MIC343

~Immunology~

Innate immunity – non specific

body defense system
Prepared by:
Ilyanie Hj. Yaacob
 Syllabus content
 Roles of the innate immunity

 Components of the innate immunity

 Innate immune response

 Innate immunity
 It is also called natural immunity.

 Immunity that is naturally present and is not due to prior sensitization to

an antigen from, for example, an infection or vaccination.

 Since it is not stimulated by specific antigens, innate immunity is

generally nonspecific.

 It involves:

i) the prevention of invasion of pathogens (by the barriers).

ii) the recognition (by the receptors) of the invaders.

iii) the response to invasion/infection.

 i) the prevention of
invasion of pathogens (by
the barriers).
ii) the recognition (by the receptors) of the invaders.
iii) the response to invasion/infection.
 Physical barrier

Skin Mucous membrane

Physical barrier

THE BARRIER

Mechanical barrier Chemical barrier

 Physical barrier
1) Skin:

 Epidermis is build up of several

layers of tightly packed epithelial
cells.

 Outer layer consists of mostly

dead cells fills with keratin, the
waterproofing protein – keratin
gives skin strength and flexibility.

 The epidermis are continuously

being sloughed off.

 The epidermis are impermeable to

foreign substances unless broken.
 Physical barrier
 Dermis is composed of connective tissue – contains blood vessels, hair
follicles, sweat glands (secrete sweat), sebaceous glands (secrete
sebum).

 Salt in sweat can inhibit growth of many microorganism (excluding

normal flora).

 Sebum is an oily substance made from fatty acids – lowers the pH of the
skin thus inhibit growth of certain microorganism.

 Hair follicles and sweat glands produce lysozyme and toxic lipids that can
kill bacteria.

 The skin is dry, acidic, and has a temperature lower than 37oC - these
conditions are not favorable to bacterial growth.
 Physical barrier
 The skin synthesize and arrange proteins with antimicrobial activity, e.g.
psoriasin (posses antibacterial activity against E. coli).

 Resident normal flora of the skin also inhibit potentially harmful microbes.

 Beneath the skin surface is skin-associated lymphoid tissue (SALT) that

contains cells for killing microbes and sampling antigens on the skin to
start adaptive immune responses against them.
 Physical barrier
2) Mucous membrane:

 Line the alimentary, respiratory and

urogenital tract, as well as eyes.

 Mucous membranes are composed of an

epithelial layer that secretes mucus, and
a connective tissue layer.

 The mucous membrane is constantly

sloughing cells to remove microbes.

 When pathogens penetrate these

membranes, the saliva, tears and
mucous secretions wash away the
pathogens.
 Physical barrier
 Mucus also:

i) contains lysozyme to degrade bacterial peptidoglycan.

ii) contains an antibody called secretory IgA that prevents microbes from
attaching to mucosal cells and traps them in the mucous.

iii) contains lactoferrin to bind iron and keep it from being used by
microbes.

iv) contains lactoperoxidase to generate toxic superoxide radicals that kill

microbes.
 Physical barrier
 Resident normal flora of the mucosa also inhibit potentially harmful
microbes.

 Beneath the mucosal membrane is mucosa-associated lymphoid tissue

(MALT) with these functions:

i) contains cells for killing microbes

ii) sampling antigens on the mucosa to start adaptive immune responses

against them.

 In the lower respiratory tract, the mucous membrane is covered by cilia –

the movement of cilia propels mucous from these tracts.
 Physical barrier

Then why you still get flu?

 Evolution of the microorganisms – e.g. virus have a surface molecule,

enables them to attach firmly to cells in the mucous membrane.

 When this happens, the receptors of innate immunity will detect the
infection and trigger a defense against it.
 Mechanical barrier
1) Cilia:

 Cilia on the surface of the epithelial cells propels

mucus and trapped microbes upwards towards the
throat where it is swallowed - this is sometimes
called the tracheal toilet.

2) The cough and sneeze reflex.

 Coughing and sneezing removes mucus and

trapped microbes from the respiratory tract.
 Mechanical barrier

3) Peristalsis, vomiting and diarrhea.

 These processes remove pathogens and

toxins in the gastrointestinal tract.

4) Flow of urine.

 This process remove pathogens and

toxins in the urogenital tract.
 Chemical barrier
1) Hydrochloric acid:

 Together with enzymes found in gastric secretions destroy microbes that

are swallowed.

2) Lactic and fatty acids:

 Found in perspiration and sebaceous secretions , inhibit microbes on the

skin.

3) Lactoferrin and transferrin:

 Found in body secretions, plasma, and tissue fluid, trap iron for use by
human cells while preventing its use by microorganisms.
 Chemical barrier
4) Defensins:

 Short peptides found in blood plasma and mucous.

