What is IgA?

Answer 14

• Primarily found in glandular secretions such as tears, mucus, saliva and semen.
• Theses antibodies attack pathogens before they gain access to internal tissues
• Fluid soluble

Looks different to other antibody types, combination of 2 antibodies. Present in fluids

Question 15

What is IgE?

Answer 15

• Attaches as an individual molecule to the exposed surfaces of basophils and mast cells

Is associated mainly with allergic reactions. Found in the lungs skin and mucous environments.

Question 16

What are the main functions of antibodies?

Answer 16

Agglutination:
- Grouping of pathogens to facilitate function of other immune cells
- Avoid spread of pathogens to other parts of the body
- Enhances phagocytosis and reduces number of infectious units to be dealt with
- IgM, IgG and IgA

Opsonisation:
- Coating antigen with antibody enhances phagocytosis e.g. from macrophages
- IgG and IgE

Neutralisation:
- Blocks adhesion of bacteria and viruses to mucosa, lower risk of entry to cell
- Blocks active site of toxin
- IgM and IgG

Activation of complement system:
- Induce inflammation
- Cell lysis
- IgG and IgM

Inflammation:
- Disruption of cell by complement/ reactive protein attracts phagocytic and other defensive immune system cells
- Lead by innate cells, activate macrophages
- IgG, IgM and IgA (lectin complement pathway)

Antibody-dependent cell-mediated cytotoxicity:
- Antibodies attached to target cell cause destruction by non-specific immune cells
- Kills pathogen
- IgG and IgE

Question 17

What are the different blood types?
Why do they vary?

Answer 17

A, B, AB and O

Depend on the proteins on the surface of the red blood cells. Different proteins for each blood type.
Also different type of antibodies in plasma for each blood type.

Type A can have A or O blood
Type B can have B or O blood
Type AB can have any type of blood, is the universal recipient - they have both antigens in the red blood cells, but don’t have any antibodies to react to the antigens
Type O can only have O, don’t have A or B antigen on the RBC. Can donate to everyone. Depends on positive and negative. Have both types of antibodies which will target the cells in the other types of blood.

Question 18

Why are some blood types incompatible to be transfused with each other?

Answer 18

Transfusion with incompatible blood leads to destruction of the transfused cells.
Blood group antigens on red blood cells determine blood type as they either has A antigen, B antigen, A and B antigens or neither (O)

Question 19

Describe the primary and secondary antibody response

Answer 19

Primary (first infection):
Whole immune response requires activation, innate cells have to recognise the virus/ bacteria and the present it to the T cells, which then activate B cells to produce antibodies.
- Day 0 –> naive B cells
- Day 5 –> Activated B cells
- Day 10 –> antibody-secreting cells in peripheral lymphoid tissues. Antibody production at its highest
- After day 10 amount of antibodies start to decrease.
- B cells, once specific antibody has been made, will keep some some B memory cells in the circulation with the specific antibodies.

May take a few days to make enough antibodies to react against pathogens

Secondary (repeat infection):
Circulatory B memory cells recognise virus quicker and produce antibodies much quicker.
- Day 5 –> peak antibody production
- Have higher ability to produce antibodies the second time
- Quicker reaction
- Increase number of memory cells
- 3rd response will be even quicker –> in healthy people

Combination of innate and adaptive response

Question 20

What are the different types of vaccine?

Answer 20

Whole agent vaccine
- Uses a whole non-virulent microorganism, very similar to the pathogen they are targeting
- Inactivated (killed)
- Activated (weakened)

Subunit vaccine
- Part of product of microorganism
- Use of adjuvants (that are no part of the pathogen) that increase effectiveness of the vaccine
- Safer than attenuated vaccine –> a weakened form of the virus which can still grow and replicate but does not cause illness

Question 21

What is a vaccine?

Answer 21

A suspension of microorganisms that induce antibody production to protect against disease

Question 22

What are some types of component/ subunit vaccines?

Answer 22

Protein subunit
- Protein from the pathogen only

Virus-like particles
- Proteins that mimic the pathogen itself

DNA based & RNA based
- Genetic material from the pathogen only
- e.g. Moderna, Pfizer

Non-replicating viral vector
- Another virus that cannot copy itself carries the pathogens genes
- e.g. Oxford, AstraZeneca, Jansen

Replicating viral vector
- Another virus that can copy itself carries the pathogens genes

Question 23

What the types of whole vaccines?

