Cell Biology and Immunology

The immune system (Chapter 24)

Lecture 3 :
Innate immunity

1
Organization of the immune system
 Innate Immunity:
The first line of internal defense

If first barriers are broken ……….

the innate immune system comes into action:

Key features:
• Initial and rapid response against invasion by a variety of pathogens

• The response is rapid (hours) but has limited specificity

• Main components:
– Humoral: Complement system, cytokines
– Cellular: Phagocytes and Natural killer cells 3
The innate immune system is ready to
respond immediately!
Activation of the innate immune
response has 2 main functions: Phagocytosis
Lysis

Innate Elimination of “danger”

immune
system

Recognition of microbes Inflammation

Activation of adaptive
immune system

Observation of “danger”

4
 Questions

• How does the innate immune system recognize

pathogens?

• How does the innate immune system eliminate

pathogens?

• Which factors (cells and soluble factors) are involved?

• How does innate immunity activate adaptive

immunity?

5
 How are pathogens recognized by the
innate immune system?
Microbes express molecules that are not
expressed by mammals

Pathogen associated molecular

Patterns (PAMPs) à
conserved molecular motifs shared
by classes of microbes e.g

- Sugar residues (e.g.mannan,

(peptido)glycans (PG))
- Glycoproteins (GP)
- Lipoproteins ( Lipoteichoic acid
(LTA), lipopolysaccharide (LPS)
- Nucleotides (ssRNA dsDNA
unmethylated nucleotides (CpG))

6
 Pattern recognition receptors:
detection of microbes (PAMPs)
Diverse receptors to recognize PAMPs
àPattern recognition receptors
(PRR)
e.g. Mannose receptors, toll-like
receptors ( LPS, CpG, viral DNA, viral
RNA)

Each individual has of fixed variety of

PRRs (few genes, germline encoded)

Non-clonal: all cells of a lineage express

the same receptors

TLR- Toll like receptors

NLR- NOD like receptors
RLR- RIG-like receptors 7
Effects of pattern recognition receptor
activation

Pathogen Pattern
Associated Recognition kinases transcription factors
Molecular Receptor
Patterns

Effect
• Enhanced phagocytose –
• Cytokines and chemokines-
• Co-stimulatory molecules-
• Antigen presentation molecules-
• Adhesion molecules-
Significance
pathogen elimination
communication
activation of adaptive immunity
activation of adaptive immunity
cell-cell interaction
8
 CD14
MD MD M M LBP
-2 -2 LBP D -2 D -2
LPS
LR
RN
T RN
T LPS LR
RN
T
LPS RN
T
LR LR

TLR4 TLR4 TLR4 TLR4 LPS and TLR4 Signaling

R
LR

LR

R
LRRNT
LRRNT

LRRNT
LRRNT
LR

LR
R

R
BTK Y187 TAB1
TRAM TIR UbIRAK Ub
Y86
TIR Ub 1 TAKTAB2/3 Ub
TIR TIR TIR
TIR
TIRMAL
TIR P Ub DD Ub
TRIF Bcl Pellino 1
T209 Ub IRAK

Kinase
T209

Kinase
D311 10 TRAF K239 TRAF 1K239

Kinase
T342 TIFA DD
My T345T209 6 T387 6 T387

Kinase
D88 S346 K2396 Bcl Bcl
IRAK DD IRAKT387 TRAF 10 10
1 4 IRAK TIFA TIFA
P TRAF DD DD 1
TAK 6 TRIF TIR
P DD

Kinase
TRAF TRAF P
1 Ub T178 T178
3 TRIF TIR 6 P
UbUbRIP1 S526 S526
T184
TAK P P TAK
T184
TAB1 TAB1
TANK NAP1 S36 MEKK3
MEKK3 1 1
TBK IKK S36
IkBa IKKg
P
Ub
P
Ub TAB2/3
Pellino
TAB2/3Ub
Ub
1 ε IkBa NFkBNFkB
Ub
TRAFBcl TRAF
Ub
p65 p50 IKK IKK TAK Bcl
Ubc13
1 Ubc13 6 1010 6
a b Uev1A
P Uev1A
IKKg P TAB1
MALT1
MALT1
PIKK IKK P P
IRF SCF b
IKKg
P P a b 5
Ub Ub Ligase
Ub S32 P P Ub
Ub
IRF IRF Ub S36 PIKK IKK P p105
P
Ub
3 7 IkBa MEKK3 p105
SCF b
a b Tpl2 Ub Ligase
IRF P IRF P S32
S36
3 7 S276 IkBa P P P P
NFkB NFkB NFkBNFkB p38 JNK1/2 Erk 1/2 Tpl2
p65 p50 p65 p50