 They forms pores in the cytoplasmic membrane of a variety of bacteria

causing leakage of cellular needs.

5) Lysozyme and phospholipase:

 Found in tears, saliva and nasal secretions.

 Can breakdown the cell wall (breaks down peptidoglycan) of bacteria and
destabilize bacterial membranes – cause osmotic lysis.
 Chemical barrier
6) Cytokines:

 Low molecular weight, soluble proteins that are produced in response to

an antigen and function as chemical messengers for regulating the innate
and adaptive immune systems.

 Produced by virtually all immune cells, especially Th lymphocytes.

 E.g.: interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor alpha

(TNF-α).
 The barrier

Gastrointestinal tract Urogenital tract Respiratory tract

Any problem?
 i) the prevention of invasion of pathogens (by the barriers).

ii) the recognition (by the

receptors) of the invaders.
iii) the response to invasion/infection.
 Recognition of antigen by innate immunity
 Recognition of antigens are made by the receptors called pattern
recognition receptors (PRRs).

 The molecular sensors recognize particular overall molecular patterns of

the pathogen that are generally absent from the host.

 The pattern found on pathogens are called pathogen-associated

molecular patterns (PAMPs).
 Recognition of antigen by innate immunity
Pathogen-Associated Molecular Patterns (PAMPs):

 Pathogens, especially bacteria, have unique microbial structural patterns

of motifs that are not shared with their host (not found associated with
mammalian cells).

 It include combinations of sugars, certain proteins, particular lipid-bearing

molecules and some nucleic acid motifs.

 The molecules are shared by groups of related microbes.

 The structures are relatively invariant; that is, do not evolve rapidly.

 These molecules are essential for the survival of those organisms.

 In addition, unique molecules displayed on stressed, injured, infected, or

transformed human cells also act as PAMPs.
 Recognition of antigen by innate immunity

 Examples:

i) the flagellin of bacterial flagella.

ii) the peptidoglycan of Gram-positive bacteria.

iii) the lipopolysaccharide (LPS, also called endotoxin) of Gram-negative

bacteria.

iv) single and double-stranded RNA.

 Recognition of antigen by innate immunity
Pattern Recognition Receptors (PRRs):

 To recognize PAMPs - capable of binding specifically to conserved portions

of these molecules.

 Present:

i) in bloodstream and tissue fluid as soluble circulating proteins.

ii) bound on membranes of macrophages, neutrophils, dendritic cells,

endothelial cells and mucosal epithelial cells.

iii) within the phagolysosomes of phagocytes where they can interact with
PAMPs located within microbes that have been phagocytosed.

iv) in the cytosol of the cell.

Any problem?
i) the prevention of invasion of pathogens (by the barriers).
ii) the recognition (by the receptors) of the invaders.

iii) the response to

invasion/infection.
 The response to invasion/infection
 Detection of PAMPs brings multiple components of immunity into play.

 It includes:

i) natural killer cells action

ii) phagocytosis

iii) inflammation

iv) fever

v) soluble molecules action

vi) complement activation

 Natural killer cells
 NK cells function is to kill cells infected by virus and tumour cells

 NK cells release:

i) perforin (and other molecules) which form pores in the cell membrane
of the target cell.

ii) granzymes which induce apoptosis or cell lysis.

 Phagocytosis
 Definition: The process of ingestion of
solid substances (e.g. cells, bacteria,
parts of necrosed tissue) by phagocytes
and transported to a site within the
phagocytes where it is broken down by
lysosomal enzymes.

 Two most active phagocytes:

i) Neutrophils: engulf between 5 to 20

bacteria - become inactive and die.

ii) Macrophages: engulf up to 100

Neutrophil (yellow) engulfing
bacteria, debris from damaged cells and Bacillus anthracis (orange).

foreign matter.
 Phagocytosis

 How they work:

1) Chemotaxis: phagocytes
are attracted to site of
infection.

2) Microbe binds to
receptors on phagocyte.
Pseudopodia surround
microbe and engulf it.
 Phagocytosis

3) The pathogen is now

contained in phagosome @
phagocytic vesicle.
Phagosome moves deeper
into cell.

4) A lysosome fuses with

the phagosome – it forms
phagolysosome.
 Phagocytosis

5) Contents from lysosome

which contain hydrolytic
enzymes and antimicrobial
proteins digests the microbe
within the phagolysosome.

6) Content of lysosome further

digest the microbe, forming
the residual body containing
indigestible material.

7) Contents of phagolysosome
is eliminated by exocytosis.
 Phagocytosis

 After a few days, the area is full of

dead cells, which form pus.

 The contents of pus are dead

neutrophils, tissue debris and some
remaining pathogens.

