Lecture 4 - Immunity Part 1

Question 1

What organs are included in the immune system?

Answer 1

Thymus
Lymph Nodes (& vessels)
Bone Marrow
Spleen
Tonsils
Mucous Membranes
Skin

Question 2

What can attack our immune system?

Answer 2

Microoragnisms / pathogen:
Virus
Bacteria
Fungi

Harmful Toxins:
Smoking
Mercury
Lead
Nickel

Question 3

What are the two types of immune responses?

Answer 3

1.INNATE immune response

2. ADAPTIVE (aka Acquired) immune Response

Question 4

What is an innate immune response?

Answer 4

Is always there – barriers, cellular mediators etc
Non Specific
Doesn’t produce a memory, doesn’t care what’s invading us.
Doesn’t matter if it’s a bacteria, virus or parasite- it will have the same response.
It doesn’t remember what it is.

Question 5

What is an adaptive immune response?

Answer 5

Is responsible to the specific type of organism you are being invaded by.
This is where we develop immunological memory
Where antigens (proteins) from a pathogen are presented, we remember them as being the “enemy”, so if we ever get invaded again, our body will know how to deal with it.
But this will take a while – can take a few weeks.
Being invaded by a virus, will take your body a few weeks to adapt and kill it off, so in the mean time we need the innate response to help take charge initially – until the adaptive come in.

Question 6

What are the barriers to our innate immune system?

Answer 6

SKIN - External Barrier

Mucosal Membrane – Internal Barriers

Question 7

Name orifices with mucosal membrane rather than skin?

Answer 7

Mouth
Anus
Nose
Eyeballs
Urino-genital
Ears

Question 8

How are mucosal membranes different to the skin?

Answer 8

Are different to the skin and have more vulnerability, so have adapted to withstand pathogens.
Still lined by epithelial cells, but they may not be stratified squamous, but instead single cuboidal or pseudo stratified.
But they are STILL epithelium  Epithelium is THE barrier!

Question 9

What varieties of fluids do mucosal membranes secrete?

Answer 9

such as saliva, acid and pancreatic juice (gastro-intestinal tract) and mucus (respiratory tract), which provide a defence against pathogenic micro-organisms.
These can also contain antibodies (IgA type)
The unidirectional flow of mucus results in expulsion of bacteria and also comprises a physical barrier e.g. respiratory tract, vaginal mucus.

Question 10

What is saliva comprised of?

Answer 10

99.5% mostly water,
Electrolytes
mucus,
white blood cells,
epithelial cells (which can be used to extract DNA),
glycoproteins, enzymes (such as amylase),
antimicrobial agents such as secretory IgA and lysozyme.
The enzymes found in saliva are essential in beginning the process of digestion of dietary starches and fats.

Question 11

What is gastric acid?

Answer 11

pH of gastric acid is 1.5-3.5 (pH of vinegar)
Is a mixture of HCl, KCl and NaCl acids

The acid plays a key role in digestion of:
Proteins
by activating digestive enzymes, and making ingested proteins unravel so that digestive enzymes break down the long chains of amino acids.

Question 12

What is the respiratory tract cilia/mucus?

Answer 12

Epithelium that produce mucus
Cilia within them – nose / trachea
Physiological response (reflex)
Coughing / sneezing

Smoking reduces our ability to protect us
Smoking kills off the cilia
Hacking cough  the cilia are damaged by the smoke, pathogens now entering the respiratory tract can come straight through down to the alveoli. You have removed the first line of defense, so you can only rely on the cough as a defense mechanism.
Smoke also reduces the elastic recoil in the lungs, so it’s even harder to cough things out.

Question 13

What is microbiome?

Answer 13

The body carries its own natural ‘flora’ of micro-organisms that we happily live with, which also prevent other more dangerous bugs from taking over. They are called commensals.
Antibiotics can disturb this arrangement
Can allow overgrowth of pathogenic bacteria e.g. Clostridum difficile – caused 29,000 deaths in US in 2011

Question 14

How to remember most abundant to least abundant leukocytes?

Answer 14

Never Let Monkey’s Eat Bananas
Neutrophils ; Lymphocytes (but in adaptive) ; Monocytes ; Esonophils ; Basophils

Question 15

What do Leukocytes do

Answer 15

They arrive at the site of damage or infection and either
Eat the invading organisms by a process called phagocytosis, or
Release chemicals toxic to the invader.
Remove the debris after such a interaction, and
Some of them also play a part in killing abnormal cells

Question 16

What are the roles of a Neutrophil?