MIP-3 a
Il-6 Rantes
Il-12 iNOS
P IkB a COX-2 H3 HH2B
CBP/p300
P P
S276
IFN b
MCP-1
Il-1 b 4
P P P IRFIRF P P P P cIAP-1
IRF IRF NFkB NFkB TNF a cIAP-2
3 7 IRF S276 P/CAF3 7 p65 p50 CRE Fos
P IRFIRF PAc
C- C- ATF
Jun
AAAAA H4 H32A
H
P IRF IRF P 5 HAT Ac B
NFkB NFkB K122 K221
3 7 p65 p50 3 7
PRR activation à Cytokines: communication
molecules of the immune system
• Large group of small
molecules (±5-20 kD)
important for cell
communication and
signaling

• Act via receptors (high

affinity, act in picomolar
range) and change
behaviour of cells

10
PRR activation à Cytokines: communication
molecules of the immune system

• Cytokine names based on:

– Source (e.g Lymphokines)
– Function (e.g Chemokines)
– Intercellular interaction (e.g. Interleukins)

• Cytokine actions:
– Pleiotroop: One cytokine affects multiple cell types
– Redundancy: Multiple cytokines affect the same
celltypes

11
PRR activation à Cytokines: communication
molecules of the immune system

Infection

LPS (PAMP)à TLR4 (PRR)

IL-1, IL-6, TNFa Pro-inflammatory cytokines

#danger#respond

Ø Pleiotropy
e.g. activation of cells Ø Redundancy 12
 Binding of viral DNA/RNA to PRRs
results in production of type I Interferons

• Inhibition of viral replication

• Upregulation of TLR’s
• Activation of cells
Type 1 IFN: • etc.
IFNα
IFNβ
13
What kind of cells are involved in innate
immunity?

Granulo-
natural cytes
celltype monocytes/ eosinophilic mast cells dendritic cells
killer cells macrophages granulocytes

function kiling of virus- phagocytosis killing of worms release of antigen presentation

Infected cells histamins

Functions: phagocytosis, antigen presentation,

antigen transport, cytotoxicity,
cytokine mediated functions, etc.
14
 Components of innate immunity
Phagocytes 1: Granulocytes
Any cell that ingests
Phagocytes microorganisms, cells,
or other substances
“vreetcellen”

Granulocytes

- circulate in the blood

- migrate readily to site of infection

Neutrophil Eosinophil Basophil Main function:

a.k.a.
Polymorphonuclear cell - phagocytosis (eliminate)
- boost inflammation
(cytokines,prostaglandines)

15
 Components of innate immunity
Phagocytes 2: Monocytes, macrophages and dendritic
cells
Blood Tissues

Monocytes Tissue macrophages:

- connective tissue
Dendritic cells
macrophages Langerhans cells
- microglial cells (skin)
- Kupffer cells
- osteoclasts
- alveolar macrophages

function: - phagocytosis
- link pathogens to
adaptive immunity
16
 Neutrophils are the most abundant
leukocytes in the blood
Cell type Blood conc. Basic function lifespan
Red blood cells 5x106/µl, O2 and CO2 transport 120 days
45% of blood vol.

Platelets 3x105/µl clotting 10 days

Neutrophil 6,000/µl phagocytose bacteria, < 1 day in blood,

secrete inflammation 1-2 days in tissues
mediators
Eosinophil 200/µl attack parasites < 1 day in blood,
weeks in tissues

Basophil 50/µl cause rapid increases in < 1 day in blood, hours

blood vessel in tissue
permeability
lymphocyte 2,000/µl Adaptive immunity (B years
and T cells)
Monocyte 400/µl scavenge debris, days in blood,
present antigen years in tissues as
to lymphocytes macrophages
17
 Components of innate immunity
Cells: The neutrophil

• Most abundant cell of

the innate immune
system
• Most abundant cell in
acute inflammation
• Rapidly recruited to
site of infection
• Upon activation
undergo an “oxidative
burst” and degranulate

18
Components of innate immunity
Cells: The neutrophil

‘Find and destroy’

19
 Neutrophil function

• Finding the bug (i.e. move from the blood to the site of
infection)
– Rolling, adhesion and transmigration
– Chemotaxis
• Eating the bug
– Phagocytosis
• Killing the bug
– Reactive oxygen species
– Lysosomal enzymes

20
 1:Rolling

2:Adhesion

3:Transmigration

4:Chemotaxis

5:Phagocytosis

21
22
 Chemotaxis

Chemotaxis: migration along a gradient of chemotactic factors

23
 Phagocytosis: most important effector
mechanism of the innate immune system
endocytosis
receptors

recognition

endocytosis

fusion with lysosome

degradation
release of
degradation
products
24
 Phagocytosis is a receptor mediated
event
Ensures that only unwanted particles are ingested.

