05: Innate Immunity 1

Cellular component that straddles innate and adaptive immune systems

Gamma-delta T cells

Non-cellular component that straddles innate and adaptive immune systems

Polyreactive antibodies

Types of immunological barriers

Physical and chemical

Examples of immunological barriers in the respiratory tract

• Hair

• Turbinate bones

• Cilia

• Mucus

• Coughing

• Sneezing

Examples of immunological barriers in the GIT

• Saliva

• Acidic pH

• Bile

Examples of immunological barriers in the urinary tract

• Acidic pH

• Urination

Normal microflora immune function

• Competes with other potential pathogens

• Keeps immune system on its toes

Sentinel cell function

Recognize and respond to invading microbes; first alarm to engage immune system

Types of sentinel cells

• Resident macrophages

• Dendritic cells

• Mast cells

Where are the highest number of sentinel cells found

Below the surface

Where are most immune components found

Blood

Bone macrophage

Osteoclast

CNS macrophage

Microglia

Skin macrophage

Langerhans cell

Liver macrophage

Kupffer cells

Lung macrophage

Alveolar macrophage

Common types of macrophage receptors

• Scavenger

• Mannose

• LPS

• Antibody

Examples of macrophage membrane receptors

• TLR

• NOD like

• Lectin

• Rig like

How do sentinel cells produce inflammation

• Widens capillaries

• Increases permeability

• Attracts leukocytes

• Recruits systemic response

First immune cells to migrate to a tissue post injury

Neutrophils

Steps of immune cell extravasation and migration to tissues

1. Tethering

2. Rolling: until receptors bind

3. Activation: receptor recognition

4. Adhesion: complete stop of cellular movement and attachment to vessel wall

5. Transmigration

6. Chemotaxis: follows chemoattractants to site

Adhesion molecules on immune cells

Selectins and integrins

Neutrophil life span

Hours or days

Do neutrophils return to blood after responding to inflammation

No, they die :)

Neutrophil defense mechanisms

• Phagocytosis

• Degranulation

• NETs of DNA, histones, and granules

Added function of neutrophilic death in tissues

Recruits monocytes (which turn into macrophages)

What limits the amount of phagocytosis a neutrophil can do

It has limited energy stores

5 specific immune functions of macrophages

1. Recruits other immune cells via cytokines

2. Longer phagocytotic activity than neutrophils

3. Antigen presenting cells

4. Part of tissue repair

5. Helps control and stop the inflammation response

Types of receptors needed on a macrophage

• For sentinel function (PRRs)

• For phagocytotic function (binds to Abs)

• For APC function (ex: MHC)

MHC class 1 v class 2

Class 1 is present in most cells, class 2 is specifically for presenting to naive T cells

Molecules that attract macrophages

• Chemoattractants

• Elastase

• Collagenase

What signaling molecule activates macrophages to enhance phagocytotic activity

IFN-γ

What is IFN-γ secreted by

NK cells and Th-cells

What causes macrophages to become hyper activated

Detection of bacterial products, like LPS

Changes in macrophages due to hyperactivation

Increased expression of MHC II

Structure that can be formed by hyperactivated macrophages in chronic infections

They are called epithelioid cells, and can fuse into giant cells to wall of and digest large pathogens

Very toxic component produced by macrophages

Nitric oxide (NO)

What other toxic derivatives can NO produce when reacted with superoxide

Peroxynitrite and nitrogen dioxide

How do macrophages help in the healing process

• Secretes proteases to break down CT (scars!)

• Regulates collagenase and fibroblast activity

• Secretes GFs for tissue remodeling

“M1” macrophage

Classically activated; phagocytotic cells that process antigens and help produce inflammation

“M2” macrophage

Alternatively activated macrophages; helps in healing and reducing inflammation