Principles Immunology

Question 1

What does our immune system do?

Answer 1

Identify and eliminate micro-organisms and other harmful substances as well as abnormal cancer cells

Question 2

How is the skin a constitutive barrier of infection?

Answer 2

Tightly packed and waterproof
Low pH: 5.5
Sebaceous glands secrete hydrophobic oils lysosymes, ammonia, antimicrobial peptide

Question 3

How are mucous membranes a constitutive barrier to infection?

Answer 3

Mucous traps the bacteria
Ciliates cells moves the mucus out
Secretory IgA stops invasion
Enzymes that kill pathogens
10^14 commensal bacteria

Question 4

Ways healthcare provision can breach constitutive barriers

Answer 4

Insertion of hardware
Antibiotics - break down commensals and damage mucous membranes
Other therapeutics - anti-acids, nasal decongestants, inflammatory response

Question 5

Natural killer cells

Answer 5

Release performing protein into membrane of target cell
Cell rupture - apoptosis
NK cells will not kill healthy cells as these express specific proteins

Question 6

What is innate immunity?

Answer 6

A defence mechanism that is presence that is present from birth

Question 7

What is adaptive/acquired immunity?

Answer 7

Induced by the presence of foreign material
Can take 5-7 days to kick in
Better than innate immune system

Question 8

A defective innate immune system results in

Answer 8

No initial killing of pathogen, adaptive takes time to kick in

Question 9

Defective adaptive immune system

Answer 9

Innate immune system OK at first but can’t keep up with it

Question 10

Macrophages develop from

Answer 10

Circulating monocytes

Question 11

Dendritic cells are

Answer 11

Phagocytic

Abundant in tissues in contact with the external environment

Question 12

Mast cells

Answer 12

Single nucleus, highly granular
In tissues and soft mucosal membranes
Step in for large parasites
Activated by danger signals and pathogen
1. Degranulation
2. Gene expression

Question 13

Recognition of pathogens

Answer 13

Pathogens express signature molecules not found in humans (PAMPs)
Innate immune cells express partner receptor on the cell surface and cytoplasm (PRRs)

Question 14

Phagocytosis

Answer 14

1. Macrophages express PRRs
2. Receptor binding to PAMPs signals the formation of the phagocytic cup
3. Cup extends around the target and pinches off, forming a phagosome
4. Fusion with lysosome to form a phagolysosome
5. Debris is released into extracellular fluid
6. Pathogen-derived peptides are expressed on special cell surface receptors
7. Pro-inflammatory mediators are released

Question 15

Define opsonisation

Answer 15

The coating of pathogens by soluble factors to enhance phagocytosis

Question 16

What are interferons?

Answer 16

Matter released by infected cells as danger signals

Question 17

Define chemokinase

Answer 17

Any substance that induces a directed movement of a cell

Question 18

What can cause neutrophilia

Answer 18

TNF alpha

Question 19

What is the role of neutrophils in inflammation?

Answer 19

Involved in the initiation and maintenance of inflammation

Question 20

What is the mechanism by which neutrophils are transported out of the blood stream?

Answer 20

Transendothelial migration

Pro-inflammatory mediators cause leaky vessels and vasodilation allowing neutrophils to move to the sides

Question 21

By what mechanisms do neutrophils kill pathogens?

Answer 21

Phagocytosis
Degranulation
Neutrophil extracellular traps (NETs)

Question 22

Name two other systemic responses

Answer 22

Fevers

Acute phase response of the liver

Question 23

The acute phase response

Answer 23

Changes in plasma concentration of specific proteins in response to inflammation
Mediated by liver hepatocytes which produce acute phase proteins for example CRP

Question 24

The complement system

Answer 24

Approx. 30 proteins

When they’re triggered complement proteins can enzymatically activate other complement proteins in a cascade reaction

Question 25

Mannose binding lectin pathway

Answer 25

Human cells don’t express mannose Mannose binding lectin binds to the bacterium to form a complex that cleaves C3 C3 —> C3b and C3a