Opsonin Pattern
Patternrecognition
Some pathogens (e.g. recognition
receptors
Some pathogens express
receptors receptors
Encapsulated bacteria) need to surface molecules that can
be ‘tagged’ first by other directly bind to PRRs and
components of the immune trigger phagocytosis.
system (antibodies,
complement--> opsonisation)
Outside
Cell membrane
Cytoplasm Fc receptor
Complement Mannose Scavenger
receptor receptor receptor

25
Intracellular digestion by phagocytes

1.Constitutive expression of
proteolytic lysosomal enzymes

2. Activation of NADPH-oxidase (à
reactive oxygen intermediates,
respiratory burst) and iNOS (à
nitric oxide intermediates,
nitrosative burst)

26
 Reactive oxygen species
Actvated neutrophils undergo an “oxidative burst”

“Bleekwater (bleach)”
27
Neutrophil granules are loaded with
destructive enzymes
Azurophilic Specific Gelatinase Secretory
granules granules granules vesicles
CD63 CD11b/CD18 Histaminase CD11b/CD18 Alkaline phosphatase
CD68 CD15 Heparanase Cytochrome b558 CD10
Presenilin 1 CD66 Lactoferrin Diacylglycerol CD11b/CD18
Stomatin CD67 Lysozyme deacetylating CD13
V-type H+-ATPase Cytochrome b558 NGAL fMLP-R CD14
b-glycerophosphatase fMLP-R uPA Leukolysin CD16
mucopolysaccharide Fibronectin-R Sialidase NRAMP-1 CD45
a1-Antitrypsin G-proteina-subunit Transcobalamin SCAMP CR1
a-Mannosidase Laminin-R ICRISP-3 SNAP-23, -25 C1q-R
Azurocidin Leukolysin (SGP-28) uPA-R Cytochrome b558
BPI NB1 antigen Gelatinase VAMP-2 Decay-accelerating
b-Glycerophosphatase 19-kDa protein hCAP-18 V-type H+-ATPase fMLP-R
b-Glucuronidase 155-kDa protein Acetyltransferase Leukolysin
Cathepsins Rap1, Rap2 B2-microglobulin VAMP-2
Defensins SCAMP CRISP-3 V-type H+-ATPase
Elastase SNAP-23, -25 Gelatinase Plasma proteins
Lysozyme Stomatin Lysozyme
MPO Thrombospondin-R
N-acetyl-b- TNF-R
glucosaminidase uPA-R
Proteinase-3 VAMP-2
Sialidase Vitronectin-R
Ubiquitin-protein b2-Microglobulin
Collagenase

28
 Components of innate immunity:
Natural Killer cells

T-lymphocyte-like cells
without antigen receptor

- first line of defense against virally

infected cells
kill virally infected cells
produce interferons that prevent
viral replication in host cells and
activate macrophages
29
 Which circulating factors play a role in
innate immunity?
In the innate immune response many circulating factors are released or activated
which help in maximizing the response:

• cytokines various

• complement bacterial lysis,opsonisation,

inflammation

• C-reative protein (CRP) opsonisation, complement activation

Serum amyloid A (SAA)
(acute phase proteins)

30
Cytokines of the innate immune system

IFNa,b (type I IFN) inhibition of virus replication

TNFa, IL-1, IL-6* activation of cells, inflammation
IL-10* inhibition cellular response
IL-12 activation NK cells; directing
cellular responses
IFNg* (type II IFN) activation of macrophages
Chemokines (e.g. IL-8) chemotaxis, recruitment of
additional leukocytes
* Also produced during adaptive immune response

31
 Components of innate immunity
Complement system
- Humoral part of innate immunity

- Collection of circulating and

membrane-associated proteins

- Many of these are (inactive )proteolytic

enzymesà enzymatic cascade

• Can be activated by one of three

pathways

32
 Complement activation serves three
important functions

Blood vessel

1. Inflammation: recruitment
and activation of neutrophils 2. Lysis of microbes
(C3a en C5a) (membrane attack
complex)
Complement
proteins

