2.

Innate Immunity: Nonspecific Defenses of the Host

- serves as a first line of defense
- lacks the ability to recognize specific pathogens
- Lacks to provide the specific protective immunity that prevents re-
infection.
- functions immediately after birth and persists its activity
throughout life
2.1 Different lines and layers of defense
A.Innate
Lines(Non-specific
of defenseimmunity) Adaptive (Acquired)
Immunity
First line of defense Second line of defense Third line of defense
 Intact skin NK and phagocytic WBC Specialized lymphocytes: T
Mucous membranes  Inflammation cells
and their secretions Fever and B cells
 Normal microbiota Antimicrobial substances  Antibodies
 mucosal surfaces
skin
• microbes invade host through
bites
wounds
Covid-19 infect humans through?
Table 2.1 Routes of infection for pathogens
 B. Layers of defense
No Type
1 Anatomic barriers
 Skin
 Mucous membranes
2 Physiologic barriers
 Temperature
 Low pH
 Chemical mediators
3 Phagocytic/endocytic barriers
4 Inflammatory barriers
Mechanism
- Mechanical barrier retards entry of microbes.
- Acidic environment (pH 3–5) retards growth of microbes.
- Normal floras compete with microbes for attachment sites and nutrients.
- Mucus entraps foreign microorganisms.
- Cilia propel microorganisms out of body.
- Normal body temperature inhibits growth of some pathogens.
- Fever response inhibits growth of some pathogens.
- Acidity of stomach contents kills most ingested microorganisms.
- Lysozyme cleaves bacterial cell wall.
- Interferon induces antiviral state in uninfected cells.
- Complement lyses microorganisms or facilitates phagocytosis.
- Toll-like receptors recognize microbial molecules, signal cell to - secrete
immunostimulatory cytokines.
- Collectins disrupt cell wall of pathogen.
- Various cells internalize (endocytose) and break down foreign macromolecules.
-Specialized cells (blood monocytes, neutrophils, tissue macrophages) internalize
(phagocytose), kill, and digest whole microorganisms.
Tissue damage and infection induce leakage of vascular fluid, containing serum
proteins with antibacterial activity, and influx of phagocytic cells into the
affected area.
2.2 pattern recognition receptors (PRR)
• receptors for adaptive and innate immunity differ.
• Antibodies and T-cell receptors recognize details of molecular
structure and can discriminate with exquisite specificity
between antigens featuring only slight structural differences.
• receptors of innate immunity recognize broad structural motifs
that are highly conserved within microbial species but absent
from the host
• Such Ag detecting receptors are called PRR.
• The ability of PRR to distinguish between self and non-self is
perfect.
• Pathogen associated molecular patterns (PAMP) can be
recognized by a series of soluble pattern-recognition receptors
in the blood that function as opsonins and initiate the
complement pathways.
• PAMPS are molecules expressed on the surface of pathogens to be
detected by PRR found on the membrane of cells like
macrophages.
• Some of the PRRs are toll like receptors, mannose receptors,
LPS receptor (CD14) and scavenger receptors.
Table 2.3. Cell surface receptors recognizing non-self
 2.3 The complement system; induced innate
responses to infections
• The complement system is a part of the immune system that
enhances (complements) the ability of antibodies and
phagocytic cells to clear microbes and damaged cells from an
organism, promotes inflammation, and attacks the pathogen's
plasma membrane.
• Synthesized by hepatocytes and monocytes
• Over 30 proteins and protein fragments make up the
complement system
• sequential activation of the proteins may mediate protection
against microbial infection.
• On activation, the major functions of the complement system
are:
 Initiation of (acute) inflammation by direct activation of mast cells (C3a,
C5a).
 Attraction of neutrophils (chemotaxis) to the site of microbial attack or
chemotaxix (C5a).
 Enhancement of the attachment of the microbe to the phagocyte
(opsonization) (C3b).
 Killing of the microbe activating the membrane attack complex (lysis)
(C9).
• They account for about 10% of the globulin fraction of blood serum and
can serve as opsonines.
• Opsonine is a substance circulating in the blood (e.g. antibody or C3b)
that binds to an antigen and enhances its phagocytosis by a process called
opsonization.
• A number of molecules called ‘opsonins’ (‘to make more tasty’ – Greek)
do this by coating the microbe.
• Opsonization - the process of making a microbe easier to be
phagocytosized.
• Phagocytes use their surface receptors which bind to C3b, or
to the fragment crystallization region or Fc region of IgG
antibody (Fc receptors, FcR) to attach to C3b or IgG coating
the microbes, respectively.
• Biochemical pathways that activate the complement
system
a) alternative/properdin pathway
- have a pivotal role in innate immunity
- triggered directly on pathogen surfaces(Bacterial and
bacterial products)
b) classical pathway-
- activated by antibodies (adaptive immunity) bound to a microbe (antibody
antigen binding)
c) Lectin pathway
• It is activated by lectin binding to sugars on the bacterial cell surface
(mannose binding protein) or triggered by mannan binding lectin
• a normal serum constituent that binds some encapsulated bacteria.
 Figure 2. 2. Opsonin activity of lectin
The three main consequences of complement activation are:
 recruitment of inflammatory cells
opsonization of pathogens and
direct killing (lyses) of pathogens.
2.4 Determinants of innate immunity
• Genetic factors
• Age
• Humoral and metabolic conditions of the individual
• Nutritional status
2.5 Protective action of innate immunity
2.5.1 Physiological and chemical barriers
• temperature, pH, and various soluble and cell associated
molecules.
• soluble proteins like lysozyme, interferon, collectins, and
complement.
 Presence of pattern recognition receptors
2.5.2 Normal bacteria flora
• suppress the growth of many potentially pathogenic bacteria
and fungi by competition for essential nutrients, colonization
sites, or by production of inhibitory substances such as
colicins or acid.
• Anaerobic bacteria produce toxic metabolic products and free
fatty acids that inhibit other organisms.
2.6 Cellular defense
• neutrophils and macrophages (involved in phagocytosis),
basophils and mast cells (involved in inflammation) and B
cells and T cells accounts for antibody mediated immunity
and cell mediated immunity, respectively.
2.7 Biologically active substances
Activated macrophages secrete
- cytokines, which are defined as proteins released by cells that
affect the behavior of other cells bearing receptors for them.
- cytokines increase the permeability of blood vessels, allowing
fluid and proteins to pass into the tissues.
- also release proteins known as chemokines that attract cells
with chemokine receptors such as neutrophils and monocytes
from the bloodstream to the site of infections.
Bacterial infection triggers an inflammatory response.
 summary

Defense Mode of Antagonism

Anatomical structures (skin, hair, blinking, nose
Provide physical barriers or motion that sweeps
hairs, cilia in the lungs and the peristaltic action of
microbes out of areas of the body
the digestive track)
Many proteins and chemicals are created by the
Tissue bactericides
body that kill or inhibit the growth of microbes
The normal flora of the body prevents pathogens
Microbial antagonism
from colonizing and causing disease.
These proteins can be triggered by microbial
Complement proteins secretions or by antibodies. They alert the immune
system and can cause cell lysis.
A reaction to tissue damage that involves a large
Inflammation
collection of cells, proteins and chemicals.

Cells that attack microorganisms engulf them and

Phagocytes
kill them. They are a major defense of the body.

Cells that roam the body and attack cells coated in

Natural killer cells
IgG.