Answer 16

Cytotoxic
Phagocytosis
Acute inflammatory response

Question 17

What are the roles of an Eosinophil?

Answer 17

Destruction of IgE coated parasites
Activation of type 2 T Helper cells

Question 18

What are the roles of Basophils/mast cells?

Answer 18

Trigger immediate hypersensitivity
Allergy

Question 19

What are the roles of Natural Killer (NK) cells?

Answer 19

Cytotoxic
Trigger IFN-Y production

Question 20

What are the roles of Macrophages?

Answer 20

Antigen capture
Antigen processing
Production of ROS
Increase lysosome number

Question 21

What are phagocytic cells?

Answer 21

Engulf “eat” cells
“phagocyte” umbrella term for cell eaters.
Macrophages are a large type of phagocytic cell “Big Eater”
You can get different types of phagocytic cells:
E.g. Neutrophils and monocytes are phagocytic
They are present in most tissues of the body, not just the blood
E.g. Dendritic cells found in epithelia.

Regardless of what is invading you, macrophages will:
Engulf it
Destroy it
Present it
Becomes an antigen presenting cell – which links to adaptive response.

Question 22

What are NK cells?

Answer 22

Same family as T and B cells
Best known for killing virally infected cells
NK cells respond to infection either directly:
Recognising virus infected cells
Indirectly
By interacting with dendritic cells which express Toll – like receptors.
NK cells also have the ability to sense stressed cells i.e. cells that are infected with a virus or are turning cancerous. They will seek them out and destroy them before they do any harm. Therefore, they serve as a role as the sentinels of the body.

Question 23

How does the body know whether what is invading you if foreign or not?

Answer 23

Think of it as FLAGS
Every living organism / virus is made up with proteins associated with them
They have proteins (think of it as a flag) which the body recognizes as not being one of us

When a macrophage (might be a neutrophil, monocyte etc) comes across it, it will:
Engulf it
Destroy it
Present it

The macrophage will present a fragment of the protein on its surface and becomes an antigen presenting cell.
The ‘Flag” (aka the Protein, or sugar) is the antigen.

It is now the antigen presenting cell which causes
the ADAPTIVE IMMUNE SYSTEM to
respond.

Question 24

What are the main cells of the adaptive immune system?

Answer 24

B cells and T cells

Question 25

What are B and T cells?

Answer 25

Both are Lymphocytes
Second most abundant white blood cells
Originate from the Bone Marrow
B cell leave the bone marrow as mature cells
T cells leave as immature cells and travel to the Thymus

Question 26

What are T cells?

Answer 26

T Cells leave the bone marrow as immature, and mature in the Thymus.
T –Cells at the thymus will separate into 2 sub populations:

T Helper Cells aka CD4+
Support B cell to produce Antibodies

Cytotoxic T Cells aka CD8 + or Killer T Cells
Act as Killer cells (bit like NK but more specific)
These bind to antigen presenting cells with MHC Class 1

Question 27

How to Cytotoxic T-Cells (CD8) Kill cells?

Answer 27

Cytotoxic T cells kill their targets by programming them to undergo apoptosis.
The principal mechanism through which cytotoxic T cells act is by the calcium-dependent release of specialized lytic granules upon recognition of antigen on the surface of a target cell.
Cytotoxic effector proteins that trigger apoptosis are contained in the granules of CD8 cytotoxic T cells.
As well as killing the host cell, the apoptotic mechanism may also act directly on cytosolic pathogens. For example, the nucleases that are activated in apoptosis to destroy cellular DNA can also degrade viral DNA.
Apoptosis is therefore preferable to necrosis as a means of killing infected cells; in necrosis, intact pathogens are released from the dead cell and these can continue to infect healthy cells, or can parasitize the macrophages that ingest them.

Question 28

What are B cells?

Answer 28

They are similar to macrohoages, but are specific, meaning they only attack one kind of intruder.

They create antibodies during an immune response

These Antibodies are Y- shaped proteins that are specific to each pathogen and can lock onto the surface of an invading cell and mark it for destruction by other immune cells.

Question 29

What are antibodies?

Answer 29

Aka Immunoglobulins
Large Y- Shaped Protein used by the immune system to identify & neutralize pathogens
Antibodies comprise 20% of the plasma proteins

Antibodies not only comprise regions of high diversity (antigen binding sites; FAB); they also have regions that are more consistent between molecules (constant regions; FC): the FC regions can have a variety of functions.
Antibodies have:
Specificity individually
Diversity as a group

Question 30

What are antigens?