3. Opsonisation
of microbes
(C3b)
33
 How does innate immunity link to
adaptive immunity ?
Activation of the innate immune
response has 2 main functions: Phagocytosis
Lysis

Innate Elimination of “danger”

immune
system

Recognition of microbes Inflammation

Activation of adaptive
immune system

Observation of “danger”

34
Professional antigen presenting cells:
dendritic cells
APC’s: antigen presentation and additional signals
Link innate with adaptive immunity- initiate immune reponses

T-

35
 Dendritic cells:
transport and presentation of antigen
Microbe

Antigen uptake
Phagocytosis
PRR’s and transport
Cytokines

Antigen presentation
and initiation immune
response

36
 Functions of the innate immune system
killing, inflammation & adaptive responses
Inflammation

Pro-inflammatory
micro-organisms cytokines

IL-1
TNFa
IL-6

Killing and destruction

of microbes

Activation of
the adaptive immune system 37
Innate immunity: summary key features

• First line of internal defense

against infection

• Fast (hours)

• Components:
– Complement, cytokines
(humoral)
– Cells (NK cells, phagocytes)

• Specificity: PAMPsàPRRs
(germline encoded)

• Diversity: limited (fixed variety of

PRRs)

• No memory à always responds

in the same way

38
 Next lecture

• Adaptive immunity: the slow but very specific

immune response

39
40
 Physiology and Therapy
The immune system (Chapter 24)

Lecture 4 :
Adaptive immunity

41
Organization of the immune system
 Innate immunity
direct recognition (and killing) of pathogens after infection:

first line of internal defense (simple and fast…)

why do we need adaptive immunity ?

innate immunity is insufficiently effective without

adaptive immunity

innate immunity is insufficient to cover

all pathogens

43
the importance of adaptive immunity

victim of smallpox infection

smallpox vaccination of a patient

with inappropriate T-cell function
44
To assure effectiveness and specificity, we have
different forms of immunity:

innate immunity
(BOA: immediately available but..
insufficiently equipped )

adaptive immunity
(special forces: fully equipped but...
must be mobilised and instructed)

45
 Types of adaptive immunity

• Adaptive immunity is mediated

by lymphocytes

• Two distinct types exist:

B lymphocytes
T lymphocytes
Helper T lymphocyte (CD4+)
Cytotoxic T Lymphocyte (CD8+)

• B lymphocytes mainly mediate humoral

immunity against extracellular
pathogens

• T lymphocytes mainly mediate celullar

immunity against intracellular
pathogens (intracellular bacteria,
viruses) and aid the innate immune
response 46
Lymphocytes patrol the body for intruders
Lymphocytes are generated and mature in bone
marrow (B cells) and thymus (T cells)… and
circulate through our body

47
Phases of adaptive immunity

48
 How is the adaptive immune
system able to recognize so many
diverse pathogens?

49
 Adaptive immune system:
Randomly generated unique antigen specific receptors
- many different B- and T-cells are needed to obtain a large enough
repertoire to recognize the variety of pathogens encountered
- each day, millions of new B- and T-cells are formed with new,
randomly generated receptors but for each specificity only a few exist
initially. Estimation 100x106 per day!

Antigen receptor
lymphocyte

Number of specificities is unlimited, but every

lymphocyte is monospecific !!
If this is true, does that mean that
our genome contains >100 106
genes that encode for antigen
specific receptors?

51
 Antigen receptor diversity is created by random
combinations of gene segments

Antigen receptors (BCR and TCR)

are not encoded by a single gene

Are created by random combinations

of gene segments of which multiple
copies are present
à Gene rearrangement

Estimates: 3x1011 variations

possible. Enormous diversity!!

52
 But if this is a random
process than there is a big
chance that self proteins
are also recognized and that
could be dangerous?

53
 Specificity and diversity
The clonal selection hypothesis

1. Large pool of antigen

reactive lymfocytes

2. Removal of self-reactive
lymphocytes

3. Pool of non-self reactive

lymphocytes

4. Proliferation and differentiation

of lymphocytes which react with
antigen to form a clone of effector
cells

54
Adaptive immune responses:
the problem
Small amounts of antigen,
somewhere in the body

?
T B
Rare specific B and T cells,
somewhere in the body
55
 Peripheral lymphoïd organs:
sites for initiation of adaptive immune responses

B and T lymphocytes are generated in

bone marrow and thymus… and circulate
through our body to monitor for intruders

The primary sites where pathogens and

cells of the adaptive immune system meet
are the peripheral lymphoid organs.

