Innate Immunity

Question 1

what are the two forms of immunity?

Answer 1

innate and adaptive

Question 2

what is innate immunity?

Answer 2

1. Non-specific (no memory)
2. Immediate

Question 3

what is adaptive immunity?

Answer 3

1. Specific (memory)
2. Delayed (due to specificity and memory)

Question 4

explain the life cycle of a normal infection.

Answer 4

Complement, cytokines, chemokines, phagocytes, NK cells, activation of macrophages, dendritic cells Migrate to lymph nodes to initiate adaptive immunity – immediate.
Infection is cleared specific antibody t cell dependant macrophage activation and cytotoxic cells.

Question 5

what mucosal epithelia?

Answer 5

Secretory/absorption surfaces. Location – lining externally exposed cavities of the body. e.g. Gut, lungs etc

Question 6

why do many cells secrete mucus?

Answer 6

Mucus-coated microbes find it harder to adhere to surfaces. Mucus flows over the surface continually, drawing microbes away also can trap the microbes. Have cilia associated with difficult for microbes to bind.

Question 7

what are antibacterial peptides?

Answer 7

• Small peptides.
• Include a/b-Defensins, S100As, cathepsins, cryptdins. Other proteins include lysozme, lactoferrin, phospholipase A, histatins etc. these proteins have a variety of impacts
• Secreted by epithelial cells naturally or upon stimulation such as infection.
• Most kill by damaging the microbial cell wall/membrane some of them act by lysosomal process or by scavenging up compounds such as iron or other compounds that the microbes need to grow.

Question 8

what are other physical defenses?

Answer 8

• Tight junctions between epithelial cells
• Gut enzymes
• Low/High pH
• Mechanical actions (talking or chewing preventing colonization)

Question 9

what is the complement cascade?

Answer 9

This occurs when the microbes pass through the barrier. Serum is rich in Complement proteins.

Question 10

what are the three pathways of the complement cascade?

Answer 10

the classical pathway
mannose-lectin pathway
alternative pathway.

Question 11

explain the classical pathway.

Answer 11

1. C1 proteins (C1q, C1r and C1s) associate and bind to antibody and then. Activated C1S cleaved C4 into C4a and C4b. C4b binds to the microbial surface.
2. C4b then binds C2 which is cleaved by C1s into C2a and C2b forming the complex C4b2b.
3. C3a this is released into the surrounding area where it act as an anaphylatoxin. This anaphylatoxin will stimulate inflammation so we get an increase in leaky blood vessels, bonds between the endothelial cells become loser.
4. C4b2b is an active C3 convertase cleaving C3 to C3a and C3b. the C3b binds to the microbial surface or to the convertase itself.
5. One molecule of C4B2B can cleave up to 1000 molecules of C3 to C3b. Many C3b molecules bind t the microbial surface.

Question 12

what is the mannose - binding lectin pathway?

Answer 12

• Similar to the Classical pathway
• Activated by Mannose-binding Lectin
• Mannose is a carbohydrate found on a majority of prokaryotic cells and a fair number of fungal cells. Very rare on animals cells if it is present, it is present with other carbohydrates.
• Lectin = carbohydrate-binding protein

Question 13

what is the alternative pathway?

Answer 13

The alternative pathway:
C3 undergoes spontaneous hydrolysis to C3(H20), which binds to factor B allowing it to be cleaved by factor D into Ba and Bb.
The C3(h20)Bb complex is a C3 convertase, cleaving more C3 into C3a and C3b. C3b is rapidly inactivated unless it binds to cell surface.

Question 14

what are the inflammatory mediator effects of complement?

Answer 14

Small complement-cleavage products act on blood vessels to increase vascular permeability and cell-adhesion molecules.

Increased permeability allows increased fluid leakage from blood vessels and extravasation of immunoglobulin and complement molecules.

