INNATE IMMUNITY

Chapter 2
 Innate Immunity
• Consists of the defenses against infection that
are ready for immediate action when a host is
attacked by a pathogen.
• Can be thought as the first responders
 2 parts of Innate Immune System
External Defense system Internal Defense System
• Consists of anatomical barriers designed to • Include cellular responses
keep microorganisms from entering the
body that recognized specific
• Composed of physical, chemical, and molecular components of
biological barriers.
• exam. Unbroken skin (keratin) and the pathogens.
mucosal membrane surfaces.
• Psoriasin- produced by human skin cells • Composed of both cells and
• Surfactant- produce in respiratory tract
• Lactic acid- soluble factors.
• Fatty acid
• Saliva • Cells that are capable of
•
•
Sweat
Hydrochloric acid
phagocytosis plays a major
•
•
Microbiota
Urine splashing
role in internal defense
• Coughing system.
• sneezing
 Pattern Recognition Receptors
• Are receptors encoded by the host’s genomic DNA
and act as sensors for extracellular infection.
• Once these receptors bind to a pathogen,
phagocytic cells become activated and are better
able to engulf and eliminate microorganisms.
• Chemokines and cytokines- chemical messengers
that make capillaries more permeable and recruit
additional phagocytic cells to the area of infection.
It also trigger Adaptive Immune respone.
 Cont.
• PRRs are enable to distinguish self from
nonself by recognizing substance known as
Pathogen-associated Molecular Patterns
(PAMPs).
• Example of PAMPs:
» Peptidoglycan in gram-positive bacteria
» Lipopolysaccharides in gram-negative bacteria
» Zymosan in yeast
» Flagellin in bacteria with flagellae.
 PRR example
1. Toll-like Receptor (TLR)- occurs mostly on
Monocytes, Macrophage, and Dendritic Cells.

- make up a large family of receptors located in

various cellular components.
 Other families of receptor:
1. C-type Lectin receptor (CLR)- are plasma membrane
receptors found on monocyte, macrophage, dendritic cell,
neutrophil, B cells and T cells.
» These receptors bind to mannan and Beta-glucans found in fungal cell walls.

2. Retinoic acid-inducible gene-I-like receptors (RLRs)-

recognizes RNA from RNA viruses in the cytoplasm of
infected cells and induces cytokines and type I Interferon
(inhibit viral replication and induce apoptosis in infected
cells).
3. Nucleotide-binding Oligomerization Domain-like receptors
(NLRs)-bind to ligands from microbial pathogens; ex.
Peptidoglycan, flagellin, viral RNA and fungal hyphae.
Pattern Recognition Receptors and Disease

• Crohn’s Disease- mutations in NLRs; a painful

inflammatory disease of the bowel.
• Systemic Lupus Erythematosus- autoimmune
disease; antibodies attacking self-nucleic
acids.
Internal Defense System in Soluble Factors:

Acute-phase Reactants- normal serum

constituents that rapidly increase or decrease
in concentration because of infection, injury,
or trauma to the tissues.
- positive acute-phase reactants-
increase concentration.
- negative acute-phase reactants-
decrease concentration; ex. Albumin and
transferrin.
 Positive Acute-phase Reactants
1. C-Reactive Protein (CRP)- antibody to the C-polysaccharide of pneumococci.
-Molecular weight: 118,000-144,000 daltons; structure that consists of
five identical subunits held together by noncovalent bonds.
-capable of opsonization, agglutination, precipitation, and activation of
complement by the classical pathway, promotes phagocytosis
-binding is calcium-dependent and nonspecific.
-main substrate: PHOSPHOCHOLINE (microbial membrane); binds also to small
ribonuclear proteins, phospholipids, peptidoglycan and other constituents of
bacteria, fungi and parasites.
- Half-life: 18 hours
-increasesly rapidly within 4-6 hours following infection, surgery, or other
traumas (viral infections, malignant diseases, bacterial infection, rheumatic
fever, TB, after heart attack, aging)
-reaching a peak value with 48 hours
-indicator of acute inflammation
Monitoring CRP in Cardiovascular disease:

CDC has recommended that:

<1mg/dL- low risk
1-3 mg/dL- average risk
>3 mg/dL- high risk
Normal levels in adult: 0.47-1.34 mg/L
Mean CRP level for people w/ no coronary artery disease
is 0.87 mg/L

-easily destroyed by heating serum @ 56 degree C for

30 mins.
 Positive Acute-phase Reactants
2. Serum Amyloid A (SAA)- an apolipoprotein that is
synthesized in the liver
-Molecular weight: 11,685 daltons
-normal levels: 5-8 ug/mL
- high affinity to HDL, transported via HDL
-act as chemical messenger, promotes phagocytosis;
increase more in bacterial infection than viral.
-reach peak between 24-48 hours after acute infection.
-increase in chronic inflammation, atherosclerosis, and
cancer
 Positive Acute-phase Reactants
3. Complement- series of serum proteins that is present and
contribute to inflammation.

4. Alpha1-Antitrypsin (AAT)- general plasma inhibitor of

proteases (elastase; degrade elastin and collagen, damages
lung tissue) released from leukocytes.
-counteract the effects of neutrophil and monocyte invasion
-AAT deficiency results premature emphysema (smoker,
exposure to noxious chemicals)
Premature Emphysema or Idiopathic pulmonary fibrosis-
destruction of parenchymal cells in the lungs
 Positive Acute-phase Reactants
5. Haptoglobin- MW: 100,000 daltons; binds
irreversibly to free hemoglobin during
intravascular hemolysis.
- provide protection against oxidative damage
mediated by free hemoglobin
-levels may drop because of intravascular
hemolysis
-increase in inflammation, stress, tissue necrosis
-Normal Levels: 40-290 mg/dL
 Positive Acute-phase Reactants
6. Fibrinogen- MW: 340,000 daltons; involved in
coagulation pathway.
- Normal Levels: 200-400 mg/dL
-critical to the healing process
-increase levels may at risk for developing
coronary artery disease.
 Positive Acute-phase Reactants
7. Ceruloplasmin- MW: 132,000 daltons; principal
copper-transporting protein
-act as enzyme by converting toxic ferrous ion (Fe2+)
to ferric form (Fe3+)
-Normal Levels: 20-40 mg/dL
-Wilsons Disease- depletion of ceruloplasmin;
genetic disorder, characterized by massive increase
of copper in the tissues.
Treatment: long-term chelation therapy to remove
copper or liver transplant.
 INFLAMMATION
• Body’s overall reaction to injury or invasion by an
infectious agent.

• The Five Cardinal Signs:

1. Redness (erythema, rubor)
2. Swelling (edema, tumor)
3. Heat (calor)
4. Pain (dolor)
5. Loss of function (functio laesa)