Antigens are concentrated in the peripheral

lymphoid organs via the blood/lymph as
free circulating antigens or transported by
phagocytes of the innate immune system

56
 Ok that’s fine, but how do
lymphocytes recognize the
pathogenic antigens?

57
 Pathogen recognition: B cells

• B lymphocytes: direct recognition

of wide variety of molecules
(proteins, carbohydrates, DNA,
etc.) by surface immunoglobulins
(BCR)

• Free antigen is passively

transported to lymphoid organs
(blood, lymph)

• Response against extracellular

(soluble) antigens
B cell receptor (BCR) à
membrane bound immunoglobulin

58
 Pathogen recognition by
T lymphocytes
• T lymphocytes indirectly
recognize parts of the pathogen
(peptide-antigens) presented by
specialized receptors : antigen
presentation

• Response against intracellular

(processed) antigens

• Antigen presentation required to

initiate cellular immune
responses and to carry out
effector functions of T-effector
cells
59
Presentation of antigens occurs via specialized receptors:
Major Histocompatibility Complex (MHC)

• Major Histocompatibilty Complex

Cell surface molecules of a cluster of genes

Originally described in transplant rejection

(histo = tissue compatibility)

Physiologically: membrane proteins that

display antigenic peptides for recognition by
T lymphocytes

Play a central role in the initiation of

immune response to protein antigens

• Two classes of MHC molecules

MHCI and MHC II

Different function in immunity

60
 Major Histocompatibility Complex
Comprises 4 million bp (0.1 % human genome) containing 200 coding loci
Chromosome 6

Class II Class III Class I

MHC class II MHC class I

• HLA-DP, DQ, DR • HLA-A, B, C
• cells of the immune system: • all cells of the body
antigen presenting cells • presentation to CD8+ T cells
• presentation to CD4+ T cells 61
 MHC locus: extensive polymorphism
MHC genes are the most polymorphic genes in our genome!
Creates diversity on population level.

Class II Class III Class I

alleles
proteins

Example: total number of combinations of MHC class I molecules possible:

817 x 263 x 486 = 104.427.306

62
MHC: extensive polymorphism

63
 Co-dominant expression of MHC
Creates diversity on the individual level.

father

mother

child

Haplotypes of parents and child Hepatocyte Dendritic cell

(of child) (of child)

64
 What is the significance of MHC
polymorphism and co-dominant expression?
At the individual level: 6 different MHCI molecules
6 different MHCII molecules

Each MHC molecule can bind and present many different

peptide antigensà maximizes the number of peptides that can
be presented à At the individual level well protected against
most pathogens

At the population level : >1017 combinations possible

Each MHC subtype has a “preference” for specific peptide

antigensà at the population level we are extremely well
protected

65
 Why do we have two types of MHC ?
Different classes of pathogens require
a different immunological approach

Cytosolic pathogens (e.g. viruses) require

a CD8 T cell (CTL) response

Extracellular pathogens (e.g. bacteria) require

a CD4+ T helper cell (Th) response

Thus, different classes of pathogens

need to be presented to immune cells
in a different way.

Extracellular pathogens are phagocytosed

à Are presented by MHCII à are seen by
CD4+ T helper cells

Intracellular pathogensà presented by MHCI

à are seen by CD8+ cytotoxic T cells (CTL)
66
Which cell types express MHC molecules?

CD4+ T lymphocyte CD8+ T lymphocyte

MHC class II MHC class I

APCs All nucleated cells

“Professional” antigen in our body!
presenting cells (APC)
that have phagocytosed Peptide of intracellular
and processed pathogens
extracellular pathogens 67
Antigen presenting cells and their function in
the immune response

68
 MHC: key properties
Feature Significance
Co-dominant expression Increased number of different MHC
Molecules that can present peptides
molecules

Polymorphic genes Different individuals are able to respond

Many different alleles To different
to different microbial
microbial peptides
peptides
present in population

MHC expressing cell types

MHC class II: CD4 T cells interact with dendritic cells

Dendritic cells macrophages and B lymfocytes to initiate
macrophages (dendritic cells) an immune response and
B cells stimulate effector functions