Migration of macrophages, polymorpho-nuclear and lymphocytes is increased. Microbial activity of macrophages and PMNs is also increased.

Question 15

what is opsonisation?

Answer 15

Many microorganisms have evolved coats (very mucous) or capsules (inert) to hide from phagocytic cells.

However, phagocytic cells such as macrophages and neutrophils have receptors for active complement proteins e.g. C3b

These receptors improve binding and recognition of the pathogen and subsequent phagocytosis.

Opsonization is an immune process which uses opsonins to tag foreign pathogens for elimination by phagocytes

Question 16

what are the immune cells?

Answer 16

• T-cells - 1.0 – 2.5 x 109 cells/litre
• B-cells - ~0.3 x 109 cells/litre
• Monocytes - 0.15 – 0.6 x 109 cells/litre
• Neutrophils - 3.0 – 5.5 x 109 cells/litre

Question 17

what is the 3 main type of phagocytic cells?

Answer 17

1. Neutrophils (also called PMNs – Polymorphonuclear cells). Constitute ~75% of all immune cells in the blood
2. Monocyte/Macrophages - Monocytes in the blood, Macrophages in tissue.
3. Dendritic cells Linked with adaptive immunity

Question 18

how is pathogen recognition?

Answer 18

• Can be via opsonisation i.e. with antibodies or Complement
• Can also be via Pathogen Recognition Receptors – PRRs

Question 19

What is PRRS?

Answer 19

PRRs recognise Pathogen Associated Molecular Patterns (PAMPs)
These are ‘types’ of molecules, rather than a specific molecule – i.e. C/G rich DNA, doublestranded RNA, oligosaccharides, lipoproteins etc.
PRRs include Toll-Like Receptors (TLRs), CType Lectins (CLRs) and others.

Question 20

What is the effect of pathogen recognition?

Answer 20

Will lead to Phagocytosis.
Activate immune cell which will lead to secretion of inflammatory mediators.
Also leads to the secretion of cytokines these a molecule which communicate between different cells.

Question 21

what are cytokines?

Answer 21

Communication within the immune system is done predominantly through cytokines.

Question 22

what are the features of cytokines?

Answer 22

• Small glycoproteins
• Similar to hormones
• Unlike hormones, they are not secreted by a specific organ – secreted by a wide variety of cells
• Involved in cellular communication
• Extensively involved in both innate and adaptive immunity

Question 23

what are categories of the cytokines?

Answer 23

1. Pro-inflammatory cytokines
2. Anti-inflammatory cytokines
3. Growth factors/Colony Stimulating Factors
4. Chemokines
5. Type I Interferons

Question 24

what does pro-inflammatory cytokines do?

Answer 24

Induce many of the effects associated with inflammation – e.g. activation of macrophages stimulation of inflammatory mediator release, activation of adaptive immunity, pyrexia

Include IL-1a, IL-1b, TNFa and Interferon-γ

Question 25

what does anti-inflammatory cytokines do?

Answer 25

They can mediate the adaptive immune response.

• Include IL-4 and TGF-b

Question 26

what does growth factors do?

Answer 26

Important in development of immune cells
* CSFs stimulate differentiation into different cell types
* Growth factors stimulate cell growth!

Question 27

what does chemokines do?

Answer 27

• Attract/recruit immune cells to the site of infection or inflammation
• Different chemokines attract different cell types

Question 28

what cells produce type 1 interferons?

Answer 28

Produced by all cells in response to viral infection.

Question 29

what do type 1 interferons?

Answer 29

1. Render surrounding cells non-permisive to infection/viral replication
   2.Activate immune cells to destroy the infected cell

Question 30

what is the timeline of infection?

Answer 30

1. Physical barrier – e.g. Epithelium
2. Natural humoral components – e.g. Antimicrobial peptides, Complement
3. Pathogen recognition by Pattern Recognition Receptors on cells
4. Recruitment and activation of phagocytic cells
5. Activation of adaptive immunity