Answer 30

Complex macromolecules (either proteins, glycoproteins or carbohydrates) that can bind to a specific antibody or T cell receptor, thus triggering and immune response.

Question 31

How do B cells work?

Answer 31

When a B cell finds a particle in the body that matches its unique receptor site, it attaches by its receptor site and digests it through a process similar to phagocytosis.
It then displays the digested viral or bacterial pieces on its cell surface which attracts Helper T cells.
If the Helper T cell also has a specific binding site that matches the digested bits on the B cell, then itknowsthat the digested particle is harmful!
If it hadn’t already been alerted (and activated) by a macrophage of the same threat, it now becomes activated.

The activated Helper T cell, in turn, activates the B cell, and this interaction causes the B cell to divide. After a few days, the young B cells will mature and differentiate into:
plasma cellsandmemory B cells.
Plasma cellsuse their machinery to produceantibodies.
Memory B cellsremain in the body and “remember” the proteins the infectious particle had. So in the future if it encounters the same particles with the same antigens then it can launch a quicker and stronger response.

Question 32

What are memory cells?

Answer 32

recognise previously encountered pathogenic organisms and then rapidly multiply by a form of natural cloning to produce large amounts of antibody.
More than 10 million varieties of antigenic site are possible.

These help form our ‘memory” of previous infections, so if we encounter it again, our immune system will remember how to fight it off!
How vaccines work!

But, can also get us into trouble with autoimmune disorders & allergies

Question 33

Plasma cells and B cells secrete immunoglobulins (antibodies).
These molecules are grouped either as?

Answer 33

IgG, IgA, IgM, IgE and IgD
Their exact function and location in the body are determined by their type.
They act by signalling the presence of an invader to other cells, which will then attack it.

Question 34

What is Ig A?

Answer 34

The main immunoglobulin in mucosal areas / secretions e.g.
gut, respiratory tract and urogenital tract, saliva, tears & breast milk.
small amounts are found in the blood.
prevents colonization by pathogens
It is able to survive in harsh conditions such as a the GI tract.

Question 35

What is Ig D?

Answer 35

Functions mainly as an antigen receptor on B cells that have not been exposed to antigens (so helps with B cell maturation)
It has been shown to activate basophils and mast cells to produce antimicrobial factors
Exact functions remain unclear.

Question 36

What is Ig E?

Answer 36

Involved in allergies!
Binds to allergens
triggers histamine release from mast cells and basophils,
Also protects against parasitic worms.

IgE’s main function is immunity to parasites such as helminths
IgE also has an essential role in type I hypersensitivity which manifests various allergic diseases such as:
allergic asthma
most types of sinusitis.
allergic rhinitis
food allergies
specific types of chronic urticaria and atopic dermatitis.
IgE also plays a pivotal role in responses to allergens, such as: anaphylactic drugs, bee stings, and antigen preparations used in desensitization immunotherapy.

Question 37

What is Ig G?

Answer 37

Most common antibody found in circulation .
provides the majority of antibody-based immunity against invading pathogens.
The only antibody capable of crossing the placenta to give passive immunity to the fetus
It is secreted in breast milk (alongside IgA) and provides immunity for the infant after birth before their own immune system develops.

Question 38

What is Ig M?

Answer 38

Expressed on the surface of B cells (monomer) and in a secreted form (pentamer) with very high binding ability.

Eliminates pathogens in the early stages of B cell-mediated immunity before there is sufficient IgG.

IgM is responsible for agglutination (clumping) of erythrocytes during a blood transfusion, if the recipient receives blood that is not compatible with their own blood type

Question 39

What are mast cells?

Answer 39

It is a type of granulocyte
They play an important role in many inflammatory settings such as:
Defence against parasitic infections
play a role in allergic reactions.
They are important in both the innate and adaptive response

There are located between the boundaries of the tissues and external environment e.g. skin and blood vessels.
They play a key part in the inflammatory response
When they become activates, they release a wide variety of inflammatory mediators
Histamine > Increase Vascular Permeability
Cytokines > Promotes tissue inflammation
Leukotrienes & Prostaglandins > Increase Vascular permeability

Question 40

What is Hapten?

Answer 40

Is a small molecule which, when combined with a larger carrier such as a protein, can elicit the production of antibodies which bind specifically to it (in the free or combined state).

In itself it can bind to an immunoglobulin, but will ONLY trigger an immune response if it is also bound to a carrier protein.

They have a role in molecular biological applications when studying immunochemical reactions.