Defensive mechanisms include:

1) Innate immunity (Natural or Non-specific)

2) Acquired immunity (Adaptive or Specific)

or

1) Cell-mediated immunity
2) Humoral immunity

Independent of innate and acquired categorization.

Innate immune response to pathogen agents will affect and stimulates the process of acquired
immunity.

Innate and acquired immunity are synchronized.

Self and non-self discrimination is a property of immune system.

Innate immunity is phylogenetically older than acquired immunity.

Innate immunity’s response does not enhance after repetitive presentation of a pathogen.

Innate immunity (Natural or Non-specific):

a. First line
1. Mechanical barriers
2. Chemical & biochemical inhibitors
3. Normal flora
b. Second line
1. Cells
i. Natural killer
ii. Phagocytes
2. Soluble factors
3. Inflammatory barriers

First line:

1. Mechanical barriers:

 Intact skin
 Mucous coat
 Mucous secretion
 Coughing and sneezing reflex

Antimicrobial psoriasin protects human skin from Escherichia coli infection.

How epithelial barrier works:

1) Physical barrier
2) Killing microbes by locally produced antibiotics. (defensins, cathelicidins, psoriasin)
3) Killing microbes and infected cells by intraepithelial lymphocytes (IEC).

It’s important to note that not all lymphocytes take part in specific immunity.

IECs carry very few varieties of antigens on their surface.

2. Chemical & Biochemical inhibitors

 Antimicrobial peptides. (defensins, cathelicidins, psoriasin)

 Sweet and sebaceous secretion.
 Hydrolytic enzymes in saliva.
 HCl of the stomach.
 Proteolytic enzyme in small intestine.
 Lysozyme in tears.
 Acidic pH in the adult vagina

3. Normal bacterial flora

 Competition for essential nutrients and space

 Production of inhibitory substances
 Immunomodulators

Lack of Normal bacteria flora will result in inflammatory diseases and more infections.

While innate immunity receptors detect molecular patterns common among a several categories of
pathogens, the specific immunity has the capacity to detect pathogens separately and specifically.

PAMP: Pathogen Associated Molecular Pattern

PRR: Pattern Recognition Receptor (receptors of innate immunity)

PRRs have a low variety. And can only detect microbial molecular patterns.
 Related microbe PAMP

Reproducing viruses Double stranded RNA (dsRNA)

Bacteria unmethylated CpG motifs

Bacteria protein Protein starting with N formyl methionine

gram negative bacteria Lipo-poly-saccharides (LPL)

gram positive bacteria Teichoic acids (TA)

microbial glycoproteins mannose rich oligosaccharides

Motif is a distinctive sequence on a protein or DNA, having a three-dimensional structure that allows
binding interactions to occur.

The CpG sites or CG sites are regions of DNA where a cytosine nucleotide is followed by a guanine
nucleotide in the linear sequence of bases along its 5' → 3' direction. Cytosines in CpG dinucleotides
can be methylated to form 5-methylcytosines.

While in eukaryotes the beginning amino-acid of peptides is methionine, in prokaryotes it is N formyl

methionine.

PRR are innate immunity sensors and can exist in soluble and cell-associated forms.

A few well-known PRRs:

 PRR)
 C-type lectins
 Scavenger receptors
 N-formyl-Methionyl receptors
 NLRs (Nod-like receptors)

Gene-rearrangement (gene-recombination) is particular to specific immune response receptors, as a

really high number of receptors need to be produced from a limited DNA. In the case of innate immunity
receptors though, Gene-rearrangement is not required, because a limited number of receptors are
required.
Toll like receptors (TLR) are a group of receptors that exist both on cell membrane and on endosomal
membrane.

 Plasma membrane:
o TLR2: Bacterial peptidoglycan
o TLR4: LPS (lipopolysaccharide)
o TLR5: bacterial flagellin
o TLR2 + TLR6: Bacterial lipopeptides
o TLR2 + TLR1: Bacterial lipopeptides
 Endosome:
o TLR3: dsRNA
o TLR7: ssRNA
o TLR8: ssRNA
o TLR9: CpG DNA

PRR (cell-associated) Location Specific examples PAMP Ligands

Toll-like receptors Plasma and endosomal TLRs 1-9 Bacterial LPS,
(TLRs) membrane pf dendritic peptidoglycans, viral
cells, phagocytes, B nucleic acids
cells, etc.
Nod-like receptors Cytoplasm of Bacterial cell-wall
(NLRs) phagocytes peptidoglycans
Rig-like receptors Cytoplasm of Viral RNA
(RLRs) phagocytes
C-type lectin-like Plasma membrane of Microbial surface
receptors phagocytes carbohydrates
Scavenger receptors Plasma membrane of CD36 Microbial
phagocytes diacylglycerides
N-formyl Met-leu-phe Plasma membrane of Peptides containing N-
receptors phagocytes formyl methionyl
residues

Lectins are mannose detective proteins in body.

PRRs generally exist in phagocytes of innate immune system (macrophage, neutrophil, dendritic, etc.)

Soluble Recognition Location Specific examples PAMP ligands

molecules
Pentraxins Plasma C-reactive protein Microbial
(CRP) phosphorylcholine and
phosphatidylethanolamine
Collectins Plasma and alveoli Mannose-binding
lectin (MBL)
Ficolins Plasma
Complement Plasma
CRP helps with opsonization of microbes. CRP is a very well-known Opsonil. Opsonils do the
opsonization process.

CRP can also activate complement proteins.

CPR amount in blood significantly increases during infective and un-infective inflammation. Such
proteins that increase during inflammation are named acute phase proteins.

Because of the tight and close correlation between CRP concentration and the status of inflammation, it
is used to assess the treatment progress of the patient.

Collectins are Soluble forms of lectin.

cell-associated PRRs can activate their respective cells or opsonize microbes.

Soluble PRRs clean the blood and other liquids from microbes, or activate neutralizing mechanisms.