8/13/2019 MBB245 Lec1 [Compatibility Mode](1)

1/26

MBB245 Lectures 3-5

r yn a ar r ge

(l.partridge@sheffield.ac.uk)

8/13/2019 MBB245 Lec1 [Compatibility Mode](1)

2/26

IMMUNE SYSTEM

Integrated system of cells and molecules that defends

reacts against infectious pathogens [bacteria,

viruses fun i arasites rotozoa

IMMUNE RESPONSE

Type of immune response depends on pathogen

than the host

8/13/2019 MBB245 Lec1 [Compatibility Mode](1)

3/26

IMMUNE SYSTEM

INNATE ADAPTIVE

Broad specificity Highly specific

a.k.a. acquired

Not affected by prior contact Enhanced by prior contact

Rapid response (hrs) Slower response (days-

Innate Adaptive

Both primarily involve white blood cells (leukocytes) +

soluble factors

8/13/2019 MBB245 Lec1 [Compatibility Mode](1)

4/26

8/13/2019 MBB245 Lec1 [Compatibility Mode](1)

5/26

Epithelial cells joined by t ight junctionsPhysical

Fatty

acids

Low pH

Enzymes (pepsin) L soz meChemical

l

CommensalsMicrobiological

Antibacterial peptides (defensins)

8/13/2019 MBB245 Lec1 [Compatibility Mode](1)

6/26

KERATINISED SKIN effective barrier unless breached

Wounds/cuts e.g. C.tetani

a es v rus. .

Japanese encephalit is virus

.

Papilloma virus Microsporum, trichophyton

8/13/2019 MBB245 Lec1 [Compatibility Mode](1)

7/26

MUCOSAL SURFACES

1. Gastro-Intestinal Tract (300m2)

Salmonella, Shigella, Listeria,

E.coli, Campylobacter.

Poliovirus, Rotavirus,

2. Respiratory Tract (100m2)

Strep pneumoniae

Haemophilus influenzae

Mycobacterium tuberculosis

enov r ae, n uenza v rus

8/13/2019 MBB245 Lec1 [Compatibility Mode](1)

8/26

3. Genito-urinary tract

sma sur ace area, u c ose con ac or ransm ss onof pathogens

Urinary tract infections.E.coli, others Kidneys

Treponema pallidum

e sser a gonorr oeae

Chlamydia trachomatis

HIVHSV

8/13/2019 MBB245 Lec1 [Compatibility Mode](1)

9/26

Infection through mucosal surfaces often leads toInfection through mucosal surfaces often leads to

..Secondary syphilisSecondary syphilis

SyphilisSyphilis

8/13/2019 MBB245 Lec1 [Compatibility Mode](1)

10/26

LEUKOCYTES

PHAGOCYTES

infections

8/13/2019 MBB245 Lec1 [Compatibility Mode](1)

11/26

PHAGOCYTES 2 main types:

Neutrophils

Main phagocyte in blood

Short-lived, fast-moving , 2 2 .

Long-lived (months- years)Help initiate adaptive

Brain - microglial cells

-

monocyte macrophage

Liver - Kupfer cells

(blood) (tissues often first to encounter pathogens )

8/13/2019 MBB245 Lec1 [Compatibility Mode](1)

12/26

Movement to the site of infection (chemotaxis)

En ulfment ha oc tosis

Phagosome/lysosome fusion

Various kil ling mechanisms

8/13/2019 MBB245 Lec1 [Compatibility Mode](1)

13/26

Chemotactic receptors on phagocytes

Bind CHEMOATTRACTANTS that guide phagocytes to

s es o n ec on:

- - - -. .

peptides (produced by bacteria)

e.g. C5a receptor, binds complement fragment C5a

8/13/2019 MBB245 Lec1 [Compatibility Mode](1)

14/26

Innate mechanisms - Pattern recognition receptors (PRRs)

recognise pathogen-associated molecular patterns (PAMPs)

complement components bound to pathogen

antibody bound to pathogen

8/13/2019 MBB245 Lec1 [Compatibility Mode](1)

15/26

Figure212

- conserved

- shared by manymicrobes

- distinct from self

8/13/2019 MBB245 Lec1 [Compatibility Mode](1)

16/26

PHAGOCYTOSIS

PRRs etc.

PHAGOCYTOSIS

Pseudopods fuse phagosome phagolyzosomeacid, peptides/proteins, toxicoxygen derivatives, competitors

enzymes

-

superoxide (O2-

,), hydrogen peroxide (H2O2), nitr ic oxide (NO), Freeradicals

8/13/2019 MBB245 Lec1 [Compatibility Mode](1)

17/26

NATURAL KILLER CELLS

Kill infected host cells

Im ortant in viral e. .Herpes), some intracellular

bacterial (e.g. Listeria

monocytogenes anprotozoal (e.g. Leishmania)

8/13/2019 MBB245 Lec1 [Compatibility Mode](1)

18/26

Natural killer cells recognise altered self

Killing regulated by

engagemen o

activating or

Inhibitor rece tors

recognise self MHC I

NK cells also recognise antibody bound to target cells

8/13/2019 MBB245 Lec1 [Compatibility Mode](1)

19/26

Important in inflammation

Found in tissues, especially underlying mucosal

surfaces

8/13/2019 MBB245 Lec1 [Compatibility Mode](1)

20/26

INFLAMMATION

Localised response to infection/damage

dilation of blood vessels

increased capillary permeability

8/13/2019 MBB245 Lec1 [Compatibility Mode](1)

21/26

SOLUBLE PROTEINS

Defensins

Positively charged peptides made by neutrophils

srup ac er a mem ranes

infections

Complement important in

ex race u ar n ec ons

8/13/2019 MBB245 Lec1 [Compatibility Mode](1)

22/26

INTERFERONS (IFN and IFN) induced by viral infection.

8/13/2019 MBB245 Lec1 [Compatibility Mode](1)

23/26

20 serum roteins activated via an enz me cascade. Man

components have enzyme (protease) activity.

Proenzyme 2 ENZYME 2Proenzyme 1 ENZYME 1

Proenzyme 2 ENZYME 2

Can be activated when antibod binds anti en

C1, 4, 2, 3, 5, 6, 7, 8, 9

8/13/2019 MBB245 Lec1 [Compatibility Mode](1)

24/26

There are 3 pathways of complement activation

Figure218

Central event is cleavage of complement

pro e n o genera e ragmen s a +

Complement activation has 3 major outcomes

8/13/2019 MBB245 Lec1 [Compatibility Mode](1)

25/26

Three major biological activit ies of complement:

1. ACTIVATION (phagocyte recruitment, induces inflammation)

C5a (C3a)

c emoattractants

anaphylatoxins mast

cell activation

2. OPSONIZATION

C3b

increased binding

and phagocytosis

3. CELL LYSIS

form pores in bacterial membranes

Gram ne ative

8/13/2019 MBB245 Lec1 [Compatibility Mode](1)

26/26

Membrane attack complex (C5b-C9)

Figure235

part

3of

3

Brock, Chapters 28 - 31