 The pus may break through the

surface of the skin or broken down and
absorbed into the surrounding tissue.
 Inflammation
 Definition: the initial, rapid and localised response of the tissue due to
damage/injury, infection, antigen challenge and physical/chemical
damage or other trauma.

 Acute inflammation plays role in innate immunity by:

i) Destroying the infectious agent and remove it and its by products and
any cell debris.

ii) localize the infectious agents by building a ‘wall’ around them so that
they do not spread to neighbouring sites.

iii) Heal, repair, and replaced the damaged tissue.

 Inflammation
 The process of inflammation:

i) Damaged mast cells (found in the connective tissue below the skin and
around blood vessels) and WBC release chemicals, e.g. histamines.

ii) The chemicals cause:

- Vasodilation of the blood vessels around the site of infection, which

increase blood flow to that area, as well as bring loads of immune system
cells to the site of infection and removes toxic products released by
invading microbes.
 Inflammation
- Increase permeability of the blood
vessels, which allows extravasation (a
process where leukocytes adhere to
endothelial cells in the inflamed region
and pass through the walls of capillaries
and into the tissue spaces). The plasma,
leukocytes and antibodies move out of
the blood vessels and leak out into the
infected tissue.
 Inflammation
iii) Leukocytes phagocytose invading pathogens and release molecular
mediators that contribute to the inflammatory response and the
recruitment and activation of effector cells.

iv) Chemokines (mediators of inflammation) are induced in response to

infection. It will act as chemoattractants – cause leukocytes to move into
various tissue sites by inducing the adherence of these cells to the
vascular endothelium.
 Inflammation
v) Leukocytes move by chemotaxis toward the higher localized
concentrations of chemokines at the site of infection.

vi) neutrophils are the first to come, whilst activated macrophages secrete
IL-1, IL-6, TNF-α which induced changes observed in the acute
inflammatory response.
 Inflammation
vii) The localized changes of the site of inflammation:

- redden: due to increased blood flow.

- warm: due to increased metabolic activity.

- swollen: due to leakage of fluid from capillaries.

- painful: The inflammatory process may also stimulate nerves and cause
pain.

- loss of function: due to multiple causes.

xi) Inflammation normally resulted in fever.

 Fever
 When infection happens, hypothalamus reset a higher body temperature.

 Symptoms of fever are different between bacterial or viral infections.

 Mild fever play roles in innate immunity by:

i) Slowing down the rate of bacterial growth thus reducing the number of
microorganism to be combated.

ii) Causing the reduction of Fe2+ and Zn2+ which are needed by bacteria
for growth.

iii) Increasing the activity of phagocytes, T-lymphocytes and repair

process.
 Fever
 Infection by bacteria:

- the temperature rises steadily and remains fairly high until treatment is
successful or the body overcomes the infection.

- One of the hallmarks of a bacterial infection is local pain, pain that is in

a specific part of the body.

 Infection by virus:

- the temperature will shoot up high every time viruses burst out of the
cell and drop down towards normal again.

- In general, viral infections are systemic - involve many different parts of

the body or more than one body system at the same time.

e.g. a runny nose, cough, body aches, etc.

 Fever
 Pyrogen: substances that can cause fever, e.g. TNF (tumour necrosis
factor), IL-1 (Interleukin 1).

 Pyogen: agent that causes pus formation, e.g. S. aureus, S. pneumoniae,

K. pneumoniae.
 Soluble molecules
 Innate immune system utilizes a variety of soluble molecules and cell
membrane-bound receptors.

 Soluble molecules can be divided into 2 groups:

i) produced at the site of infection or injury, act locally.

Eg. Antimicrobial peptides (interferon, defensins, cathelicidins).

ii) produced at distant sites, arrive at their target tissues via the blood
stream.

Eg. Complement proteins, acute phase proteins.

 Soluble molecules
Interferons:

 When cells are infected with viruses, they produce interferons – diffuses
to the surrounding uninfected cells.

 Interferons are a family of protein secreted by viral infected cells.

 Interferon bind to interferon receptor on both infected and nearby cells.

 Soluble molecules
 It helps to prevent viruses spreading to uninfected cells by:

i) inducing the synthesis of host cell proteins to inhibit production of viral

proteins – prevent viral replication.

ii) enhance other immune cells e.g. natural killer cells.

iii) activate other non-specific immune response e.g. they promote

inflammation to bring immune system cells to the site of infection.
 Complement activation
 The complement system comprises a group of soluble proteins and
glycoproteins, many of which exist in inactive forms.

 Can be activated either by molecules that recognize PAMPs or by

antibodies binding to specific foreign antigens.

 The complement system also mediates opsonization, activation of

inflammation and clearance of immune complexes.

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complement.html