History of Vaccination

Question 1

Why do people now live longer?

Answer 1

Better hygiene
Vaccine development
Anti-infectious drugs

Question 2

Smallpox?

Answer 2

Viral origin, pustules all over the body
Been around for centuries - documented in ancient Egypt
Natural infections = death rate of 15-30%
Variolation death rates = 2%
0% death rate from vaccination
Eradicated - last known case in Somalia, 1978

Question 3

Variolation

Answer 3

1500s - Ancient Iran, China and India
1717 - Lady Mary Wortley Montagu used it on her children for introduction to the UK
Not broadly taken up

Question 4

Vaccination

Answer 4

1796 - Edward Jenner, cowpox with smallpox
1800s - Pasteur for rabies vaccination
1928 - Fleming, penicillin

Question 5

Issues with vaccination in the modern world?

Answer 5

Antibiotics crisis

Anti-vaxxer movements

Question 6

Chronic diseases of old age?

Answer 6

Cancer
Atherosclerosis
Alzheimer's
Parkinson's
Obesity

Question 7

Stages of infection?

Answer 7

Entry into body
Replication and spread
Disease
Exit from body

Question 8

Components of the immune system?

Answer 8

Skin, gut, lungs, eyes/nose/oral cavity

Mechanical, chemical or microbiological

Question 9

What is our microbiome?

Answer 9

Competes with pathogens for food and the niche in the gut/body
Produces anti-microbial products, and some acidic substances to digest other bacteria

Question 10

Steps of infection?

Answer 10

Innate
Adherence to epithelium, local infection and penetrance to epithelium, local infection of tissues

Adaptive

Question 11

Progenitors of immune cells?

Answer 11

Common lymphoid and common myeloid progenitors

Question 12

Macrophages?

Answer 12

Phagocytes
Activate bactericidal mechanisms
Also have a secondary antigen-presenting role

Question 13

Monocytes?

Answer 13

Sentinel role in blood, scanning for pathogens

Enter infected tissues and differentiate to macrophages

Question 14

Stages of immune response?

Answer 14

1. Prevention
   Usually with epithelial cells
2. Awareness/recognition
   Phagocytes - cell-surface receptors

Question 15

Types of receptors for recognition?

Answer 15

Mannose 
Complement
Lipid
Scavenger
Dectin-1
Toll-like

Question 16

Mannose receptors?

Answer 16

C-type lectin receptors, binding mannose carbs on yeast, parasites and bacteria

Question 17

Complement receptors?

Answer 17

CR3, CR4
Recognise complement cascade in eukaryotes

LPS (lipophosphoglycans)
On bacteria, yeast

Question 18

Lipid receptors?

Answer 18

Directs immune system through metabolite/energy diversion, metabolising fats and sugars to adjust to this

Question 19

Scavenger receptors?

Answer 19

Binds LDLP, sialic acids from bacteria and yeast

Question 20

Dectin-1 receptors?

Answer 20

C-type

Binds beta-glucan structures, particularly useful for anti-fungal responses

Question 21

Toll-like receptors?

Answer 21

Phagocyte recognition of infection cues
Family of pattern recognition receptors, which recognise PAMPs and DAMPs
Activate a signalling cascade, leading to TF activation or antiviral products

Question 22

Other PRRs?

Answer 22

RLRs
Retinoic acid inducible gene (RIG) receptors, cytosolic, in viral cases
CLRs
C-type lectin Rs, mostly yeast
NLR
Nucleotide-binding domain-like Rs, also cytosolic, bacteria/viruses

Question 23

Damage receptors on phagocyctes?

Answer 23

Differentiate between good microbes and pathogens
NLRs (P1, P2, C4)
RAGE - binds products of damage
P2X7 - binds ATP

Question 24

Steps of phagocytosis?

Answer 24

Attachment, ingestion, killing, degradation

Question 25

Cytokines?

Answer 25

``` Hormone like, signalling molecules Interleukins Interferons Colony stimulating factors Tumour necrosis factor Chemokines ```

Question 26

What is the inflammasome?

Answer 26

Induced by some of the NLRs | It recruits signalling factors to initiate apoptosis through secreting active cytokines IL1B and IL18

Question 27

IL1?

Answer 27

In brain, induces fever and anorexia, somnolence

Question 28

IL6?

Answer 28

(IL1B, TNFa) Stimulates hepatocytes to produce acute phase proteins

Question 29

Mast cells?

Answer 29

Granulocytes containing chemicals for: Immediate release - histamine, heparin, enzymes Manufactured for later release - leukotrienes, prostaglandins, cytokines

Question 30

Acute phase proteins?

Answer 30

Produced from hepatocytes (epithelial cells) Fibrinogen, haptoglobulin, complement C3, mannose-binding lectins (MBL), serum amyloid, C-reactive protein (CRP), surfactant proteins e.g. opsonins

Question 31

Opsonins

Answer 31

Bind to molecule on microbe surface, marking it for phagocytes CRP, MBL, C3b, SP-A, SP-D

Question 32

Complement

Answer 32

Soluble proteins in inactive form, leading to classical, alternative or lectin pathway activation

Question 33

Actions of complement proteins?

Answer 33

Lysis of target cells C3b = chemotaxis C3a, C5d = activation of mast cells C3b = removal of antigen:antibody complexes

Question 34

Interferons?

Answer 34

Viral resistance, inhibiting their replication Activate macrophages and natural killer cells Produced by infected cells and act either paracrine or autocrine manner

Question 35

Natural killer cells

Answer 35

Produce IFNs Viral protection and tumour response Derive from common lymphoid progenitor Contain lytic granules

Question 36

Other innate cells?

Answer 36

Esinophils Basophils Innate lymphoid cells Dendritic cells