INNATE IMMUNITY

06/16/2021
By:

Aryaldy Zulkarnaini

Alergy Immunology Department

2015
 INNATE IMMUNITY
Anatomical barriers

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epidermis, dermis, cilia, cough, sneeze,
outward flow of urine

Chemical barriers
psoriasin on skin, acid pH of stomach,
lysozyme in tears

But some organisms can evade these barriers,

e.g., by attaching firmly to epithelial cells
by fimbriae or pili 2
 Vertebrates - Two Systems of Immunity

1. Innate immunity (early in infection)

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physical, chemical, cellular barriers

2. Adaptive immunity (or acquired immunity) -

specific response by B and T lymphocytes

memory; future exposures quicker and

more vigorous

“sensors” = specific antibodies (Ab’s) and

T cell receptors (TCR’s) 3
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p. 53
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 Connections Between Innate and
Adaptive Immunity

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Invaders must be sensed and destroyed

Invaders are recognized by soluble or membrane-

bound molecules

These molecules recognize broad structural

motifs that are in germs, but not in self

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 PRRs and PAMPs

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PRRs = Pattern Recognition Receptors

PAMPs = Pathogen-Associated Molecular

Patterns

- combinations of sugars, certain proteins,

some lipid-bearing molecules, and some
nucleic acid motifs

- found only on microbes, never on self

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In contrast, Ab’s and TCR’s of adaptive

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immunity recognize finer details of
molecular structure

Summary:

PRRs recognize broad, essential motifs,

present on many groups of microbes;

Ab’s and T-cells recognize fine differences

among different microbes
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Examples of soluble mediators of innate immunity

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1. Mannose-binding lectin (MBL)

2. C-reactive protein (CRP)

When these bind to microbes with PAMPs they

recognize, the complement system may be
activated to opsonize microbes or lyse them

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p. 58
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Dendritic cell and macrophages have Toll-like
receptors (TLRs) which detect microbial products

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11 discovered in humans, 12 in mice

When TLR combines with microbe, macrophage:

-has increased phagocytic activity
-makes toxic chemicals
-makes cytokines, like IL-1, IL-6, TNF-alpha
-thus inflammatory response is induced

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Immature dendritic cells internalize antigen,

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process it, mature, migrate to lymph node, and
present processed Ag to T cells for adaptive
immune response.

Dendritic cells also secrete a variety of cytokines that

promote inflammation.

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Defensive mechanisms include :

1) Innate immunity (Natural or Non specific)

2) Acquired immunity (Adaptive or Specific)

Cell-mediated immunity Humoral immunity

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 COMPONENT OF INNATE IMMUNITY

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Innate Immune system

First line Second line

1) Mechanical barriers A- cells
2) Chemical & biochemical inhibitors 1- Natural killer
3) Normal flora 2- Phagocytes
B- Soluble factors
C- Inflammatory
barriers 19
FIRST LINE

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1) Mechanical barriers
- Intact skin
- Mucous coat
- Mucous secretion
- Blinking reflex and tears
- The hair at the nares
- Coughing and sneezing reflex

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 FIRST LINE
2) Chemical & biochemical inhibitors

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- Sweet and sebaceous secretion

- Hydrolytic enzymes in saliva

- HCl of the stomach

- Proteolytic enzyme in small intestine

- Lysozyme in tears

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- Acidic pH in the adult vagina
FIRST LINE

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3) Normal bacterial flora

- Competition for essential nutrients

- Production of inhibitory substances

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 SECOND LINE
A) cells

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1- Natural killer (NK)
Definition: Large granular lymphocytes
Innate cytotoxic lymphocytes

Source : Bon marrow precursors

Location : 10% or 15% of lymphocytes in peripheral blood

1% or 2% of lymphocytes in spleen

Tumor cells
Function : Cytotoxic for Viral infected cells
Bacterial, fungal, parasitic infection

Responsible for antibody–dependent cell 23

mediated cytotoxicity (ADCC)

 SECOND LINE
2- Phagocytes

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Specialized cells for capture, Ingestion and destruction of invading
microorganisms

* Polymorphoniclear leucocytes, mainly neutrophils:

granulocytes circulate in blood

* Mononuclear cells (macrophages)

- Monocytes in blood

-Histocytes in connective tissues

- Fixed reticuloendothelial cells in liver spleen, lymph

nods, bon marrow 24
 SECOND LINE
B- Soluble factors

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1- Acute phase protein (Plasma protein, CRP=C reactive protein,
Fibrin.)
2- Complement (proteins in serum, body fluids)
3- Interferons (Proteins against viral infections)
4- Properdin (Complement activation)
5- Beta lysine (Antibacterial protein from Platelets)
6- Lactoferrrin,Transferrin (Iron binding protein)
7- Lactoperoxidase (Saliva & Milk)
8- Lysozyme (Hydrolyze cell wall)
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INTERFERONS

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Proteins usually produced by virally infected cells

* Types of interferons:

1- Alpha interferon Secreted by Macrophages

Induced by Viruses or Polynucleotide

2- Beta interferon Secreted by Fibroblasts, Viruses

3- Gamma interferon T- lymphocytes, Specific antigens

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INTERFERONS

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Protective action of interferons:

1) Activate T-cells

2) Activate macrophages

3) Activate NK

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 CHARACTERISTICS
CHARACTERISTICS OFOF INNATE
INNATE
AND
AND ADAPTIVE
ADAPTIVE IMMUNITY
IMMUNITY

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Innate Immunity Adaptive Immunity

Antigen independent Antigen dependent

No time lag A lag period

Not antigen specific Antigen specific

No Immunologic Development
memory of memory 28
 PHAGOCYTES:
PHAGOCYTES:
MACROPHAGES
MACROPHAGES

 phagocytosis,
intracellular and extra-
cellular killing, tissue
repair, antigen
presentation for specific
immune response
 characteristic nucleus
and CD14 membrane
marker.

