Innate immunity

Barrier defenses (1st line defense)

Mechanical/Physical barriers

ex. skin

preventing
microbes from reaching tissues

tightly joined

Chemical barriers

ex. low stomach pH, lysozyme

Biological barriers

ex. normal flora

is the term used to describe various bacteria and fungi that are permanent residents of certain body sites

Innate immune response (2nd line defense)

Characteristic of innate immunity

Rapid/quick response

Non-specific responses

No memory

Innate immune cell activation by PAMPs and DAMPs

PAMPs

Derived from components of microorganisms (pathogens)

Exogenous stimuli

DAMPs

Derived from host cells such as tumor cells, dead or dying cells, products released from cells, tissue damage, etc

Endogenous stimuli

Microbe recognition by innate immune cell PRRs

PRRs are able to recognize molecules associated with pathogens i.e. PAMPs and DAMPs

PRRs can be found on the innate immune cells

Major type of PRRs

Toll-like receptors (TLRs)

NOD-like receptors (NLRs)

RIG-like receptors (RLRs)

C-type lectin receptors (CLRs)

Tissue innate immune cells

Intraepithelial lymphocyte (IELs)

are lymphocytes found in the epithelial layer of mammalian mucosal linings

an effective first line of defense

Macrophages

secretes inflammatory cytokines that support immune responses.

Peripheral blood immune cells

NK cells

-recognize MHC I
-Produce high levels of cytokines

Neutrophils

are important effector cells in the innate arm of the
immune system.

Dendritic cells

are professional antigen-presenting cells

Eosinophils

is involved in host protection against parasite infection and
immunopathology in hypersensitivity disease

Basophils

Monocytes

Humoral substances of innate immunity

Cytokines, mediators, complement system

Inflammation and cell recruitment

Acute inflammation

Features:

Involves the innate immune system

5 cardinal signs: redness, increased heat, swelling, pain, loss of function

Outcomes:

1. Local hemodynamic changes (vasoconstriction → vasodilation)
2. Increase in vascular permeability
3. Extravasation of leukocytes
4. Phagocytosis
5. Outcome of inflammatory response

Chronic inflammation

Features:

Prolonged exposure to toxic pathogens

Mechanism involves with:

Pro-inflammatory(IFN-γ)and anti-inflammatory (IL-4andIL-13)

Outcomes:

• Scarring
• Amyloidosis
• Neoplasia

Stimulation of adaptive immunity (3rd line defense)

Interplay between innate and adaptive immunity

Activation of adaptive immunity

T cell activation and differentiation (Th1 and Th2)

Th1
-cell-mediated immunity and inflammation
-intracellular pathogens
-autoimmunity
-inflammation

Th2
-antibody-mediated immunity
-extracellular parasites
-asthma, allergy

Anti-viral immunity

type I IFNs (α/ß) or IFN-I

primary source of IFN-I for antiviral responses

detect RNA and DNA viruses with two endosomal sensors, TLR7
and TLR9