Answer 23

Inactivated
- Killed pathogen that cannot replicate itself
- e.g. Chinese vaccine to Covid-19

Live-attenuated
- Weakened form of the pathogen

Question 24

What is the response to the RNA based vaccine

Answer 24

Innate immune cells can identify the RNA molecules as a foreign particle then innate cells communicate this to T helper cells which activate B cells to begin antibody production.
The antibodies are in place ready incase of infection from that pathogen

Question 25

What can the vaccine type cause variation on?

Answer 25

Storage
Length of time and temperature

RNA
- -25->-15’ for 7 months

Pfizer
- -80 - -60 for 6 months

Chinese
- 2-8’

Can make vaccine availability difficult as require conditions for each type of vaccine

Question 26

What is the main role of vaccines?

Answer 26

To speed up the immune response to pathogens and reduce the damage of the infection on key organs.

E.g. Covid-19 and lung damage –> quicker reaction means less risk of damage. Important for those at risk of certain organ damage/infection.

Reducing the time the pathogen is active in the body, can reduce both damage and side effects of the infection.

Question 27

What are secondary immuno-deficiencies?

Answer 27

When the immune system is weakened by another treatment or illness.
Acquired immunodeficiency as a result of disease or environmental factors.
e.g. AIDS

Question 28

What defects occur if T/B cells are missing or dysfunctional?

Answer 28

Primary immunodeficiencies
- immune system does not work properly
- can be due to a genetic disorder

Secondary immunodeficiencies
- when the immune system is weakened by another treatment or illness
- acquired immunodeficiency as a result of disease or environmental factors
- e.g. AIDS –> HIV which targets T helper cells –> missing B cell activation and compromising immune response. Infections that don’t usually cause that much harm can severely harm those with HIV. No vaccine for HIV however there are some pharmacological therapies which reduce the replication of the virus in the body to help control the growth of the virus and the effect it has on T-cells. Improves quality of life.

First and second line of defence is not enough to protect the body from a lot of different pathogens. Can get recurrent infections if missing these cells.

Question 29

Why is the adaptive immune response important?

Answer 29

Provides specific and sustained response with memory against a wide range of antigens on a variety of pathogens.

Question 30

How does HIV affect the immune system?
Is there anything to prevent its actions?

Answer 30

AIDS –> HIV which targets T helper cells –> missing B cell activation and compromising immune response. Infections that don’t usually cause that much harm can severely harm those with HIV. No vaccine for HIV however there are some pharmacological therapies which reduce the replication of the virus in the body to help control the growth of the virus and the effect it has on T-cells. Improves quality of life.

Question 31

What are pathogen associated molecular patterns (PAMPs)?

Answer 31

Some compounds found on bacteria, fungus, viruses etc that are not common in the human body e.g. Peptidoglycans, lipolysaccharides, glyolipids (bacteria), Zymosan (fungus), ssRNA (virus)
Immune cells recognise these compounds and then activate the inflammatory response, produce cytokines and activate T and B cells.
Innate cells have sensitivity to these compounds.

Presence of some compounds of microbe origin that are not present in the human body which when recognised by immune cells lead to an immune response

Question 32

What are damage associated molecular patterns (DAMPs)?

Answer 32

When there is some damage which causes an immune response.
Damaged cells can release intracellular proteins out of the cell, so the immune cells identify these molecules which are not supposed to be in the interstitial space.
E.g. DNA from cell that moves out of the cell after damage, can be picked up by immune cells and activate immune response.

Creatine kinase is a measure of muscle damage
e.g. in exercise training (DOMS), also a marker of heart disease from infarction - damage to heart cells causes CK to be released into the circulation

Question 33

What are pattern recognition receptors (PRRs)?

Answer 33

Proteins that are in the surface membrane of immune cells that have the ability to recognise PAMPs and DAMPs.
Have the ability to activate immune response if molecules have been identified.
Main types are CLR and TLR.