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 CHARACTERISTICS
CHARACTERISTICS OF
OF
NEUTROPHIL
NEUTROPHIL GRANULES
GRANULES

primary granules secondary granules

azurophilic; characteristic specific for mature neutrophils

of young neutrophils;

contain cationic proteins, contain lysozyme, NADPH

lysozyme, defensins, oxidase, lactoferrin and B12-
proteases and
binding protein
myeloperoxidase

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INITIATION
INITIATION OF
OF PHAGOCYTOSIS
PHAGOCYTOSIS
Attachment via
ScavengerR
IgG FcR
CR
Toll-like R

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 RESPIRATORY BURST
Oxygen Dependent Myeloperoxidase
Independent Reactions
Glucose +NADP+ Pentose-P
G-6-P-dehydrogenase + NADPH
NADPH + O2 -
NADP++ O2
Cytochrome b558
-
2O + 2H+
2 H2O2 + 1O2
Superoxide dismutase
- .OH + OH- + 1O2
2O + H2O2
2

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 RESPIRATORY
RESPIRATORY
BURST
BURST
Oxygen Dependent Myeloperoxidase
dependent reactions
H2 O2 + Cl-
OCl- + H2O
myeloperoxidase
- - -
2OCL + H2O 1
O2 + Cl + H2O

-
2O2 + 2H+ H2O2 + O2-
Superoxide dismutase
2 H2 O2 -
H2O + O2
catalase
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 MEDIATORS
MEDIATORS OF
OF OXYGEN
OXYGEN
INDEPENDENT
INDEPENDENT KILLING
KILLING IN
IN THE
THE
PHAGO-LYSOSOME
PHAGO-LYSOSOME

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Effector Molecule Function
Cationic proteins (cathepsin) Damage to microbial
membranes
Lysozyme Hydrolyses mucopeptides in
the cell wall
Lactoferrin Deprives pathogens of iron
Hydrolytic enzymes (proteases) Digests killed organisms

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NITRIC
NITRIC OXIDE
OXIDE DEPENDENT
DEPENDENT
KILLING
KILLING

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TNF

TNF

Nitric Oxide
Nitric Oxide


IFN
γ

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 NON-SPECIFIC
NON-SPECIFIC KILLER
KILLER
CELLS
CELLS

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NK
NK and
and LAK
LAK cells
cells
ADCC
ADCC (K)
(K) cell
cell
They
They all
all kill
kill foreign
foreign
Activated
Activated and
and altered
altered selfself
macrophages
macrophages targets
targets
Eosinophils
Eosinophils
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NATURAL
NATURAL KILLER
KILLER (NK)
(NK) CELLS
CELLS

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 also
alsoknown
knownas
aslarge
largegranular
granular
lymphocytes
lymphocytes(LGL)
(LGL)
 kill
kill infected
infectedand
andmalignant
malignant
cells
cells
 are
areidentified
identifiedby
bythe
thepresence
presence
of
ofCD56
CD56&&CD16
CD16and
and
absence
absenceof ofCD3
CD3
 activated
activatedbybyIL2
IL2and
andIFN-γ
IFN-γto
to
become
becomeLAK LAKcells
cells
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 LYMPHOKINE
LYMPHOKINE ACTIVATED
ACTIVATED
KILLER
KILLER (LAK)
(LAK) CELL
CELL

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IFIF
NN kills transformed
kills
and malignant
malignant
cells
22
ILIL cells

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 KK CELLS
CELLS

 morphologically
morphologicallyundefined
undefined
 have
haveIgG
IgGFc
Fcreceptor
receptor
 recognize
recognizeantibody
antibodycoated
coated
targets
targets
 could
couldbe
beNK
NKcells
cells(IgG),
(IgG),
macrophages
macrophages(IgG),
(IgG),
eosinophils
eosinophils(IgE)
(IgE)or
orother
other
cells
cells(IgG)
(IgG)

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Cells of the Innate Immune Response

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 IL-8

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ADCC
 Antibody-Dependent, Cell Mediated Cytotoxicity: target cells coated with
antibody are destroyed by specialized killer cells (Type II hypersensitivity).

06/16/2021
 Cells that mediate ADCC are NK cells, macrophages, monocytes,
neutrophils, eosinophils. Killing cells express receptors for the Fc portion
of antibody coated targets.

• Recognition of antibody coated

target leads to release of lytic
enzymes.
• ADCC does not involve complement fixation or
phagocytosis.

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 06/16/2021
Thank You

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