MHC class I CD8 T cells can kill any virus infected

All nucleated cells cell

69
Great, so now B and T lymphocytes
have recognized an antigen and
become activated?

70
T cell-mediated responses: co-stimulation

Signal 1
Antigen
recognition

Co-stimulation Signal 2
 Interaction of phagocytes with microbes:
Innate immune system alerts adaptive immunity

Pathogen

Endocytosis receptors

TLR
CD4+ T cell

Co-stimulatory molecules, MHC class II

Cytokines

72
 B cell-mediated responses: T cell help

Signal 1
Antigen
recognition

Signal 2
CD4+ T cell
Help (cytokines
Co-stimulation)

73
T and B cell activation requires (at least) two
signals

T cell:
• Signal 1: Antigen binding to TCR
in the context of MHC
• Signal 2: Co-stimulatory
receptor-ligand pairs
Example: CD28(T cell)- B7 (APC)

B cell:
• Signal 1: Antigen binding to BCR
• Signal 2: Interaction with CD4+T cell

Significance
Signal 1: ensures specificity of response
Signal 2: ensures that response is induced only when needed

74
OK, B and T lymphocyte activation
requires two signals but what do
they do to help eliminate the
pathogen?

75
 B-cell physiology

CD4 T cell
help

- B-cell encounters antigen, becomes activated and starts to proliferate

- B-cell differentiation to antibody-producing plasma cell / memory cell
- when the antigen (pathogen) is removed: B-cells die by apoptosis
Plasma cells generate and secrete antibodies

resting B-cell + antigen plasma cell

+ CD4+ T cell help
 Plasma cells produce antibodies

• Plasma cells secrete antigen specific antibodies with

same specificity as the BCR

• Antibodies are bifunctional proteins

Antigen Effector functions

binding

78
 Antibodies: Structure

Most effector function of antibodies are

mediated by the Ig heavy chain (Fc) but require
antibody binding of antigen to the variable regions

Ensures that antibody effector pathways are activated

only when needed

Antigen Common Fc region

binding irrespective of
antigen specificityà
Effector functions
 Antibodies come in different flavours
(isotypes)
Different isotypes, different functions

B cell differentiation leads to B cells

producing different specific types of
antibodies.

The type of heavy chain determines the

isotype

Different immunoglobulin heavy chain

isotypes serve distinct effector funtions
 Effector functions of antibodies

• Antibody mediated
elimination of antigens
involves a number of effector
mechanisms

• Various cellular and humoral

components of the immune
system participate
Antibody mediated opsonization, phagocytosis
and ADCC
Opsonization
and phagocytosis

Antibody dependent
cytotoxicity

82
 T-cell physiology

- T-cell encounters antigen, becomes activated and starts to proliferate

- T-cell differentiation to effector T-cell / memory T-cell
- when the antigen (pathogen) is removed: T-cells die from apoptosis
 Effector functions: T cells

CD4 T cells (helper cells): CD8 T cells (cytotoxic cells):

Production of cytokines that Direct killing of infected cell
stimulate innate immunity and through release of perforines
B cell antibody production and granzymesà apoptosis

84
CTL-effector function: “the kiss of death”
CTL-target cell conjugate formation

CTL CTL

CTL

Target cell killing

CTL
 CD4+ T lymphocyte activation:
effector cells that orchestrate immune responses
Th-cells: different sub-sets….
different cytokine signatures….
different effector functions
macrophage activation
inflammation
humoral response

immune regulation

humoral response,
allergic reactions

inflammation

Th0=naïve T cell
 Development of CD4+ T lymphocyte subsets
is determined by dendritic cells and the (cytokine)
environment
TGFβ IFNγ

FoxP3 Tbet
TGFβ
IL-12 the nature of the
Bacteria DC
infection
Viruses PRR activation determines the
Fungi
nature of the
Protozoa
immune response:
Helminths IL-6 Tailor made
immunity

GATA3 RORγT
IL-4 TGFβ

87
 Adaptive immunity: key features
Feature Mechanism Significance
B and T lymphocytes Ensures that distinct
Specificity bind and respond to pathogens elicit specific
foreign molecules responses
(antigens) via antigen
specific receptors
Very large >108 Enables immune system
Diversity to respond to a large
variety of antigens

First exposure à Leads to enhanced

Memory Generation of long lived responses to repeated
memory lymphocytes exposures of the same
antigen
Elimination of self- Prevents injury to the
Non reactivity to reactive lymphocytes host during responses to
self foreign antigens 88
 Next lecture

• Immune response pathways: the immune system

at work

– What happens when bacteria invade our body?

– What happens when a virus invades our body

for the second time?

89