Receptors are strategically localised in the cell. They are present at the cell surface to recognise extracellular pathogens such as bacteria or fungi, in the endosomes where they sense intracellular invaders such as viruses and finally in the cytoplasm.
- links to antigen-presenting cells

Question 34

What are CLR and TLR

Answer 34

Pattern recognition receptors
Proteins in the surface of immune cells that can recognise PAMPs and DAMPs and then activate immune response.

Question 35

Describe B cell receptors

Answer 35

Similar protein structure on the cell surface to antibodies however do not detach.
Also have PRR so have the ability to recognise non-human molecules and can then activate antibody production.

Question 36

What is the major histocompatibility complex (MHC)?

Answer 36

Group of genes, usually found in chromosome 6, that code for proteins (PRR) found on the surface of cells that help the immune system recognise foreign substances.
Also known as the human leukocyte system (HLA). e.g. coeliac disease, HLA DQ2 and DQ8, expressed on dendritic cells, identifies gluten in the body as a pathogen (travel through lymphatic system and activated T cells) which initiates an immune and inflammatory response. Endogenous immune response damages gut, only way to stop this is to eliminate gluten from the diet to down-regulate dendritic cell response.

Question 37

What are class 1 MHC?

Answer 37

Found on the surface of all nucleated body cells. (90% of cells in the body eg. not RBC)
These cells, when an antigen bind to the receptors, this activate CD8, cytotoxic T cells/ T killer cells.

Identifies foreign molecule on binding which then attracts a cytotoxic cell, which then destroys the pathogen.

Question 38

What are class 2 MHC?

Answer 38

Only found on antigen-presenting cells, especially macrophages and dendritic cells. B cells also have the ability to express these types of proteins on cell surface.
They activate T helper cells, CD4 cells.

Question 39

How does MHC link to organ transplants?

Answer 39

Tissue and organ transplants MHC molecules are different among genetically non-identical individuals.
Differences in MHC molecules stimulate rejection of tissue grafts and organ transplants.
Chances of successful transplantation increase if donor and recipient MHC tissue types are well matched.
Immunosuppressive drugs facilitate transplantation.

Question 40

What is the complement system?

Answer 40

A complex system of more than 30 circulatory proteins that are linked together and in concert to help eliminate infectious microorganisms.
Specifically, the complement system causes the lysis (bursting) of foreign and infected cells, the phagocytosis of foreign particles and cell debris, and inflammation of surrounding tissue.

C3 is a circulating protein that when activated can up-regulate different immune functions and enhance inflammation, cytotoxicity and opsonisation.

The classical pathway is triggered by groups of antibodies bound to the surfaces of a microorganism. Requires days to become active as it require antibodies.

The alternative pathway is spurred into action by molecules embedded in the surface membranes of invading microorganisms and does not require the presence of antibodies. Factors B and D can activate C3

The lectin pathway is medicated by mannan-binding leptin (MBP). MBP is a protein that binds to the mannose groups found in many microbial carbohydrates but not usually found in the carbohydrates of humans.

Question 41

What is the lectin pathway?

Answer 41

The lectin pathway is medicated by mannan-binding lectin (MBP). MBP is a protein that binds to the mannose groups found in many microbial carbohydrates but not usually found in the carbohydrates of humans.
Leptin is found in lentils and pulses.

1. Lectin binds to invading cell
2. Bound lectin splits C2 into C2b and C2a and C4 into C4b and C4a
3. C2a and C4b combine and activate C3 which activates immune responses

Question 42

What are the main functions of the complement system?

Answer 42

Opsonisation and phagocytosis
- binding of c3b or c4b to microbe (opsonisation)
- recognition of bound c3b by phagocyte c3b receptor
- phagocytosis of microbe

Stimulation of inflammatory reactions
- binding od c3b to microbe, release of c3a, proteolysis of c5, releasing c5a
- recruitment and activation of leukoycytes by c5a, c3a
- destruction of microbes by leukocytes

Complement-mediated cytolysis
- binding of c3b to microbe activation of late components of complement
- formation of the membrane attack complex (mac)
- osmotic lysis of microbe

Question 43

Is the complement system part of the innate or adaptive system?

Answer 43

Innate
- enhance activity of innate cells

C3 protein doesn’t have memory however can amplify the inflammatory response to help aid innate immunity.