Question 26

Alternative activation pathway

Answer 26

C3b is unstable and rapidly degrades unless it binds to cell surfaces and can cause an amplification loop. Human cells have inhibitory processes that stop this, pathogens do not Downstream reaction will occur on the pathogen

Question 27

The membrane attack complex

Answer 27

The last 5 proteins in the complement cascade self associate to form a membrane attack complex (MAC) MACs insert themselves into pathogen membranes and allow extracellular salts and water to enter causing the pathogen to swell and burst

Question 28

C3b causes

Answer 28

An amplification loop, opsonisation and conversion to C5

Question 29

C3a and C5a causes

Answer 29

Acute inflammation | Anaphylotoxins

Question 30

C5b causes

Answer 30

MACs to cause pathogen killing

Question 31

B-cells

Answer 31

Mature in bone marrow Responsible for humoral immune response Produce antibodies that attack pathogens circulating in the lymph

Question 32

T cells

Answer 32

Mature in the thymus Responsible for cellular immune response Key role in Defense against intracellular pathogens CD4+ T cells are regulators of the entire immune system CD8+ T cells kill virally infected cells

Question 33

Define antibody

Answer 33

Protein that binds to one specific antigen | IgM, IgG, IgA, IgE, IgD

Question 34

Adaptive immune responses in secondary lymphoid tissues

Answer 34

1. Lymph flows into lymph nodes through the afferents lymphatic vessels bringing pathogens 2. B cells and T cells enter lymph nodes through high endothelial venues (HEV) 3. Once B cells come through HEV they go into the lymphoid follicle 4. Once T cells enter they form the T cell zone in the centre of the lymph node

Question 35

B cells need to receive to signals before they become fully active and proliferate

Answer 35

1. Antigen | 2. ‘Helper’ signals from T cells

Question 36

The germinal centre forms with...

Answer 36

Proliferation if enough B cells are in the germinal centre they differentiate to plasma cells

Question 37

Later in the germinal centre reaction, T cells help produce and secrete what...

Answer 37

``` ‘Better’ antibodies High affinity Other Ig classes Long lived plasma cells -> migrate to bone marrow Also stimulate memory cells production ```

Question 38

IgM

Answer 38

First Ig type produced and secreted during the humoral immune response

Question 39

Agglutination (immune complex formation)

Answer 39

The action of an antibody when it cross links multiple antigens creating clumps of antigens Mediated to IgM and IgG antibodies

Question 40

IgG

Answer 40

Second class produced in immune response Functions: agglutination, complement system activation, foetal immune protection, neutralisation, opsonisation, natural killer cell activation Transient low IgG levels at 6 months

Question 41

IgA

Answer 41

Second most abundant Ig type Monomeric form - present in serum Dimeric form - present in secretory fluids Neonatal defense, neutralisation

Question 42

Unlike B cells, T cells can only recognise what?

Answer 42

Peptide antigens

Question 43

Major Histocompatibility Complex (MHC) molecules

Answer 43

Displayed peptide antigen to T cells Also referred to as human leukocyte antigens (HLA) Able to present many different peptides

Question 44

Two classes of MHC molecules

Answer 44

Class I - expressed on all uncleared cells, will be located with all peptides in the cells allowing for T cells to scan it, present antigens to TD8+ T cells Class II - expressed only on antigen presenting cells, present peptide antigen to TD4+ T cells

Question 45

TH0

Answer 45

Result from cell proliferation, produce IL-2 to promote proliferation

Question 46

TH1

Answer 46

TH0 can differentiate into TH1 enter blood to get to the site of infection and produce IFN gamma if cell presenting antigen is found IFN gamma forms cell death

Question 47

TFH

Answer 47

Migrates into B cell zone Can help B cells become fully activated by producing co-stimulators molecules Tell B cells to differentiate into memory cells

Question 48

Antigen activated CD8+ cells differentiate into killing cells

Answer 48

Cytotoxic T lymphocytes 1. Recognises and binds virus-infected cell 2. Programmes for death 3. Moves on to new target 4. Target cell dies by apoptosis