2023-10-12

Chapter 14
The Innate Immune Response

Overview of Innate immunity

• Refers to defenses that are present at birth
• Non-specific – act against all (most) microbes in the same way
• No memory component – cannot recall previous contact with an invader
• Always present - It is active before an infection occurs
• Responds rapidly

Includes:
• First line defenses
• Physical and chemical barriers that prevent microbes from entering
the body
• Second line defenses
• Components that act to eliminate microbes that have invaded body
tissues
• Cellular defenses
• Molecular defenses
• Fever and inflammation.

The first line of defense

Physical barriers

1. Skin
• Outer surface of skin consists
of dead cells and keratin (a
protective protein)
• Frequently shed – removes
microbes
• Dry – inhibits growth of microbes

• Skin infections are more common on moist areas of skin, or in moist

environments
• Outer layer of skin is an excellent defense – rarely penetrated by
microbes
• Most infections occur under the skin – after skin has been broken

• Some microbes are able to eat dead skin cells and oils secreted by the
skin https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3535073/
https://www.science.org/content/article/scientists-discover-secret-
• Results in body odor. behind-bad-body-odor

1
 2023-10-12

2. Mucous membranes
• Involved in fluid or gas exchange
• Offer less protection than the skin
• Line our “tracts” – ex. Digestive tract
• Secrete mucous – a glycoprotein – keeps membrane from drying (cracking)
• Traps microbes

• Mucociliary
escalator*

• Cilia sweep
mucous away
https://kids.frontiersin.org/articles/10.33
89/frym.2019.00106

3. Fluid flow

• Saliva, tears, urine*, vaginal secretions – move microbes away from the
body.

Antimicrobial substances
(Chemical barriers)
1. Acidity of body fluids and
skin
• Stomach acid – pH 2
• Destroys many
bacteria and toxins
• Skin – fatty acids and lactic
acid – pH 3 – 5
• Prevents growth of
many microbes
2. Lysozyme

• Enzyme that degrades

peptidoglycan
• Found in sweat, tears,
saliva, nasal secretions.

3. Lactoferrin

• Iron binding proteins in

milk, mucous

• Makes iron unavailable

to slow growth of
microbes
4. Defensins
• Short polypeptides

• Poke holes in microbial

membranes
• Produced by epithelial
cells*
5. The normal microbiota*
• Acquired shortly after birth
• Prevent growth of pathogens

• Competitive exclusion and Microbial antagonism.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5694486/ https://my.clevelandclinic.org/health/articles/22062-epithelium

2
 2023-10-12

The second line of defense

The cells of the immune system
• Leukocytes – white blood cells
• Always found in normal blood, but increase in response to infection
• Phagocytes – white blood cells that use phagocytosis to “eat” microbes.

Leukocytes – three broad groups

1. Granulocytes (aka PMNs)
• Have large granules in their cytoplasm – visible with light microscope

Three sub-groups
i. Basophils – weak phagocytes
• Secrete chemoattractants
• Release histamine – causes inflammation,
allergies
ii. Eosinophils

• Destroy large pathogens

• ex. Parasitic worms
• Produce extracellular digestive enzymes to attack a parasite
iii. Neutrophils – strong phagocytes
• Polymorphonuclear
• Can leave the blood and migrate into tissues to destroy invading microbes.

2. Mononuclear phagocytes
• Also have granules – but they are not visible under light microscope
i. Monocytes – initially non-phagocytic
• Leave blood, enter tissues and change into macrophages* – strong
phagocytes
• Often found in organs – filter out invading pathogens as blood passes
through https://pubmed.ncbi.nlm.nih.gov/19273209/

ii. Dendritic cells

• Phagocytize foreign material and bring it to the adaptive immune
system for ‘inspection’
• Antigen presentation

3. Lymphocytes – Three types:

• Natural killer cells (NK cells) https://www.frontiersin.org/articles/10.3389/fimmu.2017.01124/full

• Responsible for killing infected body cells and tumor cells

• Attack any body cell that displays unusual proteins in the
cytoplasmic membrane
• T and B lymphocytes – part of adaptive immunity.

3
 2023-10-12

Molecular defenses

1. The Complement
System*
• About 30 Proteins
that circulate in
blood
• Work together in a
cascade

• Action of one
protein
triggers
action of the
next
• Complement can be triggered
several ways:
• Small molecules binding to
the surface of invading
microbes.
https://www.youtube.com/watch?v=Uc4nq4Lazo4 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169806/

10

Result of activating the complement cascade

1. Opsonization
• Attach to microbes and act as a flag to attract phagocytes
• Increases phagocytosis by 1000x

2. Enhance inflammation
• Increase blood vessel
permeability

• Attract phagocytes to
infection site.

11

3. Lysis of foreign cells

• Formation of membrane attack

complexes (MACs)
• Pokes holes in membranes
• Kills Gram negative bacteria, but
not Gram positive bacteria.*

https://elifesciences.org/articles/77503
https://onlinelibrary.wiley.com/doi/10.1002/bies.201900074

12

4
 2023-10-12

The Inflammatory Response

• In response to tissue damage: blood vessels dilate, fluids leak and
leukocytes migrate into tissues
• More blood reaches area
• Allows phagocytes to enter tissues – increased phagocytosis
• Brings platelets* to form blood clots, and nutrients for faster repair.

13

Signs and symptoms of inflammation:

• Pain, swelling
• Heat, Redness

• Edema
• Loss of function.

https://www.verywellhealth.com/signs-of-inflammation-4580526

14

Fever
• Can be triggered by toxins, LPS or chemicals produced by the immune
system
Results in:
• Rapid muscle contraction (shivering)
• Increased temperature
Benefits:
• Faster phagocytosis

• Slows growth of heat limited microbes

• ex. E. coli prefers to grow at 37°C, growth slows at 40°C

• Faster metabolism - healing

• Up to a certain temperature, fever is a defense against disease
Drawbacks:
• Uncomfortable

• Fever above 43°C can cause death.

15

5
 2023-10-12

Anti-viral Interferons (IFNs)

• Produced when cells
detect viral RNA
• Released by
infected cells to
warn neighboring
cells
• Induces
neighboring cells
to enter into an
antiviral state
• Does not help
cells that are
already infected
• Neighboring
cells undergo
apoptosis if
infected.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2084215/

16

17

Innate vs Adaptive Immune Response

Innate Immune Adaptive Immune
System System
Major Elements
Soluble factors Lysozyme, complement, Antibody
acute phase proteins,
e.g. C-reactive protein
Cells Phagocytes T lymphocytes
Natural killer cells
Response of microbial infections
First contact + ++
Second contact + ++++
Non-specific, no Specific, memory
memory Resistance improved by
Resistance not repeated contact
improved by repeated
contact

18

6
 2023-10-12

https://www.health.mil/Military-Health-Topics/Health-Readiness/Immunization-Healthcare/Clinical-Consultation-
Services/Immunology-Basics

19

20

21

7
 2023-10-12

22